Editing MPEP 2400

{{MPEP Chapter|2300|2500}}

'''<big>Chapter 2400 Biotechnology</big>'''

<div class="noautonum">__TOC__</div>

==2401 Introduction==

This chapter provides guidance on the practices and 
procedures for implementation of the deposit rules 
(37 CFR 1.801 - 1.809) and the sequence rules 
(37 
CFR 1.821 - 1.825). The final rule for deposits of 
biological materials for patent purposes was published 
in the Federal Register, 54 FR 34864 (August 22, 
1989) and in the Official Gazette, 1106 O.G. 37 (September 
12, 1989). The deposit rules went into effect 
on January 1, 1990. Revised deposit rules were published 
in the Federal Register at 66 FR 21090 (April 
27, 2001) and in the Official Gazette at 1246 O.G. 104 
(May 22, 2001) and went into effect on May 29, 2001. 
The final rule for the requirements for patent applications 
containing nucleotide sequence and/or amino 
acid sequence disclosures was published in the Federal 
Register, 55 FR 18230 (May 1, 1990) and in the 
Official Gazette, 1114 O.G. 29 (May 15, 1990) and 
went into effect on October 1, 1990. Revised 
sequence rules were published in the Federal Registerat 63 FR 29620 (June 1, 1998) and in the Official 
Gazette at 1121 O.G. 82 (June 23, 1998) and went into 
effect on July 1, 1998.

 Further revisions to the sequence rules were published 
in the Federal Register at 65 FR 54604 (September 
8, 2000) and in the Official Gazette at 1238 
O.G. 145 (September 19, 2000) and went into effect 
on September 8, 2000.

Additional information regarding the development 
of the deposit rules can be obtained in the text of the 
draft policy statement, published in BNA’s Patent, 
Trademark and Copyright Journal, 32 PTCJ 781 at 
76, 90 (May 22, 1986), the advanced notice of proposed 
rulemaking, published in the Federal Register, 
52 FR 34080 (September 9, 1987), and in the Official 
Gazette, 1082 O.G. 47 (September 29, 1987) and in 
the notice of proposed rulemaking, published in the 
Federal Register, 53 FR 39420 (October 6, 1988), and 
in the Official Gazette, 1095 O.G. 47 (October 25, 
1988). Additional information regarding the development 
of the sequence rules can be obtained in the text 
of the notice of proposed rulemaking, published in the 
Federal Register, 54 FR 18671 (May 2, 1989) and in 
the Official Gazette, 1102 O.G. 34 (May 16, 1989).

See MPEP § 803.04 and § 1850 for restriction and 
unity of invention practice respectively in patent 
applications claiming independent and distinct nucleotide 
sequences. See also MPEP § 2434.

2402The Deposit Rules

Every patent must contain a written description of 
the invention sufficient to enable a person skilled in 
the art to which the invention pertains to make and 
use the invention. Where the invention involves a biological 
material and words alone cannot sufficiently 
describe how to make and use the invention in a 
reproducible manner, access to the biological material 
may be necessary for the satisfaction of the statutory 
requirements for patentability under 35 U.S.C. 112. 
Courts have recognized the necessity and desirability 
of permitting an applicant for a patent to supplement 
the written disclosure in an application with a deposit 
of biological material which is essential to meet some 
requirement of the statute with respect to the claimed 
invention. See, e.g., Ajinomoto Co. v. Archer-Daniels-
Midland Co., 228 F.3d 1338, 1345-46, 56 USPQ2d 
1332, 1337-38 (Fed. Cir. 2000), cert. denied, 121 
S.Ct. 1957 (2001)(explaining how deposit may help 
satisfy enablement requirement); Merck and Co., Inc. 
v. Chase Chemical Co., 273 F. Supp. 68, 155 USPQ 
139 (D. N.J. 1967); In re Argoudelis, 434 F.2d 666, 
168 USPQ 99 (CCPA 1970). To facilitate the recognition 
of deposited biological material in patent applications 
throughout the world, the Budapest Treaty on 
the International Recognition of the Deposit of Microorganisms 
for the Purposes of Patent Procedure was 
established in 1977, and became operational in 1981. 
The Treaty requires signatory countries, like the 
United States, to recognize a deposit with any depository 
which has been approved by the World Intellectual 
Property Organization (WIPO). 

The deposit rules (37 CFR 1.801 - 1.809) set forth 
examining procedures and conditions of deposit 
which must be satisfied in the event a deposit is 
required. The rules do not address the substantive 
issue of whether a deposit is required under any particular 
set of facts. 




 

The rules are effective for all applications filed on 
or after January 1, 1990, and for all reexamination 
proceedings in which the request for reexamination 
was filed on or after January 1, 1990, except that 
deposits made prior to the effective date which were 
acceptable under the then current practice will be 
acceptable in such applications and proceedings. 
Since most of the provisions of the rules reflect policy 
and practice existing prior to January 1, 1990, little 
change in practice or burden on applicants for patent 
and patent owners relying on the deposit of biological 
material has occurred. Applicants and patent owners 
are encouraged to comply with these rules even if 
their applications and reexamination proceedings 
were filed prior to January 1, 1990. 

2403Deposit of Biological Material 

37 CFR 1.801. Biological material.

For the purposes of these regulations pertaining to the deposit 
of biological material for purposes of patents for inventions under 
35 U.S.C. 101, the term biological material shall include material 
that is capable of self-replication either directly or indirectly. 
Representative examples include bacteria, fungi including yeast, 
algae, protozoa, eukaryotic cells, cell lines, hybridomas, plasmids, 
viruses, plant tissue cells, lichens and seeds. Viruses, vectors, cell 
organelles and other non-living material existing in and reproducible 
from a living cell may be deposited by deposit of the host cell 
capable of reproducing the non-living material.

37 CFR 1.801 indicates that the rules pertaining to 
deposits for purposes of patents for inventions under 
35 U.S.C. 101 are intended to relate to biological 
material. For the purposes of these rules, the term 
“biological material” is defined in terms of a non-
exhaustive list of representative materials which can 
be deposited in accordance with the procedures 
defined in these rules. These rules are intended to 
address procedural matters in the deposit of biological 
material for patent purposes. They are not designed to 
decide substantive issues such as whether a deposit of 
a particular organism or material would be recognized 
or necessary for the purposes of satisfying the statutory 
requirements for patentability under 35 U.S.C. 
112. Although the issue of the need to make a deposit 
of biological material typically arises under the 
enablement requirement of the first paragraph of 
35 
U.S.C. 112, the issue could also arise under the 
description requirement (35 U.S.C. 112, first paragraph), 
best mode requirement (35 U.S.C. 112, first 
paragraph) or the requirements of the second paragraph 
of 35 U.S.C. 112 with respect to the claims. 

37 CFR 1.801 does not attempt to identify what 
biological material either needs to be or may be 
deposited to comply with the requirements of 
35 
U.S.C. 112. For the most part, this issue must be 
addressed on a case-by-case basis. Thus, while the 
Office does not currently contemplate that there 
would be any situations where a material that is not 
capable of self-replication either directly or indirectly 
would be acceptable as a deposit, an applicant is 
clearly not precluded by these rules from attempting 
to show in any given application why the deposit of 
such a material should be acceptable to satisfy the 
requirements of 35 U.S.C. 112.

2403.01Material Capable of Self-
Replication

Biological material includes material that is capable 
of self-replication either directly or indirectly. Direct 
self-replication includes those situations where the 
biological material reproduces by itself. Representative 
examples of materials capable of self-replication 
are defined in the rule. Indirect self-replication is 
meant to include those situations where the biological 
material is only capable of replication when another 
self-replicating biological material is present. Self-
replication after insertion in a host is one example of 
indirect self-replication. Examples of indirect replicating 
biological materials include viruses, phages, 
plasmids, symbionts, and replication defective cells. 
The list of representative examples of each type of 
replicating material includes viruses to demonstrate 
that the two lists in the rule are not intended to be 
mutually exclusive.

2403.02Plant Material 

Although plant material is included within the 
scope of the definition of biological material for purposes 
of patents for plant inventions under 35 U.S.C. 
101, the rules on deposits are not applicable to applications 
filed under the Plant Patent Act (35 U.S.C. 
161-164). The Office is of the view that a deposit is 
not required under the present provisions of 35 U.S.C. 
162. Thus, a deposit is not necessary for the grant of a 
plant patent under the provisions of 35 U.S.C. 161-
164. As with other biological material deposited for 




 

purposes of patents for inventions under 35 U.S.C. 
101, the deposit of plant material together with the 
written specification must enable those skilled in the 
art to make and use the claimed invention, in accordance 
with the requirements of 35 U.S.C. 112. 

As with some types of reproducible biological 
material, seeds can be reproduced only after a growing 
season which may be relatively long. Although 
the rules do not specify a specific number of seeds to 
be deposited to meet the requirements of these rules, 
the Office will consider 2500 to be a minimum number 
in the normal case, but will give an applicant the 
opportunity to provide justification why a lesser number 
would be suitable under the circumstances of a 
particular case. The Department of Agriculture 
requires a deposit of 2500 seeds for the grant of a 
Plant Variety Protection Certificate under the Plant 
Variety Protection Act (7 U.S.C. 2321 et seq.). As the 
reproduction of seeds will often take a substantial 
period of time, the Office will require, at a minimum 
for the grant of a patent, a number of seeds that is 
likely to satisfy demand for samples once the patent is 
granted. In one instance, the Office accepted a deposit 
of 600 seeds coupled with an undertaking to deposit 
1900 more seeds with due diligence. The particular 
situation involved a “seedless” vegetable with very 
few seeds per “fruit;” about two growing seasons 
were required to provide the additional 1900 seeds.

2404Need or Opportunity to Make
a Deposit

37 CFR 1.802. Need or opportunity to make a deposit.

(a)Where an invention is, or relies on, a biological material, 
the disclosure may include reference to a deposit of such biological 
material.

(b)Biological material need not be deposited unless access 
to such material is necessary for the satisfaction of the statutory 
requirements for patentability under 35 U.S.C. 112. If a deposit is 
necessary, it shall be acceptable if made in accordance with these 
regulations. Biological material need not be deposited, inter alia, 
if it is known and readily available to the public or can be made or 
isolated without undue experimentation. Once deposited in a 
depository complying with these regulations, a biological material 
will be considered to be readily available even though some 
requirement of law or regulation of the United States or of the 
country in which the depository institution is located permits 
access to the material only under conditions imposed for safety, 
public health or similar reasons.

(c)The reference to a biological material in a specification 
disclosure or the actual deposit of such material by an applicant or 
patent owner does not create any presumption that such material is 
necessary to satisfy 35 U.S.C. 112 or that deposit in accordance 
with these regulations is or was required.

37 CFR 1.802(a) permits a deposit of a biological 
material to be referenced in a patent application where 
an invention is, or relies on, a biological material. 
The invention may rely on a biological material for 
the purposes of making or using the invention, either 
as a preferred mode or an alternative mode of operation. 
A reference to a deposit may be included in a 
specification even though the deposit is not required 
to satisfy the requirements of 35 U.S.C. 112.

There is no necessary implication or presumption 
that can or should be made about the need for a 
deposit simply because reference to a deposit is made 
in an application disclosure, as noted in paragraph (c). 
As noted in paragraph (b), biological material need 
not be deposited unless access to such material is necessary 
for the satisfaction of the statutory requirements 
for patentability under 35 U.S.C. 112 and that 
access is not otherwise available in the absence of a 
deposit. Where a deposit is required to provide the 
necessary access, a deposit is acceptable for patent 
purposes only where it is made in accordance with 
these regulations. Even where access to biological 
material is required to satisfy these statutory requirements, 
a deposit may not be necessary if access sufficient 
to satisfy these requirements is otherwise 
available.

2404.01Biological Material That Is
Known and Readily Available
to the Public

In an application where the invention required 
access to specific biological material, an applicant 
could show that the biological material is accessible 
because it is known and readily available to the public. 
The concepts of “known and readily available” are 
considered to reflect a level of public accessibility to a 
necessary component of an invention disclosure that 
is consistent with an ability to make and use the 
invention. To avoid the need for a deposit on this 
basis, the biological material must be both known and 
readily available - neither concept alone is sufficient. 
A material may be known in the sense that its existence 
has been published, but is not available to those 
who wish to obtain that particular known biological 
material. Likewise, a biological material may be 




 

available in the sense that those having possession of 
it would make it available upon request, but no one 
has been informed of its existence.

The Board of Patent Appeals and Interferences has 
held that a description of the precise geographic location 
of marine tunicates, as a biological material, used 
in a claimed invention was adequate to satisfy the 
enablement requirement of 35 U.S.C. 112. Ex Parte 
Rinehart, 10 USPQ2d 1719 (Bd. Pat. App. & Int. 
1985). The term “readily” used in the phrase “known 
and readily available” is considered appropriate to 
define that degree of availability which would be reasonable 
under the circumstances. If the biological 
material and its natural location can be adequately 
described so that one skilled in the art could obtain it 
using ordinary skill in the art, the disclosure would 
appear to be sufficient to meet the enablement 
requirement of 35 U.S.C. 112 without a deposit so 
long as its degree of availability is reasonable under 
the circumstances. 

By showing that a biological material is known and 
readily available or by making a deposit in accordance 
with these rules, applicant does not guarantee 
that such biological material will be available forever. 
Public access during the term of the patent may affect 
the enforceability of the patent. Although there is a 
public interest in the availability of a deposited biological 
material during and after the period of 
enforceability of the patent, there should not be any 
undue concern about continued access to the public. 
See 37 CFR 1.806 (the term of deposit is “at least 
thirty (30) years and at least five (5) years after the 
most recent request” for a sample; the agreement sufficiently 
ensures that the deposit will be “available 
beyond the enforceable life of the patent”). Unless 
there is a reasonable basis to believe that the biological 
material will cease to be available during the 
enforceable life of the patent, current availability 
would satisfy the requirement. The incentives provided 
by the patent system should not be constrained 
by the mere possibility that a disclosure that was once 
enabling would become non-enabling over a period of 
time through no fault of the patentee. In re Metcalfe, 
410 F.2d 1378, 161 USPQ 789 (CCPA 1969).

If an applicant has adequately established that a 
biological material is known and readily available, the 
Office will accept that showing. In those instances, 
however, the applicant takes the risk that the material 
may cease to be known and readily available. Such a 
defect cannot be cured by reissue after the grant of a 
patent.

On the other hand, Ex parte Humphreys, 
24 
USPQ2d 1255 (Bd. Pat. App. & Int. 1992), held 
that the only manner in which applicants could satisfy 
their burden of assuring public access to the needed 
biological material, and, thereby, compliance with the 
enablement requirement of 35 U.S.C. 112, was by 
making an appropriate deposit. The fact that applicants 
and other members of the public were able to 
obtain the material in question from a given depository 
prior to and after the filing date of the application 
in issue did not establish that upon issuance of a 
patent on the application that such material would 
continue to be accessible to the public. The applicants 
did not make of record any of the facts and circumstances 
surrounding their access to the material in 
issue from the depository, nor was there any evidence 
as to the depository’s policy regarding the material if 
a patent would have been granted. Further, there was 
no assurance that the depository would have allowed 
unlimited access to the material if the application had 
matured into a patent.

There are many factors that may be used as indicia 
that a biological material is known and readily available 
to the public. Relevant factors include commercial 
availability, references to the biological material 
in printed publications, declarations of accessibility 
by those working in the field, evidence of predictable 
isolation techniques, or an existing deposit made in 
accordance with these rules. Each factor alone may or 
may not be sufficient to demonstrate that the biological 
material is known and readily available. Those 
applicants that rely on evidence of accessibility other 
than a deposit take the risk that the patent may no 
longer be enforceable if the biological material necessary 
to satisfy the requirements of 35 U.S.C. 112ceases to be accessible.

The Office will accept commercial availability as 
evidence that a biological material is known and 
readily available only when the evidence is clear and 
convincing that the public has access to the material. 
See the final rule entitled “Deposit of Biological 
Materials for Patent Purposes,” 54 FR 34864, 34875 
(August 22, 1989). A product could be commercially 
available but only at a price that effectively eliminates 
accessibility to those desiring to obtain a sample. The 




 

relationship between the applicant relying on a biological 
material and the commercial supplier is one 
factor that would be considered in determining 
whether the biological material was known and 
readily available. However, the mere fact that the biological 
material is commercially available only 
through the patent holder or the patent holder’s agents 
or assigns shall not, by itself, justify a finding that the 
necessary material is not readily available, absent reason 
to believe that access to the biological material 
would later be improperly restricted.

The mere reference to a deposit or the biological 
material itself in any document or publication does 
not necessarily mean that the deposited biological 
material is readily available. Even a deposit made 
under the Budapest Treaty and referenced in a United 
States or foreign patent document would not necessarily 
meet the test for known and readily available 
unless the deposit was made under conditions that are 
consistent with those specified in these rules, including 
the provision that requires, with one possible 
exception (37 CFR 1.808(b)), that all restrictions on 
the accessibility be irrevocably removed by the applicant 
upon the granting of the patent. Ex parte Hildebrand, 
15 USPQ2d 1662 (Bd. Pat. App. & Int. 1990).

A Budapest Treaty deposit cited in a U.S. patent 
need not be made available if it was not required to 
satisfy 35 U.S.C. 112. For this reason, 37 CFR 
1.808(c) provides that upon request made to the 
Office, the Office will certify whether a deposit has 
been stated to have been made under conditions 
which make it available to the public as of the issue 
date. See 37 CFR 1.808(c) and MPEP § 2410.02 for 
the requirements of the request. The Office will not 
certify that the aforementioned statement has been 
made unless 

(A)the deposit was necessary to overcome a 
rejection under 35 U.S.C. 112,

(B)there is, in the record, a statement by the 
examiner that a rejection would have been made “but 
for” the deposit (assumes deposit information in 
record, as filed), or 

(C)the record otherwise clearly indicates that 
the deposit was made under Budapest Treaty, and that 
all restrictions imposed by the depositor on the availability 
to the public of the deposited material will be 
irrevocably removed upon the granting of the patent 
(with the possible exception of requiring the request 
for the deposit to be in the format specified in 37 CFR 
1.808(b)).

 If a deposit is not made under the conditions 
set forth in 37 CFR 1.808(a), the deposit cannot be 
relied upon for other purposes, e.g., the deposit cannot 
be relied upon by a third party to establish “known” 
and “readily available” in another application. See 37 
CFR 1.808 and MPEP § 2410 and § 2410.02.

Once a deposit is made in a depository complying 
with these rules, and under conditions complying with 
these rules, a biological material will be considered to 
be readily available even though some requirement of 
law or regulation in the United States or in the country 
where the depository institution is located permits 
access to the material only under conditions imposed 
for health, safety or similar reasons. This provision is 
consistent with the Budapest Treaty (Article 5) and is 
designed to permit the patenting of inventions involving 
materials having restricted distribution, where the 
restrictions are imposed for the public, as opposed to 
the private, welfare.

2404.02Biological Material That Can Be
Made or Isolated Without Undue
Experimentation

Applicant may show that a deposit is not necessary 
even though specific biological materials are required 
to practice the invention if those biological materials 
can be made or isolated without undue experimentation. 
Deposits may be required to support the claims if 
an isolation procedure requires undue experimentation 
to obtain the desired biological material. Ex Parte 
Jackson, 217 USPQ 804 (Bd. App. 1982). No deposit 
is required, however, where the required biological 
materials can be obtained from publicly available 
material with only routine experimentation and a reliable 
screening test. Tabuchi v. Nubel, 559 F.2d 1183, 
194 USPQ 521 (CCPA 1977); Ex Parte Hata, 6 
USPQ2d 1652 (Bd. Pat. App. & Int. 1987).

2404.03Reference to a Deposit in
the Specification

37 CFR 1.802(c) specifically provides that the mere 
reference to a biological material in the specification 
disclosure or the actual deposit of such material does 
not create any presumption that such referenced or 
deposited material is necessary to satisfy 35 U.S.C. 




 

112, or that a deposit in accordance with these regulations 
is or was required. It should be noted, however, 
that a reference to a biological material, present in an 
application upon filing, may form the basis for making 
a deposit, where required, after the filing date of a 
given application but that the reference to the biological 
material, itself, cannot be added after filing without 
risking the prohibited introduction of new matter 
(35 U.S.C. 132). See the discussion of the Lundak 
application in MPEP § 2406.01.

2405Acceptable Depository 

37 CFR 1.803. Acceptable depository.

(a)A deposit shall be recognized for the purposes of these 
regulations if made in

(1)any International Depositary Authority (IDA) as 
established under the Budapest Treaty on the International Recognition 
of the Deposit of Microorganisms for the Purposes of 
Patent Procedure, or

(2)any other depository recognized to be suitable by the 
Office. Suitability will be determined by the Commissioner on 
the basis of the administrative and technical competence, and 
agreement of the depository to comply with the terms and conditions 
applicable to deposits for patent purposes. The Commissioner 
may seek the advice of impartial consultants on the 
suitability of a depository. The depository must:

(i)Have a continuous existence;

(ii)Exist independent of the control of the depositor;

(iii)Possess the staff and facilities sufficient to examine 
the viability of a deposit and store the deposit in a manner 
which ensures that it is kept viable and uncontaminated;

(iv)Provide for sufficient safety measures to minimize 
the risk of losing biological material deposited with it;

(v)Be impartial and objective;

(vi)Furnish samples of the deposited material in an 
expeditious and proper manner; and

(vii)Promptly notify depositors of its inability to furnish 
samples, and the reasons why.

(b)A depository seeking status under paragraph (a)(2) of 
this section must direct a communication to the Commissioner 
which shall:

(1)Indicate the name and address of the depository to 
which the communication relates;

(2)Contain detailed information as to the capacity of the 
depository to comply with the requirements of paragraph (a) 
(2) of this section, including information on its legal status, 
scientific standing, staff and facilities;

(3)Indicate that the depository intends to be available, 
for the purposes of deposit, to any depositor under these 
same conditions;

(4)Where the depository intends to accept for deposit 
only certain kinds of biological material, specify such kinds;

(5)Indicate the amount of any fees that the depository 
will, upon acquiring the status of suitable depository under paragraph 
(a) (2) of this section, charge for storage, viability statements 
and furnishings of samples of the deposit.

(c)A depository having status under paragraph (a)(2) of this 
section limited to certain kinds of biological material may extend 
such status to additional kinds of biological material by directing a 
communication to the Commissioner in accordance with paragraph 
(b) of this section. If a previous communication under paragraph 
(b) of this section is of record, items in common with the 
previous communication may be incorporated by reference.

(d)Once a depository is recognized to be suitable by the 
Commissioner or has defaulted or discontinued its performance 
under this section, notice thereof will be published in the Official 
Gazette of the Patent and Trademark Office.

37 CFR 1.803 indicates that a depository will be 
recognized as acceptable for the purposes of these 
regulations if it is either an International Depositary 
Authority (IDA) established under the Budapest 
Treaty, or if it is a depository recognized as suitable 
by the Commissioner. After the effective date of these 
regulations, a deposit of biological material which is 
made in a depository which is not recognized as 
acceptable under this regulation will not be considered 
as satisfying the requirements of 35 U.S.C. 112. 
See Ex parte Humphreys, 24 USPQ2d 1255 (Bd. Pat. 
App. & Int. 1992). On the other hand, if a deposit is 
not required to satisfy the requirements of 35 U.S.C. 
112, it is permissible to make reference to such a 
deposit even though it may not be in a depository or 
made under the conditions which are acceptable under 
these regulations. As new depositories are recognized 
as suitable by the Commissioner, their identity will be 
announced in the Official Gazette.

