Global changes to biological sequence listings from 1 July 2022

The big-bang date for implementation of the new WIPO sequence listing standard ST.26 is fast approaching. All new PCT and national/regional applications filed on or after 1 July 2022 will need to be ST.26-compliant. Ahead of the upcoming changes, we summarise the key considerations and things to watch out for.

In the life sciences and biotechnology fields, many patent offices require a formal sequence listing to be filed with any patent application disclosing nucleic acid or amino acid sequences. The sequence listing includes all the disclosed sequences in a standardised electronic format that allows for easier processing and analysis by patent offices around the world.  

The current standard format for these sequence listings – ST.25 – was established by the World Intellectual Property Organization (WIPO) in 1998, but will no longer be accepted for PCT and national/regional applications with a filing date on or after 1 July 2022. From then, all new filings must comply with the new WIPO standard ST.26.

As there will be no transition period, it is important to be aware of the changes from ST.25 to ST.26 well in advance of 1 July 2022.

Summary of changes from ST.25 to ST.26

One of the major changes in ST.26 is that sequence listings must be in electronic XML format, rather than TXT format. The XML format is designed to improve data compatibility with public searchable databases (including NCBI GenBank and EMBL-EBI) and should therefore make analysis of the sequences by patent offices simpler. As a result of this change, many features must be represented differently under ST.26, compared with ST.25, including:

• Amino acids must be represented by their one letter code, instead of their three letter code
• Uracil and thymine must both be represented by ‘t’, instead of ‘u’ for uracil and ‘t’ for thymine
• Any annotated features will require strictly defined locations

To reflect modern developments in biotechnology, it will now be mandatory to include and annotate:

• Nucleotide analogues (e.g. PNA or GNA)
• D-amino acids​
• Linear portions of branched sequences
• The molecule type, which must be further specified beyond DNA/RNA/AA using a defined list (e.g. mRNA, transcribed RNA or viral cRNA)

In addition, sequence listings must no longer include:

• Sequences having fewer than 10 specifically defined nucleotides (i.e. nucleotides other than ‘n’)​
• Sequences having fewer than four specifically defined amino acids (i.e. amino acids other than ‘X’)​

Full details of the ST.26 standard can be found here.

Key considerations for a smooth transition to ST.26

First and foremost, for any upcoming filings expected to contain nucleic acid or amino acid sequences, it is important to be clear on whether the sequence listing will need to comply with the ST.25 or ST.26 standard.

If a PCT application filed before 1 July 2022 enters the EP or GB phase after that date, ST.25 will continue to apply to the EP or GB application. However, other new filings from 1 July 2022 must comply with ST.26, including new applications claiming priority from an application filed before 1 July 2022, and new European divisional applications.

In some cases, it will be necessary to convert an existing ST.25 sequence listing into the new ST.26 format for use in a new application. For example, the EPO has confirmed that for divisional applications filed from 1 July 2022, which derive from a parent application filed before 1 July 2022, conversion of the parent ST.25 sequence listing into an ST.26-compliant listing will be necessary, along with a declaration that the new sequence listing does not add subject matter beyond the parent application. In contrast, the UKIPO requires sequence listings accompanying new GB divisional applications to be supplied in the same format as the parent application.

Applicants should be aware that additional time may be required to prepare ST.26-compliant listings, or to convert an existing ST.25 listing into the ST.26 format, particularly those which contain sequences affected by the changes, such as:

• Sequences containing nucleotide analogues or D-amino acids
• DNA containing uracil or RNA containing thymine
• Branched sequences
• Sequences with other feature annotations

Moreover, great care should be taken to avoid adding or deleting subject matter when transforming ST.25 sequence listings to ST.26-compliant listings for applications claiming an earlier priority date or European divisional applications. This could be a particular issue if the converted ST.26 sequence listing may be filed at the European Patent Office (EPO), in view of the strict approach taken by the EPO on both added subject matter and priority entitlement.

WIPO suggests that the potential impact of ST.25 to ST.26 conversion should be taken into account when drafting an original (ST.25) sequence listing and application. Of course, in most cases where conversion of an ST.25 sequence listing to ST.26 will be needed, it is too late for that because the ST.25 listing has already been filed.  However, if applicants are planning to file a first application before 1 July 2022, they can take steps to avoid future added matter and priority issues in 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, can be included in the application body as a pre-emptive measure.

Finally, if a sequence listing is filed in the incorrect format, the applicant will probably be invited to file a new listing in the correct format. At least at the EPO, such late filing of the correct listing will incur an official fee. Additionally, 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 is subject to the new ST.26 standard may incur significant official fees (due to the considerable length of most sequence listings). It is worth taking the time to ensure that the correct sequence listing format is used when the application is filed.

The above is not intended to provide legal advice: if you have any questions about how these changes may affect your applications, please get in touch.