MPEP § 2421 — MPEP § 2421
Current through: 2022-07-01

2421-Overview of the Sequence Rules under WIPO ST.25 
 
 

 
 
 
 
 
 
 
 

 

 
 
 

 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
 

 
 
 
 
 
 
 
 
 
 
 

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 Manual of Patent Examining Procedure 

 Chapter 2400 

 Section 2421 
 

 
 
 
 
 
 2421 Overview of the Sequence Rules under WIPO ST.25 [R-07.2022]

 
 2421.01 Definition of “Sequence Listing” and Computer Readable Form
 (CRF) [R-07.2022]
 

 [Editor Note: This section is not applicable to applications filed on or after
 July 1, 2022, having disclosures of nucleotide and/or amino acid sequences as defined
 in 37
 CFR 1.831(b) . See MPEP §§
 2412 - 2419 for applications filed on or
 after July 1, 2022.] 

 The sequence rules ( 37 CFR 1.821 - 1.825 ) require the
 use of standard symbols and a standard format for submitting sequence data in most
 patent applications that disclose nucleic acid or amino acid sequences. For purposes of
 the sequence rules and the discussion in MPEP Chapter 2400 , the phrase
 “disclose(d) (or disclosure(s) of) nucleic acid or amino acid sequences” is intended to
 refer to those nucleic acid or amino acid sequences that are described in the patent
 application by enumeration of their residues and that meet the length thresholds of
 37 CFR
 1.821(a) .
 

 37 CFR
 1.821(c) requires that applications containing disclosures of
 nucleotide and/or amino acid sequences that fall within the definitions of
 37 CFR
 1.821(a) contain, as a separate part, 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 is referred to as the “Sequence Listing”. See
 MPEP §
 2422.03 for additional information.
 

 37 CFR
 1.821(e) requires a separate computer readable form (CRF) of the
 “Sequence Listing” under certain circumstances. The CRF is an ASCII plain text file of
 the sequence information relating to the disclosure of the nucleotide and/or amino acid
 sequences using the symbols, format, content and file requirements of 37 CFR 1.822 . See
 37 CFR
 1.824 . The CRF may be submitted on read-only optical disc or may
 be submitted as an ASCII plain text file via the Office patent electronic filing system,
 pursuant to 37 CFR 1.821 . The requirements
 regarding the CRF are discussed in detail in MPEP § 2422.04 .
 

 

 
 2421.02 Summary of the Requirements of the Sequence Rules [R-07.2022]

 [Editor Note: This section is not applicable to applications filed on or after
 July 1, 2022, having disclosures of nucleotide and/or amino acid sequences as defined
 in 37
 CFR 1.831(b) . See MPEP §§
 2412 - 2419 for guidance on WIPO ST.26
 requirements for applications filed on or after July 1, 2022.] 

 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 in the
 “Sequence Listing” about a nucleotide or amino acid sequence that falls within the
 definitions used in the rules. Thus, 37 CFR 1.821 defines a “sequence”
 and a “Sequence Listing” for the purpose of the rules, the requirements for specific
 symbols, and formats for the “Sequence Listing”, the requirement for a computer readable
 form (CRF) of the “Sequence Listing” and the deadlines for complying with the
 requirements. 37 CFR
 1.822 to 37 CFR 1.824 set forth detailed
 descriptions of the requirements that are mandatory for the presentation of sequence
 data, and 37 CFR
 1.825 sets forth procedures that are available to an applicant in
 the event that amendments to add or replace a “Sequence Listing”, including any
 necessary CRF of the “Sequence Listing” become necessary. 
 

 The sequence rules embrace all unbranched nucleotide sequences with ten
 or more nucleotide bases and all unbranched, non-D amino acid sequences with four or
 more amino acids, provided that there are at least 10 “specifically defined” nucleotides
 or 4 “specifically defined” nucleotides or amino acids. The rules apply to all sequences
 in a given application, whether claimed or not. All such sequences are relevant for the
 purposes of building a comprehensive database and properly assessing prior art. It is
 therefore essential that all sequences, whether only disclosed or also claimed, be
 included in the database. 
 

 

 
 2421.03 Notification of a Failure to Comply [R-07.2022]

 [Editor Note: This section is not applicable to applications filed on or after
 July 1, 2022, having disclosures of nucleotide and/or amino acid sequences as defined
 in 37
 CFR 1.831(b) . See MPEP §§
 2412 - 2419 for guidance on WIPO ST.26
 requirements for applications filed on or after July 1, 2022.] 

 With respect to the Office’s determination of compliance with the
 sequence rules and the opportunities afforded applicants to satisfy the requirements of
 the rules, applicants will be notified of easily detectable deficiencies early in the
 application process. Applicants whose computer readable forms (which include a “Sequence
 Listing” submitted as an ASCII plain text file under 37 CFR
 1.821(c)(1) and separate CRFs submitted under 37 CFR 1.821(e) )
 are not readable, or are missing mandatory elements, will be notified shortly after
 receipt of the application by the Office. See 37 CFR
 1.52(e)(9) , 1.821(g) , and 1.821(h) . 
 

