MPEP § 2422 — Nucleotide and/or Amino Acid Sequence Disclosures in Patent Applications Subject to WIPO ST.25 (Annotated Rules)
§2422 Nucleotide and/or Amino Acid Sequence Disclosures in Patent Applications Subject to WIPO ST.25
This page consolidates and annotates all enforceable requirements under MPEP § 2422, including statutory authority, regulatory rules, examiner guidance, and practice notes. It is provided as guidance, with links to the ground truth sources. This is information only, it is not legal advice.
Nucleotide and/or Amino Acid Sequence Disclosures in Patent Applications Subject to WIPO ST.25
This section addresses Nucleotide and/or Amino Acid Sequence Disclosures in Patent Applications Subject to WIPO ST.25. Primary authority: 37 CFR 1.821, 37 CFR 1.822, and 37 CFR 1.495(b)(1). Contains: 2 requirements, 8 prohibitions, 4 guidance statements, 1 permission, and 1 other statement.
Key Rules
Sequence Listing Content
[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.]
(a) Nucleotide and/or amino acid sequences, as used in §§ 1.821 through 1.825, are interpreted to mean an unbranched sequence of 4 or more amino acids or an unbranched sequence of 10 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 Appendices A through F to this subpart. 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 Appendix A to this subpart. Modifications (e.g., methylated bases) may be described as set forth in Appendix B to this subpart but shall not be shown explicitly in the nucleotide sequence.
- (2) Amino acids: Amino acids are those L-amino acids commonly found in naturally occurring proteins and are listed in appendix C to this subpart. Those amino acid sequences containing D-amino acids are not intended to be embraced by this definition. Any amino acid sequence that contains post-translationally modified amino acids may be described as the amino acid sequence that is initially translated using the symbols shown in appendix C to this subpart, with the modified positions (e.g., hydroxylations or glycosylations) being described as set forth in appendix D to this subpart, 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 appendix C to this subpart, in conjunction with a description in the Feature section, to describe, for example, modified linkages, cross links and end caps, non-peptidyl bonds, etc., is embraced by this definition.
(a) Nucleotide and/or amino acid sequences, as used in §§ 1.821 through 1.825, are interpreted to mean an unbranched sequence of 4 or more amino acids or an unbranched sequence of 10 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 Appendices A through F to this subpart. 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 Appendix A to this subpart. Modifications (e.g., methylated bases) may be described as set forth in Appendix B to this subpart but shall not be shown explicitly in the nucleotide sequence.
(a) Nucleotide and/or amino acid sequences, as used in §§ 1.821 through 1.825, are interpreted to mean an unbranched sequence of 4 or more amino acids or an unbranched sequence of 10 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 Appendices A through F to this subpart. 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 Appendix A to this subpart. Modifications (e.g., methylated bases) may be described as set forth in Appendix B to this subpart but shall not be shown explicitly in the nucleotide sequence.
(a) Nucleotide and/or amino acid sequences, as used in §§ 1.821 through 1.825, are interpreted to mean an unbranched sequence of 4 or more amino acids or an unbranched sequence of 10 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 Appendices A through F to this subpart. Nucleotides and amino acids are further defined as follows:
…
(2) Amino acids:
(a) Nucleotide and/or amino acid sequences, as used in §§ 1.821 through 1.825, are interpreted to mean an unbranched sequence of 4 or more amino acids or an unbranched sequence of 10 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 Appendices A through F to this subpart. Nucleotides and amino acids are further defined as follows:
…
Amino acids are those L-amino acids commonly found in naturally occurring proteins and are listed in appendix C to this subpart.
(a) Nucleotide and/or amino acid sequences, as used in §§ 1.821 through 1.825, are interpreted to mean an unbranched sequence of 4 or more amino acids or an unbranched sequence of 10 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 Appendices A through F to this subpart. Nucleotides and amino acids are further defined as follows:
…
Those amino acid sequences containing D-amino acids are not intended to be embraced by this definition.
(a) Nucleotide and/or amino acid sequences, as used in §§ 1.821 through 1.825, are interpreted to mean an unbranched sequence of 4 or more amino acids or an unbranched sequence of 10 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 Appendices A through F to this subpart. Nucleotides and amino acids are further defined as follows:
…
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 appendix C to this subpart, with the modified positions (e.g., hydroxylations or glycosylations) being described as set forth in appendix D to this subpart, but these modifications shall not be shown explicitly in the amino acid sequence.
(b) Patent applications which contain disclosures of nucleotide and/or amino acid sequences, in accordance with the definition in paragraph (a) of this section, shall, with regard to the manner in which the nucleotide and/or amino acid sequences are presented and described, conform exclusively to the requirements of §§ 1.821 through 1.825.
(d) Where the description or claims of a patent application discuss a sequence that is set forth in the “Sequence Listing,” in accordance with paragraph (c) of this section, reference must be made to the sequence by use of the sequence identifier (§ 1.823(a)(5)), preceded by “SEQ ID NO:” or the like, 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. Where a sequence is presented in a drawing, reference must be made to the sequence by use of the sequence identifier (§ 1.823(a)(5)), either in the drawing or in the Brief Description of the Drawings, where the correlation between multiple sequences in the drawing and their sequence identifiers (§ 1.823(a)(5)) in the Brief Description is clear.
(d) Where the description or claims of a patent application discuss a sequence that is set forth in the “Sequence Listing,” in accordance with paragraph (c) of this section, reference must be made to the sequence by use of the sequence identifier (§ 1.823(a)(5)), preceded by “SEQ ID NO:” or the like, 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. Where a sequence is presented in a drawing, reference must be made to the sequence by use of the sequence identifier (§ 1.823(a)(5)), either in the drawing or in the Brief Description of the Drawings, where the correlation between multiple sequences in the drawing and their sequence identifiers (§ 1.823(a)(5)) in the Brief Description is clear.
37 CFR 1.821 and 37 CFR 1.822 reference Appendices A-F, which contain Tables 1–6 of the World Intellectual Property Organization (WIPO) Handbook on Industrial Property Information and Documentation, Standard ST.25: Standard for Nucleotide and Amino Acid Sequence Listings in Patent Applications (2009) (hereinafter WIPO Standard ST.25 (2009)). Appendices A-F are reproduced below. The current version of WIPO Standard ST.25 is available online at www.wipo.int /export/sites/ www/standards/en/pdf/03-25-01.pdf.
