Biotechnology

2401	Introduction 

2402	The Deposit Rules  

2403	Deposit of Biological Material   

2403.01	Material Capable of Self-Replication  

2403.02	Plant Material   

2404	Need or Opportunity to Make a Deposit  

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

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

2404.03	Reference to a Deposit in the Specification  

2405	Acceptable Depository  

2406	Time of Making an Original Deposit  

2406.01	Description in Application Specification  

2406.02	Deposit After Filing Date - Corroboration  

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

2407	Replacement or Supplement of Deposit  

2407.01	In a Pending Application   

2407.02	After a Patent Has Issued   

2407.03	Failure to Replace   

2407.04	Treatment of Replacement  

2407.05	Exemption From Replacement  

2407.06	Replacement May Not Be Recognized  

2408	Term of Deposit  

2409	Viability of Deposit  

2410	Furnishing of Samples  

2410.01	Conditions of Deposit  

2410.02	Certification of Accessibility of Deposit  

2411	Examination Procedures   

2411.01	Rejections Based on Deposit Issue  

2411.02	Replies to Rejections Based on Deposit Issue    

2411.03	Application in Condition for Allowance Except 
for Deposit   

2411.04	After a Patent Has Been Granted  

2411.05	Content of Application with Respect to 
Deposited Material   

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

2421	Overview of the Sequence Rules    

2421.01	Applications Affected   

2421.02	Summary of the Requirements of the Sequence 
Rules   

2421.03	Notification of a Failure to Comply  

2421.04	Future Changes to the Sequence Rules  

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

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

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

2422.03	The Requirements for a Sequence Listing and 
Sequence Identifiers; Sequences Embedded in 
Application Text; Variants of a Presented 
Sequence  

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

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

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

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

2422.08	Presumptions Regarding Compliance  

2422.09	Box Sequence; Hand Delivery of  Sequence 
Listings and Computer Readable Forms  

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

2423.01	Format and Symbols To Be Used in Sequence 
Listings   

2423.02	Depiction of Coding Regions   

2423.03	Presentation and Enumeration of Sequences   

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

2424.01	Informational Requirements for the Sequence 
Listing   

2424.02	Sequence Listing Numeric Identifiers  

2424.03	Additional Miscellaneous Requirements  

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

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

2427	Form Paragraphs and Notice to Comply  

2427.01	Form Paragraphs   

2427.02	Notice To Comply   

2428	Sample Statements   

2429	Helpful Hints for Compliance  

2430	PatentIn Information; Utilities Programs; 
Training   

2431	Sample Sequence Listing  

2434	Examination of Patent Applications Claiming 
Large Numbers of Nucleotide Sequences  

 

2401	Introduction

This chapter provides guidance on the practices and pro-
cedures 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. 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 Register at 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.

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.

2402	The 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 sup-
plement 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. Merck and Co., Inc. v. Chase Chemical Co., 273 
F. Supp. 68, 155 USPQ 139 (D. N.J. 1967);   In re Argoude-
lis, 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 Microor-
ganisms for the Purposes of Patent Procedure was estab-
lished in 1977, and became operational in 1981. The Treaty 
requires signatory countries, like the United States, to rec-
ognize 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 exam-
ining 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 proceed-
ings 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  pro-
ceedings.  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 encour-
aged to comply with these rules even if their applications 
and reexamination proceedings were filed prior to January 
1, 1990. 

2403	Deposit of Biological Material 

37 CFR 1.801.  Biological material.

For the purposes of these regulations pertaining to the deposit of bio-
logical 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 mate-
rial" is defined in terms of a non-exhaustive list of repre-
sentative 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 rec-
ognized or necessary for the purposes of satisfying the stat-
utory requirements for patentability under  35 U.S.C. 112. 
Although the issue of the need to make a deposit of biolog-
ical material typically arises under the enablement require-
ment 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 sec-
ond paragraph of  35 U.S.C. 112 with respect to the claims. 

37 CFR 1.801 does not attempt to identify what biologi-
cal material either needs to be or may be deposited to com-
ply 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.

2403.01	Material Capable of Self-
Replication

Biological material includes material that is capable of 
self-replication either directly or indirectly.  Direct self-rep-
lication 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 rep-
resentative 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.

2403.02	Plant 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 provi-
sions 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 depos-
ited 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 Pro-
tection 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 situa-
tion involved a  "seedless" vegetable with very few seeds 
per "fruit;" about two growing seasons were required to 
provide the additional 1900 seeds.

2404	Need 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 mate-
rial 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 bio-
logical material will be considered to be readily available even though 
some requirement of law or regulation of the United States or of the coun-
try 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 disclo-
sure 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 mate-
rial to be referenced in a patent application where an inven-
tion is, or relies on, a biological material.  The invention 
may rely on a biological material for the purposes of mak-
ing 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 dis-
closure, 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 stat-
utory 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 neces-
sary 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 neces-
sary if access sufficient to satisfy these requirements is oth-
erwise available.

2404.01	Biological 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 require-
ment 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 bio-
logical 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 biologi-
cal 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 availabil-
ity 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.  
Unless there is a reasonable basis to believe that the biolog-
ical material will cease to be available during the enforce-
able 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 dis-
closure 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 biologi-
cal 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 deposi-
tory 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 accessi-
ble 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 mate-
rial 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. 112 ceases to be accessible.

