Suzannah K. Sundby Canady + Lortz LLP

Sequence Listings Webinar January 9, 2018 – Updated Version

Carl Oppedahl Oppedahl Patent Law Firm LLC DISCLAIMER  These materials and views expressed today reflect only the personal views of the author and do not necessarily represent the views of other members and clients of the author’s organizations.  These materials are public information and have been prepared solely for educational purposes to contribute to the understanding of U.S. intellectual property law. While every attempt was made to ensure that these materials are accurate, errors or omissions may be contained therein, for which any liability is disclaimed. These materials and views are not a source of legal advice and do not establish any form of attorney-client relationship with the authors and their law firms. Why are some sequence errors not identified by Checker? Is “SEQ ID NO” required before sequences in Specifications? Do you recommend using the PatentIn Software? How do you correct sequence listing errors in PCTs? What about the new WIPO ST.26 Standard? Is Checker worthwhile? How can I easily edit sequence listings generated by others? Can I use other software to generate sequence listings? How do I file sequence listings using EFS-Web and ePCT? How long does it take the USPTO to review and approve? Any risk TYFNIL of using certain sequence descriptors? Help! IT locked down my computer… what do I do? Any sequence listing tips? Why Practitioners Should Know and Do  Usually lack of time to send to outside vendors  Last minute changes to applications (apps) containing sequences (seqs)  Particularly, changes to claims  Not hostage to staff/vendors, overtime, etc.  Ultimate responsibility/review  More time efficient and less expensive to clients  Will need to understand minimum requirements, and differences when new ST.26 and how such is automatically converted (what is, what isn’t)  Avoid looking really stupid and incompetent  (SL as text file and CRF) = ASCII format  ASCII  ANSI = Plain Text (*.txt)

4 Agenda  Sequence Listing (SL) Rules and Requirements  Generating a SL using PatentIn  Checking with Checker  Modifying an existing SL  Using a PatentIn Project File  Downloading from WIPO and modifying the text file  Submitting a SL  EFS-Web, ePCT, and digital media  Responding to Notices  Tips and Tricks

5 Sequence Listing Rules 37 CFR 1.821-1.825

US Applications – Utility and 371s PCT Applications 37 CFR 1.821  1.821(b) – Apps that have seqs as defined in (a) must conform with 1.821-1.825

 1.821(a) (MPEP 2421.02)  Unbranched amino acid (aa) seqs of ≥4 aa  Unbranched nucleotide (nt) seqs of ≥10 nt  Excluded sequences = branched seqs and seqs <4 specifically defined aa or <10 specifically defined nt  "Specifically defined" means aa other than "Xaa" and nt bases other than "n" as defined in the WIPO Standard ST.25, including Tables 1-6 in Appendix 2 (MPEP 2422)

7 37 CFR 1.821(a)  Nucleotides = those that can be represented using the symbols set forth in Table 1  Modified nts may be described as set forth Table 2, but not explicitly shown in the seq itself  Amino acids = L-amino acids listed in Table 3  D-amino acids are not intended to be embraced by the aa defn  Seqs containing post-translationally modified aa’s may be described as the aa seq that is initially translated using symbols of Table 3 with the modified positions described (see Table 4)  Any peptide or protein (p/p) that can be expressed as a seq using the symbols in Table 3 + description in the Feature section for, e.g., modified linkages, cross links and end caps, non-peptidyl bonds, etc.

8 D-Amino Acids

PPT by Bob Wax entitled “Sequence Compliance Soup to Nuts” states:  Not according to USPTO’s current “Amino acid sequences unwritten policy containing even one D- amino acid are excluded  Save your breath and time from the sequence rules (37  Include seqs containing D-amino acids CFR 1.821(a)(2))”. See Slide 17. in SLs with Feature Data/Name “MISC_FEATURE” indicating the D- amino acid residues

9 37 CFR 1.821(c)  Such apps must contain, as a separate part of the disclosure, a paper copy or CD copy (aka SL*) in accordance with 1.822-1.823  * Some parts of MPEP are confusing due to the EFS-Web Legal Framework, so careful of term usage in MPEP and elsewhere. See, e.g., MPEP 2421.01.  MPEP 2422.03(a) states that the text file submitted via EFS-Web may serve as both the “paper copy” and the “CRF”  For the purposes of this webinar:  Sequence Listing (SL)  The “Official” SL, i.e., legally recognized SL, whether a text copy or a paper copy  Assume SL is text copy, unless indicated otherwise  Paper copy = Actual paper or PDF file of SL  CRF = Computer Readable Form of the paper copy as the SL  Text copy = SL as ASCII text filed via EFS-Web  CD copy = SL submitted on physical media, e.g., CDRom.  This is NOT a “text copy”.  Difference from “text copy” must submit 3 physical carriers labeled “Copy 1”, “Copy 2”, and “CRF”

