LIFE TECHNOLOGIES CORPORATION

Patent Trials and Appeals BoardNov 25, 2020

2020001278 (P.T.A.B. Nov. 25, 2020)

UNITED STATES PATENT AND TRADEMARK OFFICE UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O. Box 1450 Alexandria, Virginia 22313-1450 www.uspto.gov APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 15/154,499 05/13/2016 Christian KOLLER LT01064 4525 134939 7590 11/25/2020 JONES ROBB, PLLC (w/ Life Technologies Corporation 1420 Spring Hill Road Suite 325 McLean, VA 22102 EXAMINER HARWARD, SOREN T ART UNIT PAPER NUMBER 1631 NOTIFICATION DATE DELIVERY MODE 11/25/2020 ELECTRONIC Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address(es): PatentDocketing@thermofisher.com docketing@jonesrobb.com pair_thermofisher@firsttofile.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte CHRISTIAN KOLLER and MICHAEL D. ALLEN Appeal 2020-001278 Application 15/154,499 Technology Center 1600 Before ULRIKE W. JENKS, AMEE A. SHAH, and RACHEL H. TOWNSEND Administrative Patent Judges. JENKS, Administrative Patent Judge. DECISION ON APPEAL Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from Examiner’s decision to reject claims 1, 2, 4, 7–10, 13, and 20–27 as lacking written descriptive support. Claims 3, 5, 6, 11, 12, and 14–19 have been cancelled. We have jurisdiction under 35 U.S.C. § 6(b). We REVERSE. 1 We use the word Appellant to refer to “applicant” as defined in 37 C.F.R. § 1.42(a). Appellant identifies the real party in interest as Life Technologies Corp. Appeal Br. 2. Appeal 2020-001278 Application 15/154,499 2 STATEMENT OF THE CASE The Specification describes the use of bar codes to identify the origin of samples in multiplexed sequencing procedures. See Spec. ¶¶ 32, 69. “[S]ample discriminating codes or barcodes may be bound to a target sequence, and in such cases may assist in uniquely identifying or discriminating different target sequences.” Id. ¶ 74. CLAIMED SUBJECT MATTER The claims are directed to generating barcode sequences. Claim 1, reproduced below, is illustrative of the claimed subject matter (numbering and paragraphing added for reference convenience): 1. A method of manufacturing polynucleotide templates for use in nucleic acid sequencing, the method comprising: [(A)] generating a set of flowspace codewords, the flowspace codewords comprising strings of characters, each flowspace codeword comprising a distinct string of characters; [(B)] determining a location for at least one padding character within the flowspace codewords; [(C)] inserting the at least one padding character into the flowspace codewords at the determined location; [(D)] selecting, after the inserting, a subset of flowspace codewords from the set, wherein each flowspace codeword of the subset satisfies a predetermined minimum distance and is configured to be expressed in flowspace according to a predetermined flow order; and [(E)] manufacturing polynucleotide templates, each polynucleotide template comprising: [(1)] a respective barcode sequence corresponding to a flowspace codeword from the subset, and [(2)] a series of key bases appended to the respective barcode sequence, wherein: [(a)] for a first group of the subset, the series of key bases Appeal 2020-001278 Application 15/154,499 3 appended to the respective barcode sequences terminates with a repeated base, [(b)] for a second group of the subset, the series of key bases appended to the respective barcode sequences terminates with a non-repeating base, [(c)] the subset of flowspace codewords collectively defines an error tolerant code that provides a minimum distance between flowspace codewords of the subset, and [(d)] a variance in the key bases appended to the flowspace codewords of the subset increases the minimum distance between the flowspace codewords of the subset. Appeal Br. 20–21 (Claims Appendix). REJECTION Appellant requests review of Examiner’s rejection of claims 1, 2, 4, 7–10, 13, and 20–27 under 35 U.S.C. 112(a). OPINION Examiner’s position is that the Specification does not provide sufficient written descriptive support for claim element 1(D). Ans. 3 (“selecting . . . a subset of flowspace codewords from the set, wherein each flowspace codeword of the subset . . . is configured to be expressed in flowspace according to a predetermined flow order”); Final Act. 4. Examiner finds that “the disclosure does not describe any procedure or specific steps for validating the base space sequence to which the flowspace codeword corresponds given a particular flow ordering.” Final Act. 4. According to Examiner, the Specification does not provide “an algorithm Appeal 2020-001278 Application 15/154,499 4 that is used to determine whether a flowspace codeword maps to a valid base space sequence.” Ans. 7. Additionally, Examiner finds that the Specification does not describe the step of “if the translated flowspace vector