The Office will accept commercial availability as evi-
dence that a biological material is known and readily avail-
able only when the evidence is clear and convincing that 
the public has access to the material.  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 biolog-
ical 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 avail-
able 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 rea-
son to believe that access to the biological material would 
later be improperly restricted.

The mere reference to a deposit or the biological mate-
rial itself in any document or publication does not necessar-
ily 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 docu-
ment would not necessarily meet the test for known and 
readily available unless the deposit was made under condi-
tions that are consistent with those specified in these rules, 
including the provision that requires, with one possible 
exception, that all restrictions on the accessibility be irrevo-
cably 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.  Thus, a reference to a deposit will not be certi-
fied available unless either (1) the deposit was necessary to 
overcome a rejection under  35 U.S.C. 112, or (2) there is, 
in the record, a statement by the examiner that a rejection 
under  35 U.S.C. 112 would have been made "but for" the 
deposit (assumes deposit information in record, as filed).  
Otherwise, public access cannot be certified and 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 regula-
tion in the United States or in the country where the deposi-
tory 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 distribu-
tion, where the restrictions are imposed for the public, as 
opposed to the private, welfare.

2404.02	Biological 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 bio-
logical 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).

2404.03	Reference to a Deposit in the 
Specification

37 CFR 1.802(c) specifically provides that the mere ref-
erence to a biological material in the specification disclo-
sure 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 fil-
ing date of a given application but that the reference to the 
biological material, itself, cannot be added after filing with-
out risking the prohibited introduction of new matter (35 
U.S.C. 132).  See the discussion of the Lundak application 
in  MPEP ? 2406.01.

2405	Acceptable Depository 

37 CFR 1.803.  Acceptable depository.

(a)	A deposit shall be recognized for the purposes of these regula-
tions 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 consult-
ants 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 expedi-
tious and proper manner; and

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

(b)	A depository seeking status under paragraph (a)(2) of this sec-
tion 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 depos-
itory to comply  with  the requirements  of  paragraph  (a) (2) of  this  sec-
tion, 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 cer-
tain 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 Commis-
sioner 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 recog-
nized as acceptable for the purposes of these regulations if 
it is either an International Depository Authority (IDA) 
established under the Budapest Treaty, or if it is a deposi-
tory 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 recog-
nized as acceptable under this regulation will not be consid-
ered 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 infor-
mation supplied by the organization seeking status, and 
information obtained from other sources that may be con-
sulted.

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 pub-
lic have an interest in the continued availability and acces-
sibility of the deposit during the enforceable life of the 
patent, and the public has a continuing interest in its avail-
ability when the patent is no longer enforceable.  The con-
cept 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 mis-
handling 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 depos-
ited material or may wish to resume control of its availabil-
ity when the patent is no longer enforceable, and will tend 
to preserve the interest of the public in the access to the bio-
logical 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 materi-
als 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 com-
plete list of the kinds of biological materials it will accept.

37 CFR 1.803(d) indicates that once a depository is rec-
ognized as suitable for the purposes of this rule, or has 
defaulted or discontinued its performance under this sec-
tion, 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 regula-
tions.  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 January, 
1998. 

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

All-Russian Scientific Center of Antibiotics (VNIIA)

Nagatinskaya Street 3-a

Moscow 113105 

Russian Federation

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

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 Collection

Center (CGMCC)

China Committee for Culture Collection of

Microorganisms

P.O. Box 2714

Beijing 100080

China

Colecion Espanola de Cultivos Tipo (CECT)

Universidad de Valencia

Edificio de Investigacion

Campus de Burjasot

46100 Burjasot (Valencia)

Spain

Collection Nationale De Cultures 

De Microorganismes (CNCM)  

Institut Pasteur

28, rue du Dr Roux

75724 Paris Cedex 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

Dubravska cesta 9

842 38 Bratislava,

Slovakia

Czech Collection of Microorganisms (CCM)

Masaryc University

ul. Tvrdeho [ccaron]. 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

International Mycological Institute (IMI)

Bakeham Lane

Englefield Green

Egham, Surrey TW20 9TY

United Kingdom

Korea Research Institute of Bioscience and

Biotechnology (KRIBB)

52, Oun-Dong

Yusong-Ku

Taejon 305-333

Republic of Korea

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 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

Somloi ut 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 and 

Marine Bacteria Limited (NCIMB)

23 St. Machar Drive

Aberdeen AB2 1RY

Scotland, United Kingdom

National Institute of Bioscience and 

Human-Technology (NIBH)

Agency of Industrial Science and Technology

Ministry of International Trade and Industry

1-3, Higashi 1-chome

Tsukuba-shi

Ibaraki-ken 305 

Japan

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

2406	Time 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, dur-
ing 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 state-
ment 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 recom-
mended 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 applica-
tion 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 exam-
iner 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 suffi-
ciently 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 interna-
tional 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.

2406.01	Description 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 iden-
tified in the application for patent as filed. The requirement 
for a specific identification is consistent with the descrip-
tion 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 spe-
cific 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 des-
ignating 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 speci-
fication "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). 

2406.02	Deposit After Filing Date - 
Corroboration

When the original deposit is made after the effective fil-
ing 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 consider-
ation, including the length of time between the application 
filing date and the date of deposit. While few, if any, situa-
tions can be imagined where the description requirement of  
35 U.S.C. 112 can be satisfied where the biological mate-
rial 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.

2406.03	Possible 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.

2407	Replacement 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 pro-
ceeding, 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 spec-
ification, 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 consid-
erations governing the need for making an original deposit under the pro-
visions 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  sec-
tion.