10 37 CFR 1.821(d)  Where spec, claims, or drawings discuss a seq provided in an SL, “reference must be made to the sequence by use of the sequence identifier, preceded by "SEQ ID NO:" in the text of the description or claims, even if the sequence is also embedded in the text of the description or claims of the patent application”  Sequence identifier = sequence number  “preceded by” refers to placing “SEQ ID NO:” before the seq #, e.g., SEQ ID NO: 2.  Important to use “NO” instead of “No” and a colon instead of a period, i.e., use “NO:” not “No:”, “No.”, or “NO.”  If seq is in a figure, can provide SEQ ID in description of the drawings or the figure itself (MPEP 2422.02)  I put SEQ IDs in parentheticals after the given seq when embedded in the spec and in the description of the drawings when in the figures

11 37 CFR 1.821(e)  If the SL is a paper copy or a CD copy, then a CRF in accordance with 1.824 must be submitted  Again, note difference between “CD copy” and “text copy”  The CRF will not form a legally recognized part of the patent application itself

 If the CRF is to be identical to a prior CRF of another app of the applicant on file in the USPTO, one can submit a Transfer Request (more later)  Recall, if a CRF, then the SL is a paper copy (or CD copy); if SL is a paper copy (or CD copy), then must submit a CRF

12 37 CFR 1.821(f)  When submitting a CRF, must submit a Sequence Listing Statement that "the sequence listing information recorded in computer readable form is identical to the written (paper copy or CD copy) sequence listing“  I’ve always said:  In accordance with 37 C.F.R. 1.821, the undersigned hereby states that the content of the paper copy of the Sequence Listing and the Computer Readable Form submitted herewith are the same.  But don’t use anymore because I submit “text copy” SLs via EFS-Web  See 1.824 for form and format of submitting CRFs and SLs as text files on physical data carriers rather than via EFS-Web 13 If 1.821(b)-(f) not satisfied at app filing…  1.821(g) – Provides time to comply upon receipt of a Notice for US utility apps and US 371 national phase entries  1.821(h) – For PCT apps, where US is the ISA or IPEA, provides time to provide CRF for search purposes  Usually receive a Notice  If CRF is not provided timely, then search/exam will proceed without to the possible

 Note: New Fee for Late Furnishing Fee under PCT Rule 13ter ($300)

14 37 CFR 1.822 – Symbols and Format  1.822(a) – Must use symbols and format set forth in ¶¶ (b)-(e)  1.822(b)  For nt and aa, must use codes according to Tables 1 and 3  Can show modified nt and aa in seqs of SL if provided in Tables 2 and 4  Otherwise, must use “n” or “Xaa” with a description in the Feature section  Preferably using feature keys listed in Tables 5 or 6  1.822(e)  Seqs w gaps must be provided as separate seqs  A seq comprising noncontiguous segments of a larger seq or segments from different seqs shall be presented as a separate seq

15 37 CFR 1.822(c) - Nucleotides  Lower case letters  One letter code (Table 1)  Bases of a seq (including introns) provided in groups of 10 except designated coding regions, which are then provided as groups of 3 (i.e., codons)  AAs encoded by codons are provided immediately below  Max of 16 codons or 60 bases per line, with a space provided between each codon or group of 10 bases  Presented, only by a single strand, in the 5’ to 3’ direction, from left to right  Except for circular seqs, nts are enumerated beginning with the first base of the seq as number 1  If circular seq, first nt is applicant’s option

16 37 CFR 1.822(d) – Amino Acids  Three letter abbreviations, with first letter capitalized  Max of 16 aa per line, with a space provided between each aa  N-terminal to C-terminal direction, from left to right, without providing the amino and carboxy groups  Enumeration may start at the first aa of the first mature protein, with the number 1  If pre-, pro-, prepro-, or signal seq, provided before the mature protein, then enumerate w negative numbers, counting backwards starting with the aa next to number 1  Otherwise, enumerate w first aa as number 1 and marking below the seq every 5 aa  If circular seq, first aa is applicant’s option  If internal terminator symbols, e.g., “Ter”, “*”, or “.”, must provide as separate seqs

17 37 CFR 1.823 – Paper Copy as SL  Must start on a new page and be titled "Sequence Listing"  Pages are numbered independently of the other parts of the app  No more than 66 lines per page  No more than 72 characters per line  May not include other material that is not part of SL  Should use a fixed-width font, e.g., Courier New, not Times New Roman, etc., as spacing and numbering will not align  aatgcctcgt  aatgcctcgt  Must submit CFR and identity statement

18 37 CFR 1.823 – CD Copy  If CD Copy submitted on compact disc (CD), must comply with 1.52(e)  If utility app, CD can also include table info (not accepted for PCT apps)  The MPEP is confusing, so to be on the safe side always submit Copy 1, Copy 2, and a CRF  Must submit identity statement  See rest of 1.52(e) for more requirements  1.823(b) indicates mandatory and optional info  Recommend providing only mandatory info