 The Office of Patent Application Processing (OPAP) will
 mail a notice to applicant listing the requirements that have not been met and setting a
 two month time period 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 . Applications will not be subject to examination on the
 merits until a compliant “Sequence Listing” has been submitted, as jurisdiction remains
 with Office of Patent Application Processing until compliance with the Notice to Comply
 With Requirements For Patent Applications Containing Nucleotide Sequence And/Or Amino
 Acid Sequence Disclosures. 
 

 Patent applications filed under 35 U.S.C.
 111 on or after December 18, 2013, and international patent
 applications in which the national stage commenced under 35 U.S.C. 371 on
 or after December 18, 2013, may be subject to reductions in patent terms adjustment
 pursuant to 37 CFR 1.704(c)(13) if they are not in condition for examination
 within eight months from the filing date or date of commencement, respectively. “In
 condition for examination” includes compliance with 37 CFR 1.821 - 1.825 (see
 37 CFR
 1.704(f) ). Deficiencies of a more sophisticated nature will likely
 only be detected by the examiner to whom the application is assigned. Applicant will be
 notified of any errors or inconsistencies detected by the examiner in the next Office
 action. 
 

 A notification of a failure to comply with the sequence rules will be
 accompanied by a report of errors associated with any submitted computer readable form
 (the 37
 CFR 1.821(c)(1) , the 1.821(e)(1) or 1.821(e)(2) submission). Any
 inquiries regarding a specific computer readable form that has been processed by the
 Office should be directed to the Sequence Systems Service Center (S3C) of the Scientific
 and Technical Information Center. The S3C manages the Sequence Help Desk, and responds
 to all questions or concerns, from both inside and outside the USPTO, related to
 computer readable format sequence listing submissions. The S3C may be contacted at
 571-272-2510 or via email at STIC-SSSCHelpdesk@uspto.gov. 
 

 

 
 2421.04 [Reserved]

 

 [top] 

 

 

 
 

 
 

 

 

 

 
 
 
 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 Statement of Availability 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-[Reserved] 

 2411.05-Content of Application with Respect to Deposited Material 

 
 

 2412-The Requirements for Patent Applications Containing Nucleotide Sequence and/or Amino Acid Sequence Disclosures to Include
 a Sequence Listing in XML file format 
 2412.01-Overview of the Sequence Rules 

 2412.02-Definition of “Sequence Listing XML” 
 2412.02(a)-“Enumeration of its residues” 

 
 

 2412.03-Nucleotides and Amino Acids Included and Excluded From a “Sequence Listing XML” 
 2412.03(a)-“Specifically Defined” 

 2412.03(b)-“Amino Acid” 

 2412.03(c)-“Modified Amino Acid” 

 2412.03(d)-“Nucleotide” 

 2412.03(e)-“Modified Nucleotide” 

 
 

 2412.04-Use of Sequence Identifiers to Denote Sequences Disclosed in the Description, Drawings or Claims 

 2412.05-Representation and Symbols for Nucleotide and/or Amino Acid Sequences 
 2412.05(a)-Use of Sequentially Numbered Sequence Identifiers in the “Sequence Listing XML” 

 2412.05(b)-Representation and Symbols of Nucleotide Sequence Data 

 2412.05(c)-Representation and Inclusion of Variants 

 2412.05(d)-Representation and Symbols of Amino Acid Sequence Data 

 2412.05(e)-Presentation of Special Situations 

 
 

 2412.06-The Requirement for Exclusive Conformance; Sequences Presented in Drawing Figures 

 2412.07-Examination of Patent Applications Claiming Large Numbers of Nucleotide Sequences 

 
 

 2413-Content of a “Sequence Listing XML” and Form and Format of the “Sequence Listing XML” File 
 2413.01-Parts of the “Sequence Listing XML” 
 2413.01(a)-The “Sequence Listing XML” is a Single File Encoded Using Unicode UTF-8 

 2413.01(b)-The “Sequence Listing XML” Must Be Valid According To the DTD 

 2413.01(c)-The “Sequence Listing XML” Must Contain an XML Declaration 

 2413.01(d)-The “Sequence Listing XML” Must Contain a DOCTYPE Declaration 

 2413.01(e)-The “Sequence Listing XML” Must Contain a Root Element 

 2413.01(f)-The “Sequence Listing XML” Must Contain a General Information Part 

 2413.01(g)-The “Sequence Listing XML” Must Contain a Sequence Data Part 

 2413.01(h)-Language Dependent Free Text Qualifier Values in the English Language 

 2413.01(i)-Title Element in “Sequence Listing XML” 

 
 

 2413.02-Form and Format of the XML file containing the “Sequence Listing XML” 

 2413.03-How to Submit the “Sequence Listing XML” 

 2413.04-Requirements Regarding Incorporation By Reference of the “Sequence Listing XML” 

 2413.05-Presumptions Regarding Compliance 

 
 