(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 replace-
ment or supplemental deposit;

(2)	Includes a statement from a person in a position to corrobo-
rate 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 dili gently --

(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 contami-
nated or had lost its capability to function as described in the specification;

(4)	Includes a statement that the term of the replacement or sup-
plemental 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 pen-
dency of an application for patent may be made for any reason.

(g)	In no case is a replacement or supplemental deposit of a biologi-
cal 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 pro-
vide 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 mate-
rial 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 pen-
dency 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. The procedures in these rules con-
template that only the original depositor would have a right 
to replace or supplement the original deposit.

2407.01	In a Pending Application 

37 CFR 1.805(a) relates to the procedure for replacing or 
supplementing a deposit with respect to a pending applica-
tion 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 fur-
nished by the depository, the examiner will treat the appli-
cation or reexamination proceeding, whichever is 
applicable, as if no deposit existed. A replacement or sup-
plemental 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 appli-
cant 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.

2407.02	After a Patent Has Issued 

A replacement deposit made in connection with an appli-
cation 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 cor-
rection made to the original patent will be automatically 
incorporated into the reissued or reexamined patent unless 
changes are made during examination of the reissue appli-
cation or reexamination proceeding. 

37 CFR 1.805(b) and  37 CFR 1.805(c) specify the pro-
cedures that a patent owner may follow to ensure that a 
patent contains the appropriate information about a depos-
ited 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. 

2407.03	Failure 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 provi-
sions 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 bio-
logical material was otherwise available.  For example, a 
replacement deposit would not be required under the cir-
cumstances where access to the necessary biological mate-
rial was established through commercial suppliers. 

2407.04	Treatment 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 ref-
erence to the deposit is relied on during any Office pro-
ceeding. 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 orig-
inal deposit may be made during the pendency of the appli-
cation subject to the conditions of 37 CFR 1.809, a 
replacement deposit logically cannot be held to any higher 
standard or any further requirements. 

2407.05	Exemption From Replacement

The provisions of  37 CFR 1.805(h) indicate that a 
replacement deposit is not required even though the deposi-
tory 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.

2407.06	Replacement 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 depos-
ited should not be lost through destruction or replacement if 
made in association with an existing patent. A supplemen-
tal deposit may be  accepted in an Office proceeding, how-
ever, depending on the circumstances in each case.

2408	Term 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 sen-
tence 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.

2409	Viability of Deposit

37 CFR 1.807.  Viability of deposit.

(a)	A deposit of biological material that is capable of self-replica-
tion 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 reproduc-
tion.  No evidence is necessarily required regarding the ability of the 
deposited material to perform any function described in the patent applica-
tion.

(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 con-
clusion 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 essen-
tially 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 pro-
vided that the deposited material is capable or has the abil-
ity 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 appli-
cation, 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 rep-
resentative 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 state-
ment and proceed with the examination process as if no 
deposit had been made.

2410	Furnishing 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 deposi-
tor 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.

2410.01	Conditions 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 pen-
dency of the patent application making reference to the 
deposit to one determined by the Commissioner to be enti-
tled 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 bio-
logical 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 fol-
lowed 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. Conse-
quently, 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).

2410.02	Certification of Accessibility of 
Deposit

Since the mere description of a deposit or identity of a 
deposit in a patent specification is not necessarily an indi-
cation 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 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 pro-
vided the request is made to the Director of Patent Examin-
ing Group 1640 or 1650, 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.

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 the 
availability of samples of deposited microorganisms pursu-
ant to Rule 11.3(a) of the Regulations under the Budapest 
Treaty. Copies of this form are available from the Director 
of Patent Examining Group 1640 or 1650.

2411	Examination Procedures 

37 CFR 1.809.  Examination procedures.

(a)	The examiner shall determine pursuant to ? 1.104 in each appli-
cation for patent, application for reissue patent or reexamination proceed-
ing 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 respond to a rejec-
tion under paragraph (a) of this section by-  

(1)	In the case of an applicant for patent, making an acceptable 
original or replacement or supplemental deposit 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, in the case of a patent owner, requesting a cer-
tificate 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 circum-
stances of the application or patent considered and/or why a deposit actu-
ally made should be accepted.  Other replies to the examiner s action shall 
be considered non-responsive.  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 allow-
ance except for a needed deposit and the Office has received a written 
assurance that an acceptable deposit will be made on or before payment of 
the issue fee, the Office will mail to the applicant a Notice of Allowance 
and Issue Fee Due together with a requirement that the needed deposit be 
made within three months.  The period for satisfying this requirement is 
extendible under ? 1.136.  Failure to make the needed deposit in accor-
dance with this requirement will result in abandonment of the application 
for failure to prosecute.

(d)	For each deposit made pursuant to these regulations, the specifi-
cation 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.

37 CFR 1.809 sets forth procedures that will be used by 
the examiner to address a deposit issue.  The burden is ini-
tially 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.

2411.01	Rejections Based on Deposit Issue

Under  37 CFR 1.809(a), once the examiner has deter-
mined 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 cir-
cumstances:

(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 conclu-
sion 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 para-
graph and/or  35 U.S.C. 132 (prohibition against the intro-
duction of new matter) and a requirement that the 
amendment be canceled.