37 CFR 1.821 and 37 CFR 1.822 reference Appendices A-F, which contain Tables 1–6 of the World Intellectual Property Organization (WIPO) Handbook on Industrial Property Information and Documentation, Standard ST.25: Standard for Nucleotide and Amino Acid Sequence Listings in Patent Applications (2009) (hereinafter WIPO Standard ST.25 (2009)). Appendices A-F are reproduced below. The current version of WIPO Standard ST.25 is available online at www.wipo.int /export/sites/ www/standards/en/pdf/03-25-01.pdf.
Appendix A provides that the bases of a nucleotide sequence should be represented using the following one-letter symbol for nucleotide sequence characters:
Appendix B provides that modified bases may be represented as the corresponding unmodified bases in the sequence itself, if the modification is further described in numeric identifier <223> of the Feature section of the “Sequence Listing”. The symbols from the list below may be used in the description (i.e., the specification and drawing, or in the Feature section of the “Sequence Listing”) but these symbols may not be used in the sequence itself. Modifications not listed in Appendix B may also be represented as the corresponding unmodified base in the sequence itself, and the modification should be described using its full chemical name in the Feature section of the “Sequence Listing”.
Appendix C provides that the amino acids should be represented using the following three-letter symbols with the first letter as a capital.
Appendix D provides that modified and unusual amino acids may be represented as the corresponding unmodified amino acids in the sequence itself if the modification is further described in numeric identifier <223> of the Feature section of the “Sequence Listing”. The symbols from the list below may be used in the description (i.e., the specification and drawings, or in the Feature section of the “Sequence Listing”) but these symbols may not be used in the sequence itself. Modifications not listed in Appendix D may also be represented as the corresponding unmodified amino acid in the sequence itself, and the modification should be described using its full chemical name in the Feature section of the “Sequence Listing”.
Appendix D provides that modified and unusual amino acids may be represented as the corresponding unmodified amino acids in the sequence itself if the modification is further described in numeric identifier <223> of the Feature section of the “Sequence Listing”. The symbols from the list below may be used in the description (i.e., the specification and drawings, or in the Feature section of the “Sequence Listing”) but these symbols may not be used in the sequence itself. Modifications not listed in Appendix D may also be represented as the corresponding unmodified amino acid in the sequence itself, and the modification should be described using its full chemical name in the Feature section of the “Sequence Listing”.
Sequence Listing Format
(a) Nucleotide and/or amino acid sequences, as used in §§ 1.821 through 1.825, are interpreted to mean an unbranched sequence of 4 or more amino acids or an unbranched sequence of 10 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 Appendices A through F to this subpart. Nucleotides and amino acids are further defined as follows:
…
Any peptide or protein that can be expressed as a sequence using the symbols in appendix C to this subpart, in conjunction with a description in the Feature section, to describe, for example, modified linkages, cross links and end caps, non-peptidyl bonds, etc., is embraced by this definition.
37 CFR 1.821 and 37 CFR 1.822 reference Appendices A-F, which contain Tables 1–6 of the World Intellectual Property Organization (WIPO) Handbook on Industrial Property Information and Documentation, Standard ST.25: Standard for Nucleotide and Amino Acid Sequence Listings in Patent Applications (2009) (hereinafter WIPO Standard ST.25 (2009)). Appendices A-F are reproduced below. The current version of WIPO Standard ST.25 is available online at www.wipo.int /export/sites/ www/standards/en/pdf/03-25-01.pdf.
Appendix B provides that modified bases may be represented as the corresponding unmodified bases in the sequence itself, if the modification is further described in numeric identifier <223> of the Feature section of the “Sequence Listing”. The symbols from the list below may be used in the description (i.e., the specification and drawing, or in the Feature section of the “Sequence Listing”) but these symbols may not be used in the sequence itself. Modifications not listed in Appendix B may also be represented as the corresponding unmodified base in the sequence itself, and the modification should be described using its full chemical name in the Feature section of the “Sequence Listing”.
Appendix B provides that modified bases may be represented as the corresponding unmodified bases in the sequence itself, if the modification is further described in numeric identifier <223> of the Feature section of the “Sequence Listing”. The symbols from the list below may be used in the description (i.e., the specification and drawing, or in the Feature section of the “Sequence Listing”) but these symbols may not be used in the sequence itself. Modifications not listed in Appendix B may also be represented as the corresponding unmodified base in the sequence itself, and the modification should be described using its full chemical name in the Feature section of the “Sequence Listing”.
Appendix D provides that modified and unusual amino acids may be represented as the corresponding unmodified amino acids in the sequence itself if the modification is further described in numeric identifier <223> of the Feature section of the “Sequence Listing”. The symbols from the list below may be used in the description (i.e., the specification and drawings, or in the Feature section of the “Sequence Listing”) but these symbols may not be used in the sequence itself. Modifications not listed in Appendix D may also be represented as the corresponding unmodified amino acid in the sequence itself, and the modification should be described using its full chemical name in the Feature section of the “Sequence Listing”.
With further regard to requirements (A) and (B), is noted that PatentIn Version 3.5.1 software (see MPEP § 2430) generates sequence listings that meet all of the requirements of WIPO Standard ST.25 (2009). Applicants should similarly be aware that filing requirements for sequence listings may differ between a national US application, a foreign application and an international application during international phase. For example, where an international application is filed in paper, the sequence listing part of the international application must similarly be provided in paper. In addition, a copy of the sequence listing in ASCII plain text, to be used for the purpose of the international search (PCT Rule 13ter) must be filed on read-only optical disc or via the USPTO electronic filing system. Furthermore, in contrast to US national applications, a sequence listing filed with RO/US in ASCII plain text that is 300 MB or more in size is not subject to a size fee during the international phase of an international application.
Nationals and Residents
(g) If any of the requirements of paragraphs (b) through (e) 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, the 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 amendment to add or replace a “Sequence Listing” and CRF copy thereof in reply to a requirement under this paragraph must be submitted in accordance with the requirements of § 1.825.
