Sequence listings are a critical filing requirement for patent applications that disclose qualifying nucleotide or amino acid sequences. For practitioners working with older U.S. applications, the term CRF (computer-readable form) is closely associated with the former ST.25 sequence-listing regime. For newer applications, however, the USPTO has transitioned to WIPO Standard ST.26, which requires sequence listings in XML format. Understanding this distinction is essential because submitting the wrong format can result in a USPTO notice requiring correction.
What Is a CRF Sequence Listing?
Under the former U.S. sequence-listing rules, a CRF was a computer-readable version of a sequence listing. The USPTO’s ST.25 system used an ASCII plain-text format, commonly submitted as a .txt file.
The terminology can still appear in USPTO guidance, particularly when discussing older applications, amendments, or situations in which a sequence listing was originally submitted on paper or as a PDF and a computer-readable copy was also required.
The important point for current filings is that CRF should not be confused with the sequence-listing format required for new applications under ST.26.
ST.25 vs. ST.26: The Key Change
The USPTO implemented the ST.26 sequence-listing standard for applications with a filing date, or for national-phase applications an international filing date, on or after July 1, 2022, when the application contains sequences covered by the applicable rules.
The two systems differ substantially:
| Requirement | ST.25 / Former CRF System | ST.26 / Current System |
| Basic format | ASCII plain text | XML |
| Standard | WIPO ST.25 | WIPO ST.26 |
| Encoding | ASCII | Unicode UTF-8 |
| Typical file | .txt | .xml |
| Creation software | PatentIn could be used | WIPO Sequence is recommended |
| Current applicability | Primarily older applications | Applications subject to the post-July 1, 2022 rules |
The USPTO specifically states that an application subject to ST.26 must contain a compliant sequence listing in XML format. An earlier priority application containing an ST.25 listing does not automatically “grandfather” a later application into ST.25.
When Does a USPTO Application Need a Sequence Listing?
The first step is determining whether the application contains a nucleotide or amino acid sequence that falls within the USPTO’s sequence-listing requirements.
For applications subject to ST.26, the applicable rules are found in 37 CFR §§ 1.831–1.835. The USPTO’s MPEP explains that these provisions apply to applications filed on or after July 1, 2022 and to national-phase applications based on their international filing date.
This filing-date distinction is particularly important for PCT national-stage practice.
For a U.S. national-phase application under 35 U.S.C. § 371, the relevant date for determining whether ST.26 applies is generally the PCT international filing date, not the date on which the U.S. national phase was entered.
What Does an ST.26 Sequence Listing Need to Contain?
An ST.26 sequence listing is substantially more structured than the old ASCII CRF.
The USPTO requires the XML sequence listing to comply with the WIPO ST.26 Document Type Definition (DTD).
The listing generally contains two major components:
1. General information
This section contains bibliographic information associated with the application, such as:
- Applicant information
- Inventor information
- Application information
- Filing date
- Title of the invention
- Priority information
2. Sequence information
This section provides the actual nucleotide or amino acid sequence data together with the structured information required by ST.26.
Because the data is represented using XML elements and attributes, an ST.26 sequence listing is not simply a text document containing a series of sequences.
File Format Requirements
The current ST.26 rules impose specific technical requirements on the XML file.
Under 37 CFR § 1.834, an ST.26 sequence listing must be encoded using Unicode UTF-8 and presented in XML format. The file must use the .xml extension and meet the prescribed naming requirements.
The USPTO also requires the XML to be valid according to the ST.26 DTD.
This means a file can look correct when opened in a text editor and still fail compliance if its underlying XML structure or required ST.26 elements are incorrect.
Do You Have to Use WIPO Sequence?
No.
The USPTO does not require applicants to use a particular software program to create the XML. However, the USPTO strongly recommends WIPO Sequence, the free software developed by WIPO with assistance from participating intellectual-property offices, including the USPTO.
WIPO Sequence can help applicants:
- Create ST.26 sequence listings
- Enter sequence data
- Generate the XML
- Validate the sequence listing
- Identify potential compliance problems before filing
This is a significant difference from the old PatentIn workflow. The USPTO expressly states that PatentIn does not create ST.26-compliant XML files.
For current applications, teams should therefore avoid treating an old PatentIn-generated .txt sequence listing as an acceptable substitute for the required ST.26 XML.
What Happens If You Submit the Wrong Format?
Suppose an application filed after the ST.26 implementation date requires a sequence listing, but the applicant accidentally submits an ST.25 ASCII text file.
The USPTO has procedures for this situation.