(C)	35 U.S.C. 112, first paragraph - best mode require-
ment.  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 inven-
tor(s) concealed the best mode (accidentally or intention-
ally) 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 antibod-
ies, 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 disclo-
sure 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 condi-
tions which comply with  37 CFR 1.806 and  37 CFR 
1.808(a) concerning term of deposit and permissible condi-
tions on access once the patent is granted. 

2411.02	Replies 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 biologi-
cal 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 exam-
iner 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.  

2411.03	Application 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 allow-
ance except for a required deposit and the Office has 
received a written assurance that an acceptable deposit will 
be made, the  Office will mail to the applicant a require-
ment that the required deposit be made within 3 months 
together with the Notice of Allowance and Issue Fee Due. 
Although the period for paying the issue fee cannot be 
extended under the provisions of  37 CFR 1.136, the period 
for satisfying the requirement to make an acceptable 
deposit may be extended under the provisions of that sec-
tion.  Failure to make the needed deposit in accordance 
with this requirement may be considered a failure to prose-
cute the application under  35 U.S.C. 133 and result in 
abandonment of the application. Once the deposit has been 
made, information regarding the deposit, such as the name 
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 provi-
sions of  37 CFR 1.312. A petition and fee are required if 
the  37 CFR 1.312 amendment is filed after the issue fee 
has been paid.

2411.04	After a Patent Has Been Granted

In a proceeding involving a patent, it may not be possi-
ble 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 replace-
ment 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 avail-
able 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 pro-
vide for post-issuance original deposits.

Where an applicant for patent has any doubt as to 
whether access to a biological material specifically identi-
fied 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 appli-
cant 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 specifica-
tion 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.

2411.05	Content of Application with 
Respect to Deposited Material 

37 CFR 1.809(d) sets forth the requirements for the con-
tent of the specification with respect to a deposited biologi-
cal 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 dis-
closed.  Once the patent issues, the description must be suf-
ficient 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 char-
acteristics of the deposited biological material with the 
prior art.

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

Prior to the effective date (October 1, 1990) and imple-
mentation of the sequence rules (37 CFR 1.821 through 
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 require-
ments 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 sum-
mary, the diversity and complexity of nucleotide and amino 
acid sequence data resulted in searching and analysis diffi-
culties 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 neces-
sity for the Office. As such, the Office amended its regula-
tions 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 subse-
quently revised effective July 1, 1998. See 63 FR 29634 
(June 1, 1998) and 1121 O.G. 82 (June 23, 1998)

2421	Overview of the Sequence Rules 

2421.01	Applications 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 submis-
sion 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 appli-
cations 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.

2421.02	Summary 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 for the purpose of 
the rules, the requirements for specific symbols, formats, 
paper and computer readable copies of the sequence, 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 amend-
ments 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. 
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. 

2421.03	Notification 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, appli-
cants will be notified of easily detectable deficiencies early 
in the application process. Deficiencies of a more sophisti-
cated nature will likely only be detected by the examiner to 
whom the application is assigned.  Applicants whose com-
puter readable forms are damaged in the mail, are not read-
able, or are missing mandatory elements will be notified 
shortly after receipt of the application by the Office. Other 
errors or inconsistencies will be noted by the examiner 
early in the examination process. Upon detection of dam-
age 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 1 
month.  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 1 month, 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 fide attempt to com-
ply 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 para-
graphs and a copy of the Notice to Comply to be used in 
applications subject to the sequence rules are included in  
MPEP ? 2427 through  ? 2427.02.

A notification of a failure to comply with the sequence 
rules will usually be accompanied by an analysis of a sub-
mitted 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. 

2421.04	Future 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 computer-
ization 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 broaden-
ing of the permissible types of computer readable forms 
that may be submitted. The same can be said for the com-
puter/operating-system configurations that are currently 
permitted by the rules.  As the Office becomes able to pro-
vide greater refinement and liberality in these areas, the 
Office will do so by the publication of notices in the Offi-
cial Gazette or formal rulemaking proposals, as appropri-
ate. 

2422	Nucleotide 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 Nucle-
otide and Amino Acid Sequence Listings in Patent Applications (1998), 
including Tables 1 through 6 in Appendix 2, herein incorporated by refer-
ence. (Hereinafter "WIPO Standard ST.25 (1998)''). This incorporation by 
reference was approved by the Director of the Federal Register in accor-
dance 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 Orga-
nization; 34 chemin des Colombettes; 1211 Geneva 20 Switzerland. Cop-
ies 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., methy-
lated 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 com-
monly found in naturally occurring proteins and are listed in WIPO Stan-
dard ST.25 (1998), Appendix 2, Table 3. Those amino acid sequences 
containing D-amino acids are not intended to be embraced by this defini-
tion. 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 Fea-
ture 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 para-
graph (a) of this section, shall, with regard to the manner in which the 
nucleotide and/or amino acid sequences are presented and described, con-
form 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 disclo-
sure, 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 hereinaf-
ter 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 iden-
tifier <160> shall include the total number of SEQ ID NOs, whether fol-
lowed by a sequence or by the code "000."