(h) If any of the requirements of paragraph (e)(3) of this section are not satisfied at the time of filing an international application under the PCT, and the application is to be searched by the United States International Searching Authority or examined by the United States International Preliminary Examining Authority, the applicant may be sent a notice necessitating compliance with the requirements within a prescribed time period. Where a “Sequence Listing” under PCT Rule 13ter is provided in reply to a requirement under this paragraph, it must be accompanied by a statement that the information recorded in the ASCII plain text file under paragraph (e)(3)(i) of this section is identical to the sequence listing contained in the international application as filed, or does not go beyond the disclosure in the international application as filed, as applicable. It must also be accompanied by the late furnishing fee, as set forth in § 1.445(a)(5). If the applicant fails to timely provide the required CRF, the United States International Searching Authority shall search only to the extent that a meaningful search can be performed without the CRF, and the United States International Preliminary Examining Authority shall examine only to the extent that a meaningful examination can be performed without the CRF.
(h) If any of the requirements of paragraph (e)(3) of this section are not satisfied at the time of filing an international application under the PCT, and the application is to be searched by the United States International Searching Authority or examined by the United States International Preliminary Examining Authority, the applicant may be sent a notice necessitating compliance with the requirements within a prescribed time period. Where a “Sequence Listing” under PCT Rule 13ter is provided in reply to a requirement under this paragraph, it must be accompanied by a statement that the information recorded in the ASCII plain text file under paragraph (e)(3)(i) of this section is identical to the sequence listing contained in the international application as filed, or does not go beyond the disclosure in the international application as filed, as applicable. It must also be accompanied by the late furnishing fee, as set forth in § 1.445(a)(5). If the applicant fails to timely provide the required CRF, the United States International Searching Authority shall search only to the extent that a meaningful search can be performed without the CRF, and the United States International Preliminary Examining Authority shall examine only to the extent that a meaningful examination can be performed without the CRF.
With further regard to requirements (A) and (B), is noted that PatentIn Version 3.5.1 software (see MPEP § 2430) generates sequence listings that meet all of the requirements of WIPO Standard ST.25 (2009). Applicants should similarly be aware that filing requirements for sequence listings may differ between a national US application, a foreign application and an international application during international phase. For example, where an international application is filed in paper, the sequence listing part of the international application must similarly be provided in paper. In addition, a copy of the sequence listing in ASCII plain text, to be used for the purpose of the international search (PCT Rule 13ter) must be filed on read-only optical disc or via the USPTO electronic filing system. Furthermore, in contrast to US national applications, a sequence listing filed with RO/US in ASCII plain text that is 300 MB or more in size is not subject to a size fee during the international phase of an international application.
With further regard to requirements (A) and (B), is noted that PatentIn Version 3.5.1 software (see MPEP § 2430) generates sequence listings that meet all of the requirements of WIPO Standard ST.25 (2009). Applicants should similarly be aware that filing requirements for sequence listings may differ between a national US application, a foreign application and an international application during international phase. For example, where an international application is filed in paper, the sequence listing part of the international application must similarly be provided in paper. In addition, a copy of the sequence listing in ASCII plain text, to be used for the purpose of the international search (PCT Rule 13ter) must be filed on read-only optical disc or via the USPTO electronic filing system. Furthermore, in contrast to US national applications, a sequence listing filed with RO/US in ASCII plain text that is 300 MB or more in size is not subject to a size fee during the international phase of an international application.
Receiving Office (RO/US)
(h) If any of the requirements of paragraph (e)(3) of this section are not satisfied at the time of filing an international application under the PCT, and the application is to be searched by the United States International Searching Authority or examined by the United States International Preliminary Examining Authority, the applicant may be sent a notice necessitating compliance with the requirements within a prescribed time period. Where a “Sequence Listing” under PCT Rule 13ter is provided in reply to a requirement under this paragraph, it must be accompanied by a statement that the information recorded in the ASCII plain text file under paragraph (e)(3)(i) of this section is identical to the sequence listing contained in the international application as filed, or does not go beyond the disclosure in the international application as filed, as applicable. It must also be accompanied by the late furnishing fee, as set forth in § 1.445(a)(5). If the applicant fails to timely provide the required CRF, the United States International Searching Authority shall search only to the extent that a meaningful search can be performed without the CRF, and the United States International Preliminary Examining Authority shall examine only to the extent that a meaningful examination can be performed without the CRF.
The requirements of 37 CFR 1.821 through 37 CFR 1.825 are the result of an effort to harmonize the USPTO requirements with international sequence listing requirements to the extent possible. The requirements of 37 CFR 1.821 through 37 CFR 1.825 substantially correspond to the requirements of WIPO Standard ST.25 (2009). However, the requirements of 37 CFR 1.821 through 37 CFR 1.825 are less stringent than the requirements of WIPO Standard ST.25 (2009). Thus, applicants who have filed or wish to file international applications or applications in countries that adhere to WIPO Standard ST.25 (2009) should be aware of the following requirements:
- (A) The data in numeric identifier <221> must use selections from Tables 5 and 6 of WIPO Standard ST.25 (2009) to comply with that standard. The terms from these Tables are considered language neutral vocabulary;
- (B) WIPO Standard ST.25 (2009), paragraph 24, requires a blank line between numeric identifiers in the sequence listing when the digit in the first or second position of the numeric identifier changes;
- (C) Where the sequence listing forming part of the description of the international application contains free text, e.g., free text in numeric identifier <223>, any such free text shall be repeated in the main part of the description in the language thereof (PCT Rule 5.2(b)). It is recommended that the free text in the language of the main part of the description be put in a specific section of the description called “Sequence Listing Free Text”;
- (D) A sequence listing filed after the international filing date is generally not considered to be part of the disclosure and usually will not be published as part of the international application publication (see PCT Article 34 and PCT Rules 26 and 91 for exceptions); and
- (E) Paragraph 4(v) of WIPO Standard ST.25 (2009) requires an accompanying statement with the specific wording “the information recorded in electronic form furnished under PCT Rule 13ter is identical to the sequence listing as contained in the international application ”.
Article 19 Amendment Scope
(c) Patent applications that contain disclosures of nucleotide and/or amino acid sequences, as defined in paragraph (a) of this section, must contain a “Sequence Listing,” which is a separate part of the specification containing each of those 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. The “Sequence Listing” must be submitted as follows, except for a national stage entry under § 1.495(b)(1), where the “Sequence Listing” has been previously communicated by the International Bureau or originally filed in the United States Patent and Trademark Office and complies with Patent Cooperation Treaty (PCT) Rule 5.2:
- (1) As an ASCII plain text file, in compliance with § 1.824, submitted via the USPTO patent electronic filing system or on a read-only optical disc under § 1.52(e), accompanied by an incorporation by reference statement of the ASCII plain text file, in a separate paragraph of the specification, in accordance with § 1.77(b)(5);
- (2) As a PDF file via the USPTO patent electronic filing system; or
- (3) On physical sheets of paper.