19 37 CFR 1.823 – Text Copy  As effectively modified by the EFS-Web Legal Framework  If SL is submitted via EFS-Web, then the text file serves as both the paper/CD copy and the CRF (i.e., “text copy”) – Thus, need only upload one text file  If the too large to submit via EFS-Web, then can submit on physical data carrier on the same day the app is filed under the assigned app number  Recommend 2 copies in case of damage, i.e., Copy 1 & Copy 2  You MUST submit a third carrier labeled “CRF”  Note: New fees for large (300-800 MB) and mega (>800 MB) SLs  $1k & $10k, respectively  Specification must include a “sequence listing paragraph”, i.e., an incorporation-by-reference of the text copy (see Sequence Listing Statements below)  Do not submit a PDF or a paper printout of the SL

20 37 CFR 1.824 and 1.825  1.824 (and 1.52(e))  Form and format of submitting text files (CRFs & text copies) on storage media (and via EFS-Web)  Best practice is to submit CRFs and SL text copies via EFS-Web (see EFS-Web Legal Framework)  1.825  Amendt to paper copy must be by substitute sheets, no new matter statement, CRF of SL as modified, and identity statement  If amendment to CD copy, must also submit replacement CDs (2 copies)  i.e., Copy 1 Replacement, Copy 2 Replacement, CRF replacement, no new matter statement (including an indication of support in the original application), and identity statement  Also applies when reissue or certificate of correction  If CRF is damaged or unreadable, must provide, within the time set in a Notice, a substitute copy CRF and identity statement  If substitute SL is a text copy filed via EFS-Web, include amend SL paragraph is spec and statement of no new matter

21 Sequence Listing Requirements PCT Rules 5 and 13ter

PCT Applications PCT Rules 5 and 13ter  Rule 5.2 – Nucleotide and/or Amino Acid Sequence Disclosure  (a) If IA contains sequences (4/10 Rule), must contain SL complying with the Standard  (b) If SL contains any free text, then that free text must be in the main part of the specification  Rule 13ter – Late furnishing of SL before the ISA

23 MPEP 1823.02 & 2422  MPEP 1823.02  CRF of SL not mandatory by ISA/US or US as IPEA  “However, if an electronic form (text) of a sequence listing is not provided, a search or examination will be performed only to the extent possible in the absence of the electronic form (text).”  “[F]ull compliance with the requirements of the U.S. rules will generally ensure compliance with the applicable PCT requirements”  MPEP 2422  The requirements of 1.821-1.825 substantially correspond to (but are less stringent) those required for PCTs  PatentIn 3.5.1 generates SLs that meet all of the requirements of WIPO Standard ST.25  Thus, use PatentIn 3.5.1, and  File via EFS-Web (if US/RO and US/ISA)

24 MPEP 2422  (A) The data in <221> must use Feature Keys from Tables 5 and 6 of WIPO Standard ST.25  (B) Where the sequence listing forming part of the IA contains free text, e.g., text in <223>, such free text shall be repeated in the main part of the specification  Recommended to be put in a specific section of the description called "Sequence Listing Free Text”  (C) SL filed after the IA filing date is generally not considered to be part of the disclosure and usually will not be published as part of the IA publication  (D) Paragraphs 4(v) and 4bis(iv) WIPO Standard ST.25 requires the specific wording "the information recorded in electronic form furnished under PCT Rule 13ter is identical to the sequence listing“ – but not if SL text file forms part of the PCT  (E) WIPO Standard ST.25 requires a blank line between numeric identifiers in the SL when the digit in the first or second position of the numeric identifier changes

 There are some other differences, for example:  Where a PCT is filed in paper, the SL part of the app must also be provided in paper, although the CRF must be filed in electronic form, e.g. on a CD or, in the RO/US, as an ASCII text file via EFS-Web – but not if PCT filed using EFS-Web (PCT can be filed as PDF and SL as text file)  Any tables filed in a PCT must be an integral part of the app, i.e., cannot be submitted as a separate file in text format 25 Using PatentIn PatentIn 3.5.1  Download  https://www.uspto.gov/sites/default/files/patents/resources/to ols/software/PatentIn35.exe  PatentIn User Manual  https://www.uspto.gov/patents-getting-started/patent- basics/types-patent-applications/utility-patent/patentin- version-351

the Manual and walk through step-by-step as you generate your first few SLs using PatentIn

27 PatentIn Main “Sequence” Screen

28 Save Project

29 Enter Project Data

30 Title, App No., Filing Date, and Ref. No.

31 Enter Prior Application Information

32 Enter Prior Application Information

33 Applicant Data – If entity, Organization

34 Enter Organization Name

35 Click “Add”, then enter name, e.g., 1 Then select sequence type

36 Copy & Paste or Type sequence in box

37 Copy & Paste or Type sequence in box

38 Alternatively “Import” seqs from text files

39 Be careful when importing sequences

 The “Help” button is very helpful 40 Click “Standard” and Select Organism

41 Enter Artificial Sequence Comment

42 <213>  OH NO! Artificial Sequences  Instead: Bob Wax’s PPT states that  “Based on” Homo sapiens sequence at <223> “Explain why you consider the sequence  Forward or Reverse “Primer for [X] artificial -Sequence per se is sequence” derived from human  “Synthetic construct” thought”  Always include “Sequence” after “Artificial”  “Artificial Sequence” not “Artificial”