(d)	Where the description or claims of a patent application dis-
cuss 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 appli-
cation if the computer readable form in the other application was compli-
ant 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 compli-
ant computer readable "Sequence Listing" that is already on file for the 
other application and must state that the paper copy of the "Sequence List-
ing" 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 read-
able copies are the same must be submitted with the computer readable 
form, e.g., a statement that "the information recorded in computer read-
able 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 applica-
tion under the Patent Cooperation Treaty (PCT), which application is to be 
searched by the United States International Searching Authority or exam-
ined by the United States International Preliminary Examining Authority, 
applicant will be sent a notice necessitating compliance with the require-
ments 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 disclo-
sure in the international application as filed. If applicant fails to timely 
provide the required computer readable form, the United States Interna-
tional Searching Authority shall search only to the extent that a meaning-
ful search can be performed without the computer readable form and the 
United States International Preliminary Examining Authority shall exam-
ine 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 Intel-
lectual Property Organization (WIPO) Handbook on Indus-
trial Property Information and Documentation, Standard 
ST.25 (1998), including Tables 1 through 6 of Appendix 2. 
Copies may be obtained from the World Intellection Prop-
erty 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, pro-
vides that the bases of a nucleotide sequence should be rep-
resented 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 interac-
tions 3H-
bonds

w
	a or t/u
	weak interac-
tions 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, pro-
vides that modified bases may be represented as the corre-
sponding unmodified bases in the sequence itself, if the 
modified base is one of those listed below and the modifi-
cation 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

cmnm5s2
u
	5-carboxymethylaminomethyl-2-thiou-
ridine

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-thiouri-
dine

mcm5u
	5-methoxycarbonylmethyluridine

mo5u
	5-methoxyuridine

ms2i6a
	2-methylthio-N6-isopentenyladenosine

ms2t6a
	N-((9-beta-D-ribofuranosyl-2-methylth-
iopurine-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, pro-
vides 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, pro-
vides that modified and unusual amino acids may be repre-
sented 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 descrip-
tion (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 Unusual Amino 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, pro-
vides 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 concep-
tual 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; consen-
sus=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 recombi-
nation

intron
	a segment of DNA that is transcribed, but removed from within the transcript by splic-
ing 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 can-
not 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, /provi-
ral)

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, termina-
tor, 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-transcrip-
tional 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' untrans-
lated 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 transcrip-
tion

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 (ribo-
some) 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 mem-
brane; leader sequence

snRNA
	small nuclear RNA; any one of many small RNA species confined to the nucleus; sev-
eral 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 manda-
tory; 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 bind-
ing 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 trans-
lated 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; consen-
sus=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 pro-
vides 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 resi-
due or through an ester bond to a serine or threonine residue

     FARNESYL
	farnesyl group attached through a thioether bond to a cysteine resi-
due

     GERANYL-GERANYL
	geranyl-geranyl group attached through a thioether bond to a cys-
teine residue

     GPI-ANCHOR
	glycosyl-phosphatidylinositol (GPI) group linked to the alpha-car-
boxyl 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 informa-
tion, 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 resi-
due;  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 posi-
tion, it signifies that this position is not the C-terminus of the com-
plete 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 resi-
dues between them

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

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 substan-
tially identical to the requirements of  37 CFR 1.821 
through 1.825.  PatentIn   Version 2.0 software, now avail-
able (see  MPEP ? 2430), meets 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 follow-
ing when not using PatentIn Version 2.0:

(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 1.821 through 
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 does not form 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.

2422.01	Definitions 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 inter-
preted 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 spe-
cifically 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, Stan-
dard 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 nucle-
otides, 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 com-
monly 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 repre-
senting 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 search-
ing 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 compli-
ance is, however, encouraged in these situations; the sym-
bol "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 con-
secutive 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.  How-
ever, the rules are not intended to encompass the subject 
matter that is generally referred to as synthetic resins. 

2422.02	The 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 char-
acteristics 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 nucle-
otides 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 effec-
tive 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 dis-
cussed 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 iden-
tifier ("SEQ ID NO:X") must be used, either in the drawing 
or in the Brief Description of the Drawings. 

2422.03	The Requirements for a Sequence 
Listing and Sequence Identifiers; 
Sequences Embedded in 
Application Text; Variants 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 disclo-
sure on paper copy, 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 1.822 
and  37 CFR 1.823.  This separate part of the disclosure, 
beginning on a new page within the specification, is 
referred to as the "Sequence Listing," and requires that 
each sequence disclosed in the application appear sepa-
rately in the "Sequence Listing," with each sequence fur-
ther being assigned a sequence identification number, 
referred to as "SEQ ID NO."  A plurality of sequences may, 
if feasible, be presented on a single page, and this may be 
extended to the separate presentation of both nucleotide 
and amino acid sequences on the same page. The require-
ment 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.

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 List-
ing," 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 dis-
cuss 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 follow-
ing types of sequence disclosures would be treated as noted 
herein by the Office.  With respect to "conservatively mod-
ified variants thereof" of a  sequence,  the  sequences  may  
be described as SEQ ID NO:X and "conservatively modi-
fied 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 reason-
ably require a "Sequence Listing" that would be thousands 
of pages in length.  In this latter example, only the unde-
leted sequence needs to be included in the "Sequence List-
ing," 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 require-
ment 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 identi-
fiers 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 prop-
erly 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 through-
out the specification and claims, specifically, should not 
raise any issues under  35 U.S.C. 112, first or second para-
graphs. 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.

2422.04	The Requirement for a Computer 
Readable Copy of the Official 
Paper 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 nucle-
otide 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 require-
ment 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 infor-
mation is published or matures into a patent, or as other-
wise allowed by  35 U.S.C. 122. 