Statement Under Article 19
(g) If any of the requirements of paragraphs (b) through (e) 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, the 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 amendment to add or replace a “Sequence Listing” and CRF copy thereof in reply to a requirement under this paragraph must be submitted in accordance with the requirements of § 1.825.
Request Content and Form
The requirements of 37 CFR 1.821 through 37 CFR 1.825 are the result of an effort to harmonize the USPTO requirements with international sequence listing requirements to the extent possible. The requirements of 37 CFR 1.821 through 37 CFR 1.825 substantially correspond to the requirements of WIPO Standard ST.25 (2009). However, the requirements of 37 CFR 1.821 through 37 CFR 1.825 are less stringent than the requirements of WIPO Standard ST.25 (2009). Thus, applicants who have filed or wish to file international applications or applications in countries that adhere to WIPO Standard ST.25 (2009) should be aware of the following requirements:
…
(E) Paragraph 4(v) of WIPO Standard ST.25 (2009) requires an accompanying statement with the specific wording “the information recorded in electronic form furnished under PCT Rule 13ter is identical to the sequence listing as contained in the international application ”.
Sequence Listing in PCT
With further regard to requirements (A) and (B), is noted that PatentIn Version 3.5.1 software (see MPEP § 2430) generates sequence listings that meet all of the requirements of WIPO Standard ST.25 (2009). Applicants should similarly be aware that filing requirements for sequence listings may differ between a national US application, a foreign application and an international application during international phase. For example, where an international application is filed in paper, the sequence listing part of the international application must similarly be provided in paper. In addition, a copy of the sequence listing in ASCII plain text, to be used for the purpose of the international search (PCT Rule 13ter) must be filed on read-only optical disc or via the USPTO electronic filing system. Furthermore, in contrast to US national applications, a sequence listing filed with RO/US in ASCII plain text that is 300 MB or more in size is not subject to a size fee during the international phase of an international application.
Citations
| Primary topic | Citation |
|---|---|
| Nationals and Residents Statement Under Article 19 | 35 U.S.C. § 111(a) |
| Nationals and Residents Statement Under Article 19 | 35 U.S.C. § 371 |
| Nationals and Residents Receiving Office (RO/US) | 37 CFR § 1.445(a)(5) |
| Article 19 Amendment Scope | 37 CFR § 1.495(b)(1) |
| Article 19 Amendment Scope | 37 CFR § 1.52(e) |
| Article 19 Amendment Scope | 37 CFR § 1.77(b)(5) |
| Receiving Office (RO/US) Request Content and Form Sequence Listing Content Sequence Listing Format | 37 CFR § 1.821 |
| Article 19 Amendment Scope Sequence Listing Content Sequence Listing Format | 37 CFR § 1.822 |
| Sequence Listing Content | 37 CFR § 1.823(a)(5) |
| Article 19 Amendment Scope | 37 CFR § 1.824 |
| Nationals and Residents Receiving Office (RO/US) Request Content and Form Statement Under Article 19 | 37 CFR § 1.825 |
| Sequence Listing Content | 37 CFR § 1.831(b) |
| Sequence Listing Content | MPEP § 2412 |
| Nationals and Residents Sequence Listing Format Sequence Listing in PCT | MPEP § 2430 |
| Nationals and Residents Receiving Office (RO/US) Request Content and Form Sequence Listing Format Sequence Listing in PCT | PCT Rule 13ter |
| Receiving Office (RO/US) | PCT Rules 26 |
| Receiving Office (RO/US) | PCT Article 34 |
| Receiving Office (RO/US) | PCT Rule 5.2(b) |
Source Text from USPTO’s MPEP
This is an exact copy of the MPEP from the USPTO. It is here for your reference to see the section in context.
Official MPEP § 2422 — Nucleotide and/or Amino Acid Sequence Disclosures in Patent Applications Subject to WIPO ST.25
Source: USPTO2422 Nucleotide and/or Amino Acid Sequence Disclosures in Patent Applications Subject to WIPO ST.25 [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.]
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 4 or more amino acids or an
unbranched sequence of 10 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 Appendices A through F
to this subpart. 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 Appendix A to this subpart. Modifications (e.g., methylated bases) may be described as set forth in Appendix B to this subpart but shall not be shown explicitly in the nucleotide sequence.
- (2) Amino acids: Amino acids are those L-amino acids commonly found in naturally occurring proteins and are listed in appendix C to this subpart. Those amino acid sequences containing D-amino acids are not intended to be embraced by this definition. Any amino acid sequence that contains post-translationally modified amino acids may be described as the amino acid sequence that is initially translated using the symbols shown in appendix C to this subpart, with the modified positions (e.g., hydroxylations or glycosylations) being described as set forth in appendix D to this subpart, 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 appendix C to this subpart, in conjunction with a description in the Feature section, to describe, for example, modified linkages, cross links and end caps, non-peptidyl bonds, etc., is embraced by this definition.
- Note 1 to paragraph (a): Appendices A through F to this subpart contain Tables 1– 6 of the World Intellectual Property Organization (WIPO) Handbook on Industrial Property Information and Documentation, Standard ST.25: Standard for the Presentation of Nucleotide and Amino Acid Sequence Listings in Patent Applications (2009).
- (b) Patent applications which contain disclosures of nucleotide and/or amino acid sequences, in accordance with the definition in paragraph (a) of this section, shall, with regard to the manner in which the nucleotide and/or amino acid sequences are presented and described, conform exclusively to the requirements of §§ 1.821 through 1.825.
- (c) Patent applications that contain disclosures of nucleotide and/or
amino acid sequences, as defined in paragraph (a) of this section, must contain a
“Sequence Listing,” which is a separate part of the specification containing each
of those 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. The “Sequence Listing” must be submitted as follows,
except for a national stage entry under § 1.495(b)(1), where the “Sequence Listing” has been
previously communicated by the International Bureau or originally filed in the
United States Patent and Trademark Office and complies with Patent Cooperation
Treaty (PCT) Rule 5.2:
- (1) As an ASCII plain text file, in compliance with § 1.824, submitted via the USPTO patent electronic filing system or on a read-only optical disc under § 1.52(e), accompanied by an incorporation by reference statement of the ASCII plain text file, in a separate paragraph of the specification, in accordance with § 1.77(b)(5);
- (2) As a PDF file via the USPTO patent electronic filing system; or
- (3) On physical sheets of paper.