According to USPTO guidance, the Office may issue a Notification to Comply With Requirements for Patent Applications Containing Nucleotide And/Or Amino Acid Sequence Disclosure. The applicant may then need to submit a compliant ST.26 XML sequence listing.
The USPTO has also recognized that an improperly filed ST.25 listing may provide support for preparing the compliant ST.26 XML in certain circumstances. The precise mechanism depends on the application’s filing and priority circumstances.
This is why practitioners should not assume that an incorrect sequence-listing format is harmless simply because the underlying biological sequences are present.
What About Older Applications and Traditional CRFs?
CRF requirements remain relevant when working with applications governed by the older ST.25 rules or with historical sequence-listing submissions.
For example, USPTO guidance explains that when a sequence listing was supplied as a PDF or on paper under the older framework, a copy in computer-readable form could be required. The USPTO describes that CRF in connection with the requirements of 37 CFR § 1.824.
The practical lesson is that practitioners should first determine which sequence-listing regime applies to the particular application.
Do not begin by asking only, “Do I need a CRF?”
Instead, ask:
- What is the application’s relevant filing date?
- Is it a U.S. direct filing or a PCT national-phase application?
- Does the application disclose sequences covered by the sequence rules?
- Does ST.25 or ST.26 apply?
- What sequence-listing format does that regime require?
Once those questions are answered, the appropriate file format becomes much clearer.
A Practical ST.26 Filing Checklist
Before submitting a current U.S. application containing qualifying sequences, a filing team should verify the following.
Application applicability
- Confirm the relevant filing or international filing date.
- Determine whether the application falls under ST.26.
- Confirm that the disclosed sequences require a sequence listing.
Sequence data
- Confirm that all required sequences have been identified.
- Check sequence numbering and correspondence with the specification.
- Review nucleotide and amino acid sequence data for accuracy.
- Verify relevant feature information and qualifiers.
XML
- Generate the listing in XML format.
- Confirm UTF-8 encoding.
- Confirm that the file uses the .xml extension.
- Validate the XML against the applicable ST.26 DTD.
- Run the file through the available validation tools before filing.
Filing package
- Confirm that the correct sequence-listing file is attached to the USPTO submission.
- Confirm that the application and sequence listing contain consistent bibliographic information.
- Preserve the final filed XML and validation records in the docket.
Common Mistakes to Avoid
Mistake 1: Using ST.25 because the priority application used ST.25
An earlier ST.25 sequence listing does not automatically allow a later application subject to ST.26 to use the old format. The USPTO expressly states that applications subject to the new requirements must use ST.26 XML even when they claim priority to an earlier application containing an ST.25 listing.
Mistake 2: Assuming PatentIn is still the correct tool
PatentIn was associated with the earlier ASCII sequence-listing workflow. It cannot generate an ST.26-compliant XML sequence listing.
Mistake 3: Treating XML as merely a different file extension
Simply converting a .txt file into .xml does not make it ST.26 compliant.
The file must satisfy the required XML structure and ST.26 DTD requirements.
Mistake 4: Failing to validate before filing
A sequence listing can contain correct biological information but still fail technical validation. Automated validation should therefore be part of the pre-filing quality-control process.
Mistake 5: Confusing trademark and patent terminology
Sequence listings are a patent-prosecution requirement, not a trademark filing requirement. The relevant USPTO rules concern patent applications containing qualifying nucleotide or amino acid sequences.
CRF vs. ST.26: The Bottom Line
The term CRF is primarily associated with the USPTO’s older sequence-listing requirements and the ST.25 ASCII format. For applications subject to the post-July 1, 2022 rules, the relevant standard is WIPO ST.26 and the USPTO requires a compliant XML sequence listing.
For patent teams, the safest workflow is therefore:
Determine applicability → identify all qualifying sequences → prepare ST.26 XML → validate the XML → verify application consistency → file the correct sequence listing with the USPTO.
The transition from CRF/ST.25 to ST.26 is more than a change from .txt to .xml. It represents a shift toward structured sequence data, standardized metadata, machine validation and greater interoperability between patent offices.
For complex biotechnology filings, early sequence-listing preparation can also reduce last-minute filing problems. Rather than treating the sequence listing as an administrative attachment prepared immediately before filing, patent teams should build it into the application-development and pre-filing review process.
Note: USPTO sequence-listing requirements are technical patent-prosecution rules and can depend on the application’s filing history and circumstances. The USPTO’s current MPEP, regulations and applicable WIPO ST.26 materials should be consulted for a specific filing.