An organization may be recognized as suitable by 
the Office if the procedure and conditions specified in 
37 CFR 1.803(a)(2) and 37 CFR 1.803(b) are followed. 
Generally, it is not the intention of the Office 
to recognize as suitable any organization where the 
need for a suitable depository for patent purposes is 
being met by depositories recognized as IDAs under 
the Budapest Treaty. Suitability will be judged by the 
Commissioner, based on need and the information 
supplied by the organization seeking status, and information 
obtained from other sources that may be consulted.


While there is a desire to provide flexibility to a 
patent applicant in selecting an appropriate depository, 
these rules are not intended to permit each patent 
applicant to become its own depository since both the 
patent owner and the public have an interest in the 
continued availability and accessibility of the deposit 




 

during the enforceable life of the patent, and the public 
has a continuing interest in its availability when 
the patent is no longer enforceable. The concept of a 
depository independent of the control of the depositor 
or an IDA as an acceptable depository is based on the 
need and desire to ensure the safe and reliable storage 
of a deposited biological material under circumstances 
that are substantially free of the opportunity 
for intentional mishandling or negligent handling of 
the deposited material. The use of an independent 
depository or internationally recognized depository 
will tend to preserve the integrity of the deposit process 
against those that may accidentally alter the 
deposited material, may wish to tamper with the 
deposited material or may wish to resume control of 
its availability when the patent is no longer enforceable, 
and will tend to preserve the interest of the public 
in the access to the biological material once the 
term of the patent expires.

When a depository having status under 37 CFR 
1.803(a)(2) seeks to change the kinds of biological 
materials that it will accept and maintain for the purposes 
of these rules, a communication requesting such 
a change should be directed to the Commissioner containing 
the information requested in 37 CFR 1.803(b). 
When such a change is requested, the requesting 
depository should provide a complete list of the kinds 
of biological materials it will accept.

37 CFR 1.803(d) indicates that once a depository is 
recognized as suitable for the purposes of this rule, or 
has defaulted or discontinued its performance under 
this section, notice thereof will be published in the 
Official Gazette of the Patent and Trademark Office. 
A current list (as of January, 1998) of IDAs recognized 
under the Budapest Treaty, with addresses, is 
included below. The mere fact that a deposit has been 
made in one of these depositories does not mean that 
the terms of the deposit meet either the requirements 
of the Budapest Treaty or the deposit regulations. 
Many of the depositories recognized under the Budapest 
Treaty have many different arrangements under 
which biological material may be stored.

The World Intellectual Property Organization 
(WIPO) publishes a Guide to the Deposit of Micro-
organisms under the Budapest Treaty (WIPO Publication 
No. 661 (E)) on the procedures and requirements 
concerning the deposit of biological material, including 
procedures for obtaining a sample of deposited 
material, in each of the international depository 
authorities.

CURRENT IDAs

The following constitutes the list of IDAs recognized 
under the Budapest Treaty. The list is current as 
of July, 2001. 

Advanced Biotechnology Center (ABC) 

Interlab Cell Line Collection

(Biotechnology Dept.)

Largo Rossana Benzi, 10

16132 Genova

Italy

Agricultural Research Service 

Culture Collection (NRRL) 

1815 North University Street

Peoria, Illinois 61604

USA

American Type Culture Collection (ATCC) 

10801 University Blvd.

Manassas, Virginia 20110-2209

USA

Australian Government Analytical 

Laboratories (AGAL) 

The New South Wales Regional Laboratory

1, Suakin Street

Pymble, NSW 2073

Australia

Belgian Coordinated Collections of 

Microorganisms (BCCM)

Prime Minister’s Services

Federal Office for Scientific, Technical and 

Cultural Affairs (OSTC)

Rue de la Science 8

B-1000 Brussells

Belgium

Bureau of Microbiology at Health Canada (BMHC)

Federal Laboratories for Health Canada

Room H5190

1015 Arlington Street

Winnipeg, Manitoba

Canada R3E 3R2

Centraalbureau voor Schimmelcultures (CBS) 




 

Oosterstraat 1

Postbus 273

NL-3740 AG Baarn

Netherlands

China Center for Type Culture Collection (CCTCC)

Wuhan University

Wuhan 430072

China

China General Microbiological Culture 

Center (CGMCC)

China Committee for Culture Collection of

Microorganisms

P.O. Box 2714

Beijing 100080

China

Colección Española de Cultivos Tipo (CECT)

Universidad de Valencia

Edificio de Investigación

Campus de Burjasot

46100 Burjasot (Valencia)

Spain

Collection Nationale De Cultures 

De Micro-organismes (CNCM) 

Institut Pasteur

28, rue du Dr Roux

75724 Paris Cédex 15

France

Collection of Industrial Yeasts DBVPG

Applied Microbiology Section

Department of Plant Biology

Faculty of Agriculture

University of Perugia 

Borgo 20 Giugno, 74

06122 Perugia

Italy

Culture Collection of Algae and Protozoa (CCAP) 

Institute of Freshwater Ecology

Windermere Laboratory

Ambleside, Cumbria LA22 0LP 

United Kingdom and Dunstaffnage Marine Laboratory


P.O. Box 3

Oban, Argyll PA34 4AD 

United Kingdom

Culture Collection of Yeasts (CCY)

Institute of Chemistry

Slovak Academy of Sciences

Dúbravská cesta 9

842 38 Bratislava,

Slovakia

Czech Collection of Microorganisms (CCM)

Masaryc University

ul. Tvrdého 14

602 00 Brno

Czech Republic

DSMZ-Deutsche Sammlung von Mikroorganismen 

und Zellkulturen GmbH (DSMZ) 

Mascheroder Weg 1b

D-38124 Braunschweig

Germany

European Collection of Cell Cultures (ECACC)

Vaccine Research and Production Laboratory

Public Health Laboratory Service

Centre for Applied Microbiology and Research

Porton Down

Salisbury, Wiltshire SP4 0JG 

United Kingdom

Institute of Agriculture and Food Biotechnology 
(IAFB)

Collection of Industrial Microorganisms

Ul. Rakowiecka 36

02-532 Warsaw, Poland

International Mycological Institute (IMI)

Bakeham Lane

Englefield Green

Egham, Surrey TW20 9TY

United Kingdom

International Patent Organism Depositary (IPOD)

AIST Tsukuba Central 6

1-1, Higashi 1-chome

Tsukuba-shi, Ibaraki-Ken 305-8566

Japan

Korean Cell Line Research Foundation (KCLRF)

Cancer Research Institute

Seoul National University College of Medicine

28 Yungon-dong, Chongno-gu

Seoul 110-799

Republic of Korea




 

 Korean Collection for Type Cultures (KCTC)

52, Oun-dong,

Yusong-Ku

Taejon 305-333

Republic of Korea

Korean Culture Center of Microorganisms (KCCM)

College of Engineering

Yonsei University

Sodaemun gu

Seoul 120-749

Republic of Korea

Microbial Strain Collection of Latvia (MSCL)

University of Latvia

Faculty of Biology

Blvd. Kronvalda 4

LV-1586 Riga

Latvia

National Bank for Industrial Microorganisms and 

Cell Cultures (NBIMCC) 

125, Tsarigradskochausse Blvd.

Block 2

1113 Sofia

Bulgaria

National Collection of Agricultural and Industrial 

Microorganisms (NCAIM)

Department of Microbiology and Biotechnology

University of Horticulture and the Food Industry

Somlói ût 14-16 

H-1118 Budapest

Hungary

National Collection of Type Cultures (NCTC) 

Central Public Health Laboratory

61 Colindale Avenue

London, NW9 5HT

United Kingdom

National Collection of Yeast Cultures (NCYC) 

AFRC Institute of Food Research

Norwich Laboratory

Colney Lane

Norwich NR4 7UA

United Kingdom

National Collections of Industrial, Food and 

Marine Bacteria (NCIMB)

23 St. Machar Drive

Aberdeen AB2 1RY

Scotland, United Kingdom

National Research Center of Antibiotics

Nagatinskaya Street 3-a

Moscow 113105

Russian Federation

Polish Collection of Microorganisms (PCM)

Institute of Immunology and Experimental Therapy

Polish Academy of Sciences

Ul. Weigla 12

53-114 Wroclaw

Poland

Russian Collection of Microorganisms (VKM)

Prospekt Naouki, 5

142292 Puschino (Moscow Region)

Russian Federation

Russian National Collection of Industrial

Microorganisms (VKPM)

GNII Genetika

Dorozhny proezd. 1

Moscow 113545

Russian Federation

2406Time of Making an Original
Deposit

37 CFR 1.804. Time of making an original deposit.

(a)Whenever a biological material is specifically identified 
in an application for patent as filed, an original deposit thereof 
may be made at any time before filing the application for patent 
or, subject to §
 
1.809, during pendency of the application for 
patent.

(b)When the original deposit is made after the effective filing 
date of an application for patent, the applicant must promptly 
submit a statement from a person in a position to corroborate the 
fact, stating that the biological material which is deposited is a 
biological material specifically identified in the application as 
filed.

37 CFR 1.804 specifies the time for making an 
original deposit to fulfill the requirements of 
35 
U.S.C. 112. For the reasons discussed throughout 
this section, it is recommended that a deposit be made 
before the filing date of the application. However, for 
the purposes of complying with the requirements of 
35 U.S.C. 112, a deposit of a biological material 
may 
be made at any time before filing the application 
for patent or during the pendency of the application 




 

subject to the conditions of 37 CFR 1.809. Where a 
deposit is needed to satisfy the requirements of 
35 
U.S.C. 112 and it is made during the pendency of 
the application, it must be made no later than the time 
period set by the examiner at the time the Notice of 
Allowance and Issue Fee Due is mailed. A necessary 
deposit need not be made by an applicant until the 
application is in condition for allowance so long as 
the applicant provides a written assurance that an 
acceptable deposit will be made on or before the payment 
of the issue fee. This written assurance must 
provide sufficiently detailed information to convince 
the examiner that there is no outstanding issue regarding 
deposits that needs to be resolved. 

These rules are equally applicable in the cases of 
international and national stage applications filed 
under the Patent Cooperation Treaty. Insofar as the 
rules do not permit post-issuance original deposits, 
the failure to make an original deposit in an application 
cannot be cured by filing a reissue application or 
instituting a reexamination proceeding. However, if 
an amendment of claims in a reexamination proceeding 
raises the need for a deposit, an original deposit 
may be made during the reexamination proceeding.

2406.01Description in Application
Specification

37 CFR 1.804(a) specifies not only a permissible 
time frame for making an original deposit, but also 
specifies that the biological material deposited must 
be specifically identified in the application for patent 
as filed. The requirement for a specific identification 
is consistent with the description requirement of the 
first paragraph of 35 U.S.C. 112 and provides an antecedent 
basis for the biological material which either 
has been or will be deposited before the patent is 
granted.

The description in the Lundak application as filed 
(now patent 4,594,325) provides a suitable illustration 
of the specific identification and description which are 
required in an application as filed. In that application, 
an immortal B-cell line was disclosed and claimed. 
The cell line was referred to in the application, as 
filed, as WI-L2-729 HF2. The methods of obtaining 
and using this cell line were also described in the 
application as filed. A deposit of the cell line was 
made with the American Type Culture Collection 
(ATCC) about a week after the application was filed 
in the United States. The United States Court of 
Appeals for the Federal Circuit held that the requirements 
of access by the Office to a sample of the cell 
line during pendency, and public access after grant, 
were met by Lundak's procedures. The Court further 
held that the addition of information designating the 
depository, accession number, and deposit date of the 
deposited cell line in ATCC after the filing date did 
not violate the prohibition against new matter in 
35 
U.S.C. 132. In re Lundak, 773 F.2d 1216, 
227 
USPQ 90 (Fed. Cir. 1985). However, it must be 
clear from the application as filed that the invention 
claimed and described in the specification “was fully 
capable of being reduced to practice (i.e., no technological 
problems, the resolution of which would 
require more than ordinary skill and reasonable time, 
remained in order to obtain an operative, useful process).” 
Feldman v. Aunstrup, 517 F.2d 1351, 1355, 
186 USPQ 108, 113 (CCPA 1975), cert. denied, 
424 
U.S. 912 (1976). 

2406.02Deposit After Filing Date -
Corroboration

When the original deposit is made after the effective 
filing date of an application for patent, an applicant 
is required to promptly submit a statement from a 
person in a position to corroborate that the biological 
material which is deposited is a biological material 
specifically identified in the application (the filing 
date of which is relied upon) as filed. The nature of 
this corroboration will depend on the circumstances in 
the particular application under consideration, including 
the length of time between the application filing 
date and the date of deposit. While few, if any, situations 
can be imagined where the description requirement 
of 35 U.S.C. 112 can be satisfied where the 
biological material was not in existence at the time of 
filing, the rules will not preclude such a situation as 
there is no requirement in the patent law that an actual 
reduction to practice occur as a condition precedent to 
filing a patent application.




 

2406.03Possible Loss of U.S. Filing
Date in Other Countries

Those applicants intending to file patent applications 
in a country foreign to the United States relying 
upon biological material that must be deposited to satisfy 
the requirements of 35 U.S.C. 112 when the 
application is filed in the United States are cautioned 
that in many countries the deposit must be made 
before the filing date of the priority application in 
order to obtain foreign priority rights. Thus, while the 
deposit of a biological material subsequent to the 
effective filing date of a United States application is 
sufficient to comply with 35 U.S.C. 112, an applicant 
may not be able to rely on the filing date of such a 
U.S. application if a patent is sought in certain countries 
foreign to the United States.

2407Replacement or Supplement
of Deposit

37 CFR 1.805. Replacement or supplement of deposit.

(a)A depositor, after receiving notice during the pendency 
of an application for patent, application for reissue patent or reexamination 
proceeding, that the depository possessing a deposit 
either cannot furnish samples thereof or can furnish samples 
thereof but the deposit has become contaminated or has lost its 
capability to function as described in the specification, shall notify 
the Office in writing, in each application for patent or patent 
affected. In such a case, or where the Office otherwise learns, during 
the pendency of an application for patent, application for reissue 
patent or reexamination proceeding, that the depository 
possessing a deposit either cannot furnish samples thereof or can 
furnish samples thereof but the deposit has become contaminated 
or has lost its capability to function as described in the specification, 
the need for making a replacement or supplemental deposit 
will be governed by the same considerations governing the need 
for making an original deposit under the provisions set forth in § 
1.802(b). A 
replacement or supplemental deposit made during the 
pendency of an application for patent shall not be accepted unless 
it meets the requirements for making an original deposit under 
these regulations, including the requirement set forth under § 
1.804(b). A replacement or supplemental deposit made in connection 
with a patent, whether or not made during the pendency of an 
application for reissue patent or a reexamination proceeding or 
both, shall not be accepted unless a certificate of correction under 
§ 1.323 is requested by the patent owner which meets the terms of 
paragraphs (b) and (c) of this section.

(b)A request for certificate of correction under this section 
shall not be granted unless the certificate identifies:

(1)The accession number for the replacement or supplemental 
deposit;

(2)The date of the deposit; and

(3)The name and address of the depository.

(c)A request for a certificate of correction under this section 
shall not be granted unless the request is made promptly after the 
replacement or supplemental deposit has been made and the 
request:

(1)Includes a statement of the reason for making the 
replacement or supplemental deposit;

(2)Includes a statement from a person in a position to 
corroborate the fact, and stating that the replacement or supplemental 
deposit is of a biological material which is identical to that 
originally deposited;

(3)Includes a showing that the patent owner acted diligently 
—

(i)In the case of a replacement deposit, in making the 
deposit after receiving notice that samples could no longer be furnished 
from an earlier deposit; or

(ii)In the case of a supplemental deposit, in making 
the deposit after receiving notice that the earlier deposit had 
become contaminated or had lost its capability to function as 
described in the specification;

(4)Includes a statement that the term of the replacement 
or supplemental deposit expires no earlier than the term of the 
deposit being replaced or supplemented; and

(5)Otherwise establishes compliance with these regulations.


(d)A depositor’s failure to replace a deposit, or in the case 
of a patent, to diligently replace a deposit and promptly thereafter 
request a certificate of correction which meets the terms of paragraphs 
(b) and (c) of this section, after being notified that the 
depository possessing the deposit cannot furnish samples thereof, 
shall cause the application or patent involved to be treated in any 
Office proceeding as if no deposit were made.

(e)In the event a deposit is replaced according to these regulations, 
the Office will apply a rebuttable presumption of identity 
between the original and the replacement deposit where a patent 
making reference to the deposit is relied upon during any Office 
proceeding.

(f)A replacement or supplemental deposit made during the 
pendency of an application for patent may be made for any reason.


(g)In no case is a replacement or supplemental deposit of a 
biological material necessary where the biological material, in 
accordance with § 1.802(b), need not be deposited.

(h)No replacement deposit of a biological material is necessary 
where a depository can furnish samples thereof but the 
depository for national security, health or environmental safety 
reasons is unable to provide samples to requesters outside of the 
jurisdiction where the depository is located.

(i)The Office will not recognize in any Office proceeding a 
replacement deposit of a biological material made by a patent 
owner where the depository could furnish samples of the deposit 
being replaced.

37 CFR 1.805 relates to the deposit of a biological 
material to replace or supplement a previous deposit. 
The term “replacement” is directed to those situations 
where one deposit is being substituted for another. An 
applicant may have greater latitude in replacing a 




 

deposit during the pendency of an application than 
after the patent is granted. Replacement will typically 
take place where the earlier deposit is no longer viable. 
The term “supplement” is directed to those situations 
where the earlier deposit is still viable in the 
sense that it is alive and capable of replication either 
directly or indirectly, but has lost a quality (e.g., 
purity, functionality) it allegedly possessed at the time 
the application was filed.

2407.01In a Pending Application 

37 CFR 1.805(a) relates to the procedure for replacing 
or supplementing a deposit with respect to a pending 
application or a patent. An applicant or patent 
owner is required to notify the Office when it obtains 
information that the depository possessing a deposit 
cannot furnish samples of the deposit to satisfy the 
requirements of 35 U.S.C. 112. When the Office is so 
informed or otherwise becomes aware that samples of 
the deposited material cannot be furnished by the 
depository, the examiner will treat the application or 
reexamination proceeding, whichever is applicable, as 
if no deposit existed. A replacement or supplemental 
deposit will be accepted if it meets all the requirements 
for making an original deposit. 

It should be noted that in a pending application, an 
applicant need not replace the identical material previously 
deposited, but may make an original deposit of 
a biological material which is specifically identified 
and described in the application as filed. Whether this 
alternative deposit will meet the requirements of 
35 
U.S.C. 112 with respect to the claimed subject 
matter must be resolved by the examiner on a case-
by-case basis. The conditions in 37 CFR 1.802(b) and 
37 CFR 1.804(b) must be satisfied.

2407.02After a Patent Has Issued 

A replacement deposit made in connection with an 
application for reissue patent or a reexamination proceeding 
or both shall not be accepted unless a certificate 
of correction is requested which meets the terms 
of 37 CFR 1.805(b) and 37 CFR 1.805 (c) for replacement 
deposits. Any correction made to the original 
patent will be automatically incorporated into the reissued 
or reexamined patent unless changes are made 
during examination of the reissue application or reexamination 
proceeding. 

37 CFR 1.805(b) and 37 CFR 1.805(c) specify the 
procedures that a patent owner may follow to ensure 
that a patent contains the appropriate information 
about a deposited biological material in the event 
that a replacement or supplemental deposit is made 
after the patent is granted. 37 CFR 1.805(b) describes 
the information which must be contained in the certificate 
of correction, whereas 37 CFR 1.805(c)
describes the information which must be provided in 
the request to make the correction. 

2407.03Failure to Replace 

37 CFR 1.805(d) sets forth the Office position that 
the failure to make a replacement deposit in a case 
pending before the Office, for example a reissue or 
reexamination proceeding, where a deposit is considered 
to be necessary to satisfy the requirements of 
35 
U.S.C. 112, shall cause the application or patent 
involved to be treated in any Office proceeding as if 
no deposit were made. The provisions of 37 CFR 
1.805(g) indicate that a replacement need not be made 
where, at the point in time when replacement would 
otherwise be necessary, access to the necessary biological 
material was otherwise available. For example, 
a replacement deposit would not be required 
under the circumstances where access to the necessary 
biological material was established through commercial 
suppliers. 

2407.04Treatment of Replacement

37 CFR 1.805(e) indicates that the Office will apply 
a rebuttable presumption of identity between the 
replacement deposit and an original deposit where a 
patent making reference to the deposit is relied on 
during any Office proceeding. This means that where 
a replacement deposit is permitted and made, the 
examiner will assume that the same material as 
described in the patent is accessible from the identified 
depository unless evidence to the contrary comes 
to the attention of the Office.

An applicant for patent may make a replacement 
deposit during the pendency of the application for any 
reason. The provisions of 37 CFR 1.805(f) recognize 
that since an original deposit may be made during the 
pendency of the application subject to the conditions 
of 37 CFR 1.809, a replacement deposit logically cannot 
be held to any higher standard or any further 
requirements. 




 

2407.05Exemption From Replacement

The provisions of 37 CFR 1.805(h) indicate that a 
replacement deposit is not required even though the 
depository cannot furnish samples, under certain conditions, 
to those requesting a sample outside of the 
jurisdiction where the depository is located. The conditions 
are specified in this paragraph as being limited 
to national security, health or environmental safety 
reasons. See also Article 5 of the Budapest Treaty.

2407.06Replacement May Not Be
Recognized

Finally, 37 CFR 1.805(i) indicates that the Office 
will not recognize in any Office proceeding a replacement 
deposit made by the patent owner where the 
depository could furnish samples of the original 
deposit being replaced. The best evidence of what was 
originally deposited should not be lost through 
destruction or replacement if made in association with 
an existing patent. A supplemental deposit may be 
accepted in an Office proceeding, however, depending 
on the circumstances in each case.

2408Term of Deposit

37 CFR 1.806. Term of deposit.

A deposit made before or during pendency of an application 
for patent shall be made for a term of at least thirty (30) years and 
at least five (5) years after the most recent request for the furnishing 
of a sample of the deposit was received by the depository. In 
any case, samples must be stored under agreements that would 
make them available beyond the enforceable life of the patent for 
which the deposit was made.

The term of deposit must satisfy the requirements 
of the Budapest Treaty which sets a term of at least 30 
years from the date of deposit and at least 5 years after 
the most recent request for the furnishing of a sample 
of the deposit was received by the depository. In the 
event that the 30-year term covers the 17-year term or 
20-year term of the patent plus 6 years to include the 
Statute of Limitations, no further requirement is necessary. 
Unless applicant indicates that the deposit has 
been made under the Budapest Treaty, applicant must 
indicate the term for which the deposit has been made. 
The mere possibility of patent term extension or 
extended litigation involving the patent should not be 
considered in this analysis.

In the event that the 30-year term of deposit measured 
from the date of deposit would necessarily terminate 
within the period of enforceability of the 
patent (the normal 17-year term or 20-year term plus 
6 years to include the Statute of Limitations), samples 
must be stored under agreements that would make 
them available beyond the enforceable life of the 
patent (i.e., until 23 years after issuance or 26 years 
after application filing) for which the deposit was 
made. No requirement should be made as to any particular 
period of time beyond the enforceable life of 
the patent. The purpose of the requirement is to insure 
that a deposited biological material necessary for the 
practice of a patented invention would be available to 
the public after expiration of the patent for which the 
deposit was made. The term of the deposit must comply 
with the requirements of each sentence of 37 CFR 
1.806 whether or not the deposit is made under the 
Budapest Treaty. A specific statement that the deposit 
complies with the second sentence of this section is 
required only where the 30-year term would terminate 
within the enforceable life of the patent.