The second sentence of  37 CFR 1.821(e) indicates that, 
as  between the paper copy of the "Sequence Listing" and 
the computer readable copy thereof, the paper copy serves 
as the official copy.  However, the Office may permit cor-
rection of the paper copy, at the least, during the pendency 
of a given application by reference to the computer read-
able copy thereof if both the paper and computer readable 
forms 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 
paper 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 read-
able form has been incorporated by reference into the appli-
cation when the paper and computer readable forms were 
submitted at the time of filing of the application.  The 
Office will attempt to accommodate or address all correc-
tion issues, but it must be kept in mind that the real burden 
rests with the applicant to ensure that any discrepancies 
between the paper 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 suf-
fer the consequences of any discrepancies between the two. 
The paper copy also  serves  as  the  official copy for prior-
ity purposes. 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 appro-
priate, 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 sub-
mitted by the applicant. 

2422.05	Reference 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 com-
plying 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 appli-
cation in much the same manner as applicants must now 
request the transfer of drawings in derivative or continuing 
applications. A letter must be submitted in the given appli-
cation requesting use of the previously filed sequence 
information. The letter must completely identify the other 
application, by application number, and the computer read-
able 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 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 applica-
tion number and filing date for the instant application. A paper 
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 specifica-
tion, whichever is applicable].

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

37 CFR 1.821(f) requires that the paper and computer 
readable copies of the "Sequence Listing" be accompanied 
by a statement that the content of the paper and computer 
readable copies are the same, at the time when the com-
puter readable form is submitted.  Such a statement may be 
made by the applicant. See  MPEP ? 2428 for further infor-
mation and Sample Statements.

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

37 CFR 1.821(g) requires compliance with the require-
ments 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 inad-
vertently been omitted, the applicant may be given a new 
time period to correct the omission.  See  37 CFR 1.135(c).

 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  applica-
tion.

37 CFR 1.821(h) requires compliance with the require-
ments of  37 CFR 1.821(b) through (f), as discussed above, 
within the time period prescribed in a notice requiring com-
pliance in an international application filed in the United 
States Receiving Office under the Patent Cooperation 
Treaty (PCT), if the above noted requirements are not satis-
fied at the time of filing.  Submissions in reply to require-
ments under this paragraph must be accompanied by a 
statement that the submission does not include matter 
which goes beyond the disclosure in the international appli-
cation as filed. Such a statement may be made by an appli-
cant. 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. 

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 specifica-
tions.  When a substitute specification is required because 
the number or nature of amendments would make it diffi-
cult 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 bur-
den 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.

2422.08	Presumptions Regarding 
Compliance

Neither the presence nor absence of information which is 
not required under the sequence rules will create a pre-
sumption 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 1.825 constitutes a conclusive presump-
tion that the granted patent complies with the requirements 
of these rules. 

2422.09	Box Sequence; Hand Delivery of  
Sequence Listings and Computer 
Readable Forms

To facilitate administrative processing of all papers asso-
ciated with sequence rule compliance, all computer read-
able forms, 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 Group.  In cases of hand delivery 
to the Customer Service Window or to the Group, the 
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 1.824(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 compli-
mentary copies of diskettes or tapes be delivered to exam-
iners or other Office personnel.

2423	Symbols 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 incorpo-
ration 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 modifi-
cation 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 contain-
ing 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 configura-
tion, 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 maxi-
mum 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 non-
contiguous 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.

2423.01	Format 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 used 
in setting forth the sequences, but, they may be used in the 
description and/or the "Sequence Listing" corresponding 
to, but not including, the sequence itself.  A modified base 
or amino acid may be presented in a given sequence as the 
corresponding unmodified base or amino acid if the modi-
fied base or amino acid is one of those listed in WIPO Stan-
dard ST.25 (1998), Appendix 2, Table 2 or 4 and the 
modification is also set forth in the features 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 
features 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 exam-
iner's, use of the printed patents. The three-letter codes 
must be presented using the upper case for the first charac-
ter and lower case for the remaining two characters.

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

2423.02	Depiction 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. Fur-
ther, 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 clari-
fies 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 nucle-
otide sequence are depicted, they must be depicted below 
the corresponding codons. There is absolutely no require-
ment in the rules to depict coding regions. Nor is there a 
requirement to separately list the amino acids correspond-
ing 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 dis-
cuss 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. 

2423.03	Presentation 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 nucle-
otides shall not be represented in the "Sequence Listing." A 
double stranded nucleotide may be represented as two sin-
gle 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 alter-
natives 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 nucle-
otides is set forth in  37 CFR 1.822(c)(6).  Sequences that 
are circular in configuration are intended to be encom-
passed by these rules, and numbering procedures for them 
are provided in  37 CFR 1.822(c)(7) and (d)(4).  The num-
bering 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 pro-
cedures also reflect those that have been agreed to for elec-
tronic 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 intro-
duced 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 specifica-
tion, 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."  

2424	Requirements 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 papers.

(a)	The "Sequence Listing" required by ? 1.821(c), setting forth the 
nucleotide and/or amino acid sequences and associated information in 
accordance with paragraph (b) of this section, must begin on a new page 
and must be titled "Sequence Listing". The "Sequence Listing" preferably 
should be numbered independently of the numbering of the remainder of 
the application. Each page of the "Sequence Listing" should contain no 
more than 66 lines and each line should contain no more than 72 charac-
ters. A fixed-width font should be used exclusively throughout the 
"Sequence Listing."

(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 submis-
sion 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> 
......
	Appli-
cant.........................
	Preferably max. of 10 names; one 
name per line; preferable format: Sur-
name,  Other Names and/or Initials. 
	M.