 Keep in mind proposed ST.26 (to be discussed later) and the possibility of inadvertent adverse admissions

43 Enter Artificial Sequence Comment

44 “Xaa” and “n” Defaults  <223> Xaa can be any naturally occurring amino acid  <223> n is a, c, g, or t

 If default is not to be used, then must change by entering the “feature data”

45 Enter Feature Data

46 Click “Names”, Select “misc_feature”

47 Enter residue #’s, then “Xaa” or “n” info

48 Optional Coding Region Designation  Not necessary (MPEP 2423.02)  But if using PatentIn, convenient because the encoded p/p seq is automatically generated

 Tip – When entering the nt seq into PatentIn, include the p/p seq name, i.e., if the nt seq is “16”, name it “1617” and the seq after the nt and p/p sequences as “18”

49 Designate Coding Regions

50 Designate Coding Regions  The nt seq will be shown with the codons and the aa residues corresponding to each codon on the line below

 After the nt seq, PatentIn will automatically insert the p/p seq as the next seq after the nt seq

51 Generate Sequence Listing

52 Some info and errors, if any, are shown

53 View/Print Sequence Listing

54 And Ta Da! (Remember to save)

55 Checking with Checker Checker 4.4.6  Download  https://www.uspto.gov/sites/default/files/patents/resources/to ols/software/Checker.MSI  Checker User Manual  https://www.uspto.gov/sites/default/files/patents/resources/to ols/checker/checker446UM_20110214.doc

 Read the Manual and walk through step-by-step as you use Checker the first time

57 Checker has some value  Click “Process File”  Find and select the text file to check

58 Checker has some value  Will catch some things like “placeholders”  Will remind you to check “n” and “Xaa”  Will catch alpha numerical issues, i.e., symbols and foreign fonts

59 Checker has some value  Will catch invalid aa and nt designators

 Will catch inconsistent seq lengths

60 Modifying Sequence Listings PatentIn Project Files – “”  In PatentIn, use “Open” function to open a *.prj file

 Careful – “Open” function will over- the original file unless “save as” with a new name 62 PatentIn Project Files – “Import”  In PatentIn, use “Import” function to import a *.prj file

 “Import” function will automatically create a new *.prj file that must be saved 63 Editing Text Files  Import ST.25 file into PatentIn  Checker “Edit File” function, but you have to “Process” the file first  MS Notepad/Wordpad  MS Word

 Always save as a new file before any edits (so the original remains unchanged – you may need it later)  Then regularly save as you edit the file

64 Text Files from WIPO  From WIPO, go to “Documents” tab and click “ZIP”

 Save Zip file to computer  The text file in the Zip may have  *.txt file extension  *.app file extension  Drag and drop the file outside of the Zip file  Change the “.app” extension to “.txt”

65 Text Files from USPTO  Go to PAIR, select “Supplemental Content” tab

 Select version to download, then click “Download” button  Sub-Version “0” is original submission without changes by USPTO  The downloaded file will have a *.raw file extension  Change the “.raw” extension to “.txt”

66 Import ST.25 file into PatentIn

67 Import ST.25 file into PatentIn

68 Import ST.25 file into PatentIn  PatentIn will automatically indicate some errors upon import

 And will automatically fix some errors

 Remember to save the PatentIn project 69 Word – Open SL text file as Word Doc

70 Word – Save as “Plain Text”  Be careful of formatting requirements  Save as “Plain Text”

 Same applies for editing using Wordpad 71 Notepad  Copy *.txt file and paste, then change  Or “open with” Notepad, then “save as”

 Ensure “*.txt” file extension with “ANSI” encoding

72 After editing a text file, use Checker  If saved in encoding formats other than ANSI (or ASCII), e.g., Unicode, Checker will give an alpha numeric error

 Usually, opening the non-ANSI file, and saving as “Plain Text” (WordPad) or “*.txt” file with ANSI encoding (Notepad) will fix alpha numeric errors

73 Sometimes…  When I need to add just a few seqs  Use PatentIn to generate text file of the seqs to be added or modified  Renumber the seq numbers, i.e., <210> and <400>, in the SL text file  Copy the portion of the SL text file having the seq parts, i.e., <210> to <400>  Paste the portion (<210> to <400>) in the original SL (either using Word or Notepad/Wordpad)  Then change the number of seqs at <160> if seqs are added

 Do with caution! Not recommended for beginners

74 Submitting Sequence Listings

US Utility and PCT applications EFS-Web and PCTEasy USPTO and US/RO EFS-Web and SL Submissions  When AIPLA Biotech Committee Chair, I incorrectly filed “text copy” SLs  Sue Wolski was kind enough to call to “educate” me  I volunteered her to present at the April 2015 BCP Meeting (her PPT is a must read)  I learned of the April 2011 Legal Framework for EFS-Web mods to SL submissions  I talked with Drew Hirschfeld, who ensured the Legal Framework was incorporated into MPEP sections concerning biological sequences  MPEP 2422.03(a) – Sequence Listings Submitted as ASCII Text Files via EFS-Web [R-07.2015]  Sue’s most recent version of SL in Int’l and US 371 apps (December 2017) can be obtained here *** Special thanks to Sue and Drew ***