- (d) Where the description or claims of a patent application discuss a sequence that is set forth in the “Sequence Listing,” in accordance with paragraph (c) of this section, reference must be made to the sequence by use of the sequence identifier (§ 1.823(a)(5)), preceded by “SEQ ID NO:” or the like, 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. Where a sequence is presented in a drawing, reference must be made to the sequence by use of the sequence identifier (§ 1.823(a)(5)), either in the drawing or in the Brief Description of the Drawings, where the correlation between multiple sequences in the drawing and their sequence identifiers (§ 1.823(a)(5)) in the Brief Description is clear.
- (e)
- (1) If the “Sequence Listing” under paragraph
(c) of this section is submitted in an application filed under
35 U.S.C. 111(a) as a PDF file (§ 1.821(c)(2)) via the USPTO patent electronic filing
system or on physical sheets of paper (§ 1.821(c)(3)), then the following must be submitted:
- (i) A CRF of the “Sequence Listing,” in accordance with the requirements of § 1.824; and
- (ii) A statement that the sequence information contained in the CRF submitted under paragraph (e)(1)(i) of this section is identical to the sequence information contained in the “Sequence Listing” under paragraph (c) of this section.
- (2) If the “Sequence Listing” under paragraph (c)
of this section in an application submitted under 35 U.S.C.
371 is a PDF file (paragraph (c)(2) of this section)
or on physical sheets of paper (paragraph (c)(3) of this section), and not
also as an ASCII plain text file, in compliance with § 1.824
(paragraph (c)(1) of this section), then the following must be
submitted:
- (i) A CRF of the “Sequence Listing,” in accordance with the requirements of § 1.824; and
- (ii) A statement that the sequence information contained in the CRF submitted under paragraph (e)(2)(i) of this section is identical to the sequence information contained in the “Sequence Listing” under paragraph (c)(2) or (3) of this section.
- (3) If a “Sequence Listing” in ASCII plain text
format, in compliance with § 1.824, has not been submitted for an
international application under the PCT, and that application contains
disclosures of nucleotide and/or amino acid sequences, as defined in
paragraph (a) of this section, and is to be searched by the United States
International Searching Authority or examined by the United States
International Preliminary Examining Authority, then the following must be
submitted:
- (i) A CRF of the “Sequence Listing,” in accordance with the requirements of § 1.824;
- (ii) The late furnishing fee for providing a “Sequence Listing” in response to an invitation, as set forth in § 1.445(a)(5); and
- (iii) A statement that the sequence information contained in the CRF, submitted under paragraph (e)(3)(i) of this section, does not go beyond the disclosure in the international application as filed, or a statement that the information recorded in the ASCII plain text file, submitted under paragraph (e)(3)(i) of this section, is identical to the sequence listing contained in the international application as filed, as applicable.
- (4) The CRF may not be retained as a part of the patent application file.
- (1) If the “Sequence Listing” under paragraph
(c) of this section is submitted in an application filed under
35 U.S.C. 111(a) as a PDF file (§ 1.821(c)(2)) via the USPTO patent electronic filing
system or on physical sheets of paper (§ 1.821(c)(3)), then the following must be submitted:
- (f) [reserved]
- (g) If any of the requirements of paragraphs (b) through (e) 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, the 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 amendment to add or replace a “Sequence Listing” and CRF copy thereof in reply to a requirement under this paragraph must be submitted in accordance with the requirements of § 1.825.
- (h) If any of the requirements of paragraph (e)(3) of this section are not satisfied at the time of filing an international application under the PCT, and the application is to be searched by the United States International Searching Authority or examined by the United States International Preliminary Examining Authority, the applicant may be sent a notice necessitating compliance with the requirements within a prescribed time period. Where a “Sequence Listing” under PCT Rule 13ter is provided in reply to a requirement under this paragraph, it must be accompanied by a statement that the information recorded in the ASCII plain text file under paragraph (e)(3)(i) of this section is identical to the sequence listing contained in the international application as filed, or does not go beyond the disclosure in the international application as filed, as applicable. It must also be accompanied by the late furnishing fee, as set forth in § 1.445(a)(5). If the applicant fails to timely provide the required CRF, the United States International Searching Authority shall search only to the extent that a meaningful search can be performed without the CRF, and the United States International Preliminary Examining Authority shall examine only to the extent that a meaningful examination can be performed without the CRF.
37 CFR 1.821 and 37 CFR 1.822 reference Appendices A-F, which contain Tables 1–6 of the World Intellectual Property Organization (WIPO) Handbook on Industrial Property Information and Documentation, Standard ST.25: Standard for Nucleotide and Amino Acid Sequence Listings in Patent Applications (2009) (hereinafter WIPO Standard ST.25 (2009)). Appendices A-F are reproduced below. The current version of WIPO Standard ST.25 is available online at www.wipo.int /export/sites/ www/standards/en/pdf/03-25-01.pdf.
Appendix A provides that the bases of a nucleotide sequence should be represented using the following one-letter symbol for nucleotide sequence characters:
| Symbol | Meaning | Origin of designation |
|---|---|---|
| a | a | adenine. |
| g | g | guanine. |
| c | c | cytosine. |
| t | t | thymine. |
| u | u | uracil. |
| r | g or a | purine. |
| y | t/u or c | pyrimidine. |
| m | a or c | amino. |
| k | g or t/u | keto. |
| s | g or c | strong interactions 3H-bonds. |
| w | a or t/u | weak interactions 2H-bonds. |
| b | g or c or t/u | not a. |
| d | a or g or t/u | not c. |
| h | a or c or t/u | not g. |
| v | a or g or c | not t, not u. |
| n | a or g or c or t/u, unknown, or other | any. |
Appendix B provides that modified bases may be represented as the corresponding unmodified bases in the sequence itself, if the modification is further described in numeric identifier <223> of the Feature section of the “Sequence Listing”. The symbols from the list below may be used in the description (i.e., the specification and drawing, or in the Feature section of the “Sequence Listing”) but these symbols may not be used in the sequence itself. Modifications not listed in Appendix B may also be represented as the corresponding unmodified base in the sequence itself, and the modification should be described using its full chemical name in the Feature section of the “Sequence Listing”.
