A new standard for sequence listings from 1 July 2022

Roona Deb, European Patent Attorney at Page White Farrer in London discusses key considerations for the new standard.

 

Background

The majority of patent offices require patent applications which disclose nucleotide or amino acid sequences to be accompanied by an appropriately formatted sequence listing. The sequence listing provides the disclosed sequences in a standardised format that facilitates searching and analysis by patent offices.

 

The current standard for sequence listings that is implemented by patent offices of all World Intellectual Property Organization (WIPO) member states is ST.25. To date, software programs such as PatentIn and BiSSAP (provided by the US Patent and Trademark Office (USPTO) and European Patent Office (EPO), respectively) have been used to generate ST.25-compliant sequence listings. ST.25-compliant sequence listings are provided to patent offices in a TXT format or as a hard paper copy.

 

However, the existing ST.25 standard has some drawbacks. ST.25 does not comply with International Nucleotide Sequence Database Collaboration (INSDC) requirements which can result in data loss from public databases. The ST.25 rules are arguably also unclear, leading to inconsistent interpretation and enforcement across different patent offices. In addition, the ST.25 standard does not account for nucleotide analogues, D-amino acids or branched sequences which are commonly used in the field of Biotechnology today.

 

The new standard ST.26 aims to address these drawbacks.

 

Summary of changes

The key differences between ST.25 and ST.26 are as follows:

1. WIPO standard ST.26 requires sequence listings to be in electronic XML format rather than the existing TXT format. The XML format enables a closer alignment with sequence formats used in public databases, thereby facilitating data exchange and searching. The XML format also permits indication of nucleotide analogues, D-amino acids and branched sequences that are not currently supported by WIPO standard ST.25.
2. WIPO standard ST.26 requires a mandatory annotation of D-amino acids, linear portions of branched sequences and nucleotide analogues in sequence listings which are not required for ST.25. The new standard also enables incorporation of selenocysteine and pyrrolysine as two additional proteinogenic amino acids.
3. Sequences comprising less than ten specifically defined nucleotides or less than four specifically defined amino acids are not permitted under WIPO standard ST.26. Under ST.26, an undefined nucleotide residue ‘n’ or an undefined amino acid residue “X” does not count to the towards the minimum length requirements. Linear regions of branched sequences meeting the above length criteria will need to be included under a separate SEQ ID.
4. WIPO standard ST.26 provides further options for the annotation of sequences. For example, insertions and substitutions may be included as feature annotations of a sequence, provided that they are independent of each other. If they are not independent of each other, separate sequences are required. If any insertion or substitution sequences themselves meet the minimum sequence length criteria, they should additionally be listed as separate sequences with their own sequence ID.
5. Under WIPO standard ST.26, each sequence must have a “moltype” indication (DNA, RNA, AA). The new standard does not allow ‘mixed mode’ sequences with both nucleotide and accompanying protein sequence. It is still possible to include a translation as a feature of a nucleotide sequence but the protein sequence must be listed separately under a new SEQ ID.
6. Sequence identifiers are more precisely defined in ST.26 (for example, “genomic DNA”, “genomic RNA”, “mRNA”, “tRNA”, “rRNA”, “other RNA”, “other DNA”, “transcribed RNA”, “viral cRNA”, “unassigned DNA”, and “unassigned RNA”). Non-naturally occurring sequences (synthetic constructs) must be indicated as other RNA or other DNA. Naturally occurring (in vivo) sequences of unknown subtype should be indicated as unassigned RNA or unassigned DNA.
7. Minor changes include the use of “T” instead of “U” to represent Uracil in RNA sequences, and the use of the one-letter, as opposed to the three-letter, amino acid code.

 

Full details of the ST.26 standard can be found at WIPO Standard ST.26.

 

Implementation of WIPO standard ST.26

The implementation date of WIPO ST.26 is currently 1 July 2022. 

 

The patent application filing date (and not the priority date) will be the reference date that determines if an application falls under ST.25 or ST.26 sequence rules. 