 2414-Notification of a Failure to Comply with Sequence Listing Requirements and Amendments Relating to “Sequence Listing XML” Files
 Under 37 CFR 1.835 
 2414.01-Issuance of a Notice Relating to the Requirements For Patent Applications Containing Nucleotide and/or Amino Acid Sequence
 Disclosures 

 2414.02-Amendment to Add an Initial “Sequence Listing XML” under 37 CFR 1.835(a) 

 2414.03-Amendment Adding to, Deleting from, or Replacing Sequence Information in a “Sequence Listing XML” under 37 CFR 1.835(b) 

 2414.04-Translation of “Sequence Listing XML” is Not an Amended “Sequence Listing XML” under 37 CFR 1.835(b) 

 2414.05-Notifications for Failure to Submit a “Sequence Listing XML” in an International Application under the PCT to be Searched
 by the United States International Searching Authority or Examined by International Preliminary Examination Authority 

 2414.06-Amendment of a “Sequence Listing XML” in a Patent 

 
 

 2415-Applicability date of “Sequence Listing XML” Requirements to Applications Based on Filing Date of Application and Procedures
 for Failure to Submit Correct Format of Sequence Listing 
 2415.01-Determining if a “Sequence Listing XML” Must be Submitted 

 2415.02-Provisional Applications Containing Disclosures of Nucleotides and/or Amino Acids, Compliance with 37 CFR 1.831-1.834 

 2415.03-Improper Submissions of “Sequence Listing” under 1.821(c) When a “Sequence Listing XML” was Required 

 
 

 2416-Form Paragraphs 

 2417-Helpful Hints for Sequence Rules Compliance under WIPO Standard ST.26 

 2418-WIPO Sequence Tool 

 2419-Publishing of Patent Grants and Patent Application Publications with a “Sequence Listing XML” 
 2419.01-Patent Grants and Patent Application Publications Containing a Non-Lengthy “Sequence Listing XML” 

 2419.02-Patent Grants and Patent Application Publications Containing a Lengthy “Sequence Listing XML” 

 2419.03-Patent Grants and Patent Application Publications Containing a “Sequence Listing XML” of 1GB or Larger 

 
 

 2420-The Requirements for Patent Applications Containing Nucleotide Sequence and/or Amino Acid Sequence Disclosures under World
 Intellectual Property Office Standard ST.25 (WIPO ST.25) - the Sequence Rules 

 2421-Overview of the Sequence Rules under WIPO ST.25 
 2421.01-Definition of “Sequence Listing” and Computer Readable Form (CRF) 

 2421.02-Summary of the Requirements of the Sequence Rules 

 2421.03-Notification of a Failure to Comply 

 2421.04-[Reserved] 

 
 

 2422-Nucleotide and/or Amino Acid Sequence Disclosures in Patent Applications Subject to WIPO ST.25 
 2422.01-Nucleotide and/or Amino Acids Disclosures Requiring a “Sequence Listing” 

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

 2422.03-Sequence Listing Submission 

 2422.03(a)-“Sequence Listing” Submitted as ASCII Plain Text Files 

 2422.04-The Requirement for a Computer Readable Copy of the “Sequence Listing” 

 2422.05-[Reserved] 

 2422.06-Requirement for Statement Regarding Information Contained in the “Sequence Listing” and Separate Computer Readable Form 

 2422.07-Requirements for Compliance and Consequences of Non-Compliance 

 2422.08-Presumptions Regarding Compliance 

 2422.09-[Reserved] 

 
 

 2423-Symbols and Format To Be Used for Nucleotide and/or Amino Acid Sequence Data for WIPO ST.25 
 2423.01-Format and Symbols To Be Used in a “Sequence Listing” 

 2423.02-Depiction of Coding Regions 

 2423.03-Presentation and Numbering of Sequences 

 
 

 2424-Requirements for Content of a “Sequence Listing” Part of the Specification under WIPO ST.25. 
 2424.01-Informational Requirements for the “Sequence Listing” 

 2424.02-“Sequence Listing” Numeric Identifiers 

 2424.03-Additional Miscellaneous Requirements 

 
 

 2425-Form and Format for a Nucleotide and/or Amino Acid Sequence Submission as an ASCII Plain Text File under WIPO ST.25 

 2426-Amendments to Add or Replace a “Sequence Listing” and CRF Copy Thereof Subject to WIPO ST. 25 

 2427-Form Paragraphs for Applications Subject to WIPO ST.25 

 2428-Sample Statements under WIPO ST.25 

 2429-Helpful Hints for Sequence Rules Compliance under WIPO ST.25 

 2430-PatentIn Information 

 2431-Sample “Sequence Listing” under WIPO ST.25 

 2432-[Reserved] 

 2433-Box Sequence; Hand Delivery of a “Sequence Listing” and Computer Readable Forms 

 2434-Examination of Patent Applications Claiming Large Numbers of Nucleotide Sequences 

 2435-Publishing of Patents and Patent Application Publications with a Lengthy “Sequence Listing” 

 

 

 
 

 
 
 

 
 

 

 
 
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 03/09/2026 20:49:36