| Symbol | Meaning |
|---|---|
| ac4c | 4-acetylcytidine. |
| chm5u | 5-(carboxyhydroxymethyl)uridine. |
| cm | 2′-O-methylcytidine. |
| cmnm5s2u | 5-carboxymethylaminomethyl-2- thiouridine. |
| cmnm5u | 5-carboxymethylaminomethyluridine. |
| d | dihydrouridine. |
| fm | 2′-O-methylpseudouridine. |
| gal q | beta, D-galactosylqueuosine. |
| gm | 2′-O-methylguanosine. |
| i | inosine. |
| i6a | N6-isopentenyladenosine. |
| m1a | 1-methyladenosine. |
| m1f | 1-methylpseudouridine. |
| m1g | 1-methylguanosine. |
| m1i | 1-methylinosine. |
| m22g | 2,2-dimethylguanosine. |
| m2a | 2-methyladenosine. |
| m2g | 2-methylguanosine. |
| m3c | 3-methylcytidine. |
| m5c | 5-methylcytidine. |
| m6a | N6-methyladenosine. |
| m7g | 7-methylguanosine. |
| mam5u | 5-methylaminomethyluridine. |
| mam5s2u | 5-methoxyaminomethyl-2-thiouridine. |
| man q | beta, D-mannosylqueuosine. |
| mcm5s2u | 5-methoxycarbonylmethyl-2- thiouridine. |
| mcm5u | 5-methoxycarbonylmethyluridine. |
| mo5u | 5-methoxyuridine. |
| ms2i6a | 2-methylthio-N6- isopentenyladenosine. |
| ms2t6a | N-((9-beta-D-ribofuranosyl-2- methylthiopurine-6- yl)carbamoyl)threonine. |
| mt6a | N-((9-beta-D-ribofuranosylpurine-6- yl)N-methylcarbamoyl)threonine. |
| mv | uridine-5-oxyacetic acid-methylester. |
| o5u | uridine-5-oxyacetic acid. |
| osyw | wybutoxosine. |
| p | pseudouridine. |
| q | queuosine. |
| 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. |
Appendix C provides that the amino acids should be represented using the following three-letter symbols with the first letter as a capital.
| 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. |
Appendix D provides that modified and unusual amino acids may be represented as the corresponding unmodified amino acids in the sequence itself if the modification is further described in numeric identifier <223> of the Feature section of the “Sequence Listing”. The symbols from the list below may be used in the description (i.e., the specification and drawings, or in the Feature section of the “Sequence Listing”) but these symbols may not be used in the sequence itself. Modifications not listed in Appendix D may also be represented as the corresponding unmodified amino acid in the sequence itself, and the modification should be described using its full chemical name in the Feature section of the “Sequence Listing”.
| 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. |
Appendix E provides for 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 upstream of the start point of eukaryotic transcription units which may be involved in RNA polymerase binding; consensus=GG (C or T) CAATCT. |
| CDS | coding sequence; sequence of nucleotides that corresponds with the sequence of amino acids in a protein (location includes stop codon); feature includes amino acid conceptual translation. |
| conflict | independent determinations of the “same” sequence differ at this site or region. |
| D-loop | displacement loop; a region within mitochondrial DNA in which a short stretch of RNA is paired with one strand of DNA, displacing the original partner DNA strand in this region; also used to describe the displacement of a region of one strand of duplex DNA by a single stranded invader in the reaction catalyzed by RecA protein. |
| D-segment | diversity segment of immunoglobulin heavy chain, and T-cell receptor beta chain. |
| enhancer | a cis-acting sequence that increases the utilization of (some) eukaryotic promoters, and can function in either orientation and in any location (upstream or downstream) relative to the promoter. |
| exon | region of genome that codes for portion of spliced mRNA; may contain 5’UTR, all CDSs, and 3’UTR. |
| GC_signal | GC box; a conserved GC-rich region located upstream of the start point of eukaryotic transcription units which may occur in multiple copies or in either orientation; consensus=GGGCGG. |
| gene | region of biological interest identified as a gene and for which a name has been assigned. |
| iDNA | intervening DNA; DNA which is eliminated through any of several kinds of recombination. |
| intron | a segment of DNA that is transcribed, but removed from within the transcript by splicing together the sequences (exons) on either side of it. |
| J_segment | joining segment of immunoglobulin light and heavy chains, and T-cell receptor alpha, beta, and gamma chains. |
| LTR | long terminal repeat, a sequence directly repeated at both ends of a defined sequence, of the sort typically found in retroviruses. |
| mat_peptide | mature peptide or protein coding sequence; coding sequence for the mature or final peptide or protein product following post- translational modification; the location does not include the stop codon (unlike the corresponding CDS). |
| misc_binding | site in nucleic acid which covalently or non-covalently binds another moiety that cannot be described by any other Binding key (primer_bind or protein_bind). |
| misc_difference | feature sequence is different from that presented in the entry and cannot be described by any other Difference key (conflict, unsure, old_sequence, mutation, variation, allele, or modified_base). |
| misc_feature | region of biological interest which cannot be described by any other feature key; a new or rare feature. |
| misc_recomb | site of any generalized, site-specific or replicative recombination event where there is a breakage and reunion of duplex DNA that cannot be described by other recombination keys (iDNA and virion) or qualifiers of source key (/insertion_seq, /transposon, /proviral). |
| misc_RNA | any transcript or RNA product that cannot be defined by other RNA keys (prim_transcript, precursor_RNA, mRNA, 5’clip, 3’clip, 5’UTR, 3’UTR, exon, CDS, sig_peptide, transit_peptide, mat_peptide, intron, polyA_site, rRNA, tRNA, scRNA, and snRNA). |
| misc_signal | any region containing a signal controlling or altering gene function or expression that cannot be described by other Signal keys (promoter, CAAT_signal, TATA_signal, –35_signal, –10_signal, GC_signal, RBS, polyA_signal, enhancer, attenuator, terminator, and rep_origin). |
| misc_structure | any secondary or tertiary structure or conformation that cannot be described by other Structure keys (stem_loop and D-loop). |
