ST.25 sequence listing format
“ST.25” refers to an international standard, adopted in 2009, that describes how nucleotide and amino acid sequences are to be presented in a sequence listing. The U.S. sequence rules (37 CFR 1.821 – 1.825) are based upon WIPO Standard ST.25. All applications requiring sequence listings with a filing date or international filing date before July 1, 2022 MUST contain sequence listings in ST.25 format.
The <110> through the <170> fields of an ST.25 sequence listing are collectively known as the “header” fields of the sequence listing. These header fields are only included once, at the beginning of the sequence listing, and relate to all of the sequences included in that sequence listing. As sequence listings are often filed as documents separate from the specification of a patent application, the header fields serve to associate the sequence data in the sequence listing with the appropriate patent application.
Each sequence in an ST.25 sequence listing is assigned a numbered sequence identifier. The sequence identifiers begin with “1” and increase sequentially by integers. The sequence identifier for each sequence is found in the <210> field and in the first line of the <400> field. In the description, claims, or drawings of a patent application, sequences are referred to by the sequence identifier to which each is assigned in the sequence listing, preceded by “SEQ ID NO:”.
See MPEP 2424 for a definition of, and additional details for, each field in a sequence listing as well as direction as to which fields are mandatory and which are optional.
The USPTO provides a computer program, PatentIn version 3.5.1, that generates sequence listings that comply with ST.25 formatting requirements. See the section on PatentIn for guidance on how to download and use PatentIn version 3.5.1.
See an example of the ST.25 sequence listing format.
Creating an ST.25 ASCII text format sequence listing
Because the sequence rules have very specific format requirements, the USPTO developed software to make it easier to create compliant sequence listings. It is possible to create such listings manually, but it is extremely time consuming and very difficult to ensure that the listing is compliant with (ST.25 and 37 CFR 1.821 – 1.825). The USPTO software are PatentIn and Checker.
Creation of a sequence listing with PatentIn starts with compiling the sequences that form a part of the invention and placing them into a text file. PatentIn can import the sequence information in text format, which can then be refined as needed. PatentIn puts the information into the format that will comply with ST.25.
Checker is verification software provided by the USPTO for preliminary evaluation of a sequence listing for compliance with a subset of Standard ST.25 formatting requirements. While it is not identical to the software used within the agency, it can detect errors that would cause the USPTO validation software to reject the sequence listing, and thereby permits applicants to preemptively correct these errors. Since Checker is unable to validate whether the information in free text fields is proper, it is possible for a sequence listing to pass Checker yet still be found not compliant by the USPTO validation software.
You can download both programs from the USPTO website:
How to file an ST.25 sequence listing in a U.S. national application (35 U.S.C. 111(a))
Applications that disclose specifically enumerated sequences of nucleotides and/or amino acids are required by the USPTO to contain a sequence listing. A sequence listing is a separate part of the disclosure of the application that represents disclosed nucleotide and/or amino acid sequences and associated information, and uses the format and symbols set forth in 37 CFR 1.822 and 1.823. In accordance with 37 CFR 1.821(c)(1)-37 CFR 1.821(c)(3), the sequence listing can be submitted:
- As an ASCII .txt file submitted through the USPTO's patent electronic filing system or on read-only optical discs (where the specification contains an incorporation by reference statement of the ASCII plain text file),
- As a PDF file via the USPTO's electronic filing system or
- On physical sheets of paper
When submitting via 1 above, an incorporation by reference statement of the content of the ASCII .txt file in a separate paragraph, preferably on the first page, of the specification is required identifying:
- the name of the ASCII .txt file
- the size of the ASCII .txt file in bytes and
- the date of creation
REFERENCE TO AN ELECTRONIC SEQUENCE LISTING
The contents of the electronic sequence listing (sequencelisting.txt; Size: 107,643 bytes; and Date of Creation: February 28, 2021) is herein incorporated by reference in its entirety.
Further guidance for incorporating a sequence listing by reference into a specification is provided in the Legal Framework for EFS-Web, MPEP § 502.05 L(l), and MPEP 2422.03(a).
If the sequence listing is supplied as a PDF file or on physical sheets of paper, 37 CFR 1.821(e) requires submission of a copy of the sequence listing in computer readable form (CRF) where the CRF meets the requirements of 37 CFR 1.824.