that results differs from the original flowspace codeword [], then the translated base space sequence is deemed not to be valid.” Id. Appellant contends that an algorithm is not recited in the claim and is not required. Appeal Br. 14. “Appellant’s specification explains in prose, figures, and step-by-step examples, the sequence of steps that can be taken to determine if a known flowspace codeword provides a translated base space sequence that can be remapped back to the known flowspace codeword according to a predetermined flow ordering.” Id. Appellant contends that “given a flowspace codeword and a predetermined flow ordering, the method and steps for determining the flowspace vector from a base sequence and vice versa is demonstrated.” Reply Br. 3 (citing Spec. ¶¶ 66, 67, Fig. 6A and 6B). There are four different dNTP that can be added sequentially to the reaction chambers in a sequencing procedure, so that each reaction is exposed to one of the four different dNTPs at a time. Spec. ¶ 58. “The exposure to a nucleotide followed by a washing step can be considered a ‘nucleotide flow.’ In some examples, four consecutive nucleotide flows can be considered a ‘cycle.’ For example, a two cycle nucleotide flow order can be represented by: dATP, dCTP, dGTP, dTTP, dATP, dCTP, dGTP, dTTP, with each exposure being followed by a wash step.” Id. The flow ordering can also be based on cyclical, repeating patterns, as well as random patterns. Id. The important thing is that a flow order does not repeat the same dNTP in consecutive flows. Appeal 2020-001278 Application 15/154,499 5 As explained in the Specification, “a barcode sequence and a flowspace codeword have a mapping relationship to each other for a given flow ordering.” Spec. ¶ 86. Figure 6A and 6B are reproduced below: “As shown in FIG. 6A, the base space sequence AGTCCA may be translated to a flowspace vector 101001021 under a cyclical flow ordering of TACG. As shown in FIG. 6B . . . , the flowspace vector may be mapped back to the base space sequence associated with the sample given a predetermined flow ordering.” Id. ¶ 67. The figures demonstrate the relationship between a base space sequence and a flowspace vector for particular flow order sequence of TACG that is repeated. See id. ¶ 66. Flowspace vector, sequence, or string Appeal 2020-001278 Application 15/154,499 6 may comprise a series of symbols such as 1, 2, 3, and the like. Id. “When a predetermined flow order is known in combination with a flowspace vector, a translation to base space may be produced.” Id. Starting with a flowspace codeword which is a string of numbers, for example “20012220010121,” and following the procedure in Figure 6B (shown above) using a particular flow order, it is possible to determine a base sequence. Once the base sequence is established, the same procedure outlined in Figure 6A (shown above) should produce a flowspace vector that is identical to the starting flowspace codeword. See e.g. Spec. ¶¶ 104–105. In the event that these two numbers are not identical, then it is determined that the flowspace codeword does not map to a valid base sequence. Id. ¶ 104. We agree with Appellant that based on these teachings in the Specification one of skill in the art could determine whether a flowspace codeword in a given flowspace according to a predetermined flow order is configured to be expressed according to that flow order. Here, the disclosure in the Specification provides sufficiently detailed instructions that would allow one of ordinary skill in the art using pencil and paper to determine whether a particular randomly generated flowspace codeword given a predetermined flow order is associated with a valid base sequence. Accordingly, we are not persuaded by Examiner’s contention that the Specification does not provide sufficient written descriptive support for claim element 1(D). The fact that the selection and determination of codeword validity could be made much faster using a computer does not detract from the fact that the Specification provides sufficient descriptive support for one of skill in the art to select a subset of flowspace codewords Appeal 2020-001278 Application 15/154,499 7 that “satisfies a predetermined minimum distance and is configured to be expressed in flowspace according to a predetermined flow order,” as recited in the claim. CONCLUSION In sum, as we are not persuaded, for the reasons discussed, that Examiner has adequately explained why the disclosure in the Specification is insufficient to carry out the presently claimed method of manufacturing a polynucleotide. In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 1, 2, 4, 7-10, 13, 20–27 112(a) Written Description 1, 2, 4, 7-10, 13, 20–27 TIME PERIOD FOR RESPONSE No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a). See 37 C.F.R. § 1.136(a)(1)(iv). REVERSED