Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
1. The Applicant’s response to the office action filed on December 16, 2025 is acknowledged.
Status of the Application
2. Claims 1, 3-4, 7-13 and 21-23 are pending under examination. Claim 14-17 and 19 were previously withdrawn from further consideration as being drawn to non-elected group. Claims 2, 5-6, 18 and 20 were canceled. The Applicant’s arguments and the amendment have been fully considered and found persuasive in-part for the following reasons.
Claim Rejections - 35 USC § 102-Withdrawn
3. The rejection of claims under 35 USC 102(a)(1) as being anticipated by Reuter et al. in view of the amendment.
Claim Rejections - 35 USC § 103-maintained
4. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art. 2. Ascertaining the differences between the prior art and the claims at issue. 3. Resolving the level of ordinary skill in the pertinent art. 4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 3-4, 7-13 and 21-23 are rejected under 35 U.S.C. 103 as being unpatentable over Reuter et al. (Nat Methods, Vol. 13(11) p. 953-958, (2016), published November 2016, page 1-21) in view of Kaper et al. (US 2017/0044525).
Reuter et al. teach a method of claims 1, 22, for amplifying nucleic acids in a sample, comprising: a) fragmenting nucleic acids in a sample to produce a fragmented nucleic acid sample comprising fragmented RNA and fragmented genomic DNA, wherein the fragmenting comprises tagmenting the genomic DNA by a transposase and fragmenting RNA by enzymatic shearing (paragraph under subheading DNA/RNA extraction’, ‘Ribosomal depletion’ and ‘Simul-seq protocol’ under online methods on page 7-8);
b) contacting a fragmented nucleic acid sample comprising fragmented DNA and RNA with a cDNA deoxyribonucleic acid synthesis primer comprising an RNA originating domain (SR RT primer), wherein the cDNA deoxyribonucleic acid synthesis primer does not relay on hybridization to a poly(A) tail under cDNA synthesis conditions to produce a product nucleic acid composition (paragraph under subheading ‘Simul-seq protocol’ under online methods on page 7-8); and c) amplifying the product nucleic acid composition (paragraph under subheading ‘Simul-seq protocol’ under online methods on page 7-8).
With reference to claim 3, Reuter et al. teach that the transposase attaches adaptors to the genomic DNA during tagmenting and the adaptors comprise DNA origination domain (paragraph under subheading ‘Simul-seq protocol’ under online methods on page 7-8, page 2, paragraph 2).
With reference to claim 11-12, Reuter et al. teach that the method further comprises sequencing the nucleic acids of the product nucleic acid composition and determining whether a nucleic acid of the product nucleic acid composition originated from RNA or DNA depending on the presence of the RNA origination domain (paragraph under subheading ‘Simul-seq protocol’ under online methods on page 7-8 and paragraphs under subheading ‘read processing and alignment’ and page 2, paragraph under ‘results’ section, fig. 1 on page 16).
With reference to claim 21, Reuter et al. teach the product nucleic acid composition comprises a product nucleic acid comprising an RNA origination domain and a product nucleic acid that does not comprise an RNA origination domain (paragraph under subheading ‘Simul-seq protocol’ under online methods on page 7-8).
With reference to claim 23, Reuter et al. teach that the shearing is acoustic (sonication) shearing (paragraph under subheading ‘kinesin-microtubule interaction assays’ on page 12).
However, Reuter et al. did not specifically teach template switch oligonucleotide (TSO) wherein TSO comprising RNA origination domain (barcode or UMI) and sample from a single cell.
Kaper et al. teach a single cell gene expression analysis using template switch and tagmentation, wherein Kaper et al. teach that the cDNA synthesis comprises a primer comprising a tag (sample barcode or unique molecular identifier (RNA origination domain)) and a template switch oligonucleotide (TSO) comprising said tag, which is incorporated into the cDNA product, wherein TSO and cDNA synthesis primer comprises same or differ by at least one nucleotide (para 0008-0021, 0028-0030, 0048-0064).
It would be prima facie obvious to an ordinary person skilled in the art before the effective filing date of the invention to modify the method as taught by Reuter et al. with a template switch oligonucleotide, wherein the TSO comprising RNA origination domain as taught by Kaper et al. to develop an improved method for amplifying nucleic acids in a sample. The ordinary person skilled in the art would have motivated to modify the method as taught by Reuter et al. with a template switch oligonucleotide as taught by Kaper et al. and have a reasonable expectation of success that the combination would result in an improved sensitive method for amplifying nucleic acids because Kaper et al. explicitly taught use of a template switch oligonucleotide as a primer in amplification, tagmenting DNA with adapters for downstream analysis and reduce/minimize formation of by-products (para 0008, 0048-0064) and such a modification is considered obvious over the cited prior art.
Response to Arguments:
4. With reference to the rejection of claims under 35 USC 103 as being unpatentable over Reuter et al. in view of Kaper et al. the arguments were found unpersuasive. With reference to the Applicant’s arguments drawn to no teaching of contacting fragmented nucleic acid with cDNA synthesis primer, the arguments have been found unpersuasive because as required by the claim 1, 22-23, Reuter teach fragmenting RNA by shearing (sonication) and fragmenting genomic DNA by tagmentation (paragraph under subheading DNA/RNA extraction’, ‘Ribosomal depletion’ and ‘Simul-seq protocol’ under online methods on page 7-8). As discussed in the rejection Reuter et al. teach amplifying fragmented nucleic acids with a cDNA synthesis primer and amplifying to produce the first cDNA synthesis product. With reference to the Applicant’s arguments drawn to Simul-seq method of Reuter is for different purpose and teaches away from template switching, and the method of Kaper et al. is for a different purpose of determining mRNA content of single cells, the arguments were found unpersuasive. As noted in MPEP 2144-IV, which states the reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006) (motivation question arises in the context of the general problem confronting the inventor rather than the specific problem solved by the invention); Cross Med. Prods., Inc. v. Medtronic Sofamor Danek, Inc., 424 F.3d 1293, 1323, 76 USPQ2d 1662, 1685 (Fed. Cir. 2005) ("One of ordinary skill in the art need not see the identical problem addressed in a prior art reference to be motivated to apply its teachings."); In re Lintner, 458 F.2d 1013, 173 USPQ 560 (CCPA 1972) (discussed below); In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990), cert. denied, 500 U.S. 904 (1991). In the instant context, as discussed in the rejection, Reuter et al. teach fragmented nucleic acids and amplifying the fragmented nucleic acids with a cDNA synthesis primer. Reuter et al. also teach that the sample is from a single cell as required by claim 13. As discussed in the rejection, Kaper et al. teach single cell amplification using a cDNA synthesis primer and a template switching oligonucleotide (TSO) in reverse transcription. As discussed in the rejection, it would be obvious to modify the cDNA synthesis with a TSO to improve the method by minimizing/reducing by-products or background noise. For all the above, the rejection has been maintained and restated to address the amendment.
Conclusion
No claims are allowable.
THIS ACTION IS MADE FINAL. 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.
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Suryaprabha Chunduru
Primary Examiner
Art Unit 1681
/SURYAPRABHA CHUNDURU/Primary Examiner, Art Unit 1681