DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application is being examined under the pre-AIA first to invent provisions.
Applicants’ arguments and amendments, filed May 11, 2026, have been fully considered and they are persuasive in-part. The following rejections are reiterated. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
Status of the Claims
Claims 21, 23, 25-27, and 29-33 are under examination.
Claims 22, 24, and 28 are withdrawn.
Claim Rejections - 35 USC § 112
2. The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 32 and 33 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Instant claim 32 has been amended to recite “calculating a probability that a variant is present in the second sequence information above an expected error rate. However, in the preceding steps, the instant claims recite “determining if the variant is present in the second sequence information” and “calculating, when the variant is present in the second sequence information, a total number of reads covering a variant position and a number of reads showing the variant in the second sequence information”. It is unclear the newly amended step requires the step of “determining if the variant is present in the second sequence information” to result in the determination that a variant is present in the second sequence information. For purposes of examination, the amended step will be interpreted as requiring that the step of “determining if the variant is present in the second sequence information” results in a variant is present in the second sequence information. Clarification via clearer claim language is required.
This rejection is necessitated by amendment.
Claim Rejections - 35 USC § 103
3. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 32-33 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Li (“A Statistical Framework for SNP Calling, Mutation Discovery, Association Mapping and Population Genetical Parameter Estimation from Sequencing Data” Bioinformatics (2011) volume 27, number 21, pages 2987-2993) as applied to claims 21, 23, 25-27, and 29 above, further in view of Xie et al. (US 2014/0155274 A1).
The instant claims 32 and 33 include a step of “determining if the variant is present in the second sequence information”. As written, this step is a contingent limitation. According the MPEP §2111.04 (II), “The broadest reasonable interpretation of a method (or process) having contingent limitations requires only those steps that must be performed and does not include steps that are not required to be performed because the condition(s) precedent are not met. In this instance, the instant claims requires attaching an adapter with a barcode sequence to a nucleic acid sample, sequencing the nucleic acid samples, classifying the reads corresponding to the samples, and identifying a variant in the first sequence information.
Regarding claims 32 and 33, while Li teaches identifying a variant, where the first nucleic acid sample comprises a tumor sample and the second nucleic acid sample comprises a non-tumor sample (“page 2990, under “2.4 Discovering somatic and germline mutations”).
Li does not teach an adapter with a barcode.
Regarding claims 32 and 33, Xie et al. teach a method that includes attaching a first and second adapter including a barcode to fragments of a first and second nucleic acid sample in a NGS assay (paragraph [0007]; paragraph [0045]), simultaneously generating a plurality of reads (paragraph [0045]; paragraph [0157]); classifying reads as corresponding to a first or second nucleic acid sample based on the barcode sequence (paragraph [0088]).
It would have been obvious for one of ordinary skill in the art, at the time of invention, to combine the references of Xie et al. and Li. Xie et al. teach a method of detecting nucleic acids (paragraph [0006]). One of ordinary skill in the art would have wanted to analyze the data collected from Xie et al.’s method. Li teaches a method of analyzing nucleic acids to discover somatic mutations (abstract). One of ordinary skill in the art, at the time of invention, would have been motivated to use Li’s method of analyzing on the data obtained from Xie et al.’s method of detecting nucleic acids. Furthermore, one of ordinary skill in the art would have had a reasonable expectation of success, since one of ordinary skill in the art may readily perform Li’s analysis on the data collected from Xie et al.
Response to Arguments
4. Applicants have responded by stating that the prior art does not teach “calculating a probability that a variant is present in the second sequence information above an expected error rate“. However, this step is preceded by “determining if the variant is present in the second sequence information” and “calculating, when the variant is present in the second sequence information, a total number of reads covering a variant position and a number of reads showing the variant in the second sequence information.” The preceding steps are written as contingent limitations. In instances where the variant is not present in the second sequence information, the instant claims does not require “calculating, when the variant is present in the second sequence information, a total number of reads covering a variant position and a number of reads showing the variant in the second sequence information” or “calculating a probability that a variant is present in the second sequence information above an expected error rate”. Under the broadest reasonable interpretation, the instant claims only require the steps of attaching an adapter with a barcode sequence to a nucleic acid sample, sequencing the nucleic acid samples, classifying the reads corresponding to the samples, and identifying a variant in the first sequence information. As stated above, Li and Xie et al. teach these limitations.
The Examiner suggests amending instant claim 32 to remove the contingent language from the limitations. The step of “determining if the variant is present in the second sequence information” may be written as “determining the variant is present in the second sequence information”. The step of “calculating, when the variant is present in the second sequence information, a total number of reads covering a variant position and a number of reads showing the variant in the second sequence information” may be written as “calculating a total number of reads covering a variant position and number of reads showing the variant in the second sequence information”. Such amendments would eliminate the contingent language, and the instant claims would then require the steps of “determining the variant is present in the second sequence information”, “calculating a total number of reads covering a variant position and number of reads showing the variant in the second sequence information” and “calculating a probability that a variant is present in the second sequence information above an expected error rate”.
Double Patenting
5. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
6. Claims 21, 23, 25-27, and 29-33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11,468,968. Although the claims at issue are not identical, they are not patentably distinct from each other.
Instants claims 21, 23, 25-27 and 29-33 recite the similar limitations as claims 1-19 the U.S. Patent. The claims differ in that the instant claims recites a non-transitory machine readable storage medium. However, the system in claim 10 of the U.S. Patent would include a machine readable storage medium. Thus, the claims at issue are not patentably distinct from each other.
Response to Arguments
7. Applicants have requested this rejection be held in abeyance. This rejection is maintained.
Withdrawn Rejections
8. Applicant’s arguments, filed May 11, 2026, with respect to the rejections made under 35 U.S.C. §101 and §102 have been fully considered and are persuasive. Given the volume of data produced by next generation sequence, one of ordinary skill in the art would not be able to perform the claimed method mentally. The rejection made under 35 USC §101 is withdrawn.
Instant claims 21, 23, 25-27, and 29 -31 are drawn to a non-transitory computer readable medium. Although, instant claims 21, 23, 25-27, and 29 -31 recites steps that are written as contingent limitations, the MPEP §2111.04 (II) states that “The system claim interpretation differs from a method claim interpretation because the claimed structure must be present in the system regardless of whether the condition is met and the function is actually performed.” As stated by the Applicant, Li does not teach “identifying the variant as a somatic mutation when the variant in the second sequence information is due to sequencing error and the first and second coverage levels are above a coverage threshold.” The rejection under 35 U.S.C. §102 is withdrawn. The rejection of claims 30 and 31 under 35 U.S.C. §103 is also withdrawn.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JERRY LIN whose telephone number is (571)272-2561. The examiner can normally be reached T-F 7am-5pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Olivia Wise can be reached at (571) 272-2249. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JERRY LIN/Primary Examiner, Art Unit 1685
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