76 EFS-Web and SL Submissions  ASCII text file serves as “text copy”, i.e., both paper copy (or CD copy) and CRF  If a printout (PDF or paper) of the SL is not also submitted  Thus, do not submit  PDF file or printed copy the SL,  Identity statement (between paper copy and CRF), and/or  Transfer Request  PDF file of SL submitted with app papers is considered a paper copy and a CRF and identity statement are required  Even if a text file of the SL is also filed (as the text file is considered to be the CRF)  If a text copy is filed the same day as the app papers, it forms a part of the app and does not count towards extra page fees 77 EFS-Web Upload  There are 2 “Document Descriptions”  Sequence Listing  Use only for SLs as PDFs, i.e., paper copy SLs  Sequence Listing (Text File)  Obviously use when submitting a *.txt file, i.e., CRFs and text copies

 Must separately upload *.txt files from other docs, e.g., PDF files  After uploading and validating other docs being submitted, go back to “Attach Documents” tab and “Upload & Validate” your *.txt file

78 PCTEasy (then EFS-Web upload)  Click “Biology”, then check “sequence” box

79 PCTEasy (then EFS-Web upload)  Click “Contents”  Double click “Sequence listing part of description”

80 PCTEasy (SL text copy via EFS-Web)  Do not check the box, if filing SL text copy via EFS-Web  Do not select pdf format

81 PCTEasy (SL text copy on physical carrier)  Check the box, if filing SL text copy on physical data carrier the same day as filing the app via EFS-Web  2 copies, “Copy 1” and “Copy 2” and other labeling (1.52(e))

 Do not select pdf

82 PCTEasy (SL as PDF “paper copy” via EFS-Web)  Recall, a SL as a PDF file is a “paper copy”  Advise against submitting “paper copy” as it counts towards extra page fees

83 FATALLY DEFECTIVE!!!  101 PCT Request must indicate that the “text copy” forms part of the International Application (IA)  May result in a FATALLY DEFECTIVE 371 app, even if the text file was submitted at the same time as the Request  When seqs are not sufficiently disclosed, i.e., enumerated (embedded) in spec or figs

 The Sequence Listing paragraph (i.e., incorp by ref of the SL as a text file or CD copy) is not sufficient  Some countries do not recognize  In fact, some countries require incorp by refs to be removed

84 SL (Paper Copy) forming part of the IA

 Graphic from Sue Wolski’s December 2017 PPT 85 SL (Text Copy) forming part of the IA

 Graphic from Sue Wolski’s December 2017 PPT 86 PCTEasy (SL as PDF as “paper copy” via EFS-Web)  CRF is required at time of filing or after (with a fee)

 Sequence Listing Statement of identity between paper copy and CRF is required

87 Transfer Requests – Only if you must  MPEP 2422.05  Use Form SB/93  Only acceptable when  CRF is from an app on file in the USPTO  i.e., prior app and CRF was filed in the USPTO  CRF is to be identical  New app must also contain a SL that forms a part of the app (paper or CD copy)  i.e., transferred CRF only serves as a CRF in new app  CRF being transferred cannot be the SL as a text file

88 Submitting Sequence Listings

US 371 Applications Text Copy or CRF?  When filing a US 371 application, it is important to know whether the text file of the SL in the PCT is a “CRF” or a “text copy”  That is, does the text file form a part of the PCT app or is it merely a “CRF”?  Why important?  Extra page fees  Whether a paper copy (and a CRF) must be filed  Whether a prelim amendt is recommended  PTA reduced if seq issues as not in a condition for exam within 8 mos commencement date (also applies to 111(a) filing date)

90 WIPO Patent Scope “Documents” Tab  Text file of SL forms part of the IA (i.e., is a text copy)

 Paper copy forms part of the IA

 Graphics from Sue Wolski’s December 2017 PPT 91 Filing US 371 apps with SLs  If SL in the PCT is a paper copy that forms a part of the IA, must submit CRF, and identity statement (to paper copy)  USPTO will retrieve paper copy if published as part of the IA  If SL in the PCT is a text copy, i.e., forms a part of the IA, the text copy should be communicated to or obtained by the USPTO  No need to file text copy with 371 app papers unless the SL retrieved by the IB was noncompliant  If file text copy with 371 app papers, must include identity statement (to text copy of PCT)  If text file of SL is not a part of the IA, must submit text copy, prelim amendt (SL paragraph in specification), and no new matter statement (including an indication of support in the original application)  Also identity statement (to CRF if filed in PCT)