Use the PatentIn software program to create the ASCII plain text file (37 CRF 1.821(e) or CRF version) of the sequence listing.
There is a 100 MB file size limit for file uploads to the USPTO electronic filing system. For those CRFs that are greater than 100 MB in size, the 37 CRF 1.821(c) and 1.821(e) versions of the sequence listing will need to be submitted separately; i.e., the CRF version filed via the USPTO electronic filing system will not count as both the 37 CFR 1.821(c) version and the 1.821(e) version.
There is a 100 MB file size limit for sequence listing text file uploads to the USPTO electronic filing system. For those ASCII text files that are greater than 100 MB in size, a single copy of the ASCII plain text file sequence listing should be submitted on read-only optical discs.
Checklist for filing a ST.25 sequence listing on read-only optical discs
The following checklist includes guidance from 37 CFR 1.52(e) with respect to filing the sequence listing, in compliance with 37 CFR 1.821-1.825, on read-only optical discs. The submission must:
- Be saved as a single ASCII text file on one or more read-only optical discs.
- Utilize a disc spanning feature of CD/ DVD burner software to save the single file across multiple discs, if the ASCII text file is too large to include on a single read-only optical disc.
- Be a compressed file in accordance with 1.824(b)(2)(ii)-(iv), if file compression is necessary.
- Have each read-only optical disc enclosed in a hard read-only optical disc case within an unsealed padded and protective mailing envelope.
- Include a transmittal letter for read-only optical disc submissions that list for each read-only optical disc:
- First-named inventor (if known),
- Title of the invention,
- Attorney docket or file reference number (if applicable),
- Operating system (e.g., MS-DOS®, MS-Windows®, Mac OS®, or Unix®/Linux®) used to produce the disc and
- A list of files contained on the read-only optical disc including the name of the file, size of the file in bytes, and dates of creation.
- Ensure that the specification contains an incorporation by reference of the sequence listing ASCII plain text file submitted on the read-only optical disc as set forth in 37 CFR 1.821(c)(1), identifying, as required by 37 CFR 1.52(e)(8):
- The name of each file,
- The date of creation of each file and
- The size in bytes of each file.
Recognize that read-only optical discs submitted will not be returned to the applicant.
Amending a U.S. nonprovisional application filed under 35 U.S.C. 111(a) to include an ST.25 sequence listing
Here are some examples of when an application may need to be amended to include a sequence listing:
- A sequence listing is filed after the initial application filing date (e.g., in response to a Notice to File Missing Parts), or
- The sequence listing in ASCII text format submitted under 37 CFR 1.821(c) was found to be noncompliant with Standard ST.25 (i.e. CRFD).
A number of statements are required to support amending an application to add a sequence listing (37 CFR 1.825(a)) or to amend a sequence listing (37 CFR 1.825(b) after the original filing date. These include:
- A “no new matter” statement as per 37 CFR 1.825(a)(4) or 1.825(b)(5),
- A statement under 37 CFR 1.825(a)(3) or 37 CFR 1.825(b)(4) indicating the basis (with specific references to particular parts of the application) for all new or amended sequence data in the application as filed,
- A statement under 37 CFR 1.825(b)(3) that identifies the locations of all deletions, replacements, or additions to the sequence listing, if amended and
- An incorporation by reference statement under 37 CFR 1.825(a)(2)(i) or 1.825(b)(2)(i).
Other statements may also be required, e.g., if an amended or added sequence listing is submitted on physical sheets of paper or as a PDF file, then a separate CRF of the sequence listing is required. In that case, a statement that the paper or PDF sequence listing is the same as the CRF sequence listing copy would be required under 37 CFR 1.825(a)(6) or 1.825(b)(7).
Reminder: When amending an application to include a sequence listing in ASCII text format as a part of the description, an incorporation by reference paragraph will either need to be added to the specification or, if already present, updated to reflect the new sequence listing file name, date of creation, and size in bytes. Keep in mind that the provisions of 37 CFR § 1.111, § 1.116 and § 1.312 apply to making such an amendment to the specification.
When the USPTO mails a Notice to Comply regarding a Sequence Listing requirement, in response, along with the required “Sequence Listing,” a substitute specification in accordance with 37 CFR 1.125(a) will be required to include the new or updated incorporation by reference statement.