| modified_base | the indicated nucleotide is a modified nucleotide and should be substituted for by the indicated molecule (given in the mod_base qualifier value). |
| mRNA | messenger RNA; includes 5′ untranslated region (5’UTR), coding sequences (CDS, exon) and 3′ untranslated region (3’UTR). |
| mutation | a related strain has an abrupt, inheritable change in the sequence at this location. |
| N_region | extra nucleotides inserted between rearranged immunoglobulin segments. |
| old_sequence | the presented sequence revises a previous version of the sequence at this location. |
| polyA_signal | recognition region necessary for endonuclease cleavage of an RNA transcript that is followed by polyadenylation; consensus=AATAAA. |
| polyA_site | site on an RNA transcript to which will be added adenine residues by post-transcriptional polyadenylation. |
| precursor_RNA | any RNA species that is not yet the mature RNA product; may include 5′ clipped region (5’clip), 5′ untranslated region (5’UTR), coding sequences (CDS, exon), intervening sequences (intron), 3′ untranslated region (3’UTR), and 3′ clipped region (3’clip). |
| prim_transcript | primary (initial, unprocessed) transcript; includes 5′ clipped region (5’clip), 5′ untranslated region (5’UTR), coding sequences (CDS, exon), intervening sequences (intron), 3′ untranslated region (3’UTR), and 3′ clipped region (3’clip). |
| primer_bind | non-covalent primer binding site for initiation of replication, transcription, or reverse transcription; includes site(s) for synthetic, for example, PCR primer elements. |
| promoter | region on a DNA molecule involved in RNA polymerase binding to initiate transcription. |
| protein_bind | non-covalent protein binding site on nucleic acid. |
| RBS | ribosome binding site. |
| repeat_region | region of genome containing repeating units. |
| repeat_unit | single repeat element. |
| rep_origin | origin of replication; starting site for duplication of nucleic acid to give two identical copies. |
| rRNA | mature ribosomal RNA; the RNA component of the ribonucleoprotein particle (ribosome) which assembles amino acids into proteins. |
| S_region | switch region of immunoglobulin heavy chains; involved in the rearrangement of heavy chain DNA leading to the expression of a different immunoglobulin class from the same B-cell. |
| satellite | many tandem repeats (identical or related) of a short basic repeating unit; many have a base composition or other property different from the genome average that allows them to be separated from the bulk (main band) genomic DNA. |
| scRNA | small cytoplasmic RNA; any one of several small cytoplasmic RNA molecules present in the cytoplasm and (sometimes) nucleus of a eukaryote. |
| sig_peptide | signal peptide coding sequence; coding sequence for an N-terminal domain of a secreted protein; this domain is involved in attaching nascent polypeptide to the membrane; leader sequence. |
| snRNA | small nuclear RNA; any one of many small RNA species confined to the nucleus; several of the snRNAs are involved in splicing or other RNA processing reactions. |
| source | identifies the biological source of the specified span of the sequence; this key is mandatory; every entry will have, as a minimum, a single source key spanning the entire sequence; more than one source key per sequence is permissible. |
| stem_loop | hairpin; a double-helical region formed by base-pairing between adjacent (inverted) complementary sequences in a single strand of RNA or DNA |
| STS | Sequence Tagged Site; short, single-copy DNA sequence that characterizes a mapping landmark on the genome and can be detected by PCR; a region of the genome can be mapped by determining the order of a series of STSs. |
| TATA_signal | TATA box; Goldberg-Hogness box; a conserved AT-rich septamer found about 25 bp before the start point of each eukaryotic RNA polymerase II transcript unit which may be involved in positioning the enzyme for correct initiation; consensus=TATA(A or T)A(A or T). |
| terminator | sequence of DNA located either at the end of the transcript or adjacent to a promoter region that causes RNA polymerase to terminate transcription; may also be site of binding of repressor protein. |
| transit_peptide | transit peptide coding sequence; coding sequence for an N-terminal domain of a nuclear-encoded organellar protein; this domain is involved in post-translational import of the protein into the organelle. |
| tRNA | mature transfer RNA, a small RNA molecule (75-85 bases long) that mediates the translation of a nucleic acid sequence into an amino acid sequence. |
| unsure | author is unsure of exact sequence in this region. |
| V_region | variable region of immunoglobulin light and heavy chains, and T-cell receptor alpha, beta, and gamma chains; codes for the variable amino terminal portion; can be made up from V_segments, D_segments, N_regions, and J_segments. |
| V_segment | variable segment of immunoglobulin light and heavy chains, and T-cell receptor alpha, beta, and gamma chains; codes for most of the variable region (V_region) and the last few amino acids of the leader peptide. |
| variation | a related strain contains stable mutations from the same gene (for example, RFLPs, polymorphisms, etc.) which differ from the presented sequence at this location (and possibly others). |
| 3’clip | 3′-most region of a precursor transcript that is clipped off during processing. |
| 3’UTR | region at the 3′ end of a mature transcript (following the stop codon) that is not translated into a protein. |
| 5’clip | 5′-most region of a precursor transcript that is clipped off during processing. |
| 5’UTR | region at the 5′ end of a mature transcript (preceding the initiation codon) that is not translated into a protein. |
| –10_signal | pribnow box; a conserved region about 10 bp upstream of the start point of bacterial transcription units which may be involved in binding RNA polymerase; consensus=TAtAaT. |
| –35_signal | a conserved hexamer about 35 bp upstream of the start point of bacterial transcription units; consensus=TTGACa [ ] or TGTTGACA [ ]. |
Appendix F provides for feature keys related to protein sequences.