92 How I file US 371 apps with SLs  If SL in the PCT is a text copy, i.e., forms a part of the IA, file:  The “text copy””,  Prelim amendt to provide SL paragraph, and  Identity statement (to the text copy of PCT)  Why? Reduces hassles, SL paragraph will be required anyway  If PCT does not have an SL text file forming part of the IA, file:  A text copy,  Prelim amendt to provide SL paragraph,  And to replace the paper copy of the PCT (if paper copy filed in PCT) with the text copy being submitted,  No new matter statement, and  If a CRF was filed in the PCT, an identity statement (to the CRF)  Why? Reduces hassles and any extra page fees 93 SL Paragraph in Specification  Text copy

 I have not had any issue putting before the Government Support paragraph

 Text copy for US 371 apps

94 SL Paragraph in Specification  CD copy  MPEP  Specification must contain an incorporation-by-reference of the material on the compact disc in a separate paragraph (1.77(b)(5)), identifying each compact disc by the names of the files contained on each of the compact discs, their date of creation, and their sizes in bytes  The total number of compact discs including duplicates and the files on each compact disc shall be specified  And, when I suspect a SL Notice will be sent when I am absolutely 100% positive the app has no seqs requiring an SL, I sometimes provide:

95 Sample Sequence Listing Statements  Identity Statements  37 CFR 1.821(f) - I hereby state that the information recorded in computer readable form is identical to the written (on paper or compact disc) sequence listing.  37 CFR 1.52(e)(4) - I hereby state that the two compact discs are identical.  37 CFR 1.825(b) - I hereby state that the substitute copy of the computer readable form, submitted in accordance with 37 CFR 1.825(b), is the same as the amended Sequence Listing.  37 CFR 1.825(d) - I hereby state that the substitute copy of the computer readable form, submitted in accordance with 37 CFR 1.825(d), is identical to that originally filed. From MPEP 2428 96 Sample Sequence Listing Statements  No New Matter Statements  37 CFR 1.821(g) - I hereby state that the submission, filed in accordance with 37 CFR 1.821(g), herein does not include new matter.  37 CFR 1.821(h) - I hereby state that the submission, filed in accordance with 37 CFR 1.821(h), herein does not include matter which goes beyond the disclosure in the international application.  37 CFR 1.825(a) - I hereby state that the amendments, made in accordance with 37 CFR 1.825(a), included in the substitute sheet(s) or compact disc(s) of the Sequence Listing are supported in the application, as filed, at ______. I hereby state that the substitute sheet(s) of the Sequence Listing does (do) not include new matter. From MPEP 2428 97 Submitting Sequence Listings

PCT applications ePCT Reasons for a sequence listing filer to learn to use ePCT  Filers who file in RO/US are accustomed to using PCT- SAFE to generate the ZIP file  PCT-SAFE will eventually be retired  Eventually there will be little choice but to use ePCT to generate the ZIP file for RO/US  Sometimes you will need to file in RO/IB  If you are going to file in RO/IB it is a Best Practice to use ePCT

 Today's discussion of ePCT and sequence listings assumes that you already know how to use ePCT generally

99 Filing in RO/IB  You launch ePCT, select RO/IB  Go to “names” section, click “add applicant”  Add your applicant or applicants  Only now is ePCT able to figure out which ISAs are available to you  Go to “international search” section, click “add”  We will use the example of ISA/EP

100  Check the “sequence listing” box  Part of the application?  Click “add”

101 txt or app or zip?  ePCT will accept four kinds of files:  *.txt file  *.app file  ZIP file that contains *.txt file  ZIP file that contains *.app file

102 Why a ZIP file?  ePCT will puke if you try to upload any file that is bigger than 20MB  Maybe your txt or app file is in the range of about 20MB to 60MB in size

 If so, then you can ZIP it to bring the file size below 20MB  Then you can upload it

103 ePCT validates the SL/CRF  ePCT checks these fields:  <110> applicant name  <120> title of invention  <130> file reference  <170> software  <400> sequence

 In future versions, ePCT will validate more fields

104 Who checks for SL/CRF being in proper format?  Not the RO  The first Office to check this is the ISA

105 Who checks to see if applicant provided an SL as required?  Not the RO  The ISA might not complain that a CRF was failed to be provided even if there is a SL in the body of the application  The DO/EO might be the first to complain about lack of a computer-readable sequence listing

106 Sequence listing part of the description

This filer avoided malpractice☺

107 Receipt of Electronic Submission

108 Front page preview (expand “international publication”)

109 Front page preview

110 Frequently made mistakes  Applicant failed to say the SL was “part of the application”  Applicant provided SL as PDF instead of or in addition to TXT/APP file, thus incurring extra-page fees  Applicant responded to Form ISA/225 (Invitation to Furnish Nucleotide and/or Amino Acid Sequence Listing) to the IB instead of to the ISA  Applicant that picked an ISA other than ISA/US responded to Form ISA/225 (Invitation to Furnish Nucleotide and/or Amino Acid Sequence Listing) via EFS- Web

111 Responding to Notices

Initial and Substitute SLs US Utility and US 371 Notices  If text copy or CRF is defective  In Private PAIR, if eOAs elected, will usually see the “Error Report” before the actual Notice  Recommend waiting to submit a substitute SL until after the Notice or else likely docketing and USPTO processing issues  If a Notice is received without the Error Report, can obtain in PAIR  Error Report is similar to that produced by Checker  Create Substitute SL (by modifying prior SL) that addresses each issue noted  Call USPTO if any questions