2409Viability of Deposit

37 CFR 1.807. Viability of deposit.

(a)A deposit of biological material that is capable of self-
replication either directly or indirectly must be viable at the time 
of deposit and during the term of deposit. Viability may be tested 
by the depository. The test must conclude only that the deposited 
material is capable of reproduction. No evidence is necessarily 
required regarding the ability of the deposited material to perform 
any function described in the patent application.

(b)A viability statement for each deposit of a biological 
material defined in paragraph (a) of this section not made under 
the Budapest Treaty on the International Recognition of the 
Deposit of Microorganisms for the Purposes of Patent Procedure 
must be filed in the application and must contain:

(1)The name and address of the depository;

(2)The name and address of the depositor;

(3)The date of deposit;

(4)The identity of the deposit and the accession number 
given by the depository;

(5)The date of the viability test;

(6)The procedures used to obtain a sample if the test is 
not done by the depository; and

(7)A statement that the deposit is capable of reproduction.


(c)If a viability test indicates that the deposit is not viable 
upon receipt, or the examiner cannot, for scientific or other valid 
reasons, accept the statement of viability received from the applicant, 
the examiner shall proceed as if no deposit has been made. 




 

The examiner will accept the conclusion set forth in a viability 
statement issued by a depository recognized under §
 
1.803(a).

37 CFR 1.807 requires that the deposit of biological 
material that is capable of self-replication either 
directly or indirectly must be viable at the time of 
deposit and during the term of deposit. This requirement 
for viability is essentially a requirement that the 
deposited material is capable of reproduction. For the 
purpose of making a deposit under these rules, there is 
no requirement that evidence be provided that the 
deposited material is capable or has the ability to perform 
any function described in the patent application. 
However, as with any other issue of description or 
enablement, if the examiner has evidence or reason to 
question the objective statements made in the patent 
application, applicants may be required to demonstrate 
that the deposited biological material will perform 
in the manner described.

Under the Budapest Treaty, there is a requirement 
that the deposit be tested for viability before it is 
accepted. Thus, a mere statement by an applicant, an 
authorized representative of applicant or the assignee 
that the deposit has been accepted under the Budapest 
Treaty would satisfy 37 CFR 1.807.

For each deposit which is not made under the 
Budapest Treaty, a viability statement must be filed in 
the patent application and contain the information 
listed in paragraph (b) of this section. Under 37 CFR 
1.807(c), the examiner will accept the conclusion set 
forth in a viability statement which is issued by a 
depository recognized under 37 CFR 1.803(a). If the 
viability test indicates that the deposit is not viable 
upon receipt, or the examiner cannot, for scientific or 
other valid reasons, accept the statement of viability 
received from the applicant, the examiner shall so 
notify the applicant stating the reasons for not accepting 
the statement and proceed with the examination 
process as if no deposit had been made.

2410Furnishing of Samples

37 CFR 1.808. Furnishing of samples.

(a)A deposit must be made under conditions that assure 
that:

(1)Access to the deposit will be available during pendency 
of the patent application making reference to the deposit to 
one determined by the Commissioner to be entitled thereto under 
§ 1.14 and 35 
U.S.C. 122, and

(2)Subject to paragraph (b) of this section, all restrictions 
imposed by the depositor on the availability to the public of the 
deposited material will be irrevocably removed upon the granting 
of the patent.

(b)The depositor may contract with the depository to 
require that samples of a deposited biological material shall be 
furnished only if a request for a sample, during the term of the 
patent:

(1)Is in writing or other tangible form and dated;

(2)Contains the name and address of the requesting party 
and the accession number of the deposit; and

(3)Is communicated in writing by the depository to the 
depositor along with the date on which the sample was furnished 
and the name and address of the party to whom the sample was 
furnished.

(c)Upon request made to the Office, the Office will certify 
whether a deposit has been stated to have been made under conditions 
which make it available to the public as of the issue date of 
the patent grant provided the request contains:

(1)The name and address of the depository;

(2)The accession number given to the deposit;

(3)The patent number and issue date of the patent referring 
to the deposit; and

(4)The name and address of the requesting party.

2410.01Conditions of Deposit

37 CFR 1.808 requires that the deposit of biological 
material be made under two conditions:

(A)access to the deposit will be available during 
pendency of the patent application making reference 
to the deposit to one determined by the Commissioner 
to be entitled thereto under 37 CFR 1.14 and 
35 
U.S.C. 122, and

(B)with one exception, that all restrictions 
imposed by the depositor on the availability to the 
public of the deposited biological material be irrevocably 
removed upon the granting of the patent.

The one exception that is permitted is specified in 
37 CFR 1.808(b) which permits the depositor to contract 
with the depository to require that samples of a 
deposited biological material shall be furnished only 
if a request for a sample, during the term of the patent, 
meets any one or all of the three conditions specified 
in this paragraph. These conditions are:

(A)the request is in writing or other tangible form 
and dated; and/or

(B)the request contains the name and address of 
the requesting party and the accession number of the 
deposit; and/or

(C)the request is communicated in writing by the 
depository to the depositor along with the date on 
which the sample was furnished and the name and 




 

address of the party to whom the sample was furnished.


It should be noted that this exception to the general 
rule that all restrictions will be removed must be 
strictly followed and that no variations of this explicit 
exception will be accepted as meeting the conditions 
of this section. Although this exception is consistent 
with the provisions in the Budapest Treaty and its implementing 
regulations (Rule 11.4), other conditions 
on accessibility are permitted under the Budapest 
Treaty as prescribed by national law. Consequently, 
the mere indication that a deposit has been made under 
conditions prescribed by the Budapest Treaty 
would satisfy all conditions of these regulations except 
the requirement that all restrictions on access be 
removed on grant of the patent. Ex parte Hildebrand, 
15 USPQ2d 1662 (Bd. Pat. App. & Int. 1990).

2410.02Certification of Statement of 
Availability of Deposit

Since the mere description of a deposit or identity 
of a deposit in a patent specification is not necessarily 
an indication that a requirement for deposit was made 
or that a deposit which complies with these rules has 
been made, accessibility to a deposited material referenced 
in a patent may depend on the satisfaction of 
conditions not apparent on the face of the patent. For 
these reasons, and upon request made to the U.S. 
Patent and Trademark Office, the Office will certify 
whether a deposit has been stated to have been made 
under conditions which would make it available to the 
public as of the issue date of the patent grant provided 
the request is made to a Director of Technology Center 
(TC) 1600, and contains the following information:


(A)the name and address of the depository;

(B)the accession number given to the deposit;

(C)the patent number and issue date of the patent 
referring to the deposit; and

(D)the name and address of the requesting party.

See also MPEP § 2404.01.

For those deposits made pursuant to the Budapest 
Treaty, the World Intellectual Property Organization 
provides a form (Form BP-12) for requesting a certification 
of legal entitlement to receive samples of 
deposited microorganisms pursuant to Rule 11.3(a) of 
the Regulations under the Budapest Treaty. Copies of 
this form are available from a TC 1600 Director.

2411Examination Procedures 

37 CFR 1.809. Examination procedures.

(a)The examiner shall determine pursuant to §
 
1.104 in each 
application for patent, application for reissue patent or reexamination 
proceeding if a deposit is needed, and if needed, if a deposit 
actually made is acceptable for patent purposes. If a deposit is 
needed and has not been made or replaced or supplemented in 
accordance with these regulations, the examiner, where appropriate, 
shall reject the affected claims under the appropriate provision 
of 35 U.S.C. 112, explaining why a deposit is needed and/or why 
a deposit actually made cannot be accepted.

(b)The applicant for patent or patent owner shall reply to a 
rejection under paragraph (a) of this section by—

(1)In the case of an applicant for patent, either making an 
acceptable original, replacement, or supplemental deposit, or 
assuring the Office in writing that an acceptable deposit will be 
made; or, in the case of a patent owner, requesting a certificate of 
correction of the patent which meets the terms of paragraphs (b) 
and (c) of § 1.805, or

(2)Arguing why a deposit is not needed under the circumstances 
of the application or patent considered and/or why a 
deposit actually made should be accepted. Other replies to the 
examiner’s action shall be considered nonresponsive. The rejection 
will be repeated until either paragraph (b)(1) of this section is 
satisfied or the examiner is convinced that a deposit is not needed.

(c)If an application for patent is otherwise in condition for 
allowance except for a needed deposit and the Office has received 
a written assurance that an acceptable deposit will be made, applicant 
will be notified and given a period of time within which the 
deposit must be made in order to avoid abandonment. This time 
period is not extendable under § 1.136(a) or (b) if set forth in a 
“Notice of Allowability” or in an Office action having a mail date 
on or after the mail date of a “Notice of Allowability” (see 
§
 
1.136(c)).

(d)For each deposit made pursuant to these regulations, the 
specification shall contain:

(1)The accession number for the deposit;

(2)The date of the deposit;

(3)A description of the deposited biological material sufficient 
to specifically identify it and to permit examination; and

(4)The name and address of the depository.

(e)Any amendment required by paragraphs (d)(1), (d)(2) or 
(d)(4) of this section must be filed before or with the payment of 
the issue fee (see §
 
1.312).

37 CFR 1.809 sets forth procedures that will be 
used by the examiner to address a deposit issue. The 
burden is initially on the Office to establish that 
access to a biological material is necessary for the satisfaction 
of the statutory requirements for patentability 
under 35 U.S.C. 112. Once the Office has met this 
burden, the burden shifts to the applicant or patent 




 

owner to demonstrate that access to such biological 
material either is not necessary, or is already available, 
or that a deposit of such material will be made in 
accordance with these regulations.

2411.01Rejections Based on Deposit
Issue

Under 37 CFR 1.809(a), once the examiner has 
determined that access to a biological material is necessary, 
and there is no information that would support 
the conclusion that access is currently available in 
accordance with these regulations, the examiner 
should make an appropriate rejection under 35 U.S.C. 
112 until such time as a deposit in accordance with 
these regulations is actually made or a written assurance 
is received in the patent application that such a 
deposit will be made upon an indication of allowability 
of the application. The examiner should clearly 
indicate the statutory basis for the rejection and the 
reasons that are relied upon by the examiner to conclude 
that the application does not comply with some 
requirement of 35 U.S.C. 112. Although not exhaustive, 
the following grounds of rejection may be applicable 
in appropriate circumstances:

(A)35 U.S.C. 112, first paragraph - lack of an 
enabling disclosure without access to a specific biological 
material. This ground of rejection should be 
accompanied by evidence of scientific reasoning to 
support the conclusion that a person skilled in the art 
could not make or use the invention defined in and 
commensurate with the claims without access to the 
specific biological material. 

(B)35 U.S.C. 112, first paragraph - description 
requirement. This ground of rejection typically arises 
in the context that the application as filed does not 
contain a description to support an amendment to the 
specification or claims. An amendment to the claims 
that is not described in the application as filed would 
justify a rejection of the affected claims under 
35 
U.S.C. 112, first paragraph. If an amendment is 
made to the application, other than the claims, that is 
not described in the application as filed, this would 
justify an objection under 35 U.S.C. 112, first paragraph 
and/or 35 U.S.C. 132 (prohibition against the 
introduction of new matter) and a requirement that the 
amendment be canceled.

(C)35 U.S.C. 112, first paragraph - best mode 
requirement. This ground of rejection will be rare in 
the ex parte examination process because it requires 
(1) a finding by the examiner that, at the time the 
application was filed, the inventor(s) knew of a specific 
material that was considered by the inventor(s) 
to be better than any other, and (2) if a best mode was 
contemplated at that time, that the inventor(s) concealed 
the best mode (accidentally or intentionally) by 
failing to adequately describe that best mode. See 
Chemcast Corp. v. Arco Industries Corp., 913 F.2d 
923, 16 USPQ2d 1033 (Fed. Cir. 1990). The Court of 
Appeals for the Federal Circuit has at least twice 
resolved a best mode issue arising in the context of a 
biotechnology invention in favor of the patentee. See 
Scripps Clinic and Research Foundation v. Genentech 
Inc., 927 F.2d 1565, 18 USPQ2d 1001 (Fed. Cir. 
1991) with respect to monoclonal antibodies, and 
Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 
927 
F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991) 
with respect to mammalian host cells.

(D)35 U.S.C. 112, second paragraph - indefiniteness. 
This ground of rejection, as applied to a deposit 
issue, requires the examiner to provide reasons why 
the terms in the claims and/or scope of the invention 
are unclear because of an incomplete or inaccurate 
description or the absence of a reference to a biological 
material.

(E)35 U.S.C. 112, second paragraph - claims do 
not set forth what applicants regard as their invention. 
This ground of rejection requires the citation of some 
evidence, not contained in the application as filed, 
that the claims do not set forth what applicants regard 
as their invention. In re Prater, 415 F.2d 1393, 
162 
USPQ 541 (CCPA 1969). Any disagreement 
between the content of the application disclosure and 
the scope of the claims should be addressed under 35 
U.S.C. 112, first paragraph. See In re Ehrreich, 590 
F.2d 902, 200 USPQ 504 (CCPA 1979). 

Where a deposit is required to satisfy 35 U.S.C. 
112, a deposit must be made in accordance with these 
regulations. A deposit accepted in any IDA under the 
Budapest Treaty shall be accepted for patent purposes 
if made under conditions which comply with 37 CFR 
1.806 and 37 CFR 1.808(a) concerning term of 
deposit and permissible conditions on access once the 
patent is granted. 




 

2411.02Replies to Rejections Based
on Deposit Issue 

Once a rejection under 35 U.S.C. 112 has been 
made by the examiner directed to the absence of 
access to a biological material, applicant may reply, 
pursuant to 37 CFR 1.809 (b)(1), by either making an 
acceptable original or replacement deposit in accordance 
with these regulations, or assuring the Office in 
writing that an acceptable deposit will be made on or 
before the date of payment of the issue fee, or by submitting 
an argument of why a deposit is not required 
under the circumstances of the application being considered. 
Other replies to such a rejection by the examiner 
shall be considered nonresponsive and may result 
in abandonment of the application. The rejection will 
be repeated and made final until the requirements of 
37 CFR 1.809(b)(1) are satisfied or the examiner is 
convinced that a deposit is not required for the 
claimed subject matter. Once the rejection is made 
final, the requirements of 37 CFR 1.116 apply to further 
submissions. The written assurance will be 
accepted by the Office if it clearly states that an 
acceptable deposit will be made within the required 
time and under conditions which satisfy these rules. In 
the case that an acceptable written assurance has been 
made by the applicant, the rejection under 35 U.S.C. 
112 directed to the absence of access to the biological 
material should be removed. 

2411.03Application in Condition
for Allowance Except for Deposit 

As set forth in 37 CFR 1.809(c), in the event that an 
application for patent is otherwise in condition for 
allowance except for a required deposit and the Office 
has received a written assurance that an acceptable 
deposit will be made, applicant will be notified and 
given a period of time within which the deposit must 
be made in order to avoid abandonment. This time 
period is not extendable under 37 CFR 1.136(a) or (b) 
if set forth in a “Notice of Allowability” or in an 
Office action having a mail date on or after the mail 
date of a “Notice of Allowability” (see 37 CFR 
1.136(c). Failure to make the needed deposit in accordance 
with this requirement will be considered a failure 
to prosecute the application under 35 U.S.C. 133and result in abandonment of the application. 

Once the deposit has been made, information 
regarding the deposit, such as the name and address of 
the depository, the accession number and the date of 
the deposit, that is to be added to the specification 
must be added by means of filing an amendment 
under the provisions of 37 CFR 1.312. Such an 
amendment must be filed before or with the payment 
of the issue fee. Therefore, applicants need to make 
any necessary deposit of biological material well prior 
to payment of the issue fee such that the accession 
number is received with sufficient time remaining to 
amend the specification as required by 37 CFR 
1.809(d) on or before the date the issue fee payment is 
paid. See 37 
CFR 1.809(e).

2411.04After a Patent Has Been Granted

In a proceeding involving a patent, it may not be 
possible to request a certificate of correction of the 
patent which meets the terms of 37 CFR 1.805(b) and 
37 CFR 1.805(c). For example, if the patent owner is 
on notice that samples of an original deposit can no 
longer be furnished by the depository, failure to diligently 
make a replacement deposit will preclude grant 
of a certificate of correction. A replacement deposit 
subsequently made will not be recognized by the 
Office nor will a request for certificate of correction, 
even if made promptly thereafter, be granted. It would 
also not be possible to request a certificate of correction 
of the patent which meets the terms of 37 CFR 
1.805(b) and 37 CFR 1.805(c) where no original 
deposit was made before or during the pendency of 
the application which matured into the patent.

A patent defective because of lack of a necessary 
deposit is necessarily fatally defective for failure to 
comply with the first paragraph of 35 U.S.C. 112. 
Reissue is not available in such cases. See In re Hay, 
534 F.2d 917, 189 USPQ 790 (CCPA 1976). Whether 
reissue is available where a biological material necessary 
for compliance with 35 U.S.C. 112 was known 
and readily available at the time of issuance of the 
patent and subsequently ceased to be readily available 
is problematic. Nevertheless, the rules do not provide 
for post-issuance original deposits.

Where an applicant for patent has any doubt as to 
whether access to a biological material specifically 
identified in the specification is necessary to satisfy 
35 U.S.C. 112 or whether such a material, while currently 
freely available, may become unavailable in the 




 

future, the applicant would be well-advised to make a 
deposit thereof before any patent issues. Similarly, 
where a patent owner has any doubt whether a deposit 
referred to in the specification is a biological material 
necessary to satisfy 35 U.S.C. 112 and, if the material 
is necessary, whether it is otherwise known and 
readily available, the patent owner would be well-
advised to follow the procedures set forth in 37 CFR 
1.805(b) and 37 CFR 1.805(c) after receiving the 
notice specified in those paragraphs.

2411.05Content of Application with
Respect to Deposited Material 

37 CFR 1.809(d) sets forth the requirements for the 
content of the specification with respect to a deposited 
biological material. Specifically, the specification 
shall contain the accession number for the deposit, the 
date of the deposit, the name and address of the 
depository, and a description of the deposited biological 
material sufficient to specifically identify it and to 
permit examination. The description also must be sufficient 
to permit verification that the deposited biological 
material is in fact that disclosed. Once the patent 
issues, the description must be sufficient to aid in the 
resolution of questions of infringement. As a general 
rule, the more information that is provided about a 
particular deposited biological material, the better the 
examiner will be able to compare the identity and 
characteristics of the deposited biological material 
with the prior art.

2420The Requirements for Patent
Applications Containing NucleotideSequence and/or Amino Acid
Sequence Disclosures - the
Sequence Rules 

Prior to the effective date (October 1, 1990) and 
implementation of the sequence rules (37 CFR 1.821through 1.825), applications for patents that included 
nucleotide or amino acid sequence information posed 
special problems for the Office. While not related to 
the disclosure requirements of an invention, problems 
existed in the presentation, examination and printing 
of nucleotide and amino acid sequence data that 
appeared in patent applications because of the lack of 
uniformity in submission of sequence data to the 
Office and the impracticality of properly searching 
and examining sequences submitted in paper form. In 
summary, the diversity and complexity of nucleotide 
and amino acid sequence data resulted in searching 
and analysis difficulties both within the Office and 
outside the Office, decreased accuracy of search and 
reproduction and increased costs. These difficulties 
made the development and implementation of the 
sequence rules a critical necessity for the Office. As 
such, the Office amended its regulations to establish a 
standardized format for descriptions of nucleotide and 
amino acid sequence data submitted as a part of patent 
applications, in conjunction with the required submission 
of that data in computer readable form. The final 
rules were published in the Federal Register at 55 FR 
18230 (May 1, 1990) and in the Official Gazette at 
1114 O.G. 29 (May 15, 1990). The sequence rules 
went into effect on October 1, 1990. The sequence 
rules were subsequently revised effective July 1, 
1998. See 63 FR 29634 (June 1, 1998) and 1121 O.G. 
82 (June 23, 1998).

 The sequence rules were further revised on September 
8, 2000 to allow submissions of the nucleotide 
and/or amino acid sequences and associated information 
on compact discs. See 65 FR 54604 (Sept. 8, 
2000) and 1238 O.G. 145 (Sept. 19, 2000). See also 
MPEP § 608.05 and § 2422.03.

2421Overview of the Sequence Rules 

2421.01Applications Affected 

The sequence rules require the use of standard symbols 
and a standard format for sequence data in most 
sequence-type patent applications. They further 
require the submission of that data in computer readable 
form. Compliance is required for most disclosures 
of sequence data in new applications filed on or 
after October 1, 1990. The revised sequence rules 
apply to most new applications filed on or after July 1, 
1998. See the final rule publications as cited in MPEP 
§ 2420 for more detailed applicability information. 

The Office encourages voluntary compliance for 
applications not subject to the rules, but all aspects of 
the rules must be complied with before data will be 
entered into the database. This includes submission of 
all statements required by the rules. In exceptional circumstances, 
it should be noted that the Office may 
waive the rules via a 37 CFR 1.183 petition.




 

2421.02Summary of the Requirements 
of the Sequence Rules 

Basically, the sequence rules define a set of symbols 
and procedures that are both mandatory and the 
only way that an applicant is permitted to describe 
information about a sequence that falls within the definitions 
used in the rules. Thus, 37 CFR 1.821 defines 
a “sequence” and a “Sequence Listing” for the purpose 
of the rules, the requirements for specific symbols, 
and formats for the “Sequence Listing,” the 
requirement for a computer readable form (CRF) of 
the “Sequence Listing,” and the deadlines for complying 
with the requirements. 37 CFR 1.822 to 37 CFR 
1.824 set forth detailed descriptions of the requirements 
that are mandatory for the presentation of 
sequence data, and 37 CFR 1.825 sets forth procedures 
that are available to an applicant in the event 
that amendments to the sequence information or 
replacement of the computer readable copy become 
necessary. 

The sequence rules embrace all unbranched nucleotide 
sequences with ten or more bases and all 
unbranched, non-D amino acid sequences with four or 
more amino acids, provided that there are at least 4 
“specifically defined” nucleotides or amino acids. The 
rules apply to all sequences in a given application, 
whether claimed or not. All such sequences are relevant 
for the purposes of building a comprehensive 
database and properly assessing prior art. It is therefore 
essential that all sequences, whether only disclosed 
or also claimed, be included in the database. 

2421.03Notification of a Failure
to Comply

With respect to the Office’s determination of compliance 
with the sequence rules and the opportunities 
afforded applicants to satisfy the requirements of 
the rules, applicants will be notified of easily detectable 
deficiencies early in the application process. 
Applicants whose computer readable forms are damaged 
in the mail, are not readable, or are missing mandatory 
elements will be notified shortly after receipt 
of the application by the Office. Applications filed on 
or after November 29, 2000, will be retained in the 
Office of Initial Patent Examination (OIPE) until any 
noncompliant sequence listing that renders an application 
unsuitable for examination is corrected. Deficiencies 
of a more sophisticated nature will likely only be 
detected by the examiner to whom the application is 
assigned. Applicant will be notified of any errors or 
inconsistencies detected by the examiner early in the 
examination process. Other errors or inconsistencies 
will be noted by the examiner early in the examination 
process. 