 

Accordingly, ST.25 will remain effective for patent applications with a filing date prior to 1 July 2022. However, if a patent application has a filing date after 1 July 2022, whilst claiming priority from an application with an ST.25 sequence listing, it will be necessary to convert that sequence listing from ST.25 to ST.26.

 

With specific regard to PCT applications, the relevant date is the international filing date. Accordingly, if a PCT application filed before 1 July 2022 enters, for example, the EP regional or GB national phase after that date, ST.25 will continue to apply to the EP or GB application.

 

The European Patent Office has confirmed that for divisional applications filed from 1 July 2022 which originate from a parent application filed before 1 July 2022, conversion of the parent ST.25 sequence listing into an ST.26 listing will be required. It will also be necessary to file a declaration that the new sequence listing does not add new subject-matter beyond the content of the parent application. In contrast, the UK Intellectual Property Office will permit sequence listings accompanying new GB divisional applications to be supplied in the same format as the parent application.

 

When converting ST.25 sequence listings to ST.26 listings for applications claiming an earlier priority date or for European divisional applications, care will be needed to avoid deleting or adding subject-matter, particularly, in view of the strict stance taken by the EPO on added subject-matter and entitlement to priority. If applicants are intending to file a first (priority-forming) application before 1 July 2022, precautionary measures may be taken to avoid future added-matter and priority entitlement  issues arising when converting that sequence listing to ST.26. For example, features that will become mandatory under ST.26, but which are not covered by ST.25, may be included in the application body.

 

A sequence listing is not required at the EPO for the accordance of a filing date. However, with reference to a decision of the EPO President dated 9 Dec 2021 on the filing of sequence listings, when an applicant does not file a ST.26- compliant sequence listing on the date of filing of a European Patent Application, the EPO will invite the applicant to file a ST.26-compliant sequence listing within a two-month term, and require payment of a late furnishing fee.

 

Similar provisions exist for PCT applications where the EPO acts as the International Searching Authority, Supplementary International Searching Authority or International Preliminary Examination Authority. In these instances, the applicant will be invited to furnish the listing and pay the late furnishing fee within a period of one month from the invitation. A sequence listing filed after the filing date must be accompanied by a statement that it does not include matter which goes beyond the content of the application as filed.

 

It is also worth noting that only sequence listings filed in the correct format are exempt from official page fees at the EPO. Therefore, an ST.25 sequence listing which is filed as part of an application which falls under the new ST.26 standard may incur significant official fees if it is of considerable length.

 

With regard to GB applications, non-compliant sequence listings will be a formalities issue raised in the preliminary examination report. Failure to comply with the correct standard will not delay the search but will prevent publication, and will eventually result in an application being refused.

 

How do you prepare a sequence listing under WIPO standard ST.26?

It is understood that there are currently no plans to update either PatentIn or BiSSAP which are commonly used to generate ST.25 sequence listings.

 

Instead, WIPO has developed and released new software for the generation and validation of ST.26 sequence listings – WIPO Sequence Suite. The software includes an instruction manual, test data set and a sequence validator.

 

The new software may also be used to convert old ST.25 TXT sequence listings into the new ST.26 XML format. The need to convert ST.25 sequences will be particularly relevant for divisional applications filed on or after 1 July 2022, given that ST.26 will apply to these cases at least for the USPTO and EPO (see comments above for the requirements at the UKIPO). The WIPO software may also be used to check for errors in an ST.26 sequence, and to view ST.26 XML files in a human-readable format within a browser.

 

Our attorneys will be happy to provide further assistance with sequence listings or any other aspects of patent practice. Contact us via our online enquiry form, or email webenquiry@pagewhite.com.

 

This briefing is for general information purposes only and should not be used as a substitute for legal advice relating to your particular circumstances. We can discuss specific issues and facts on an individual basis. Please note that the law may have changed since the day this was first published in May 2022.