113 US Utility and US 371 Notices  Prepare Response – just like any other amendt

 Replace the prior SL (skip if initial SL)

114 US Utility and US 371 Notices  Amend (or add) the SL paragraph

 Provide requisite Sequence Listing Statements in Remarks

115 US Utility and US 371 Notices  Example of Substitute SL Statements

 Check PAIR for entry  If entered, accepted 116 PCTs and the International Phase  Our goal of course is to try to file a PCT application so as to avoid receiving such an Invitation  This means we figure out which applications require a SL (four and ten rule) and in such applications we try to avoid failing to hand in a SL/CRF on filing day  This means that we try to avoid handing in a SL/CRF that is defective  This means we avoid merely handing in a PDF SL (paper SL) while failing to hand in a CRF  We also try to avoid failing to say that the SL is “part of” the application  We also try to avoid unnecessarily incurring extra-page fees with unnecessary PDFs of SLs

117 Invitation to furnish nucleotide and/or amino acid sequence listing  Despite all of this, we might receive such an invitation

 Form PCT/ISA/225  INVITATION TO FURNISH NUCLEOTIDE AND/OR AMINO ACID SEQUENCE LISTING AND TO PAY, WHERE APPLICABLE, LATE FURNISHING FEE

118 Invitation to furnish nucleotide and/or amino acid sequence listing  Who sends this Invitation?  The Receiving Office? No  The ISA!

 The RO personnel are not technically trained  The ISA has people who are technically trained

119 Invitation to furnish nucleotide and/or amino acid sequence listing  When does this Invitation arrive?  Shortly after filing? No!  Some time after the ISA receives the Search Copy

120 Invitation to furnish nucleotide and/or amino acid sequence listing  Where do you send your response to this Invitation?  Do you send it to the IB? No!  Do you file it in EFS-Web? No!  (not unless you picked ISA/US as your ISA)  Do you file it in ePCT? No!  (at least, not in an ePCT submission to the IB)

 You send it directly to the ISA  And you pay the Late Furnishing Fee  (€230 if you picked ISA/EP)

121 Invitation to furnish nucleotide and/or amino acid sequence listing  Consequences of failure to comply fully and timely to the Invitation?  The application will only be searched to the extent possible given the failure to furnish the required item or items  Application may not be searched at all  PCT application will not be deemed withdrawn  You can still proceed in national/regional phase

122 Invitation to furnish nucleotide and/or amino acid sequence listing  How to comply?  You may need to create a disk and send it by courier to the ISA  You may need to send a bank wire to pay the Late Furnishing Fee

123 Form ISA/225 – Important  Form ISA/225 – Invitation to Furnish Nucleotide and/or Amino Acid Sequence Listing  Must respond to the ISA, not the IB  Can only respond using EFS-Web if the ISA is the ISA/US  Cannot use EFS-Web if the ISA is other than the ISA/US  Use EFS-Web only if the ISA is the ISA/US  Do not use EFS-Web if the ISA is not the ISA/US  Can use EFS-Web if the ISA is the ISA/US  etc.

124 Tips & Tricks Suzannah’s Tips & Tricks  Put seq paragraph as first paragraph in spec (use a template that provides the form paragraph)  Embed all sequences in spec  Do not specifically enumerate all variants  Do the minimum in the SL, and describe the maximum in words the specification  Make sure free text <223>, e.g., Artificial Sequence and “n” and “Xaa” info is in specification  Describe or show important fragments, e.g., by graphics  Include important fragments that will likely be claim limitations as separate seqs with their own SEQ ID NOs

126 Suzannah’s Tips & Tricks  Have inventors provide sequences to you in editable text so you need only copy & paste  Refer to prior art seqs by accession number, and other identifying info, e.g., version and date, without enumerating the seqs  Use SEQ ID placeholders, e.g., (SEQ ID NO: *)  Then when just about final, do “find” for “*” and consecutively number  Prepare SL last and copy & paste seqs in order

127 Suzannah’s Tips & Tricks  Docket ticklers for  When amendt for seq paragraph needed  Check “CRF entered” in PAIR  Understand when SL text file forms part of a PCT  If PCT Request is in a foreign language, use Google Translate cell phone app  If manually entering seqs by typing  Touch type twice using a fixed-width font, e.g., Courier New and then compare, or  Use computer “read that” function to review and double check seqs

128 Most Importantly Saying it doesn't make it so  Suppose a practitioner only a paper SL (e.g., a PDF)  Later the practitioner hands in a CRF along with the required statement that it is the same as the PDF  TYFNIL an adversary finds some real or imagined bit of information that is in the CRF but not in the PDF  If this happens, then the mere fact that the practitioner said they were the same does not make it so  Practice Tip: Be super careful when preparing a CRF that is to be handed in after filing date