Upon detection of damage or a deficiency, a notice 
will be sent to the applicant detailing the damage or 
deficiency and setting at least a 30-day period for 
reply. The period for reply will usually be 2 months 
when sent during the preexamination processing of an 
application. However, if the notice is sent out with an 
Office communication having a longer period for 
reply, the period for reply may be longer than 
2 
months, e.g., where the notice is sent with an Office 
action on the merits setting a 3-month period for 
reply. Extensions of time in which to reply will be 
available pursuant to 37 CFR 1.136. When an action 
by the applicant, such as a reply to a Notice to Comply 
from the Office, is determined to be a bona fideattempt to comply with the rules and it is apparent that 
compliance with some requirement has inadvertently 
been omitted, the applicant may be given a new time 
period to correct the omission. See 37 CFR 1.135(c). 
The relevant form paragraphs and a copy of the 
Notice to Comply to be used in applications subject to 
the sequence rules are included in MPEP § 2427through § 2427.02.

A notification of a failure to comply with the 
sequence rules will be accompanied by an analysis of 
any submitted computer readable form. Any inquiries 
regarding a specific computer readable form that has 
been processed by the Office should be directed to the 
Systems Branch of the Chemical/Biotechnology Division 
of the Scientific and Technical Information Center. 


2421.04Future Changes to the Sequence
Rules

With general regard to the symbols and format to 
be used for nucleotide and/or amino acid sequence 
data set forth in 37 CFR 1.822 and the form and format 
for sequence submissions in computer readable 
form set forth in 37 CFR 1.824, the Office intends to 
accommodate progress in the areas of both standardization 
and computerization as they relate to sequence 
data by subsequently amending the rules to take into 




 

account any such progress. This progress will probably 
be reflected in the refinement of or liberalization 
of the rules. For example, progress in the area of the 
standardization of sequence data will likely result in a 
more comprehensive rule. For example, the D-amino 
acids and branched sequences that are currently 
excluded from the rule may, in the future, be brought 
within the scope of the rule once the necessary standardization 
technology becomes available. As a further 
example, the computer readable form is currently 
limited to certain forms of electronic media, but it can 
readily be seen that progress in the technology for 
developing databases of the type the Office has envisioned 
will likely permit a broadening of the permissible 
types of computer readable forms that may be 
submitted. The same can be said for the computer/
operating-system configurations that are currently 
permitted by the rules. As the Office becomes able to 
provide greater refinement and liberality in these 
areas, the Office will do so by the publication of 
notices in the Official Gazette or formal rulemaking 
proposals, as appropriate. 

2422Nucleotide and/or Amino Acid
Sequence Disclosures in Patent 
Applications

37 CFR 1.821. Nucleotide and/or amino acid sequence 
disclosures in patent applications.

(a)Nucleotide and/or amino acid sequences as used in 
§§
 
1.821 through 1.825 are interpreted to mean an unbranched 
sequence of four or more amino acids or an unbranched sequence 
of ten or more nucleotides. Branched sequences are specifically 
excluded from this definition. Sequences with fewer than four 
specifically defined nucleotides or amino acids are specifically 
excluded from this section. “Specifically defined” means those 
amino acids other than “Xaa” and those nucleotide bases other 
than “n” defined in accordance with the World Intellectual Property 
Organization (WIPO) Handbook on Industrial Property Information 
and Documentation, Standard ST.25: Standard for the 
Presentation of Nucleotide and Amino Acid Sequence Listings in 
Patent Applications (1998), including Tables 1 through 6 in 
Appendix 2, herein incorporated by reference. (Hereinafter 
“WIPO Standard ST.25 (1998)''). This incorporation by reference 
was approved by the Director of the Federal Register in accordance 
with 5 U.S.C. 552(a) and 1 CFR part 51. Copies of WIPO 
Standard ST.25 (1998) may be obtained from the World Intellectual 
Property Organization; 34 chemin des Colombettes; 1211 
Geneva 20 Switzerland. Copies of ST.25 may be inspected at the 
Patent Search Room; Crystal Plaza 3, Lobby Level; 2021 South 
Clark Place; Arlington, VA 22202. Copies may also be inspected 
at the Office of the Federal Register, 800 North Capitol Street, 
NW, Suite 700, Washington, DC. Nucleotides and amino acids are 
further defined as follows:

(1)Nucleotides: Nucleotides are intended to embrace 
only those nucleotides that can be represented using the symbols 
set forth in WIPO Standard ST.25 (1998), Appendix 2, Table 1. 
Modifications, e.g., methylated bases, may be described as set 
forth in WIPO Standard ST.25 (1998), Appendix 2, Table 2, but 
shall not be shown explicitly in the nucleotide sequence.

(2)Amino acids: Amino acids are those L-amino acids 
commonly found in naturally occurring proteins and are listed in 
WIPO Standard ST.25 (1998), Appendix 2, Table 3. Those amino 
acid sequences containing D-amino acids are not intended to be 
embraced by this definition. Any amino acid sequence that contains 
post-translationally modified amino acids may be described 
as the amino acid sequence that is initially translated using the 
symbols shown in WIPO Standard ST.25 (1998), Appendix 2, 
Table 3 with the modified positions; e.g., hydroxylations or glycosylations, 
being described as set forth in WIPO Standard ST.25 
(1998), Appendix 2, Table 4, but these modifications shall not be 
shown explicitly in the amino acid sequence. Any peptide or protein 
that can be expressed as a sequence using the symbols in 
WIPO Standard ST.25 (1998), Appendix 2, Table 3 in conjunction 
with a description in the Feature section to describe, for example, 
modified linkages, cross links and end caps, non-peptidyl bonds, 
etc., is embraced by this definition.

(b)Patent applications which contain disclosures of 
nucleotide and/or amino acid sequences, in accordance with the 
definition in paragraph (a) of this section, shall, with regard to the 
manner in which the nucleotide and/or amino acid sequences are 
presented and described, conform exclusively to the requirements 
of §§ 1.821 through 1.825.

(c)Patent applications which contain disclosures of 
nucleotide and/or amino acid sequences must contain, as a separate 
part of the disclosure, a paper copy disclosing the nucleotide 
and/or amino acid sequences and associated information using the 
symbols and format in accordance with the requirements of §§ 
1.822 and 1.823. This paper copy is hereinafter referred to as the 
“Sequence Listing.” Each sequence disclosed must appear separately 
in the “Sequence Listing.” Each sequence set forth in the 
“Sequence Listing” shall be assigned a separate sequence identifier. 
The sequence identifiers shall begin with 1 and increase 
sequentially by integers. If no sequence is present for a sequence 
identifier, the code “000” shall be used in place of the sequence. 
The response for the numeric identifier 160 shall include the 
total number of SEQ ID NOs, whether followed by a sequence or 
by the code “000.”

(d)Where the description or claims of a patent application 
discuss a sequence that is set forth in the “Sequence Listing” 
in accordance with paragraph (c) of this section, reference must be 
made to the sequence by use of the sequence identifier, preceded 
by “SEQ ID NO:” in the text of the description or claims, even if 
the sequence is also embedded in the text of the description or 
claims of the patent application.

(e)A copy of the “Sequence Listing” referred to in paragraph 
(c) of this section must also be submitted in computer readable 
form in accordance with the requirements of § 1.824. The 
computer readable form is a copy of the “Sequence Listing” and 




 

will not necessarily be retained as a part of the patent application 
file. If the computer readable form of a new application is to be 
identical with the computer readable form of another application 
of the applicant on file in the Patent and Trademark Office, reference 
may be made to the other application and computer readable 
form in lieu of filing a duplicate computer readable form in the 
new application if the computer readable form in the other application 
was compliant with all of the requirements of these rules. 
The new application shall be accompanied by a letter making such 
reference to the other application and computer readable form, 
both of which shall be completely identified. In the new application, 
applicant must also request the use of the compliant computer 
readable “Sequence Listing” that is already on file for the 
other application and must state that the paper copy of the 
“Sequence Listing” in the new application is identical to the computer 
readable copy filed for the other application.

(f)In addition to the paper copy required by paragraph 
(c) of this section and the computer readable form required by 
paragraph (e) of this section, a statement that the content of the 
paper and computer readable copies are the same must be submitted 
with the computer readable form, e.g., a statement that “the 
information recorded in computer readable form is identical to the 
written sequence listing.”

(g)If any of the requirements of paragraphs (b) through 
(f) of this section are not satisfied at the time of filing under 
35 
U.S.C. 111(a) or at the time of entering the national stage under 
35 U.S.C. 371, applicant will be notified and given a period of 
time within which to comply with such requirements in order to 
prevent abandonment of the application. Any submission in reply 
to a requirement under this paragraph must be accompanied by a 
statement that the submission includes no new matter.

(h)If any of the requirements of paragraphs (b) through 
(f) of this section are not satisfied at the time of filing an international 
application under the Patent Cooperation Treaty (PCT), 
which application is to be searched by the United States International 
Searching Authority or examined by the United States 
International Preliminary Examining Authority, applicant will be 
sent a notice necessitating compliance with the requirements 
within a prescribed time period. Any submission in reply to a 
requirement under this paragraph must be accompanied by a statement 
that the submission does not include matter which goes 
beyond the disclosure in the international application as filed. If 
applicant fails to timely provide the required computer readable 
form, the United States International Searching Authority shall 
search only to the extent that a meaningful search can be performed 
without the computer readable form and the United States 
International Preliminary Examining Authority shall examine 
only to the extent that a meaningful examination can be performed 
without the computer readable form.

37 CFR 1.821 incorporates by reference the World 
Intellectual Property Organization (WIPO) Handbook 
on Industrial Property Information and Documentation, 
Standard ST.25 (1998), including Tables 1 
through 6 of Appendix 2. Copies may be obtained 
from the World Intellectual Property Organization; 34 
chemin des Colombettes; 1211 Geneva 20 Switzerland. 
Copies may be inspected at the Patent Search 
Room; Crystal Plaza 3, Lobby Level; 2021 South 
Clark Place; Arlington, VA 22202. Copies may also 
be inspected at the Office of the Federal Register, 800 
North Capitol Street, NW, Suite 700, Washington, DC 
20408. These tables are reproduced below.

WIPO Standard ST.25 (1998), Appendix 2, Table 1, 
provides that the bases of a nucleotide sequence 
should be represented using the following one-letter 
code for nucleotide sequence characters:


Table 1: List of Nucleotides
Symbol

Meaning

Origin of 
designation

a

a

adenine

g

g

guanine

c

c

cytosine

t

t

thymine

u

u

uracil

r

g or a

purine

y

t/u or c

pyrimidine

m

a or c

amino

k

g or t/u

keto

s

g or c

strong interactions 
3H-bonds

w

a or t/u

weak interactions 
2H-bonds

b

g or c or t/u

not a

d

a or g or t/u

not c

h

a or c or t/u

not g

v

a or g or c 

not t, not u

n

a or g or c or t/u, 
unknown, or other

any





WIPO Standard ST.25 (1998), Appendix 2, Table 2, 
provides that modified bases may be represented as 




 

the corresponding unmodified bases in the sequence 
itself, if the modified base is one of those listed below 
and the modification is further described in the Feature 
section of the Sequence Listing. The codes from 
the list below may be used in the description (i.e., the 
specification and drawing, or in the Sequence Listing) 
but these codes may not be used in the sequence itself.


Table 2: List of Modified Nucleotides
Symbol

Meaning

ac4c

4-acetylcytidine

chm5u

5-(carboxyhydroxymethyl)uridine

cm

2'-O-methylcytidine

cmnm5s2u

5-carboxymethylaminomethyl-2-thiouridine


cmnm5u

5-carboxymethylaminomethyluridine

d

dihydrouridine

fm

2'-O-methylpseudouridine

gal q

beta, D-galactosylqueuosine

gm

2'-O-methylguanosine

i

inosine

i6a

N6-isopentenyladenosine

m1a

1-methyladenosine

m1f

1-methylpseudouridine

m1g

1-methylguanosine

m1i

1-methylinosine

m22g

2,2-dimethylguanosine

m2a

2-methyladenosine

m2g

2-methylguanosine

m3c

3-methylcytidine

m5c

5-methylcytidine

m6a

N6-methyladenosine

m7g

7-methylguanosine





mam5u

5-methylaminomethyluridine

mam5s2u

5-methoxyaminomethyl-2-thiouridine

man q

beta, D-mannosylqueuosine

mcm5s2u

5-methoxycarbonylmethyl-2-thiouridine


mcm5u

5-methoxycarbonylmethyluridine

mo5u

5-methoxyuridine

ms2i6a

2-methylthio-N6-isopentenyladenosine

ms2t6a

N-((9-beta-D-ribofuranosyl-2-methylthiopurine-
6-yl)carbamoyl)threonine

mt6a

N-((9-beta-D-ribofuranosylpurine-6-
yl)N-methylcarbamoyl)threonine

mv

uridine-5-oxyacetic acid-methylester

o5u

uridine-5-oxyacetic acid

osyw

wybutoxosine

p

pseudouridine

q

queuosine

s2t

5-methyl-2-thiouridine

s2c

2-thiocytidine

s2t

5-methyl-2-thiouridine

s2u

2-thiouridine

s4u

4-thiouridine

t

5-methyluridine

t6a

N-((9-beta-D-ribofuranosylpurine-6-
yl)-carbamoyl)threonine

tm

2'-O-methyl-5-methyluridine

um

2'-O-methyluridine

yw

wybutosine

x

3-(3-amino-3-carboxy-propyl)uridine, 
(acp3)u








 

WIPO Standard ST.25 (1998), Appendix 2, Table 3, 
provides that the amino acids should be represented 
using the following three-letter code with the first letter 
as a capital.


Table 3: List of Amino Acids
Symbol

Meaning

Ala

Alanine

Cys

Cysteine

Asp

Aspartic Acid

Glu

Glutamic Acid

Phe

Phenylalanine

Gly

Glycine

His

Histidine

Ile

Isoleucine

Lys

Lysine

Leu

Leucine

Met

Methionine

Asn

Asparagine

Pro

Proline

Gln

Glutamine

Arg

Arginine

Ser

Serine

Thr

Threonine

Val

Valine

Trp

Tryptophan

Tyr

Tyrosine

Asx

Asp or Asn

Glx

Glu or Gln

Xaa

unknown or other 





WIPO Standard ST.25 (1998), Appendix 2, Table 4, 
provides that modified and unusual amino acids may 
be represented as the corresponding unmodified 
amino acids in the sequence itself if the modified or 
unusual amino acid is one of those listed below and 
the modification is further described in the Feature 
section of the Sequence Listing. The codes from the 
list below may be used in the description (i.e., the 
specification and drawings, or in Sequence Listing) 
but these codes may not be used in the sequence itself.


Table 4: List of Modified and UnusualAmino Acids
Symbol

Meaning

Aad

2-Aminoadipic acid

bAad

3-Aminoadipic acid

bAla 

beta-Alanine, beta-Aminopropionic 
acid

Abu

2-Aminobutyric acid

4Abu

4-Aminobutyric acid, piperidinic 
acid

Acp

6-Aminocaproic acid

Ahe

2-Aminoheptanoic acid

Aib

2-Aminoisobutyric acid

bAib

3-Aminoisobutyric acid

Apm

2-Aminopimelic acid

Dbu

2,4-Diaminobutyric acid

Des

Desmosine

Dpm

2,2' -Diaminopimelic acid

Dpr

2,3-Diaminopropionic acid

EtGly

N-Ethylglycine

EtAsn

N-Ethylasparagine

Hyl

Hydroxylysine

aHyl

allo-Hydroxylysine

3Hyp

3-Hydroxyproline

4Hyp

4-Hydroxyproline








 

Ide

Isodesmosine

aIle

allo-Isoleucine

MeGly

N-Methylglycine, sarcosine

MeIle

N-Methylisoleucine

MeLys

6-N-Methyllysine

MeVal

N-Methylvaline

Nva

Norvaline

Nle

Norleucine

Orn

Ornithine





WIPO Standard ST.25 (1998), Appendix 2, Table 5, 
provides for feature keys related to DNA sequences.


Table 5: List of Feature Keys Related to Nucleotide Sequences
Key

Description

allele

a related individual or strain contains stable, alternative forms of the same gene 
which differs from the presented sequence at this location (and perhaps others)

attenuator

(1) region of DNA at which regulation of termination of transcription occurs, 
which controls the expression of some bacterial operons; (2) sequence segment 
located between the promoter and the first structural gene that causes partial 
termination of transcription

C_region

constant region of immunoglobulin light and heavy chains, and T-cell receptor 
alpha, beta, and gamma chains; includes one or more exons depending on the 
particular chain

CAAT_signal

CAAT box; part of a conserved sequence located about 75 bp up-stream of the 
start point of eukaryotic transcription units which may be involved in RNA 
polymerase binding; consensus=GG (C or T) CAATCT

CDS

coding sequence; sequence of nucleotides that corresponds with the sequence 
of amino acids in a protein (location includes stop codon); feature includes 
amino acid conceptual translation

conflict

independent determinations of the “same” sequence differ at this site or region

D-loop

displacement loop; a region within mitochondrial DNA in which a short stretch 
of RNA is paired with one strand of DNA, displacing the original partner DNA 
strand in this region; also used to describe the displacement of a region of one 
strand of duplex DNA by a single stranded invader in the reaction catalyzed by 
RecA protein

D-segment

diversity segment of immunoglobulin heavy chain, and T-cell receptor beta 
chain

enhancer

a cis-acting sequence that increases the utilization of (some) eukaryotic promoters, 
and can function in either orientation and in any location (upstream or 
downstream) relative to the promoter








 

exon

region of genome that codes for portion of spliced mRNA; may contain 5'UTR, 
all CDSs, and 3'UTR

GC_signal

GC box; a conserved GC-rich region located upstream of the start point of 
eukaryotic transcription units which may occur in multiple copies or in either 
orientation; consensus=GGGCGG

gene

region of biological interest identified as a gene and for which a name has been 
assigned

iDNA

intervening DNA; DNA which is eliminated through any of several kinds of 
recombination

intron

a segment of DNA that is transcribed, but removed from within the transcript 
by splicing together the sequences (exons) on either side of it

J_segment

joining segment of immunoglobulin light and heavy chains, and T-cell receptor 
alpha, beta, and gamma chains

LTR

long terminal repeat, a sequence directly repeated at both ends of a defined 
sequence, of the sort typically found in retroviruses

mat_peptide

mature peptide or protein coding sequence; coding sequence for the mature or 
final peptide or protein product following post-translational modification; the 
location does not include the stop codon (unlike the corresponding CDS)

misc_binding

site in nucleic acid which covalently or non-covalently binds another moiety 
that cannot be described by any other Binding key (primer_bind or 
protein_bind)

misc_difference

feature sequence is different from that presented in the entry and cannot be 
described by any other Difference key (conflict, unsure, old_sequence, mutation, 
variation, allele, or modified_base)

misc_feature

region of biological interest which cannot be described by any other feature 
key; a new or rare feature

misc_recomb

site of any generalized, site-specific or replicative recombination event where 
there is a breakage and reunion of duplex DNA that cannot be described by 
other recombination keys (iDNA and virion) or qualifiers of source key (/
insertion_seq, /transposon, /proviral)

misc_RNA

any transcript or RNA product that cannot be defined by other RNA keys 
(prim_transcript, precursor_RNA, mRNA, 5'clip, 3'clip, 5'UTR, 3'UTR, exon, 
CDS, sig_peptide, transit_peptide, mat_peptide, intron, polyA_site, rRNA, 
tRNA, scRNA, and snRNA)

misc_signal

any region containing a signal controlling or altering gene function or expression 
that cannot be described by other Signal keys (promoter, CAAT_signal, 
TATA_signal, -35_signal, -10_signal, GC_signal, RBS, polyA_signal, 
enhancer, attenuator, terminator, and rep_origin)








 

misc_structure

any secondary or tertiary structure or conformation that cannot be described by 
other Structure keys (stem_loop and D-loop)

modified_base

the indicated nucleotide is a modified nucleotide and should be substituted for 
by the indicated molecule (given in the mod_base qualifier value)

mRNA

messenger RNA; includes 5' untranslated region (5'UTR), coding sequences 
(CDS, exon) and 3' untranslated region (3'UTR)

mutation

a related strain has an abrupt, inheritable change in the sequence at this location

N_region

extra nucleotides inserted between rearranged immunoglobulin segments

old_sequence

the presented sequence revises a previous version of the sequence at this location


polyA_signal

recognition region necessary for endonuclease cleavage of an RNA transcript 
that is followed by polyadenylation; consensus=AATAAA

polyA_site

site on an RNA transcript to which will be added adenine residues by post-transcriptional 
polyadenylation

precursor_RNA

any RNA species that is not yet the mature RNA product; may include 5' 
clipped region (5'clip), 5' untranslated region (5'UTR), coding sequences (CDS, 
exon), intervening sequences (intron), 3' untranslated region (3'UTR), and 3' 
clipped region (3'clip)

prim_transcript

primary (initial, unprocessed) transcript; includes 5' clipped region (5'clip), 5' 
untranslated region (5'UTR), coding sequences (CDS, exon), intervening 
sequences (intron), 3' untranslated region (3'UTR), and 3' clipped region 
(3'clip)

primer_bind

non-covalent primer binding site for initiation of replication, transcription, or 
reverse transcription; includes site(s) for synthetic, for example, PCR primer 
elements

promoter

region on a DNA molecule involved in RNA polymerase binding to initiate 
transcription

protein_bind

non-covalent protein binding site on nucleic acid

RBS

ribosome binding site

repeat_region

region of genome containing repeating units

repeat_unit

single repeat element

rep_origin

origin of replication; starting site for duplication of nucleic acid to give two 
identical copies

rRNA

mature ribosomal RNA; the RNA component of the ribonucleoprotein particle 
(ribosome) which assembles amino acids into proteins








 

S_region

switch region of immunoglobulin heavy chains; involved in the rearrangement 
of heavy chain DNA leading to the expression of a different immunoglobulin 
class from the same B-cell

satellite

many tandem repeats (identical or related) of a short basic repeating unit; many 
have a base composition or other property different from the genome average 
that allows them to be separated from the bulk (main band) genomic DNA

scRNA

small cytoplasmic RNA; any one of several small cytoplasmic RNA molecules 
present in the cytoplasm and (sometimes) nucleus of a eukaryote

sig_peptide

signal peptide coding sequence; coding sequence for an N-terminal domain of a 
secreted protein; this domain is involved in attaching nascent polypeptide to the 
membrane; leader sequence

snRNA

small nuclear RNA; any one of many small RNA species confined to the 
nucleus; several of the snRNAs are involved in splicing or other RNA processing 
reactions

source

identifies the biological source of the specified span of the sequence; this key is 
mandatory; every entry will have, as a minimum, a single source key spanning 
the entire sequence; more than one source key per sequence is permissable

stem_loop

hairpin; a double-helical region formed by base-pairing between adjacent 
(inverted) complementary sequences in a single strand of RNA or DNA

STS

Sequence Tagged Site; short, single-copy DNA sequence that characterizes a 
mapping landmark on the genome and can be detected by PCR; a region of the 
genome can be mapped by determining the order of a series of STSs

TATA_signal

TATA box; Goldberg-Hogness box; a conserved AT-rich septamer found about 
25 bp before the start point of each eukaryotic RNA polymerase II transcript 
unit which may be involved in positioning the enzyme for correct initiation; 
consensus=TATA(A or T)A(A or T)

terminator

sequence of DNA located either at the end of the transcript or adjacent to a promoter 
region that causes RNA polymerase to terminate transcription; may also 
be site of binding of repressor protein

transit_peptide

transit peptide coding sequence; coding sequence for an N-terminal domain of 
a nuclear-encoded organellar protein; this domain is involved in post-translational 
import of the protein into the organelle

tRNA

mature transfer RNA, a small RNA molecule (75-85 bases long) that mediates 
the translation of a nucleic acid sequence into an amino acid sequence

unsure

author is unsure of exact sequence in this region

V_region

variable region of immunoglobulin light and heavy chains, and T-cell receptor 
alpha, beta, and gamma chains; codes for the variable amino terminal portion; 
can be made up from V_segments, D_segments, N_regions, and J_segments








 

V_segment

variable segment of immunoglobulin light and heavy chains, and T-cell receptor 
alpha, beta, and gamma chains; codes for most of the variable region 
(V_region) and the last few amino acids of the leader peptide

variation

a related strain contains stable mutations from the same gene (for example, 
RFLPs, polymorphisms, etc.) which differ from the presented sequence at this 
location (and possibly others)

3'clip

3'-most region of a precursor transcript that is clipped off during processing

3'UTR

region at the 3' end of a mature transcript (following the stop codon) that is not 
translated into a protein

5'clip

5'-most region of a precursor transcript that is clipped off during processing

5'UTR

region at the 5' end of a mature transcript (preceding the initiation codon) that is 
not translated into a protein

-10_signal

pribnow box; a conserved region about 10 bp upstream of the start point of bacterial 
transcription units which may be involved in binding RNA polymerase; 
consensus=TAtAaT

-35_signal

a conserved hexamer about 35 bp upstream of the start point of bacterial transcription 
units; consensus=TTGACa [ ] or TGTTGACA [ ]





WIPO Standard ST.25 (1998), Appendix 2, Table 6 
provides for feature keys related to protein sequences
.