| Key | Description |
|---|---|
| CONFLICT | different papers report differing sequences. |
| VARIANT | authors report that sequence variants exist. |
| VARSPLIC | description of sequence variants produced by alternative splicing. |
| MUTAGEN | site which has been experimentally altered. |
| MOD_RES | post-translational modification of a residue. |
| ACETYLATION | N-terminal or other. |
| AMIDATION | generally at the C-terminal of a mature active peptide. |
| BLOCKED | undetermined N- or C-terminal blocking group. |
| FORMYLATION | of the N-terminal methionine. |
| GAMMA-CARBOXYGLUTAMIC ACID HYDROXYLATION | of asparagine, aspartic acid, proline, or lysine. |
| METHYLATION | generally of lysine or arginine. |
| PHOSPHORYLATION | of serine, threonine, tyrosine, aspartic acid or histidine. |
| PYRROLIDONE CARBOXYLIC ACID | N-terminal glutamate which has formed an internal cyclic lactam. |
| SULFATATION | generally of tyrosine. |
| LIPID | covalent binding of a lipidic moiety. |
| MYRISTATE | myristate group attached through an amide bond to the N-terminal glycine residue of the mature form of a protein or to an internal lysine residue. |
| PALMITATE | palmitate group attached through a thioether bond to a cysteine residue or through an ester bond to a serine or threonine residue. |
| FARNESYL | farnesyl group attached through a thioether bond to a cysteine residue. |
| GERANYL-GERANYL | geranyl-geranyl group attached through a thioether bond to a cysteine residue. |
| GPI-ANCHOR | glycosyl-phosphatidylinositol (GPI) group linked to the alpha- carboxyl group of the C-terminal residue of the mature form of a protein. |
| N-ACYL DIGLYCERIDE | N-terminal cysteine of the mature form of a prokaryotic lipoprotein with an amide- linked fatty acid and a glyceryl group to which two fatty acids are linked by ester linkages. |
| DISULFID | disulfide bond; the ‘FROM’ and ‘TO’ endpoints represent the two residues which are linked by an intra-chain disulfide bond; if the `FROM’ and `TO’ endpoints are identical, the disulfide bond is an interchain one and the description field indicates the nature of the cross-link. |
| THIOLEST | thiolester bond; the ‘FROM’ and ‘TO’ endpoints represent the two residues which are linked by the thiolester bond. |
| THIOETH | thioether bond; the ‘FROM’ and ‘TO’ endpoints represent the two residues which are linked by the thioether bond. |
| CARBOHYD | glycosylation site; the nature of the carbohydrate (if known) is given in the description field. |
| METAL | binding site for a metal ion; the description field indicates the nature of the metal. |
| BINDING | binding site for any chemical group (co- enzyme, prosthetic group, etc.); the chemical nature of the group is given in the description field. |
| SIGNAL | extent of a signal sequence (prepeptide). |
| TRANSIT | extent of a transit peptide (mitochondrial, chloroplastic, or for a microbody). |
| PROPEP | extent of a propeptide. |
| CHAIN | extent of a polypeptide chain in the mature protein. |
| PEPTIDE | extent of a released active peptide. |
| DOMAIN | extent of a domain of interest on the sequence; the nature of that domain is given in the description field. |
| CA_BIND | extent of a calcium-binding region. |
| DNA_BIND | extent of a DNA-binding region. |
| NP_BIND | extent of a nucleotide phosphate binding region; the nature of the nucleotide phosphate is indicated in the description field. |
| TRANSMEM | extent of a transmembrane region. |
| ZN_FING | extent of a zinc finger region. |
| SIMILAR | extent of a similarity with another protein sequence; precise information, relative to that sequence, is given in the description field. |
| REPEAT | extent of an internal sequence repetition. |
| HELIX | secondary structure: Helices, for example, Alpha-helix, 3(10) helix, or Pi- helix. |
| STRAND | secondary structure: Beta-strand, for example, Hydrogen bonded beta-strand, or Residue in an isolated beta-bridge. |
| TURN | secondary structure Turns, for example, H-bonded turn (3-turn, 4-turn, or 5-turn). |
| ACT_SITE | amino acid(s) involved in the activity of an enzyme. |
| SITE | any other interesting site on the sequence. |
| INIT_MET | the sequence is known to start with an initiator methionine. |
| NON_TER | the residue at an extremity of the sequence is not the terminal residue; if applied to position 1, this signifies that the first position is not the N- terminus of the complete molecule; if applied to the last position, it signifies that this position is not the C-terminus of the complete molecule; there is no description field for this key. |
| NON_CONS | non consecutive residues; indicates that two residues in a sequence are not consecutive and that there are a number of unsequenced residues between them. |
| UNSURE | uncertainties in the sequence; used to describe region(s) of a sequence for which the authors are unsure about the sequence assignment. |
The requirements of 37 CFR 1.821 through 37 CFR 1.825 are the result of an effort to harmonize the USPTO requirements with international sequence listing requirements to the extent possible. The requirements of 37 CFR 1.821 through 37 CFR 1.825 substantially correspond to the requirements of WIPO Standard ST.25 (2009). However, the requirements of 37 CFR 1.821 through 37 CFR 1.825 are less stringent than the requirements of WIPO Standard ST.25 (2009). Thus, applicants who have filed or wish to file international applications or applications in countries that adhere to WIPO Standard ST.25 (2009) should be aware of the following requirements:
- (A) The data in numeric identifier <221> must use selections from Tables 5 and 6 of WIPO Standard ST.25 (2009) to comply with that standard. The terms from these Tables are considered language neutral vocabulary;
- (B) WIPO Standard ST.25 (2009), paragraph 24, requires a blank line between numeric identifiers in the sequence listing when the digit in the first or second position of the numeric identifier changes;
- (C) Where the sequence listing forming part of the description of the international application contains free text, e.g., free text in numeric identifier <223>, any such free text shall be repeated in the main part of the description in the language thereof (PCT Rule 5.2(b)). It is recommended that the free text in the language of the main part of the description be put in a specific section of the description called “Sequence Listing Free Text”;
- (D) A sequence listing filed after the international filing date is generally not considered to be part of the disclosure and usually will not be published as part of the international application publication (see PCT Article 34 and PCT Rules 26 and 91 for exceptions); and
- (E) Paragraph 4(v) of WIPO Standard ST.25 (2009) requires an accompanying statement with the specific wording “the information recorded in electronic form furnished under PCT Rule 13ter is identical to the sequence listing as contained in the international application”.
With further regard to requirements (A) and (B), is noted that PatentIn Version 3.5.1 software (see MPEP § 2430) generates sequence listings that meet all of the requirements of WIPO Standard ST.25 (2009). Applicants should similarly be aware that filing requirements for sequence listings may differ between a national US application, a foreign application and an international application during international phase. For example, where an international application is filed in paper, the sequence listing part of the international application must similarly be provided in paper. In addition, a copy of the sequence listing in ASCII plain text, to be used for the purpose of the international search (PCT Rule 13ter) must be filed on read-only optical disc or via the USPTO electronic filing system. Furthermore, in contrast to US national applications, a sequence listing filed with RO/US in ASCII plain text that is 300 MB or more in size is not subject to a size fee during the international phase of an international application.