129 More to Come WIPO Standard ST.26

aka XML format WIPO Standard ST.26 (XML)  January 2022 – Big Bang transition

 2016 USPTO public comment page  WIPO Standard ST.26 and Annexes and Guidance Docs  Standard ST.26 - Main Body - revised*  Annex I – Controlled vocabulary - revised  Annex II – Document Type Definition for Sequence Listing (DTD) - not revised  Annex III – Sequence Listing Specimen (XML file) - not revised  Annex IV/V – Character Subset from the Unicode Basic Latin Code Table - not revised and Additional data exchange requirements (for patent offices only) - not revised  Annex VI – Guidance Document - newly proposed  Guidance Document Index - newly proposed  Guidance Document SEQL (Sample XML sequence listing) – newly proposed

 * The identification of each document as being either revised, not revised, or newly proposed is in relation to the interim version adopted in March 2016.

 There will be a “Tool” to generate SLs in the ST.26 Standard  USPTO says the Tool will convert most ST.25 info to ST.26 format 131 Transition from ST.25 to ST.26

 ST.25 looks like this:  <130> FILE REFERENCE: N024.P013  <160> NUMBER OF SEQ ID NOS: 9

 ST.26 looks like this:  N024.P0139

132 Transition from ST.25 to ST.26  You might think that the Offices could promise the availability of a tool that would convert an ST.25 listing into an ST.26 listing  No! USPTO says:  Unfortunately, direct conversion from one standard to the other is not possible, due to numerous differences between the two standards, including inter alia, the types of required sequences, representation and annotation of the sequences, and sequence data structure.  (81 FR 74775, October 27, 2016)

133 Transition from ST.25 to ST.26  Difficult fact pattern 1:

 Parent case relies upon an ST.25 sequence listing

 Now applicant plans to file a continuation or divisional application at a time when the rules may say that you are required to use an ST.26 sequence listing and are not permitted to use an ST.25 sequence listing

 TYFNIL will a court decide that the continuation was really a CIP?

134 Transition from ST.25 to ST.26  Difficult fact pattern 2:

 Parent case relies upon an ST.25 sequence listing and was filed prior to March 16, 2013

 Now it is after March 16, 2013, and applicant plans to file a child case at a time when the rules may say that you are required to use an ST.26 sequence listing and are not permitted to use an ST.25 sequence listing

 TYFNIL will a court decide that the “new law” (post-AIA) applies to that child case?

135 Transition from ST.25 to ST.26  Desperate times will call for desperate measures. When a date is announced that ST.25 listings will no longer be accepted:

 Filers may feel the need to file continuations and divisionals prior to that date

 For new filings after that date, filers may feel the need to “age” the submission of the ST.26 listing by one day to eliminate the risk of accidentally filing a CIP or accidentally bringing a case under the post-AIA law

136 Transition from ST.25 to ST.26  Present version of PatentIn does not generate ST.26 format; it only generates ST.25 format

 Filers will need to have the ability to do several things:  Convert an existing ST.25 TXT file into a new ST.26 XML file  Generate a new ST.26 XML file  Import a PatentIn *.prj file and generate an ST.26 XML file  Edit ST.26 XML files using Notepad and other direct editing tools

137 Suzannah’s Tips – Planning for Big Bang  Start getting familiar with the new WIPO Standard ST.26  Do the minimum in the SL, and describe the maximum in words in the specification  But do not specifically enumerate variants in the specification  Make sure free text <223>, e.g., Artificial Sequence and “n” and “Xaa” info is in specification  Include ST.25 in the file name of the SL text file (so its indicated in the seq paragraph of the spec)  Use “Artificial Sequence”  Even if based on a standard organism, e.g., Homo sapiens  Say the minimum in the Artificial Sequence comment

138 Future Webinar on ST.26  We will offer future webinars on ST.26

 How to learn when such webinars are offered?

 Join the PCT listserv

 Subscribe to the Ant-Like Persistence blog

139 Questions? USPTO Help  Any inquiries regarding a specific computer readable form that has been processed by the Office should be directed to the Sequence Systems Service Center of the Scientific and Technical Information Center at 571-272-2510 or via email at [email protected].

141 Suzannah K. Sundby, Esq. Canady + Lortz LLP 1050 30th Street, NW Washington, DC 20007 T: 202.486.8020 F: 202.540.8020 [email protected]

Suzannah practices all aspects of intellectual property law including patent preparation, and prosecution, licensing, opinion work, strategic planning, and client counseling relating to diverse technologies including biochemistry, molecular biology, pharmaceuticals, microfluidics, diagnostics, medical devices, and nanotechnology. Carl Oppedahl, Esq. Oppedahl Patent Law Firm LLC 12000 Pecos Street - Suite 252 Westminster, CO 80234-2011 T: 303.252.8800 F: 303.651.9654 [email protected]

Carl is technically trained in physics, electrical engineering, mathematics, and software engineering. He has written and prosecuted numerous patent applications in electrical engineering, computer software system, and mechanical areas. He is an active computer programmer and holds an Extra-class amateur radio license.