Table 6: List of Feature Keys Related to Protein Sequences
Key

Description

CONFLICT

different papers report differing sequences

VARIANT

authors report that sequence variants exist

VARSPLIC

description of sequence variants produced by alternative splicing


MUTAGEN

site which has been experimentally altered

MOD_RES

post-translational modification of a residue

 ACETYLATION

N-terminal or other

 AMIDATION

generally at the C-terminal of a mature active peptide

 BLOCKED

undetermined N- or C-terminal blocking group

 FORMYLATION

of the N-terminal methionine








 

 GAMMA-CARBOXYGLUTAMIC 
ACID HYDROXYLATION

of asparagine, aspartic acid, proline or lysine

 METHYLATION

generally of lysine or arginine

 PHOSPHORYLATION

of serine, threonine, tyrosine, aspartic acid or histidine

 PYRROLIDONE CARBOXYLIC 
ACID

N-terminal glutamate which has formed an internal cyclic lactam


 SULFATATION

generally of tyrosine

LIPID

covalent binding of a lipidic moiety

 MYRISTATE

myristate group attached through an amide bond to the N-terminal 
glycine residue of the mature form of a protein or to an 
internal lysine residue

 PALMITATE

palmitate group attached through a thioether bond to a cysteine 
residue or through an ester bond to a serine or threonine residue


 FARNESYL

farnesyl group attached through a thioether bond to a cysteine 
residue

 GERANYL-GERANYL

geranyl-geranyl group attached through a thioether bond to a 
cysteine residue

 GPI-ANCHOR

glycosyl-phosphatidylinositol (GPI) group linked to the alpha-
carboxyl group of the C-terminal residue of the mature form of 
a protein

 N-ACYL DIGLYCERIDE

N-terminal cysteine of the mature form of a prokaryotic lipoprotein 
with an amide-linked fatty acid and a glyceryl group to 
which two fatty acids are linked by ester linkages

DISULFID

disulfide bond; the ‘FROM’ and ‘TO’ endpoints represent the 
two residues which are linked by an intra-chain disulfide bond; 
if the ‘FROM’ and ‘TO’ endpoints are identical, the disulfide 
bond is an interchain one and the description field indicates the 
nature of the cross-link

THIOLEST

thiolester bond; the ‘FROM’ and ‘TO’ endpoints represent the 
two residues which are linked by the thiolester bond

THIOETH

thioether bond; the ‘FROM’ and ‘TO’ endpoints represent the 
two residues which are linked by the thioether bond

CARBOHYD

glycosylation site; the nature of the carbohydrate (if known) is 
given in the description field

METAL

binding site for a metal ion; the description field indicates the 
nature of the metal








 

BINDING

binding site for any chemical group (co-enzyme, prosthetic 
group, etc.); the chemical nature of the group is given in the 
description field

SIGNAL

extent of a signal sequence (prepeptide)

TRANSIT

extent of a transit peptide (mitochondrial, chloroplastic, or for 
a microbody)

PROPEP

extent of a propeptide

CHAIN

extent of a polypeptide chain in the mature protein

PEPTIDE

extent of a released active peptide

DOMAIN

extent of a domain of interest on the sequence; the nature of 
that domain is given in the description field

CA_BIND

extent of a calcium-binding region

DNA_BIND

extent of a DNA-binding region

NP_BIND

extent of a nucleotide phosphate binding region; the nature of 
the nucleotide phosphate is indicated in the description field

TRANSMEM

extent of a transmembrane region

ZN_FING

extent of a zinc finger region

SIMILAR

extent of a similarity with another protein sequence; precise 
information, relative to that sequence is given in the description 
field

REPEAT

extent of an internal sequence repetition

HELIX

secondary structure: Helices, for example, Alpha-helix, 3(10) 
helix, or Pi-helix

STRAND

secondary structure: Beta-strand, for example, Hydrogen 
bonded beta-strand, or Residue in an isolated beta-bridge 

TURN

secondary structure: Turns, for example, H-bonded turn (3-
turn, 4-turn, or 5-turn)

ACT_SITE

amino acid(s) involved in the activity of an enzyme

SITE

any other interesting site on the sequence

INIT_MET

the sequence is known to start with an initiator methionine








 

NON_TER

the residue at an extremity of the sequence is not the terminal 
residue; if applied to position 1, this signifies that the first 
position is not the N-terminus of the complete molecule; if 
applied to the last position, it signifies that this position is not 
the C-terminus of the complete molecule; there is no description 
field for this key

NON_CONS

non consecutive residues; indicates that two residues in a 
sequence are not consecutive and that there are a number of 
unsequenced residues between them

UNSURE

uncertainties in the sequence; used to describe region(s) of a 
sequence for which the authors are unsure about the sequence assignment






FILING INTERNATIONALLY

The revisions to 37 CFR 1.821 through 1.825 are 
the result of an effort to harmonize the PTO, PCT, 
EPO and JPO Sequence Listing requirements to the 
extent possible. The requirements of WIPO Standard 
ST.25 are substantially identical to the requirements 
of 37 CFR 1.821 through 1.825. PatentIn Version 
3.1 software, now available (see MPEP § 2430), generates 
sequence listings that meet all of the requirements 
of WIPO Standard ST.25 (1998). The 
requirements of 37 CFR 1.821 through 1.825, however, 
are less stringent than the requirements of WIPO 
Standard ST.25 (1998). Thus, applicants who wish to 
file in countries which adhere to WIPO Standard 
ST.25 (1998) should consider the following when not 
using PatentIn Version 3.1:

(A)The WIPO Standard ST.25 (1998) does not 
permit submissions using a Macintosh computer;

(B)The WIPO Standard ST.25 (1998) does not 
accept the range of media permitted by 37 CFR 1.821through 1.825;

(C)The answers in fields 221 and 222 must 
use selections from Tables 5 and 6 of WIPO Standard 
ST.25 (1998) to comply with that standard. The terms 
from these Tables are considered language neutral 
vocabulary;

(D)Any free text in numeric identifier 223 of a 
Sequence Listing will not be translated and thus must 
also appear in the specification of applications filed 
under WIPO Standard ST.25 (1998) for compliance;

(E)A CRF filed after the filing of an application 
under the PCT is not considered to be part of the disclosure 
and will not be published in the pamphlet;

(F)Paragraph 39 of WIPO Standard ST.25 (1998) 
requires the specific wording “the information 
recorded on the form is identical to the written 
sequence listing”; and 

(G)WIPO Standard ST.25 (1998), paragraph 24, 
requires spaces between specified numeric identifiers 
in the Sequence Listing.

2422.01Definitions of Nucleotide 
and/or Amino Acids for 
Purpose of Sequence Rules

37 CFR 1.821(a) presents a definition for “nucleotide 
and/or amino acid sequences.” This definition 
sets forth limits, in terms of numbers of amino acids 
and/or numbers of nucleotides, at or above which 
compliance with the sequence rules is required. 
Nucleotide and/or amino acid sequences as used in 
37 CFR 1.821 through 1.825 are interpreted to mean 
an unbranched sequence of four or more amino acids 
or an unbranched sequence of ten or more nucleotides. 
Branched sequences are specifically excluded 
from this definition. Sequences with fewer than four 
specifically defined nucleotides or amino acids are 
specifically excluded from this section. “Specifically 
defined” means those amino acids other than “Xaa” 
and those nucleotide bases other than “n” defined in 
accordance with the World Intellectual Property Organization 
(WIPO) Handbook on Industrial Property 
Information and Documentation, Standard ST.25: 
Standard for the Presentation of Nucleotide and 
Amino Acid Sequence Listings in Patent Applications 
(1998), including Tables 1 through 6 in Appendix 2 
(see MPEP § 2422). 




 

 The limit of four or more amino acids was established 
for consistency with limits in place for industry 
database collections whereas the limit of ten or more 
nucleotides, while lower than certain industry database 
limits, was established to encompass those 
nucleotide sequences to which the smallest probe will 
bind in a stable manner. The limits for amino acids 
and nucleotides are also consistent with those established 
for sequence data exchange with the Japanese 
Patent Office and the European Patent Office.

37 CFR 1.821(a)(1) and 37 CFR 1.821(a)(2) 
present further definitions for those nucleotide and 
amino acid sequences that are intended to be 
embraced by the sequence rules. Situations in which 
the applicability of the rules are in issue will be 
resolved on a case-by-case basis. 

Nucleotide sequences are further limited to those 
that can be represented by the symbols set forth in 
37 
CFR 1.822(b), which incorporates by reference 
WIPO Standard ST.25 (1998), Appendix 2, Table 1 
(see MPEP § 2422). The presence of other than typical 
5' to 3' phosphodiester linkages in a nucleotide 
sequence does not render the rules inapplicable. The 
Office does not want to exclude linkages of the type 
commonly found in naturally occurring nucleotides, 
e.g., eukaryotic end capped sequences. 

Amino acid sequences are further limited to those 
listed in 37 CFR 1.822(b), which incorporates by reference 
WIPO Standard ST.25 (1998), Appendix 2, 
Table 3 (see MPEP § 2422), and those L-amino acids 
that are commonly found in naturally occurring proteins. 
The limitation to L-amino acids is based upon 
the fact that there currently exists no widely accepted 
standard nomenclature for representing the scope of 
amino acids encompassed by non-L-amino acids, and, 
as such, the process of meaningfully encoding these 
other amino acids for computerized searching and 
printing is not currently feasible. The presence of one 
or more D-amino acids in a sequence will exclude that 
sequence from the scope of the rules. (Voluntary compliance 
is, however, encouraged in these situations; 
the symbol “Xaa” can be used to represent D-amino 
acids.) The sequence rules embrace “[a]ny peptide or 
protein that can be expressed as a sequence using the 
symbols in WIPO Standard ST.25 (1998), Appendix 
2, Table 3 in conjunction with a description in the 
Feature section to describe, for example, modified 
linkages, cross links and end caps, non-peptidyl 
bonds, etc.” 37 CFR 1.821(a)(2). 

With regard to amino acid sequences, the use of the 
terms “peptide or protein” implies, however, that the 
amino acids in a given sequence are linked by at least 
three consecutive peptide bonds. Accordingly, an 
amino acid sequence is not excluded from the scope 
of the rules merely due to the presence of a single 
non-peptidyl bond. If an amino acid sequence can be 
represented by a string of amino acid abbreviations, 
with reference, where necessary, to a features table to 
explain modifications in the sequence, the sequence 
comes within the scope of the rules. However, the 
rules are not intended to encompass the subject matter 
that is generally referred to as synthetic resins. 

2422.02The Requirement for Exclusive
Conformance; Sequences
Presented in Drawing Figures 

37 CFR 1.821(b) requires exclusive conformance, 
with regard to the manner in which the nucleotide 
and/or amino acid sequences are presented and 
described, with the sequence rules for all applications 
that include nucleotide and amino acid sequences that 
fall within the definitions. This requirement is necessary 
to minimize any confusion that could result if 
more than one format for representing sequence data 
was employed in a given application. It is also 
expected that the required standard format will be 
more readily and widely accepted and adopted if its 
use is exclusive, as well as mandatory.

In view of the fact that many significant sequence 
characteristics may only be demonstrated by a figure, 
the exclusive conformance requirement of this section 
may be relaxed for drawing figures. This is especially 
true in view of the fact that the representation of double 
stranded nucleotides is not permitted in the 
“Sequence Listing” and many significant nucleotide 
features, such as “sticky ends” and the like, will only 
be shown effectively by reference to a drawing figure. 
Further, the similarity or homology between/among 
sequences can only be depicted in an effective manner 
in a drawing figure. Similarly, drawing figures are 
recommended for use with amino acid sequences 
to 
depict structural features of the corresponding protein, 
such as finger regions and Kringle regions. The 
situations discussed herein are given by way of example 
only and there may be many other reasons for 




 

relaxing the requirements of this section for the drawing 
figures. It should be noted, though, that when a 
sequence is presented in a drawing, regardless of the 
format or the manner of presentation of that sequence 
in the drawing, the sequence must still be included 
in the Sequence Listing and the sequence identifier 
(“SEQ ID NO:X”) must be used, either in the drawing 
or in the Brief Description of the Drawings. 

2422.03The Requirements for a
Sequence Listing and Sequence
Identifiers; Sequences Embed-
ded in Application Text; Vari-
ants of a Presented Sequence

37 CFR 1.821(c) requires that applications containing 
nucleotide and/or amino acid sequences that fall 
within the above definitions, contain, as a separate 
part of the disclosure on paper or compact disc, a disclosure 
of the nucleotide and/or amino acid 
sequences, and associated information, using the format 
and symbols that are set forth in 37 CFR 1.822and 37 CFR 1.823. This separate part of the disclosure 
is referred to as the “Sequence Listing.” The 
“Sequence Listing” submitted pursuant to 37 CFR 
1.821(c), whether on paper or compact disc, is the 
official copy of the “Sequence Listing.” 

37 CFR 1.821(c) requires that each sequence disclosed 
in the application appear separately in the 
“Sequence Listing,” with each sequence further being 
assigned a sequence identification number, referred to 
as “SEQ ID NO.” The sequence identifiers must begin 
with 1 and increase sequentially by integers. The 
requirement for sequence identification numbers, at a 
minimum, requires that each sequence be assigned a 
different number for purposes of identification. However, 
where practical and for ease of reference, 
sequences should be presented in the separate part of 
the application in numerical order and in the order in 
which they are discussed in the application.

 If submitted on paper, the “Sequence Listing” is a 
separate part of the disclosure which must begin on a 
new page within the specification. A plurality of 
sequences may, if feasible, be presented on a single 
page; the separate presentation of both nucleotide and 
amino acid sequences on the same page is also permitted.


 If the “Sequence Listing” is submitted on compact 
disc, the specification must contain an incorporation 
by reference of the material on the compact disc in a 
separate paragraph, identifying each compact disc by 
the names of the files contained on each of the compact 
discs, their date of creation and their sizes in 
bytes (37 CFR 1.52(e)). The total number of compact 
discs including duplicates and the files on each compact 
disc shall be specified (37 CFR 1.77(b)(4)). The 
compact disc used to submit the sequence listing may 
also contain table information if the table has more 
than 50 pages of text. See 37 CFR 1.823(a)(2) and 
1.52(e)(1)(iii). The compact disc and duplicate copy 
must be labeled “Copy 1” and “Copy 2,” respectively, 
and a statement stating that the copies are identical 
must be included. If the two compact discs are not 
identical, the Office will use the disc labeled “Copy 
1” for further processing (37 CFR 1.52(e)(4)). See 
also MPEP § 608.05. 

The compact disc submitted under 37 CFR 1.821(c)
may, if it contains no tables, be identical to the computer 
readable form (CRF) submitted under 37 CFR 
1.821(e) and 37 CFR 1.824, if that CRF is submitted 
on a compact disc. Even if the compact discs submitted 
under both 37 CFR 1.821(c) and (e) are identical, 
each compact disc submitted under 37 CFR 1.821(c) 
must be submitted in duplicate, in addition to the CRF 
under 37 CFR 1.821(e).

The requirement for compliance in 37 CFR 
1.821(c) is directed to “disclosures of nucleotide and/
or amino acid sequences.” (Emphasis added.) All 
sequence information, whether claimed or not, that 
meets the length thresholds in 37 CFR 1.821(a) is subject 
to the rules. The goal of the Office is to build a 
comprehensive database that can be used for, inter 
alia, the purpose of assessing the prior art. It is therefore 
essential that all sequence information, whether 
only disclosed or also claimed, be included in the 
database. In those instances in which prior art 
sequences are only referred to in a given application 
by name and a publication or accession reference, 
they need not be included as part of the “Sequence 
Listing,” unless an examiner considers the referred- to 
sequence to be “essential material,” per MPEP 
§
 
608.01(p). However, if the applicant presents the 
sequence as a string of particular bases or amino 
acids, it is necessary to include the sequence in 
the 
“Sequence Listing,” regardless of whether the 




 

applicant considers the sequence to be prior art. In 
general, any sequence that is disclosed and/or claimed 
as a sequence, i.e., as a string of particular bases or 
amino acids, and that otherwise meets the criteria of 
37 CFR 1.821(a), must be set forth in the “Sequence 
Listing.” 

It is generally acceptable to present a single, general 
sequence in accordance with the sequence rules 
and to discuss and/or claim variants of that general 
sequence without presenting each variant as a separate 
sequence in the “Sequence Listing.” By way of example 
only, the following types of sequence disclosures 
would be treated as noted herein by the Office. With 
respect to “conservatively modified variants thereof” 
of a sequence, the sequences may be described as 
SEQ ID NO:X and “conservatively modified variants 
thereof,” if desired. With respect to a sequence that 
“may be deleted at the C-terminus by 1, 2, 3, 4, or 5 
residues,” all of the implied variations do not need to 
be included in the “Sequence Listing.” If such a situation 
were encompassed by the rules, it would introduce 
far too much complexity into the “Sequence 
Listing” and the Office's database. The possible mathematical 
variations that could result from this type of 
language could reasonably require a “Sequence Listing” 
that would be thousands of pages in length. In 
this latter example, only the undeleted sequence needs 
to be included in the “Sequence Listing,” and the 
sequences may be described as SEQ ID NO:X from 
which deletions have been made at the C-terminus by 
1, 2, 3, 4, or 5 residues. The Office's database will 
only contain the undeleted sequence. 

37 CFR 1.821(d) requires the use of the assigned 
sequence identifier in all instances where the description 
or claims of a patent application discuss 
sequences regardless of whether a given sequence is 
also embedded in the text of the description or claims 
of an application. This requirement is also intended to 
permit references, in both the description and claims, 
to sequences set forth in the “Sequence Listing” by 
the use of assigned sequence identifiers without 
repeating the sequence in the text of the description or 
claims. Sequence identifiers can also be used to discuss 
and/or claim parts or fragments of a properly presented 
sequence. For example, language such as 
“residues 14 to 243 of SEQ ID NO:23” is permissible 
and the fragment need not be separately presented in 
the “Sequence Listing.” Where a sequence is embedded 
in the text of an application, it must be presented 
in a manner that complies with the requirements of 
the sequence rules.

The rules do not alter, in any way, the requirements 
of 35 U.S.C. 112. The implementation of the rules has 
had no effect on disclosure and/or claiming requirements. 
The rules, in general, or the use of sequence 
identifiers throughout the specification and claims, 
specifically, should not raise any issues under 
35 
U.S.C. 112, first or second paragraphs. The use of 
sequence identification numbers (SEQ ID NO:X) only 
provides a shorthand way for applicants to discuss 
and claim their inventions. These identification numbers 
do not in any way restrict the manner in which an 
invention can be claimed.

2422.04The Requirement for a
Computer Readable 
Copy of the Official Copy
of the Sequence Listing 

37 CFR 1.821(e) requires the submission of a copy 
of the “Sequence Listing” in computer readable 
form. The information on the computer readable form 
will be entered into the Office’s database for searching 
and printing nucleotide and amino acid sequences. 
This electronic database will also enable the Office to 
exchange patented sequence data, in electronic form, 
with the Japanese Patent Office and the European 
Patent Office. It should be noted that the Office’s 
database complies with the confidentiality requirement 
imposed by 35 U.S.C. 122. Pending application 
sequences are maintained in the database separately 
from published or patented sequences. That is, the 
Office will not exchange or make public any information 
on any sequence until the patent application containing 
that information is published or matures into a 
patent, or as otherwise allowed by 35 U.S.C. 122. 

The “Sequence Listing” submitted pursuant to 
37 
CFR 1.821(c), whether on paper or compact disc, 
is the official copy of the “Sequence Listing.” However, 
the Office may permit correction of the official 
copy, at the least, during the pendency of a given 
application by reference to the computer readable 
copy thereof submitted pursuant to 37 CFR 1.821(e) if 
both the official copy and computer readable 
form 
were submitted at the time of filing of the application 
and the totality of the circumstances otherwise 




 

substantiate the proposed correction. A mere discrepancy 
between the official copy and the computer readable 
form may not, in and of itself, be sufficient to 
justify a proposed correction. In this regard, the Office 
will assume that the computer readable form has been 
incorporated by reference into the application when 
the official copy and computer readable form were 
submitted at the time of filing of the application. The 
Office will attempt to accommodate or address all 
correction issues, but it must be kept in mind that the 
real burden rests with the applicant to ensure that any 
discrepancies between the official copy and the computer 
readable form are eliminated or minimized. 
Applicants should be aware that there will be 
instances where the applicant may have to suffer the 
consequences of any discrepancies between the two. 

The Office does not desire to be bound by a 
requirement to permanently preserve computer readable 
forms for support, priority or correction purposes. 
For example, the Office will make corrections, 
where appropriate, by reference to the computer readable 
form as long as the computer readable form is 
still available to the Office. However, once use of the 
computer readable form by the Office for processing 
has ended, i.e., once the Office has entered the data 
contained on the computer readable form into the 
appropriate database, the Office does not intend to 
further preserve the computer readable form submitted 
by the applicant. 