<120> 
......
	Title of Inven-
tion.............
	.............................................................
...
	M.

<130> 
......
	File Refer-
ence..................
	Personal file refer-
ence............................
	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 Num-
ber. 
	Specify as: US 07/999,999 or  PCT/
US96/99999. 
	M, if applicable include priority docu-
ments under  35 USC 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> 
......
	Soft-
ware.............................
	Name of software used to create the 
Sequence Listing. 
	O.

<210> 
......
	SEQ ID 
NO:#:..................
	Response shall be an integer repre-
senting 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 com-
bined DNA/  RNA molecule shall be 
further described in the  <220> to 
<223> feature section.  
	M.

<213> 
......
	Organ-
ism.........................
	Scientific name, i.e. Genus/ species, 
Unknown or  Artificial Sequence. In  
addition, the "Unknown" or "Artifi-
cial Sequence" organisms shall be fur-
ther described in the <220> to <223> 
feature section. 
	M.

<220> 
......
	Fea-
ture.............................
	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 fea-
ture, 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. 

<222> 
......
	Loca-
tion...........................
	Specify location within sequence; 
where appropriate state number of 
first and last bases/amino acids in fea-
ture.
	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 Informa-
tion............
	Other relevant information; four lines 
maxi-
mum................................................
	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 Informa-
tion... 
	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>
	Jour-
nal.............................  
	.............................................................
...
	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 data-
base 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 exam-
ple, 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 Resi-
dues............ 
	FROM (position) TO (posi-
tion)................. 
	O.

<400>
	Sequence.......................
...
	SEQ ID NO should follow the 
numeric identifier and should appear 
on the line preceding the actual 
sequence.
	M.

2424.01	Informational 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 
copy (the "Sequence Listing") that must be submitted in 
accordance with  37 CFR 1.821(c).  This section lists the 
items of information that are to be included in the 
"Sequence Listing," which constitutes the separate part of 
the disclosure on paper copy.  The items of information are 
to be presented in the "Sequence Listing" in the order in 
which those items are listed in  37 CFR 1.823. Page and 
line length requirements are set forth. The requirement to 
use a fixed width font to present sequence data is also set 
forth. This latter requirement is made to ensure that the 
desired sequence character spacing and numbering is main-
tained upon printing. The numeric identifier for each item 
of information shall not include the explanatory informa-
tion included in  37 CFR 1.823. 

2424.02	Sequence 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: Sur-
name,  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 Num-
ber. 
	Specify as: US 07/999,999 or  PCT/
US96/99999. 
	M, if applicable include priority docu-
ments under  35 USC 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 repre-
senting 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 com-
bined 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 "Artifi-
cial Sequence" organisms shall be fur-
ther 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 fea-
ture, 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. 

<222> ...
	Location........................
	Specify location within sequence; 
where appropriate state number of 
first and last bases/amino acids in fea-
ture.
	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 Informa-
tion.... 
	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 data-
base 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 exam-
ple, 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.

2424.03	Additional 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 stan-
dards 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 fil-
ing 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 doc-
uments 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 lim-
ited 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 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  let-
ters  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 "Fea-
tures" or the description of the points of biological signifi-
cance in a given sequence, it is recommended, but not 
required, that the information that is provided by the appli-
cant 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 infor-
mation 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 informa-
tion 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.

2425	Form 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 specifications:

(1)	The computer readable form shall contain a single 
"Sequence Listing" as either a diskette, series of diskettes, or other per-
missible 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 Inter-
change (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 specifications 
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 sec-
tion.

(5)	Page numbering shall not appear within the computer read-
able form version of the "Sequence Listing" file.

(6)	All computer readable forms shall 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 ref-
erence number, and an application serial number and filing date, if known.

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

(1)	Computer: IBM PC/XT/AT, or compatibles, or Apple Mac-
intosh;

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

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

(4)	Pagination: Continuous file (no "hard page break" codes per-
mitted);

(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 stor-
age; 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)	CD-ROM: 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 produc-
ing 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 read-
able forms that are submitted in accordance  with these 
rules.

2426	Amendments 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 the paper copy of the "Sequence Listing" (? 
1.821(c)) must be made by the submission of substitute sheets. Amend-
ments must be accompanied by a statement that indicates support for the 
amendment in the application, as filed, and a statement that the substitute 
sheets include 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 dam-
aged 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 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 ? 2428 for further information and Sample 
Statements.) 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 cor-
rection, reissue or reexamination. 37 CFR 1.825 (d) 
addresses the possibility and presents a remedy for the situ-
ation where the computer readable form may be found by 
the Office to be damaged or unreadable.

2427	Form Paragraphs and Notice to 
Comply

2427.01	Form Paragraphs 

In order to minimize the extension of pendency due to 
the implementation of the sequence rules, all compliance 
issues should be addressed in a single communication with 
the applicant. That communication should set a 1-month 
(not less than 30 days) period for reply that may be 
extended in accordance with the provisions of  37 CFR 
1.136.  However, depending upon the nature of applicant's 
reply, a follow-up communication regarding the sequence 
rules may be necessary. The form paragraphs that follow 
are to be used in these communications. The form para-
graphs should be used as follows:

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

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

7.202 - 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.

7.203 - 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. 

?  7.200 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 on the attached Notice To Comply With Requirements For Patent 
Applications Containing Nucleotide Sequence And/Or Amino Acid 
Sequence Disclosures.

