Sequence Listings Looking Towards the "Big Bang"

The beginning of July sees a shake up in how sequence listings are to be presented in patent applications around the world. After almost 25 years, WIPO has updated its standard from ST.25 to ST.26, and relevant patent applications at the International Bureau and in all WIPO contracting states (including both the EPO and the UK IPO) will need to include sequence listings meeting the new standard. WIPO Sequence software can be used to generate XML files compliant with ST.26.

In the UK and Europe (and in many other countries), patent applications are required to present any DNA, RNA or peptide/protein sequences in a standard format having a prescribed content. This is to facilitate searching of prior art during examination.The current (and soon to be obsolete) standard ST.25 was adopted in 1998, and is a 24 page document.By contrast ST.26 comprises 181 pages, and is far more complex.

ST.26 will be more compatible with formats used in public databases, therefore preventing loss of data when entered into INSDC (International Nucleotide Sequence Database Collaboration) databases. ST.25 was also proving inadequate to cover nucleotide and amino acid sequences that are now commonly found in patent applications.

The so-called "Big Bang" date is 1 July 2022, and the implications of this are discussed below.If you have any applications that may be affected by this change, please ensure we have early instructions so that a properly compliant sequence listing can be prepared.

What has changed?

Major changes include:

• XML format instead of TXT format.
• Amino acids to be represented using the single letter code.
• "Amino acid" will no longer refer only to the standard 20 L-amino acids, but will include the 22 proteinogenic amino acids, D-amino acids and amino acids with modified or synthetic side chains (default interpretation is an unmodified L-amino acid unless otherwise described).
• Sequences of less than four specifically defined amino acids or less than 10 specifically defined nucleotides must not be included.(Residues denoted by "n" or "x" do not count towards the minimum.)
• Modified nucleotide used for any nucleotide that is not dAMP, dGMP, dCMP, dTMP, AMP, GMP, CMP or UMP.
• Sequence listings will need to include unbranched sequences, and also linear regions of branched sequences (as long as they are made up of the minimum at least four amino acids or at least 10 nucleotides).
• "t" will be used to represent uracil in RNA sequences.
• Amino acid sequences use the one letter abbreviation code instead of three letter abbreviations.
• Sequences must have an assigned organism, preferably the full Latin name if known, unless (for a natural sequence) it is "unidentified" (though the term "synthetic construct" is to be used in place of "artificial sequence").
• All sequences are specified as DNA, RNA or amino acid, and then the sub-type of the molecule given (e.g. gDNA, mRNA, tRNA, "other RNA/DNA" (for synthetic construct), "unassigned RNA/DNA" (for a natural but unknown molecule)).
• Only the earliest priority details can be included.
• Only a single ("primary") applicant and inventor can be included.
• Non-Latin characters can be used in applicant/inventor names (but must be accompanied by a transliteration).

Potential Issues

For the UK and Europe, all patent applications with a filing date from 1 July 2022 that include a sequence listing will need to be ST.26 compliant. National/regional phase applications derived from PCT applications having a filing date before 1 July 2022 should continue to include sequence listings in ST.25 format even though national/regional phase entry is effected after 1 July 2022.

In view of the different requirements for ST.25 and ST. 26, an ST.26 compliant sequence listing could include information that would not be included in an ST.25 compliant sequence listing. This could potentially lead to problems relating to added subject matter or loss of priority (particularly in Europe where requirements are strict).

Where a first application has its sequence listing in ST.25 format, but a later application claiming priority to that first application has to comply with ST.26, the safest practice would be to file the ST.26 sequence listing as part of the later application as filed. The worst case scenario would then be a lack of entitlement to priority for any new subject matter, rather than a potentially unresolvable added subject matter issue.

One important issue to be aware of is the differing approach to divisional applications taken by the UK IPO and the EPO. The UK IPO will not require ST.26 format in a divisional application if the parent was filed before 1 July 2022.However, the EPO will require ST.26 compliance. If the additional information required by ST.26 is not present in the parent European application as filed, this will lead to added subject matter issues at the EPO.

How to Prepare an ST.26 Sequence Listing

WIPO has released software called WIPO Sequence. This should be used to produce a sequence listing to maximise the chance of it being properly compliant with ST.26. It can be used in two ways to prepare an ST.26 sequence listing.

1. Import a sequence listing in ST.25 format 
This goes some way to automating the process from an already existing ST.25 sequence listing, though some user input will still be required (for example, indicating the mol_type).A report is created informing the user of all the changes that have been made, or what additional information is required to meet the new format.Annex VII of ST.26 sets out a review that should be undertaken to ensure that all necessary information has been incorporated into the ST.26 sequence listing without adding matter, and to what extent automated conversions of annotations need to be proof-read.Preparing an ST.26 sequence listing by conversion from an ST.25 listing should not be too onerous if there are no more than about 25 sequences to be included.However, before carrying out this conversion, a user should be sure that the sequence listing is properly ST.25 compliant.

2. Manually input data
This involves manually entering all of the relevant application and sequence data.Each sequence can be added separately, either by manual typing/copy-pasting, or by import of a .txt, .xml or .FASTA file.Multiple sequences can be imported simultaneously using .txt format, though a subsequent validation check will reveal that the mol_type field will need to be entered manually.

We have tested the WIPO Sequence software, and are ready to produce ST.26 compliant sequence listings. However, in view of potential complications relating to converting sequence listings from ST.25 to ST.26, or preparing new ST.26 compliant sequence listings, please ensure that all instructions relating to relevant applications are received by us well in advance of the Big Bang date or relevant filing deadline. You may also wish to consider filing priority claiming and divisional applications in advance of 1 July 2022 where possible.

Please contact us if you need further advice.