2422.05Reference to Previously Filed
Identical Computer Readable
Form; Continuing or Derivative
Applications; Request for
Transfer of Computer Readable
Form

The last three sentences of 37 CFR 1.821(e) set 
forth the procedure to be followed when a computer 
readable form of a given application is identical with 
a computer readable form of another application. In 
that situation, an applicant may make reference to the 
other application and computer readable form therein 
in lieu of filing a duplicate computer readable form in 
the given application. That is, additional computer 
readable forms will not be required in derivative or 
continuing applications if the sequence information is 
exactly the same, i.e., with no additions or deletions, 
as that in a parent or previously filed application in 
which a complying computer readable form had been 
filed. If sequence information is deleted from or 
added to that submitted in a previously filed application, 
the procedure in this paragraph is not available 
and a new computer readable form is required. To 
take advantage of the procedure outlined in this section, 
applicants must request that the previously submitted 
sequence information be used in the given 
application. A letter must be submitted in the given 
application requesting use of the previously filed 
sequence information. The letter must completely 
identify the other application, by application number, 
and the computer readable form, by indicating 
whether it was the only computer readable form filed 
in that application or whether it was the second, or 
subsequent, computer readable form filed. 

A sample letter requesting transfer of the previously 
filed sequence information is set forth below:

The paper or compact disc copy of the Sequence Listing 
in this application [application number], is identical to 
the computer readable copy of the Sequence Listing filed 
in application [application number], filed [date]. In accordance 
with 37 CFR 1.821(e), please use the [first-filed, 
last-filed or only, whichever is applicable] computer readable 
form filed in that application as the computer readable 
form for the instant application. It is understood that 
the Patent and Trademark Office will make the necessary 
change in application number and filing date for the 
instant application. A paper or compact disc copy of the 
Sequence Listing is [included in the originally-filed specification 
of the instant application, included in a separately 
filed preliminary amendment for incorporation into the 
specification, whichever is applicable].

2422.06Requirement for Statement
Regarding Content of Official
and Computer Readable Copies
of Sequence Listing

37 CFR 1.821(f) requires that the official 
“Sequence Listing” (submitted on paper or compact 
disc pursuant to 37 CFR 1.821(c)) and computer readable 
copies of the “Sequence Listing” (submitted pursuant 
to 37 CFR 1.821(e)) be accompanied by a 
statement that the content of the official and computer 
readable copies are the same, at the time when the 
computer readable form is submitted. Such a statement 
may be made by the applicant. See MPEP 




 

§
 
2428 for further information and Sample Statements.


2422.07Requirements for Compliance,
Statements Regarding New
Matter, and Sanctions for
Failure to Comply

37 CFR 1.821(g) requires compliance with the 
requirements of 37 CFR 1.821(b) through (f), as discussed 
above, if they are not satisfied at the time of 
filing under 35 U.S.C. 111(a) or at the time of entering 
the national stage of an international application 
under 35 U.S.C. 371, within the period of time set in a 
notice requiring compliance. Failure to comply will 
result in the abandonment of the application. Submissions 
in reply to requirements under this paragraph 
must be accompanied by a statement that the submission 
includes no new matter. Such a statement may be 
made by the applicant. Extensions of time in which to 
reply to a requirement under this paragraph are available 
pursuant to 37 CFR 1.136. When an action by the 
applicant is a bona fide attempt to comply with these 
rules and it is apparent that compliance with some 
requirement has inadvertently been omitted, the applicant 
may be given a new time period to correct the 
omission. See 37 CFR 1.135(c).

 Provisional applications filed under 35 U.S.C. 
111(b) need not comply with 37 CFR 1.821 through 
1.825, however, applicants are encouraged to file a 
Sequence Listing as defined in 37 CFR 1.821(c) for 
ease of identification of the sequence information 
contained in the provisional application.

37 CFR 1.821(h) requires compliance with the 
requirements of 37 CFR 1.821(b) through (f), as discussed 
above, within the time period prescribed in a 
notice requiring compliance in an international application 
filed in the United States Receiving Office 
under the Patent Cooperation Treaty (PCT), if the 
above noted requirements are not satisfied at the time 
of filing. Submissions in reply to requirements under 
this paragraph must be accompanied by a statement 
that the submission does not include matter which 
goes beyond the disclosure in the international application 
as filed. Such a statement may be made by an 
applicant. International applications that fail to comply 
with any of the requirements of 37 CFR 1.821(b)-
(f) will be searched to the extent possible without the 
benefit of the information in computer readable form. 
See PCT Administrative Instructions Section 513(c). 

The requirement to submit a statement that a submission 
in reply to the requirements of this section 
does not include new matter or matter which goes 
beyond the disclosure in the application as filed is not 
the first instance in which the applicant has been 
required to ensure that there is not new matter upon 
amendment. The requirement is analogous to that 
found in 37 CFR 1.125 regarding substitute specifications. 
When a substitute specification is required 
because the number or nature of amendments would 
make it difficult to examine the application, the applicant 
must include a statement that the substitute specification 
includes no new matter. The necessity of 
requiring a substitute “Sequence Listing,” or pages 
thereof, is similar to the necessity of requiring a substitute 
specification and, likewise, the burden is on the 
applicant to ensure that no new matter is added. 
Applicants have a duty to comply with the statutory 
prohibition (35 U.S.C. 132 and 35 U.S.C. 251) against 
the introduction of new matter.

It should be noted that the treatment accorded 
errors in sequencing or any other errors prior to the 
implementation date of the sequence rules will be no 
different for those applications filed on or after the 
implementation date of these rules. The correction of 
errors in sequencing or any other errors that are made 
in describing an invention are, as they have always 
been, subject to the statutory prohibition (35 U.S.C. 
132 and 35 U.S.C. 251) against the introduction of 
new matter.

2422.08Presumptions Regarding
Compliance

Neither the presence nor absence of information 
which is not required under the sequence rules will 
create a presumption that such information is necessary 
to satisfy any of the requirements of 35 U.S.C. 
112. Further, the grant of a patent on an application 
that is subject to 37 CFR 1.821 through 37 CFR 1.825constitutes a presumption that the granted patent complies 
with the requirements of these rules. 




 

2422.09Box Sequence; Hand Delivery of 
Sequence Listings and ComputerReadable Forms

To facilitate administrative processing of all papers 
and compact discs associated with sequence rule compliance, 
all computer readable forms, compact discs, 
fees, and papers accompanying them filed in the 
Office should be marked “Box SEQUENCE.” 

Correspondence relating to the sequence rules may 
also be hand-delivered to the Technology Center 
(TC). In cases of hand delivery to the Customer Service 
Window or to the TC, the compact disc, floppy 
disk or tape should be placed in a protective mailer 
labeled with at least the application number, if available. 
The labeling requirements of 37 CFR 1.52(e) 
and 1.824(a)(6) must also be complied with. The use 
of staples and clips, if any, should be confined to carefully 
attaching the mailer to the submitted papers 
without contact or compression of the magnetic media 
which may cause the disk or tape to be unreadable. In 
no situations should additional or complimentary 
electronic copies be delivered to examiners or other 
Office personnel.

2423Symbols and Format To Be Used
for Nucleotide and/or Amino Acid
Sequence Data 

37 CFR 1.822. Symbols and format to be used for 
nucleotide and/or amino acid sequence data.

(a)The symbols and format to be used for nucleotide and/or 
amino acid sequence data shall conform to the requirements of 
paragraphs (b) through (e) of this section.

(b)The code for representing the nucleotide and/or amino 
acid sequence characters shall conform to the code set forth in the 
tables in WIPO Standard ST.25 (1998), Appendix 2, Tables 1 and 
3. This incorporation by reference was approved by the Director 
of the Federal Register in accordance with 5 U.S.C. 552(a) and 1 
CFR part 51. Copies of ST.25 may be obtained from the World 
Intellectual Property Organization; 34 chemin des Colombettes; 
1211 Geneva 20 Switzerland. Copies of ST.25 may be inspected at 
the Patent Search Room; Crystal Plaza 3, Lobby Level; 2021 
South Clark Place; Arlington, VA 22202. Copies may also be 
inspected at the Office of the Federal Register, 800 North Capitol 
Street, NW, Suite 700, Washington, DC. No code other than that 
specified in these sections shall be used in nucleotide and amino 
acid sequences. A modified base or modified or unusual amino 
acid may be presented in a given sequence as the corresponding 
unmodified base or amino acid if the modified base or modified or 
unusual amino acid is one of those listed in WIPO Standard ST.25 
(1998), Appendix 2, Tables 2 and 4, and the modification is also 
set forth in the Feature section. Otherwise, each occurrence of a 
base or amino acid not appearing in WIPO Standard ST.25 (1998), 
Appendix 2, Tables 1 and 3, shall be listed in a given sequence as 
“n” or “Xaa,” respectively, with further information, as appropriate, 
given in the Feature section, preferably by including one or 
more feature keys listed in WIPO Standard ST.25 (1998), Appendix 
2, Tables 5 and 6.

(c)Format representation of nucleotides. (1) A nucleotide 
sequence shall be listed using the lower-case letter for representing 
the one-letter code for the nucleotide bases set forth in WIPO 
Standard ST.25 (1998), Appendix 2, Table 1.

(2)The bases in a nucleotide sequence (including introns) 
shall be listed in groups of 10 bases except in the coding parts of 
the sequence. Leftover bases, fewer than 10 in number, at the end 
of noncoding parts of a sequence shall be grouped together and 
separated from adjacent groups of 10 or 3 bases by a space.

(3)The bases in the coding parts of a nucleotide sequence 
shall be listed as triplets (codons). The amino acids corresponding 
to the codons in the coding parts of a nucleotide sequence shall be 
typed immediately below the corresponding codons. Where a 
codon spans an intron, the amino acid symbol shall be typed 
below the portion of the codon containing two nucleotides.

(4)A nucleotide sequence shall be listed with a maximum 
of 16 codons or 60 bases per line, with a space provided 
between each codon or group of 10 bases.

(5)A nucleotide sequence shall be presented, only by a 
single strand, in the 5 to 3 direction, from left to right.

(6)The enumeration of nucleotide bases shall start at the 
first base of the sequence with number 1. The enumeration shall 
be continuous through the whole sequence in the direction 5 to 3. 
The enumeration shall be marked in the right margin, next to the 
line containing the one-letter codes for the bases, and giving the 
number of the last base of that line.

(7)For those nucleotide sequences that are circular in 
configuration, the enumeration method set forth in paragraph 
(c)(6) of this section remains applicable with the exception that 
the designation of the first base of the nucleotide sequence may be 
made at the option of the applicant.

(d)Representation of amino acids. (1) The amino acids in a 
protein or peptide sequence shall be listed using the three-letter 
abbreviation with the first letter as an upper case character, as in 
WIPO Standard ST.25 (1998), Appendix 2, Table 3.

(2)A protein or peptide sequence shall be listed with a 
maximum of 16 amino acids per line, with a space provided 
between each amino acid.

(3)An amino acid sequence shall be presented in the 
amino to carboxy direction, from left to right, and the amino and 
carboxy groups shall not be presented in the sequence.

(4)The enumeration of amino acids may start at the first 
amino acid of the first mature protein, with the number 1. When 
presented, the amino acids preceding the mature protein, e.g., pre-
sequences, pro-sequences, pre-pro-sequences and signal 
sequences, shall have negative numbers, counting backwards 
starting with the amino acid next to number 1. Otherwise, the enumeration 
of amino acids shall start at the first amino acid at the 
amino terminal as number 1. It shall be marked below the 
sequence every 5 amino acids. The enumeration method for amino 




 

acid sequences that is set forth in this section remains applicable 
for amino acid sequences that are circular in configuration, with 
the exception that the designation of the first amino acid of the 
sequence may be made at the option of the applicant.

(5)An amino acid sequence that contains internal terminator 
symbols (e.g., “Ter”, “”, or “.”, etc.) may not be represented 
as a single amino acid sequence, but shall be presented as 
separate amino acid sequences.

(e)A sequence with a gap or gaps shall be presented as a 
plurality of separate sequences, with separate sequence identifiers, 
with the number of separate sequences being equal in number to 
the number of continuous strings of sequence data. A sequence 
that is made up of one or more noncontiguous segments of a larger 
sequence or segments from different sequences shall be presented 
as a separate sequence.

Tables 1-6 of WIPO Standard ST.25 (1998), 
Appendix 2, are reproduced in MPEP § 2422.

2423.01Format and Symbols To Be
Used in Sequence Listings 

37 CFR 1.822 sets forth the format and symbols to 
be used for listing nucleotide and/or amino acid 
sequence data. The codes for representing the nucleotide 
and/or amino acid characters in the sequences 
are set forth in the tables of WIPO Standard ST.25 
(1998), Appendix 2, Tables 1 and 3. See MPEP 
§
 
2422. No other symbols shall be used in nucleotide 
and amino acid sequences. The “modified base” and 
“modified and unusual amino acid” codes appearing 
in WIPO Standard ST.25 (1998), Appendix 2, Tables 
2 and 4 (see 37 CFR 1.822 and MPEP § 2422) are 
not to be set forth in the sequences recited in the 
Sequence Listing. However, “modified base” or 
“modified and unusual amino acid” codes may be 
used in the written description and/or drawing portions 
of the specification. To properly enter notations 
for modified codes in the Sequence Listing, the Feature 
section of the Sequence Listing should be used. 
That is, a modified base or amino acid may be presented 
in a given sequence as the corresponding 
unmodified base or amino acid if the modified base or 
amino acid is one of those listed in WIPO Standard 
ST.25 (1998), Appendix 2, Table 2 or 4 and the modification 
is also set forth in the Feature section of the 
Sequence Listing. Otherwise, all bases or amino acids 
not appearing in WIPO Standard ST.25 (1998), 
Appendix 2, Table 1 or 3 must be listed in a given 
sequence as “n” or “Xaa,” respectively, with further 
information given in the Feature section of the 
“Sequence Listing.” See 37 CFR 1.823(b).

In 37 CFR 1.822(b) and 37 CFR 1.822(d), the use 
of three-letter codes for amino acids is required. The 
use of the three-letter codes for amino acids is preferred 
over the one-letter codes from the perspective 
of facilitating the examiner’s review of the application 
papers, including the “Sequence Listing”, and the 
public’s, as well as the examiner’s, use of the printed 
patents. The three-letter codes must be presented 
using the upper case for the first character and lower 
case for the remaining two characters.

37 CFR 1.822(c) through (e) set forth the format for 
presenting sequence data. These paragraphs set forth 
the manner in which the characters in sequences are to 
be grouped, spaced, presented and numbered. 

2423.02Depiction of Coding Regions 

If applicant chooses to depict coding regions, 
37 
CFR 1.822 (c)(3) requires the amino acids corresponding 
to the codons in the coding parts of a nucleotide 
sequence to be typed immediately below the 
corresponding codons. Further, in 37 CFR 1.822(c)(3), the situation in which a codon spans an intron 
has been addressed. In those situations, the “amino 
acid symbol shall be typed below the portion of the 
codon containing two nucleotides.” This requirement 
clarifies the representation of an amino acid that corresponds 
to a codon that spans an intron.

It should be noted that the sequence rules do not, in 
any way, require the depiction of coding regions or 
the amino acids corresponding to the codons in those 
coding regions. 37 CFR 1.822 (d) only requires that 
where amino acids corresponding to the codons in the 
coding parts of a nucleotide sequence are depicted, 
they must be depicted below the corresponding 
codons. There is absolutely no requirement in the 
rules to depict coding regions. Nor is there a requirement 
to separately list the amino acids corresponding 
to the codons in the coding parts of a nucleotide 
sequence unless the applicant desires to discuss the 
amino acids as a separate sequence. That is, when the 
coding parts of a nucleotide sequence and their corresponding 
amino acids have been identified, if applicant 
desires to discuss those amino acids in the coding 
parts of the nucleotide as a separate sequence, those 
amino acids must also be set forth as a separate 
sequence. The separate submission of the amino acid 




 

sequence that corresponds to the coding parts of a 
nucleotide sequence is, however, recommended and 
encouraged because the amino acid sequence may not 
be captured in the sequence database if it is only presented 
in the “Sequence Listing” as a mixed nucleotide 
and amino acid sequence. 

2423.03Presentation and Enumeration
of Sequences 

37 CFR 1.822(c)(5) provides that nucleotide 
sequences shall only be represented by a single strand, 
in the 5' to 3' direction, from left to right. That is, double 
stranded nucleotides shall not be represented in 
the “Sequence Listing.” A double stranded nucleotide 
may be represented as two single stranded nucleotides, 
and any relationship between the two may be 
shown in the drawings. 

The procedures for presenting and numbering 
amino acid sequences are set forth in 37 CFR 
1.822(d). Two alternatives are presented for numbering 
amino acid sequences. Amino acid sequences may 
be numbered with respect to the identification of the 
first amino acid of the first mature protein or with 
respect to the first amino acid appearing at the amino 
terminal. The enumeration procedure for nucleotides 
is set forth in 37 CFR 1.822(c)(6). Sequences that are 
circular in configuration are intended to be encompassed 
by these rules, and numbering procedures for 
them are provided in 37 CFR 1.822(c)(7) and (d)(4). 
The numbering procedures set forth in 37 CFR 
1.822(c) and (d) are not necessarily intended to be 
consistent with all currently employed numbering 
procedures. The objective here is to establish a reasonable 
numbering procedure that can readily be followed 
and adhered to. These formatting procedures 
also reflect those that have been agreed to for electronic 
data exchange with the JPO and the EPO.

In 37 CFR 1.822(e) the procedures for presenting 
and numbering hybrid and gapped sequences are set 
forth. A sequence that is made up of one or more noncontiguous 
segments of a larger sequence or segments 
from different sequences, i.e., a hybrid sequence, shall 
be presented as a separate sequence. A “gap” for the 
purpose of this section is not intended to embrace a 
gap or gaps that is/are introduced into the presentation 
of otherwise continuous sequence information in, e.g., 
a drawing figure, to show alignments or similarities 
with other sequences. The “gaps” referred to in this 
section are gaps representing unknown or undisclosed 
regions in a sequence between regions that are known 
or disclosed. In the situation where a contiguous fragment 
of a sequence that has already been properly set 
forth in a “Sequence Listing” is discussed and/or 
claimed, the fragment does not need to be separately 
included in the “Sequence Listing.” It may be referred 
to in the specification, claims or drawings as, e.g., 
“residues 2 through 33 of SEQ ID NO:12,” assuming 
that SEQ ID NO:12 has been properly included in the 
“Sequence Listing.” 

2424Requirements for Nucleotide and/
or Amino Acid Sequences as Part of 
the Application Papers 

37 CFR 1.823. Requirements for nucleotide and/or amino 
acid sequences as part of the application.

(a)(1) If the “Sequence Listing” required by §
 
1.821(c) is 
submitted on paper: The “Sequence Listing,” setting forth the 
nucleotide and/or amino acid sequence and associated information 
in accordance with paragraph (b) of this section, must begin on a 
new page and must be titled “Sequence Listing.” The pages of the 
“Sequence Listing” preferably should be numbered independently 
of the numbering of the remainder of the application. Each page 
of the “Sequence Listing” shall contain no more than 66 lines and 
each line shall contain no more than 72 characters. A fixed-width 
font should be used exclusively throughout the “Sequence Listing.”


(2)If the “Sequence Listing” required by §
 
1.821(c) is 
submitted on compact disc: The “Sequence Listing” must be submitted 
on a compact disc in compliance with § 1.52(e). The compact 
disc may also contain table information if the application 
contains table information that may be submitted on a compact 
disc (§ 1.52(e)(1)(iii)). The specification must contain an incorporation-
by-reference of the Sequence Listing as required by § 
1.52(e)(5). The presentation of the “Sequence Listing” and other 
materials on compact disc under § 1.821(c) does not substitute for 
the Computer Readable Form that must be submitted on disk, 
compact disc, or tape in accordance with § 1.824.

(b)The “Sequence Listing” shall, except as otherwise indicated, 
include the actual nucleotide and/or amino acid sequence, 
the numeric identifiers and their accompanying information as 
shown in the following table. The numeric identifier shall be used 
only in the “Sequence Listing.” The order and presentation of the 
items of information in the “Sequence Listing” shall conform to 
the arrangement given below. Each item of information shall 
begin on a new line and shall begin with the numeric identifier 
enclosed in angle brackets as shown. The submission of those 
items of information designated with an “M” is mandatory. The 
submission of those items of information designated with an “O” 
is optional. Numeric identifiers 110 through 170 shall only 




 

be set forth at the beginning of the “Sequence Listing.” The following 
table illustrates the numeric identifiers.

Numeric 
Identifier

Definition

Comments and format

Mandatory (M) or Optional (O)

110 

Applicant......................


Preferably max. of 10 names; one 
name per line; preferable format: 
Surname, Other Names and/or Initials.


M.

120 

Title of Invention..........


.......................................................
......

M.

130 

File Reference...............


Personal file reference.........................


M when filed prior to assignment 
or appl. number

140 

Current Application 
Number.

Specify as: US 07/999,999 or 
PCT/US96/99999.

M, if available.

141 

Current Filing 
Date.......

Specify as: yyyy-mm-
dd......................

M, if available.

150 

Prior Application 
Number.

Specify as: US 07/999,999 or 
PCT/US96/99999.

M, if applicable include priority 
documents under 35 U.S.C. 119 
and 120

151 

Prior Application Filing 
Date.

Specify as: yyyy-mm-dd 
.....................

M, if applicable

160 

Number of SEQ ID 
NOs.

Count includes total number of 
SEQ ID 
NOs................................................
.

M.

170 

Software.......................


Name of software used to create 
the Sequence Listing.

O.

210 

SEQ ID 
NO:#:..............

Response shall be an integer representing 
the SEQ ID NO shown.

M.

211 

Length.......................
....

Respond with an integer expressing 
the number of bases or amino 
acid residues.

M.








 

212 

Type...........................
...

Whether presented sequence molecule 
is DNA, RNA, or PRT (protein). 
If a nucleotide sequence 
contains both DNA and RNA fragments, 
the type shall be “DNA.” In 
addition, the combined DNA/ 
RNA molecule shall be further 
described in the 220 to 223 
feature section.

M.

213

Organism......................


Scientific name, i.e. Genus/ species, 
Unknown or Artificial 
Sequence. In addition, the 
“Unknown” or “Artificial 
Sequence” organisms shall be further 
described in the 220 to 
223 feature section.

M.

220 

Feature..........................


Leave blank after 220. 221-
223 provide for a description of 
points of biological significance in 
the sequence.

M, under the following conditions: 
if “n,” “Xaa,” or a modified or 
unusual L-amino acid or modified 
base was used in a sequence; if 
ORGANISM is “Artificial 
Sequence” or “Unknown”; if molecule 
is combined DNA/RNA.

221 

Name/
Key.....................

Provide appropriate identifier for 
feature, preferably from WIPO 
Standard ST.25 (1998), Appendix 
2, Tables 5 and 6.

M, under the following conditions: 
if “n,” “Xaa,” or a modified or 
unusual L-amino acid or modified 
base was used in a sequence.

Numeric 
Identifier

Definition

Comments and format

Mandatory (M) or Optional (O)

222 

Location........................


Specify location within sequence; 
where appropriate state number of 
first and last bases/amino acids in 
feature.

M, under the following conditions: 
if “n,” “Xaa,” or a modified or 
unusual L-amino acid or modified 
base was used in a sequence.

223 

Other Information.........


Other relevant information; four 
lines maximum.............................................


M, under the following conditions: 
if “n,” “Xaa,” or a modified or 
unusual L-amino acid or modified 
base was used in a sequence; if 
ORGANISM is “Artificial 
Sequence” or “Unknown”; if molecule 
is combined DNA/RNA.








 

300

Publication Information


Leave blank after 300

O.

301

Authors......................
...

Preferably max. of ten named 
authors of publication; specify one 
name per line; preferable format: 
Surname, Other Names and/or Initials.


O.

302

Title...........................
....