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 7.203 or 7.203 for subsequent communications.

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

3.	Print this paragraph on a PTOL-90 and 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.

?  7.201 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 pro-
cessed 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 Prob-
lem Report with the reply.

Examiner Note:

1.	Use this form paragraph only for the initial communication to the 
applicant.  Use either 7.203 or 7.203 for subsequent communications.

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

3.	Print this paragraph on a PTOL-90 and attach the CRF Diskette 
Problem Report.

?  7.202 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 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 exam-
iner has no authority to grant an extension if the six-month period for reply 
has expired.  Use form paragraph 7.203 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.	Print this paragraph on a PTOL-90 and attach a Notice To Comply 
With Requirements For Patent Applications Containing Nucleotide 
Sequence And/Or Amino Acid Sequence Disclosures, 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.

?  7.203 CRF Submission Is Not Fully Responsive

The communication filed [1] is not fully responsive to the communica-
tion mailed [2] for the reason(s) set forth on the attached Notice To Com-
ply 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 defi-
ciency 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 pro-
vide a complete reply, use form paragraph 7.202.

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.	Print this paragraph on a PTOL-90 and attach a Notice To Comply 
With Requirements For Patent Applications Containing Nucleotide 
Sequence And/Or Amino Acid Sequence Disclosures, along with a 
marked-up copy of the Raw Sequence Listing, or CRF Diskette Problem 
Report.

2427.02	Notice 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.  A copy of the "Raw Sequence List-
ing," 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 Disclosures

2428	Sample Statements 

Sample language for the statements required to support 
sequence rule submissions is provided below. These  state-
ments 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 and computer read-
able 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 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 writ-
ten sequence listing.

       

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 dis-
closure 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 substi-
tute sheet(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 List-
ing.

       

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. 

2429	Helpful 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 a new matter issue. The standard 
for resolution of inconsistencies between the paper and the 
electronic copies and/or errors in the paper copy of 
sequence information is based on the new matter standard. 

-Compliance can be achieved via amendment. 

-The paper copy of Sequence Listing is an integral part 
of the application. 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 num-
bering 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.

-Substitute pages must be used for changes to the 
Sequence Listing.

-Angle brackets and numeric identifiers listed in  37 
CFR 1.823 are very important for our database. Extra punc-
tuation 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. 

-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 process-
ing file should be saved as an ASCII text file for submis-
sion. 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 state-
ments 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 Fil-
ing 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 identifi-
ers <140> and <141> should be left blank. This would nor-
mally 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 identifi-
ers 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 identifed in  MPEP ? 2424.02 
Sequence Listing Numeric Identifiers.

-Figures can be used to convey information not readily 
conveyed by the Sequence Listing.  The exclusive con-
formance 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 per-
mitted in amino acid sequences.

 -Punctuation should not be used in a sequence to indi-
cate 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 confu-
sion 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)n Ile 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 Fea-
tures section that the amino acid (or nucleotide) at a speci-
fied 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 com-
bined with an explanation in the Features section of the list-
ing that any one or all of amino acids 4-8 can either be 
present or absent.

-Single letter amino acid abbreviations are not accept-
able 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 pro-
tein.

-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 trivial-
ity of the amendment. Amendments to the paper copy of 
the "Sequence Listing" must be made by substitute sheets.  

-Note field length limitations. For specific in stances, 
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/Biotech-
nology Division of the Scientific and Technical Informa-
tion Center.

2430	PatentIn 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 pur-
pose 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 has made available to the public an input program 
that is based on the AuthorIn program produced by Gen-
Bank. This input program, called PatentIn version 1.3, was 
specifically tailored to the requirements of the sequence 
rules which were in effect prior to July 1, 1998.

The Office has completed an updated version of the Pat-
entIn program, called PatentIn version 2.0.  This new ver-
sion is compliant with Microsoft Windows 3.1x, 95, and 
NT.  This new version also incorporates changes in the 
required format for the Sequence Listing to ensure compli-
ance with the new World Intellectual Property Office 
(WIPO) Standard ST.25 which became effective July 1, 
1998 and with revisions to the U.S. sequence rules which 
became effective July 1, 1998.  This new WIPO Standard 
simplifies the Sequence Listing requirements, and harmo-
nizes the format among all Trilateral Patent Offices and 
many other patent offices around the world. By using Pat-
entIn version 2.0, customers will be 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 pre-
pared 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.  

The new PatentIn version 2.0, and the companion User 
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 are also available on 3 1/2 
inch floppy diskette at a cost of $25.00 for each item.  Pat-
entIn version 2.0 has similar space, memory, and system 
requirements as those for PatentIn version 1.3, except that 
to function properly PatentIn 2.0 requires a Microsoft Win-
dows operating system. 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 rec-
ommended as Office experience has shown that submis-
sions 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 environ-
ment. 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 Wash-
ington, D.C. To express interest in such classes, please con-
tact the Search and Information Resources Administration.

2431	Sample Sequence Listing

A sample "Sequence Listing" is included below.  

2434	Examination of Patent Applications 
Claiming Large Numbers of 
Nucleotide Sequences

The Patent and Trademark Office recently 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 dis-
tinct 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 is presumed to represent an independent and dis-
tinct 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 1.141 and will permit a reason-
able 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 pursu-
ant to  37 CFR 1.181 for examination of additional nucle-
otide 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 exami-
nation procedures, see the above cited O.G. Notice.  See 
also  MPEP ? 803.04.

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