.......................................................
......

O.

303

Journal..........................


.......................................................
......

O.

304

Volume 
.........................

.......................................................
......

O.

305

Issue 
.............................

.......................................................
......

O.

306

Pages 
............................

.......................................................
......

O.

307

Date..............

Journal date on which data published; 
specify as yyyy- mm-dd, 
MMM-yyyy or Season- yyyy.

O.

308

Database Accession 
Number.

Accession number assigned by 
database including database name.

O.

309

Database Entry 
Date........

Date of entry in database; specify 
as yyyy-mm-dd or MMM-yyyy.

O.

310

Patent Document 
Number.

Document number; for patent-type 
citations only. Specify as, for 
example, US 07/ 999,999.

O.

311

Patent Filing 
Date..............

Document filing date, for patent-
type citations only; specify as 
yyyy-mm-dd.

O.

312

Publication 
Date................

Document publication date, for 
patent-type citations only; specify 
as yyyy-mm-dd.

O.

313

Relevant 
Residues............

FROM (position) TO (position)...........


O.








 

400

Sequence...................
....

SEQ ID NO should follow the 
numeric identifier and should 
appear on the line preceding the 
actual sequence.

M.





2424.01Informational Requirements for 
the Sequence Listing 

37 CFR 1.823 sets forth the informational requirements 
for inclusion in the separate part of the disclosure 
on paper or compact disc (the “Sequence 
Listing”) that must be submitted in accordance with 
37 CFR 1.821(c). 37 CFR 1.823(a)(1) sets forth page 
and line length requirements for any “Sequence Listing” 
submitted on paper. The requirement to use a 
fixed width font to present sequence data is also set 
forth therein. This latter requirement is made to ensure 
that the desired sequence character spacing and 
numbering is maintained. 37 CFR 1.823(a)(2) requires 
any “Sequence Listing” submitted on compact 
disc to be in compliance with 37 CFR 1.52(e). The 
compact disc “Sequence Listing” submitted under 
37 
CFR 1.821(c) may also contain table information 
if the application contains table information that is 
over 50 pages. See 37 CFR 1.52(e)(1)(iii). 37 
CFR 
1.823(b) lists the items of information that are to be 
included in the “Sequence Listing” in the order in 
which those items are to appear. The numeric identifier 
for each item of information shall not include the 
explanatory information included in 37 CFR 1.823(b). 

2424.02Sequence Listing Numeric
Identifiers

37 CFR 1.823(b) sets forth the order and presentation 
of the items of information in the Sequence Listing. 
Each item of information in the Sequence Listing 
must include the appropriate numeric identifier and its 
accompanying information as shown in the table 
below. Each item of information must begin on a new 
line with the numeric identifier enclosed in angle 
brackets. The submission of those items of information 
designated with an “M” is mandatory. The submission 
of those items of information designated with 
an “O” is optional. Numeric identifiers 110 through 
170 must be set forth at the beginning of the 
Sequence Listing. 

The following table illustrates the numeric identifiers. 
See MPEP § 2431 for a sample Sequence Listing.

Numeric 
Identifier

Definition

Comments and format

Mandatory (M) or Optional (O)

110 

Applicant......................


Preferably max. of 10 names; one 
name per line; preferable format: 
Surname, Other Names and/or Initials.


M.

120 

Title of Invention..........


.......................................................
......

M.

130 

File Reference...............


Personal file reference.........................


M when filed prior to assignment 
or appl. number

140 

Current Application 
Number.

Specify as: US 07/999,999 or 
PCT/US96/99999.

M, if available.








 

141 

Current Filing 
Date.......

Specify as: yyyy-mm-
dd......................

M, if available.

150 

Prior Application 
Number.

Specify as: US 07/999,999 or 
PCT/US96/99999.

M, if applicable include priority 
documents under 35 U.S.C. 119 
and 120

151 

Prior Application Filing 
Date.

Specify as: yyyy-mm-dd 
.....................

M, if applicable

160 

Number of SEQ ID 
NOs.

Count includes total number of 
SEQ ID 
NOs................................................
.

M.

170 

Software.......................


Name of software used to create 
the Sequence Listing.

O.

210 

SEQ ID 
NO:#:..............

Response shall be an integer representing 
the SEQ ID NO shown.

M.

211 

Length.......................
....

Respond with an integer expressing 
the number of bases or amino 
acid residues.

M.

212 

Type...........................
...

Whether presented sequence molecule 
is DNA, RNA, or PRT (protein). 
If a nucleotide sequence 
contains both DNA and RNA fragments, 
the type shall be “DNA.” In 
addition, the combined DNA/ 
RNA molecule shall be further 
described in the 220 to 223 
feature section.

M.

213

Organism......................


Scientific name, i.e. Genus/ species, 
Unknown or Artificial 
Sequence. In addition, the 
“Unknown” or “Artificial 
Sequence” organisms shall be further 
described in the 220 to 
223 feature section.

M.








 

220 

Feature..........................


Leave blank after 220. 221-
223 provide for a description of 
points of biological significance in 
the sequence.

M, under the following conditions: 
if “n,” “Xaa,” or a modified or 
unusual L-amino acid or modified 
base was used in a sequence; if 
ORGANISM is “Artificial 
Sequence” or “Unknown”; if molecule 
is combined DNA/RNA.

221 

Name/
Key.....................

Provide appropriate identifier for 
feature, preferably from WIPO 
Standard ST.25 (1998), Appendix 
2, Tables 5 and 6.

M, under the following conditions: 
if “n,” “Xaa,” or a modified or 
unusual L-amino acid or modified 
base was used in a sequence.

Numeric 
Identifier

Definition

Comments and format

Mandatory (M) or Optional (O)

222 

Location........................


Specify location within sequence; 
where appropriate state number of 
first and last bases/amino acids in 
feature.

M, under the following conditions: 
if “n,” “Xaa,” or a modified or 
unusual L-amino acid or modified 
base was used in a sequence.

223 

Other Information.........


Other relevant information; four 
lines maximum.............................................


M, under the following conditions: 
if “n,” “Xaa,” or a modified or 
unusual L-amino acid or modified 
base was used in a sequence; if 
ORGANISM is “Artificial 
Sequence” or “Unknown”; if molecule 
is combined DNA/RNA.

300

Publication Information


Leave blank after 300

O.

301

Authors......................
...

Preferably max. of ten named 
authors of publication; specify one 
name per line; preferable format: 
Surname, Other Names and/or Initials.


O.

302

Title...........................
....

.......................................................
......

O.

303

Journal..........................


.......................................................
......

O.

304

Volume 
.........................

.......................................................
......

O.

305

Issue 
.............................

.......................................................
......

O.








 

306

Pages 
............................

.......................................................
......

O.

307

Date..............

Journal date on which data published; 
specify as yyyy- mm-dd, 
MMM-yyyy or Season- yyyy.

O.

308

Database Accession 
Number.

Accession number assigned by 
database including database name.

O.

309

Database Entry 
Date........

Date of entry in database; specify 
as yyyy-mm-dd or MMM-yyyy.

O.

310

Patent Document 
Number.

Document number; for patent-type 
citations only. Specify as, for 
example, US 07/ 999,999.

O.

311

Patent Filing 
Date..............

Document filing date, for patent-
type citations only; specify as 
yyyy-mm-dd.

O.

312

Publication 
Date................

Document publication date, for 
patent-type citations only; specify 
as yyyy-mm-dd.

O.

313

Relevant 
Residues............

FROM (position) TO (position)...........


O.

400

Sequence...................
....

SEQ ID NO should follow the 
numeric identifier and should 
appear on the line preceding the 
actual sequence.

M.





2424.03Additional Miscellaneous
Requirements

Throughout 37 CFR 1.823(b), the items of information 
relating to patent applications and patent publications 
should be provided keeping in mind the 
appropriate standards that have been established by 
the World Intellectual Property Organization (WIPO). 
In general, an application should be identified by a 
country code, a number and a filing date, while a published 
patent document should be identified by a 
country code, a number and kind code. Proper citation 
of priority patent applications is covered in MPEP 
§
 
201.14(d). For published patent documents, the 
country code, number and kind code will appear on 
the front page of the document. Unpublished PCT 
applications are identified by the letters PCT, the 
country code of the Receiving Office, the last two digits 
of the year of filing and a number, e.g., PCT/AT81/
00033, PCT/FR88/00100. A published PCT application 
is identified by the letters WO, the last two digits 
of the year of publication, a number and a kind code, 
e.g., WO82/02827A, WO88/06811A. Country codes 
from WIPO Standard ST.3 Annex A and kind codes 
from WIPO Standard ST.16 are reproduced in MPEP 
§ 1851. Questions on proper citation of patent documents 
should be directed to the Search and Information 
Resources Administration, International Liaison 
Staff.




 

In 37 CFR 1.823(b), numeric identifier 110, the 
item of information relating to “APPLICANT” should 
be limited to a maximum of the first ten named applicants 
in the application. Similarly, in numeric identifier 
301, the item of information relating to 
“AUTHORS” should be limited to a maximum of the 
first ten named authors in the publication. 

In 37 CFR 1.823(b) “yyyy-mm-dd” is the format 
for the presentation of patent related date information 
in the “Sequence Listing.” Other date information 
may also be presented as MMM-yyyy or Season-
yyyy. The lower case letters designate numeric 
responses and the upper case letters designate alphabetical 
responses. As such, March 2, 1988, would be 
presented as 1988-03-02 or MAR 1988. 

In numeric identifiers 220 - 223, relating to 
“Features” or the description of the points of biological 
significance in a given sequence, it is recommended, 
but not required, that the information that is 
provided by the applicant conform to the controlled 
vocabulary that is set forth in GenBank's “Feature 
Representation in Nucleotide Sequence Data Libraries,” 
Release 57.0, as may be amended. Further, the 
feature “LOCATION” should be specified using the 
syntax of the DDBJ/EMBL/GenBank Feature Table 
Definition. See MPEP § 2422 when filing in countries 
which adhere to WIPO Standard ST.25.

In numeric identifiers 300 - 312, publication 
information for a given sequence is collected. The 
publication information encompasses both patent-type 
publications and non-patent literature publications. 
Numeric identifier 313, Relevant Residues, is 
intended to collect information relating to the correspondence 
between a sequence set forth in the 
“Sequence Listing” and published sequence information. 
The starting (FROM) and end (TO) positions in 
the listed sequence that correspond to the published 
sequence information should be set forth.

2425Form and Format for Nucleotide
and/or Amino Acid Sequence
Submissions in Computer
Readable Form 

37 CFR 1.824. Form and format for nucleotide and/or 
amino acid sequence submissions in computer readable 
form.

(a)The computer readable form required by §
 
1.821(e) shall 
meet the following requirements:

(1)The computer readable form shall contain a single 
“Sequence Listing” as either a diskette, series of diskettes, or 
other permissible media outlined in paragraph (c) of this section.

(2)The “Sequence Listing” in paragraph (a)(l) of this section 
shall be submitted in American Standard Code for Information 
Interchange (ASCII) text. No other formats shall be allowed.

(3)The computer readable form may be created by any 
means, such as word processors, nucleotide/amino acid sequence 
editors’ or other custom computer programs; however, it shall 
conform to all requirements detailed in this section.

(4)File compression is acceptable when using diskette 
media, so long as the compressed file is in a self-extracting format 
that will decompress on one of the systems described in paragraph 
(b) of this section.

(5)Page numbering must not appear within the computer 
readable form version of the “Sequence Listing” file.

(6)All computer readable forms must have a label permanently 
affixed thereto on which has been hand-printed or typed: 
the name of the applicant, the title of the invention, the date on 
which the data were recorded on the computer readable form, the 
operating system used, a reference number, and an application 
number and filing date, if known. If multiple diskettes are submitted, 
the diskette labels must indicate their order (e.g., “1 of X”).

(b)Computer readable form submissions must meet these 
format requirements:

(1)Computer Compatibility: IBM PC/XT/AT or Apple 
Macintosh;

(2)Operating System Compatibility: MS-DOS, MS-Windows, 
Unix or Macintosh;

(3)Line Terminator: ASCII Carriage Return plus ASCII 
Line Feed; and

(4)Pagination: Continuous file (no “hard page break” 
codes permitted).

(c)Computer readable form files submitted may be in any of 
the following media:

(1)Diskette: 3.50 inch, 1.44 Mb storage; 3.50 inch, 720 
Kb storage; 5.25 inch, 1.2 Mb storage; 5.25 inch, 360 Kb storage.

(2)Magnetic tape: 0.5 inch, up to 24000 feet; Density: 
1600 or 6250 bits per inch, 9 track; Format: Unix tar command; 
specify blocking factor (not “block size”); Line Terminator: 
ASCII Carriage Return plus ASCII Line Feed.

(3)8mm Data Cartridge: Format: Unix tar command; 
specify blocking factor (not “block size”); Line Terminator: 
ASCII Carriage Return plus ASCII Line Feed.

(4)Compact disc: Format: ISO 9660 or High Sierra Format.


(5)Magneto Optical Disk: Size/Storage Specifications: 
5.25 inch, 640 Mb.

(d)Computer readable forms that are submitted to the Office 
will not be returned to the applicant.

37 CFR 1.824 sets forth the requirements for 
sequence submissions in computer readable form. 
Any computer operating system may be utilized to 
produce a sequence submission, provided that the system 
is capable of producing a file having the characteristics 
specified in 37 CFR 1.824, and is capable of 




 

writing the properly formatted file to one of the 
acceptable electronic media. If a given sequence and 
its associated information cannot practically or possibly 
fit on the electronic media required in 37 CFR 
1.824(c), an exception via a non-fee petition to waive 
this provision will normally be granted. As set forth in 
37 CFR 1.824(d), the computer readable forms that 
are submitted in accordance with these rules will not 
be returned to the applicant. 37 CFR 1.824(a)(6) 
requires the labeling, with appropriate identifying 
information, of the computer readable forms that are 
submitted in accordance with these rules.

2426Amendments to or Replacement
of Sequence Listing and Computer
Readable Copy Thereof 

37 CFR 1.825. Amendments to or replacement of sequence 
listing and computer readable copy thereof.

(a)Any amendment to a paper copy of the “Sequence Listing” 
(§ 1.821(c)) must be made by the submission of substitute 
sheets and include a statement that the substitute sheets include no 
new matter. Any amendment to a compact disc copy of the 
“Sequence Listing” (§ 1.821(c)) must be made by the submission 
of a replacement compact disc (2 copies) in compliance with 
§
 
1.52(e). Amendments must also be accompanied by a statement 
that indicates support for the amendment in the application, as 
filed, and a statement that the replacement compact disc includes 
no new matter.

(b)Any amendment to the paper copy of the “Sequence Listing,” 
in accordance with paragraph (a) of this section, must be 
accompanied by a substitute copy of the computer readable form 
(§ 1.821(e)) including all previously submitted data with the 
amendment incorporated therein, accompanied by a statement that 
the copy in computer readable form is the same as the substitute 
copy of the “Sequence Listing.”

(c)Any appropriate amendments to the “Sequence Listing” 
in a patent; e.g., by reason of reissue or certificate of correction, 
must comply with the requirements of paragraphs (a) and (b) of 
this section.

(d)If, upon receipt, the computer readable form is found to 
be damaged or unreadable, applicant must provide, within such 
time as set by the Commissioner, a substitute copy of the data in 
computer readable form accompanied by a statement that the substitute 
data is identical to that originally filed.

37 CFR 1.825 sets forth the procedures for amending 
the “Sequence Listing” and the computer readable 
copy thereof. The procedures that have been defined 
in 37 CFR 1.825 involve the submission of either substitute 
sheets or substitute compact discs of the 
“Sequence Listing” or substitute copies of the computer 
readable form, in conjunction with statements 
that indicate support for the amendment in the application, 
as filed, and that the substitute sheets or copies 
include no new matter. (See MPEP § 608.05 and 
§
 
2428 for further information.) An amendment to the 
material on a compact disc must be done by submitting 
a replacement compact disc with the amended 
file(s). The amendment should include a corresponding 
amendment to the description of the compact disc 
and the files contained thereon in the paper portion of 
the specification. A replacement compact disc containing 
the amended files also must contain all of the 
files of the original compact disc that were not 
amended. This will insure that the Office, printer, and 
public can quickly access all of the current files in an 
application or patent by referencing only the latest 
compact disc.The requirement for statements regarding 
the absence of new matter follows current practice 
relating to the submission of substitute specifications, 
as set forth in 37 CFR 1.125. 37 CFR 1.825 (c) 
addresses the situation where amendments to the 
“Sequence Listing” are made after a patent has been 
granted, e.g., by a certificate of correction, reissue or 
reexamination. 37 CFR 1.825 (d) addresses the possibility 
and presents a remedy for the situation where 
the computer readable form may be found by the 
Office to be damaged or unreadable.

2427Form Paragraphs and Notice
to Comply

2427.01Form Paragraphs 

 See MPEP § 608.05 for form paragraphs which 
should be used when notifying applicant that a compact 
disc submitted in accordance with 37 CFR 
1.52(e) (i.e., containing a computer program listing, 
Sequence Listing, and/or table) does not comply with 
all of the requirements of the 37 CFR 1.52(e). See 
also MPEP § 608.05(b) for form paragraphs which 
should be used when a table submitted on compact 
disc does not comply with 37 CFR 1.52(e). 

 In order to expedite the processing of applications, 
minor errors pertaining to compliance with the 
sequence rules may be handled with the first Office 
action. Examples of minor errors are: when the 
“Sequence Listing” under 37 CFR 1.821(c) is submitted 
on compact disc, missing statement in the transmittal 
letter stating that the two compact discs are 
identical, missing an incorporation-by-reference of 




 

the “Sequence Listing” in the specification, or missing 
a listing of the files and required information in 
the transmittal letter; missing statement in the transmittal 
letter stating that the sequence listing information 
in computer readable form is identical to the 
written (on paper or compact disc) “Sequence Listing,” 
etc. Since the application is ready for examination, 
the examiner may act on the application and 
include any objections to the application based on 
minor errors related to the “Sequence Listing” with 
his/her Office action. In addition to the form paragraphs 
reproduced in MPEP § 608.05 and 
§
 
608.05(b), the following form paragraphs are particular 
to Sequence Listings and should be used as 
appropriate when notifying applicant of errors in the 
Sequence Listing: 

 24.01 - This form paragraph should be used for 
the first mailing of a Notice to Comply. 

 24.02 - This form paragraph should be used for 
the first mailing of a CRF Diskette Problem 
Report.

 24.03 - This form paragraph should be used when 
an applicant has made a bona fide attempt to comply 
but the reply generates an error listing from the 
Scientific and Technical Information Center 
(STIC). This should be used for a second mailing 
to applicant unless it is evident that there has been 
a deliberate omission; this form paragraph may 
also be used to extend the period for reply for the 
initially mailed notice.

 24.04 - This form paragraph should be used when 
there has been a deliberate omission in the reply or 
where the reason the reply is incomplete cannot be 
characterized as an apparent oversight or instance 
of inadvertence. 

 24.05 – This form paragraph should be used 
whenever there is no statement in the transmittal 
letter that the sequence listing information 
recorded in computer readable form is identical to 
the written (on paper or compact disc) sequence 
listing. 

 24.05.01 – This form paragraph should be used 
whenever an amendment is filed with a CRF and 
there is no statement in the transmittal letter stating 
that the Sequence Listing information recorded in 
the CRF is identical to the written sequence listing.

¶ 24.01 Cover Letter for Use With Notice To Comply With 
Sequence Rules

This application contains sequence disclosures that are encompassed 
by the definitions for nucleotide and/or amino acid 
sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, 
this application fails to comply with the requirements of 37 CFR 
1.821 through 1.825 for the reason(s) set forth below or on the 
attached Notice To Comply With Requirements For Patent Applications 
Containing Nucleotide Sequence And/Or Amino Acid 
Sequence Disclosures. [1]

Applicant is given ONE MONTH, or THIRTY DAYS, whichever 
is longer, from the mailing date of this letter within which to 
comply with the sequence rules, 37 CFR 1.821 - 1.825. Failure to 
comply with these requirements will result in ABANDONMENT 
of the application under 37 CFR 1.821(g). Extensions of time may 
be obtained by filing a petition accompanied by the extension fee 
under the provisions of 37 CFR 1.136(a). In no case may an applicant 
extend the period for reply beyond the SIX MONTH statutory 
period. Direct the reply to the undersigned. Applicant is 
requested to return a copy of the attached Notice to Comply with 
the reply.

Examiner Note:

1.Use this form paragraph only for the initial communication 
to the applicant. Use either form paragraph 24.03 or 24.04 for 
subsequent communications.

2.In bracket 1, insert how the application fails to comply with 
the requirements of 37 CFR 1.821 through 1.825.

3.Conclude action with appropriate form paragraph(s) 7.100-
7.102.

4.When mailing the Office action, attach a Notice To Comply 
With Requirements for Patent Applications Containing Nucleotide 
And/Or Amino Acid Sequence Disclosures, along with a 
marked-up copy of the Raw Sequence Listing, if any.

¶ 24.02 Cover Letter for Use with CRF Diskette Problem 
Report

This application contains sequence disclosures that are encompassed 
by the definitions for nucleotide and/or amino acid 
sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). A computer 
readable form (CRF) of the sequence listing was submitted. However, 
the CRF could not be processed by the Scientific and Technical 
Information Center (STIC) for the reason(s) set forth on the 
attached CRF Diskette Problem Report.

Applicant is given ONE MONTH, or THIRTY DAYS, whichever 
is longer, from the mailing date of this letter within which to 
comply with the sequence rules, 37 CFR 1.821 - 1.825. Failure to 
comply with these requirements will result in ABANDONMENT 
of the application under 37 CFR 1.821(g). Extensions of time may 
be obtained by filing a petition accompanied by the extension fee 
under the provisions of 37 CFR 1.136(a). In no case may an applicant 
extend the period for reply beyond the SIX MONTH statutory 
period. Direct the reply to the undersigned. Applicant is 
requested to return a copy of the attached CRF Diskette Problem 
Report with the reply.

Examiner Note:




 

1.Use this form paragraph only for the initial communication 
to the applicant. Use either form paragraph 24.03 or 24.04 for 
subsequent communications.

2.Conclude action with appropriate form paragraph(s) 7.100-
7.102.

3.When mailing the Office action, attach the CRF Diskette 
Problem Report.

¶ 24.03 Compact Disc/CRF Submission Is Not Fully 
Responsive, Bona Fide Attempt

The reply filed [1] is not fully responsive to the Office communication 
mailed [2] for the reason(s) set forth below or on the 
attached Notice To Comply With The Sequence Rules or CRF 
Diskette Problem Report.

Since the above-mentioned reply appears to be bona fide, 
applicant is given a TIME PERIOD of ONE (1) MONTH or 
THIRTY (30) DAYS from the mailing date of this notice, whichever 
is longer, within which to supply the omission or correction 
in order to avoid abandonment. EXTENSIONS OF THIS TIME 
PERIOD MAY BE GRANTED UNDER 37 CFR 1.136(a).

Examiner Note:

1.This form paragraph may be used whether or not the six-
month period for reply has expired. It is intended for use whenever 
a bona fide reply has been submitted. This practice does not 
apply where there has been a deliberate omission of some necessary 
part of a complete reply or where the reason the reply is 
incomplete cannot be characterized as an apparent oversight or 
apparent inadvertence. Under such cases the examiner has no 
authority to grant an extension if the six-month period for reply 
has expired. Use form paragraph 24.04 under such circumstances.

2.In bracket 1, insert the date of the reply and in bracket 2, 
insert the mail date of the communication requiring compliance.

3.When mailing the Office action, attach a Notice To Comply 
With Requirements For Patent Applications Containing Nucleotide 
Sequence And/Or Amino Acid Sequence Disclosures, if any, 
along with a marked-up copy of the Raw Sequence Listing, or 
CRF Diskette Problem Report.

4.See 37 CFR 1.135(c), 1.821(g); MPEP §§ 710.02(c), 
711.02(a), 714.02 and 714.03.

¶ 24.04 Compact Disc/CRF Submission Is Not Fully 
Responsive

The communication filed [1] is not fully responsive to the communication 
mailed [2] for the reason(s) set forth below or on the 
attached Notice To Comply With The Sequence Rules or CRF 
Diskette Problem Report.

If a complete reply has not been submitted by the time the 
shortened statutory period set in the communication mailed [3]
has expired, this application will become abandoned unless applicant 
corrects the deficiency and obtains an extension of time 
under 37 CFR 1.136(a). In no case may an applicant extend the 
period for reply beyond the SIX MONTH statutory period.

Examiner Note:

1.This form paragraph may not be used when the six month 
period for reply has expired. Use this form paragraph in the situation 
where, in the reply (within the six-months), there has been a 
deliberate omission of some necessary part of a complete reply. 
When the reply appears to be bona fide, but through an apparent 
oversight or inadvertence failed to provide a complete reply, use 
form paragraph 24.03.

2.In bracket 1, insert the date of the reply and in brackets 2 and 
3, insert the mail date of the communication requiring compliance.


3.When mailing the Office action, attach a Notice To Comply 
With Requirements For Patent Applications Containing Nucleotide 
Sequence And/Or Amino Acid Sequence Disclosures, if any, 
along with a marked-up copy of the Raw Sequence Listing, or 
CRF Diskette Problem Report.

¶ 24.05 CD-ROM/CD-R Requirements (Missing Sequence 
Listing/CRF Statement)

This application is objected to because it does not include the 
statement “the sequence listing information recorded in computer 
readable form is identical to the written (on paper or compact 
disc) sequence listing” and, where applicable, a statement that the 
submission includes no new matter, as required by 37 CFR 
1.821(e), 1.821(f), 1.821(g), 1.825(b) or 1.825(d). Correction is 
required.

Examiner Note:

Use this form paragraph when there is no statement in the 
transmittal letter stating that the sequence listing information 
recorded in the CRF is identical to the written sequence listing

¶ 24.05.01 CD-ROM/CD-R Requirements (Missing 
Sequence Listing/CRF Statement in an Amendment Filed 
with a CRF)

The amendment filed [1] is objected to because it does not 
include the statement “the sequence listing information recorded 
in computer readable form is identical to the written (on paper or 
compact disc) sequence listing” and, where applicable, a statement 
that the submission includes no new matter, as required by 
37 CFR 1.821(e), 1.821(f), 1.821(g), 1.825(b) or 1.825(d). A 
statement that the sequence listing information is identical is 
required.

Examiner Note:

1.Use this form paragraph when there is no statement in the 
transmittal letter stating that the sequence listing information 
recorded in the CRF is identical to the written sequence listing.

2.In bracket 1, insert the date of the amendment.




 

2427.02Notice To Comply 

The text of the Notice to Comply With Requirements 
For Patent Applications Containing Nucleotide 
Sequence and for Amino Acid Sequence Disclosures, 
Form PTO-1661, follows. The appropriate box on the 
notice should be checked depending upon the particular 
deficiencies that have been identified. In the alternative, 
a letter may be written notifying applicant of 
any deficiencies that have been identified. A copy of 
the “Raw Sequence Listing,” where available, should 
also be sent to the applicant. The “Raw Sequence 
Listing” should also be entered into the application 
file upon receipt from STIC. 




 

Form PTO-1661. Notice to Comply with Requirements for Patent Applications Containing Nucleotide Sequence and/or Amino Acid Sequence DisclosuresForm PTO-1661. Notice to Comply with Requirements for Patent Applications Containing Nucleotide Sequence and/or Amino Acid Sequence Disclosures





 

2428Sample Statements 

Sample language for the statements required to support 
sequence rule submissions is provided below. 
These statements are given by way of example only; 
other language may, of course, be used. For the statements 
that relate to the assertion that the content of 
the paper or compact disc and computer readable copies 
are the “same,” it is acknowledged that there may 
be some nonsubstantive differences between the two, 
e.g., page numbers and page breaks may be present in 
the paper copy but not in the computer readable copy 
thereof. This requirement for sameness relates to the 
informational content of the paper or compact disc 
and computer readable copies relevant to the requirements 
of the sequence rules. 

37 CFR 1.821(f) - I hereby state that the information 
recorded in computer readable form is identical to the 
written (on paper or compact disc) sequence listing.

 

37 CFR 1.52(e)(4) - I hereby state that the two compact 
discs are identical.

 

37 CFR 1.821(g) [or (h)] - I hereby state that the submission, 
filed in accordance with 37 CFR 1.821(g) [or 
(h)], herein does not include new matter [or matter 
which goes beyond the disclosure in the international 
application].

 

37 CFR 1.825(a) - I hereby state that the amendments, 
made in accordance with 37 CFR 1.825(a), included in 
the substitute sheet(s) or compact disc(s) of the 
Sequence Listing are supported in the application, as 
filed, at _____________. I hereby state that the substitute 
sheet(s) of the Sequence Listing does (do) not 
include new matter.

 

37 CFR 1.825(b) - I hereby state that the substitute 
copy of the computer readable form, submitted in 
accordance with 37 CFR 1.825(b), is the same as the 
amended Sequence Listing.

 

37 CFR 1.825(d) - I hereby state that the substitute 
copy of the computer readable form, submitted in 
accordance with 37 CFR 1.825(d), is identical to that 
originally filed. 

2429Helpful Hints for Compliance

The Office has now had a good deal of experience 
in the implementation of the sequence rules. The following 
list sets forth helpful hints, for both examiners 
and applicants, for compliance. For the most part, the 
list is a compilation of frequently asked questions. 

—Compliance is not a filing date issue. 

—Compliance is not a 35 U.S.C. 112 issue.

—Compliance is not a 35 U.S.C. 119/120 issue.

—Compliance is not per se a new matter issue. The 
standard for resolution of inconsistencies between the 
official “Sequence Listing” (submitted on paper or 
compact disc pursuant to 37 CFR 1.821(c)) and the 
computer readable form thereof and/or errors in the 
official copy of sequence information is based on the 
new matter standard. If there are inconsistencies in 
compact discs submitted in accordance with 37 CFR 
1.52(e) between “Copy 1” and “Copy 2”, the compact 
disc labeled “Copy 1” will be used for further processing.


—Compliance can be achieved via amendment. 

—The paper or compact disc copy of the Sequence 
Listing is an integral part of the application. If submitted 
on paper, the Sequence Listing must begin on a 
new page, should appear at the end of the application, 
and preferably should be numbered independently of 
the numbering of the remainder of the application. 
The new page that begins the “Sequence Listing” 
should be entitled “Sequence Listing.” If not submitted 
as such at filing, the Sequence Listing must be 
inserted into the application via amendment, e.g., by 
preliminary amendment. If submitted on compact 
disc, the specification must contain an incorporation 
by reference of the material on the compact disc in a 
separate paragraph identifying each compact disc.

—Substitute pages or replacement compact discs 
must be used for changes to the Sequence Listing for 
each respective format.

—Angle brackets and numeric identifiers listed in 
37 CFR 1.823 are very important for our database. 
Extra punctuation should not be used in Sequence 
Listings.

—The computer readable form cannot contain page 
numbers. Page numbers should only be placed on the 
paper copy of the Sequence Listing. Page numbers 
should not be placed on the compact disc copy of the 
Sequence Listing. 

—The PatentIn computer program is not the only 
means by which to comply with the rules. Any word 
processing program can be used to generate a 
Sequence Listing if it has the capability to convert a 
file into ASCII text.




 

—If a word processing program is used to generate 
a “Sequence Listing,” hard page break controls 
should not be used and margins should be adjusted to 
the smallest setting.

—Word processing files should not be submitted to 
the Office; the Sequence Listing generated by a word 
processing file should be saved as an ASCII text file 
for submission. Most word processing programs provide 
this feature.

—Statements in accordance with 37 CFR 1.821(f), 
(g), (h) and 37 CFR 1.825 and proper labeling in 
accordance with 37 CFR 1.824(a)(6) should be noted. 
Sample statements to support filings and submissions 
in accordance with 37 CFR 1.821 through 1.825 are 
provided in MPEP § 2428 Sample Statements.

—Use Box SEQUENCE.

—Three and a half inch disks are less fragile than 
five and a quarter inch disks.

—On nucleotide sequences, since only single 
strands may be depicted in the “Sequence Listing,” 
show strands in 5' to 3' direction.

—The single stranded nucleotide depicted in the 
“Sequence Listing” may represent a strand of a nucleotide 
sequence that may be single or double stranded 
which may be, further, linear or circular. An amino 
acid sequence or peptide may be linear or circular. In 
some instances, a sequence may be both single 
stranded and double stranded and/or both linear and 
circular. The response “not relevant” is also an acceptable 
response for both “Strandedness” and “Topology.” 


—Numeric identifiers “140, Current Application 
Number,” “141, Current Filing Date,” “150, 
Prior Application Number,” and “151, Prior Application 
Filing Date,” should appear in the “Sequence 
Listing” in all cases. If the information about the current 
application is not known or is unavailable at the 
time of completing the Sequence Listing, then the 
lines following numeric identifiers 140 and 141 
should be left blank. This would normally be the case 
when the “Sequence Listing” is included in a newly 
filed application. Similarly, if information regarding 
prior applications is inapplicable, or not known at the 
time of completing the “Sequence Listing” but will be 
later filed, then the numeric identifiers 150 and 
151 should appear with the line following the 
numeric identifiers left blank. 

—If you receive a Notice to Comply that should not 
have been sent to you, send a letter in the form of a 
request for reconsideration of the notice to the organization 
sending the notice.

—There are a limited number of mandatory items 
of information. They are identified in MPEP 
§
 
2424.02 Sequence Listing Numeric Identifiers.

—Figures can be used to convey information not 
readily conveyed by the Sequence Listing. The exclusive 
conformance requirement of 37 CFR 1.821(b)
will be relaxed for drawing figures. However, the 
sequence information so conveyed must still be 
included in a “Sequence Listing” and the sequence 
identifier (“SEQ ID NO:X”) must be used, either in 
the drawing or in the “Brief Description of the Drawings.” 


—Extra copies of computer readable forms should 
not be sent to examiners.

 —Inosine may be represented by the use of “I” in 
the features section, otherwise use “n.”

 —Stop codons, represented by an asterisk, are not 
permitted in amino acid sequences.

 —Punctuation should not be used in a sequence to 
indicate unknown nucleotide bases or amino acid residues 
nor should punctuation be used to delimit active 
or functional regions of a sequence. These regions 
should be noted as Features of the sequence per 
37 
CFR 1.823(b) (see numeric identifiers 220 - 
223.

—The presence of an unnatural amino acid in a 
sequence does not have the same effect as the presence 
of a D-amino acid. The sequence may still be 
subject to the rules even though one or more of the 
amino acids is not naturally occurring.

—Cyclic and branched peptides are causing some 
confusion in the application of the rules. Specific 
questions should be directed to Group 1650 personnel. 


—A cyclic peptide with a tail is regarded as a 
branched sequence, and thereby exempt from the 
rules, if all bonds adjacent to the amino acid from 
which the tail emanates are normal peptide bonds.

—Sequences that have variable-length regions 
depicted as, for example, Ala Ala Leu Leu (Xaa Xaa)nIle Pro where n=0-234 or agccttgggaca(nnnnn)mgtcatt 
where m=0-354 or Ser Met Ala Xaa Ser where Xaa 
could be 1, 2, 3, 4 and/or 5 amino acids must still 
comply with the Sequence Rules. The method to use 




 

is to repeat the variable-length region as many times 
as the maximum length and specify in the Features 
section that the amino acid (or nucleotide) at a specified 
position is either absent or present. The variables 
Xaa and n may stand for only one residue, hence the 
need to repeat the variable. The correct way to submit 
the third example is Ser Met Ala Xaa Xaa Xaa Xaa 
Xaa Ser combined with an explanation in the Features 
section of the listing that any one or all of amino acids 
4-8 can either be present or absent.

—Single letter amino acid abbreviations are not 
acceptable within the Sequence Listing but may 
appear elsewhere in the application.

—Zero (0) is not used when the numbering of 
amino acids uses negative numbers to distinguish the 
mature protein.

—Subscripts or superscripts are not permitted in a 
Sequence Listing. 

—If a “Sequence Listing” is amended, an entirely 
new computer readable form is required regardless of 
the triviality of the amendment. Amendments to the 
paper copy of the “Sequence Listing” must be made 
by replacement section in compliance with 37 CFR 
1.121. Amendments to the compact disc copy of the 
“Sequence Listing” must be made by replacement 
discs. 

—Note field length limitations. For specific 
instances, they may be waived, but compliance is 
encouraged.

—The exclusive conformance requirement of 
37 
CFR 1.821(b) requires that any amendment of the 
sequence information in a “Sequence Listing” be 
accompanied by an amendment to the corresponding 
information, if any, embedded in the text of the specification 
or presented in a drawing figure. 

—Any inquiries regarding a specific computer 
readable form that has been processed by the Office 
should be directed to the Systems Branch of the 
Chemical/Biotechnology Division of the Scientific 
and Technical Information Center.

2430PatentIn Information; Utilities
Programs; Training 

In those areas of biotechnology in which nucleotide 
and/or amino acid sequence information is significant, 
many patent applicants are accustomed to, or familiar 
with, the submission of such sequence information, in 
electronic form, to various sequence databases, such 
as GenBank, which is produced by the National Institutes 
of Health. In order to facilitate such submissions, 
or merely for the purpose of researching and 
developing sequence information, many eventual 
patent applicants also generate or encode 
sequence 
information in computer readable form. In 
order to further facilitate compliance with the 
sequence rules, the Office previously made available 
to the public an input program based on the AuthorIn 
program produced by GenBank. This input program, 
called PatentIn version 1.3, was specifically tailored 
to the requirements of the sequence rules which were 
in effect between October 1, 1990 and July 1, 1998.

The current sequence rules, which are embodied in 
37 CFR 1.821-1.825 and World Intellectual Property 
Organization (WIPO) Standard ST.25, became effective 
July 1, 1998. The rules simplify the 
Sequence 
Listing requirements, and harmonize the 
format among all Trilateral Offices and many other 
patent offices around the world. The Office deployed 
PatentIn versions 2.0 and 2.1, in 1998 and 1999, 
respectively, incorporating changes in the required 
format for the Sequence Listing to ensure compliance 
with the sequence rules that became effective July 1, 
1998. These versions operated under Microsoft Windows 
3.1x, 95, 98 and NT. By using PatentIn version 
2.0 or 2.1, customers were able to generate a 
Sequence Listing once and use that same listing to file 
at multiple patent offices worldwide. Applications 
filed in the U.S. after July 1, 1998 containing 
Sequence Listings prepared using PatentIn version 1.3 
will not be in compliance with the U.S. sequence 
rules. Applications filed in the member countries of 
WIPO after July 1, 1998 containing Sequence Listings 
prepared using PatentIn version 1.3 will not be in 
compliance with ST.25. 

In June 2000 another update of PatentIn was 
deployed, version 3.0. This version differs from earlier 
versions in that the capabilities have been 
extended. PatentIn 3.0 has several advantages over 
PatentIn 2.1. PatentIn 3.0 processes large sequences 
(over one million bases) and applications with a large 
number of sequences (over 100,000); it imports multiple 
sequences from a single file as well as multiple 
sequences from multiple files. Features defined for 
nucleic acid sequences are carried over to the supplemental 
amino acid sequences generated by the 
CDS 
feature. PatentIn 3.0 is more user-friendly than 




 

PatentIn 2.1 and looks and feels more like other Windows-
based programs. Unlike PatentIn 2.1, projects 
are portable from one computer to another provided 
PatentIn 3.0 is installed. From a programming viewpoint, 
the advantages include that the overall lines of 
code have been reduced to 25 percent of that required 
by PatentIn 2.1, maintenance of the code is easier 
since it is written in Visual C++ and it is easier to 
modify the code. 

In March of 2001 PatentIn 3.1 was released. This 
newest version builds on the success of PatentIn 3.0 
and expands its capabilities. One difference is that the 
capability to import a single sequence from a single 
file without a header has been added. The definition 
of variable characters has been enhanced in PatentIn 
3.1. If the nucleotide sequence has the variable “n” 
and the CDS feature is selected, PatentIn 3.1 will calculate 
the position of the necessary Xaa in the supplemental 
protein sequence and provide the definition 
automatically based on the codon in which the “n” 
appears. 

PatentIn version 3.1, and the companion User’s 
Manual, are available on the Office World Wide Web 
site (www.uspto.gov) for free downloading. Copies of 
both the program and the user manual may also be 
purchased from the Office on 3 1/2-inch floppy diskette 
or compact disc. PatentIn 3.1 operates in a Windows 
95/98/NT/2000 environment and has similar 
space, memory and system requirements as those for 
PatentIn version 3.0. A minimum of 64 MB of memory 
is recommended for smaller projects. Otherwise 
128 MB is recommended. Even more additional 
memory may be required for larger sequence listings. 
The disk space required to install PatentIn 3.0 is 1.6 
MB. Additional disk space is required to store project 
files and sequence listing files.

See MPEP § 1730 for additional information 
regarding ordering and using PatentIn.

While use of the PatentIn program is not required 
for compliance with the sequence rules, its use is 
highly recommended as Office experience has shown 
that submissions developed with PatentIn are far less 
likely to include errors than those developed without 
the program. The many automatic features of the PatentIn 
program also greatly ease the generation of 
Sequence Listings when compared to generating them 
by hand in a word processing environment. This is 
especially true for Sequence Listings that include 
many sequences and/or sequences having great 
lengths. 

The Office provides hands-on training in the use of 
the PatentIn and associated utilities programs. The 
classes are held in Washington D.C. as demand warrants. 
In addition, on site training may be arranged at 
locations outside Washington, D.C. To express interest 
in such classes, please contact the Search and 
Information Resources Administration.

2431Sample Sequence Listing

A sample “Sequence Listing” is included below. 




 

Sequence Listing





 

Sequence Listing


2434Examination of Patent Applications
Claiming Large Numbers of
Nucleotide Sequences

The U.S. Patent and Trademark Office published its 
policy for the examination of patent applications that 
claim large numbers of nucleotide sequences in the 
Official Gazette, 1192 O.G. 68 (November 19, 1996). 
Nucleotide sequences encoding different proteins are 
structurally distinct chemical compounds and are 
unrelated to one another. These sequences are thus 
deemed to normally constitute independent and distinct 
inventions within the meaning of 35 U.S.C. 121. 
Absent evidence to the contrary, each such nucleotide 
sequence is presumed to represent an independent and 
distinct invention, subject to a restriction requirement 
pursuant to 35 U.S.C. 121 and 37 CFR 1.141. In 
establishing the new policy, the Commissioner has 
partially waived the requirements of 37 CFR 1.141and will permit a reasonable number of such nucleotide 
sequences to be claimed in a single application. 
Under this policy, in most cases, up to 10 independent 
and distinct nucleotide sequences will be examined in 
a single application without restriction.Those 
sequences which are patentably indistinct from the 
sequences selected by the applicant will also be examined. 
Nucleotide sequences encoding the same protein 
are not considered to be independent and distinct and 
will continue to be examined together. In some exceptional 
cases, the complex nature of the claimed material 
may necessitate that the reasonable number of 
sequences to be selected be less than 10. In other 
cases, applicants may petition pursuant to 37 CFR 
1.181 for examination of additional nucleotide 
sequences by providing evidence that the different 
nucleotide sequences do not cover independent and 
distinct inventions. For examples of typical nucleotide 
sequence claims and additional information on the 
search and examination procedures, see the above 
cited O.G. Notice. See also MPEP § 803.04.

2435Publishing of Patents and Patent 
Application Publications with 
Lengthy Sequence Listings

 Due to the high cost and limited usefulness of the 
printed paper or composed electronic image versions 
of nucleotide and/or amino acid sequences, if the 
“Sequence Listing” portion is lengthy (i.e., at least 
600 Kb (about 300 typed pages)), it will no longer be 
printed with the paper and composed electronic image 
(page image) versions of patents and patent application 
publications. The “Sequence Listing” will 
only 
be published in electronic form and will 
be 
available 
on the USPTO sequence homepage 
(http://seqdata.uspto.gov) as an ASCII text file. 

 Neither the paper copies of patents and patent 
application publications that are in the search rooms 
nor those sold through the Office of Public Records, 
Certification Division, will include a sequence listing 
if the sequence listing is not included in the composed 




 

electronic image (page image) version of the patent or 
patent application publication. Furthermore, any copy 
used as a reference in an Office action will include 
only the paper portion of the document. If an applicant 
requires an electronic copy of a “Sequence Listing” 
that was not printed in the document, applicant 
must specifically request and pay for the electronic 
copy. Both applicants and members of the general 
public can obtain an electronic copy of the “Sequence 
Listing” through the Certification Division for a separate 
fee as set forth in 37 CFR 1.19(b)(3). See the 
paragraph entitled “Copies of Documents” in MPEP § 
1730 for contact information for Certification Division. 


The patent mailed to applicant will include a copy 
of the patent on paper and a copy of the sequence listing 
on an electronic medium (e.g., compact disc), if 
the “Sequence Listing” is not printed in the patent. 

 If the “Sequence Listing” is not included in the 
page images of a patent or patent application publication, 
a standardized statement will appear. Additionally, 
in the electronic text version of the patent or 
patent application publication, the statement will 
include an active hyperlink to a web page containing 
the “Sequence Listing.” The standardized statement 
for a patent will read, for example:

SEQUENCE LISTING

The patent contains a lengthy “Sequence Listing” section. A 
copy of the “Sequence Listing” is available in electronic form 
from the USPTO web site (http://seqdata.uspto.gov/
sequence.html?DocID=6183957B1). An electronic copy of 
the “Sequence Listing” will also be available from the USPTO 
upon request and payment of the fee set forth in 37 CFR 
1.19(b)(3).

The standardized statement for a patent application 
publication will read, for example:

SEQUENCE LISTING

The patent application contains a lengthy “Sequence Listing” 
section. A copy of the “Sequence Listing” is available in electronic 
form from the USPTO web site (http://seqdata.
uspto.gov/sequence.html?DocID=20010000241). An 
electronic copy of the “Sequence Listing” will also be available 
from the USPTO upon request and payment of the fee set 
forth in 37 CFR 1.19(b)(3).

 Sequence data may also be accessed in a 
more 
readily searchable manner from the National 
Center for Biotechnology Information (NCBI) at 
http://www.ncbi.nlm.nih.gov or from a commercial 
vendor. The USPTO forwards a copy of the sequence 
data to NCBI when a patent including a “Sequence 
Listing” is granted, and when an application containing 
a sequence is published pursuant to 35 U.S.C. 
122(b). If NCBI elects to include the sequence data in 
one of its databases, NCBI indexes the sequence data 
according to patent or patent application publication 
number. There is currently no fee for the public to use 
the NCBI site.