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
Status of Application/Amendment/Claims
Applicant's response filed 01/13/2026 has been considered. Rejections and/or objections not reiterated from the previous office action mailed 09/17/2025 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
With entry of the amendment filed on 01/13/2026, claims 307-326 are pending. Claim 323 is withdrawn as being drawn to a non-elected invention.
The substitute specification filed 01/13/2026 has been accepted.
The replacement drawings filed 01/13/2026 have been accepted.
Maintained Rejections
Claim Rejections - 35 USC § 112
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 308 remains 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.
Claim 308 recites “wherein said single-stranded nucleic acid molecule comprises said second strand of said nucleic acid molecule, or a portion thereof”. The recitation of “a portion thereof” is indefinite because the metes and bounds of this portion is not defined. The portion could be any number of nucleotides of the nucleic acid molecule of any size. Thus the claim is indefinite.
Applicant points to [0422] that recites a portion is at least 25-100% but does not say what the portion is referring to. Paragraph [0421] discusses a first strand or second strand comprise a portion of a sequence complementary to a barcode. This does not provide evidence of definiteness for claim 308. Further what does 25-100% refer to in the context of claim 308. The claim recites “said second strand of said nucleic acid or a portion thereof” and it is unclear what 25-100% of a nucleic acid represents because when claiming a portion of a nucleic acid, the recitation is describing how many nucleic acids are represented by the portion, not a percentage. The claims is still indefinite for failing to particularly point out and distinctly claim the subject matter.
Claim Rejections - 35 USC § 103
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 rejection of claims 307-322, 324-326 rejected under 35 U.S.C. 103 as being unpatentable over Fu Guoliang (WO 2005/090599) and of Salk et al. (WO 2019/094651) is maintained for then reasons of record.
Applicant’s arguments are acknowledged but not found persuasive. Applicant argues that Fu nor Sulk teaches the isolation of a double-stranded nucleic acid molecule that initially comprises a cleavable or excisable moiety near one end and that remains attached to a support after cleavage or excision has occurred, as accomplished by the claimed methods. Applicant points to step b) of claim 307 for the limitation that the nucleic acid remains attached to the support after cleavage or excision has occurred. This argument is not persuasive because step b) of claim 307 does not make it clear that the nucleic acid remains attached to the support.
Further Applicant’s entire argument is based on claim 307 and reasons why Fu does not teach cleavable or excisable moieties and attachment to the support. Claim 307 does not make it clear that the nucleic acid remains attached to the support.
Applicant argues Fu et al does not teach cleavable bases and this argument is not persuasive because it was never alleged that Fu et al. teach cleavable bases as stated on page 7 of O.A. mailed 09/17/2025.
Applicant argues that only double-stranded nucleic acid molecules in Fu that can be captured to a solid support via a capturing moiety (and as such would be indirectly bound to a support) are the target molecules that do not comprise a "cleavable or excisable moiety". As stated above, it was never alleged that Fu et al. teach cleavable bases as stated on page 7 of O.A. mailed 09/17/2025.
Applicant appears to argue against the prior art references separately and not as a whole. In response, MPEP 2145 (IV) states one cannot show nonobvious by attacking references individually where the rejections are based on combinations of references.
One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Where a rejection of a claim is based on two or more references, a reply that is limited to what a subset of the applied references teaches or fails to teach, or that fails to address the combined teaching of the applied references may be considered to be an argument that attacks the reference(s) individually. Where an applicant’s reply establishes that each of the applied references fails to teach a limitation and addresses the combined teachings and/or suggestions of the applied prior art, the reply as a whole does not attack the references individually as the phrase is used in Keller and reliance on Keller would not be appropriate. This is because "[T]he test for obviousness is what the combined teachings of the references would have suggested to [a PHOSITA]." In re Mouttet, 686 F.3d 1322, 1333, 103 USPQ2d 1219, 1226 (Fed. Cir. 2012)
Applicant further argues Likewise, any double-stranded nucleic acid molecules in Fu that initially comprised cleavable bases, the biotinylated moiety would have been cleaved off, rendering these by-products incapable of binding to a functionalized support (contrary to the requirements of claim 307 step b). This argument appears to be conjecture by Applicant as it is not clear where this is taught by Fu.
Applicant then argues Salk et al. does not teach the isolation of a double-stranded nucleic acid molecule of interest that remains attached to a support after cleavage has occurred either. Salk was not relied upon for teaching isolation of double stranded nucleic acid but was relied upon for teach double stranded nucleic acids and the use of cleavable bases.
Applicant argues Sulk teach a different method for duplex adaptor synthesis and teach a method for isolating a double-stranded nucleic acid molecule that initially comprises a cleavable or excisable moiety near one end and that remains attached to a support after cleavage has occurred, as it is the case for the claimed method. This argument is not persuasive because it appears Applicant is arguing Sulk individually one cannot show nonobvious by attacking references individually where the rejections are based on combinations of references as stated above.
Applicant argues Fu and Salk provide no motivation for a POSITA to modify the teachings of Fu and Salk to create double-stranded molecules coupled to a solid support after cleavage, as accomplished by the claimed methods. "Obviousness can be established by "modifying the teachings of the prior art to produce the claimed invention," but only when "there is some teaching, suggestion, or motivation to do so." M.P.E.P. § 2143.01. In response Fu et al. teach a method for enriching desired nucleic acid sequences from a library by using repeated hybridization and cleavage reactions. It would have been obvious to use the methods of Salk in the methods taught by Fu to process multiple nucleic acid molecules by capturing said molecules using supports and cleaving multiple cleavable bases as taught by the prior art. One of skill would have been motivated to improve methods of processing nucleic acid molecules.
Applicant argues that even if a POSITA was motivated to create such duplex adapters and ligate them to a target nucleic sequence, the resulting adapter/target molecule ligation product would be coupled to a support on both ends. However, once the adapter/target molecule ligation product has been amplified with PCR, the plurality of amplified products will no longer contain the support initially present, discouraging the POSITA from adding the support in the first place. Alternatively, the supports at the ends of the ligation product might even interfere with sequencing (e.g., if both ends of the ligation product would be coupled to the same support). Applicant admits this is a hypothecia scenario and does not provide evidence that this would occur or that this would be a reason to dissuade a POSITA.
Applicant argues a POSITA seeking to arrive at the claimed invention would not be motivated to combine Salk and Fu because the POSITA would not review Fu at all, considering that Fu teaches away from the claimed invention. Applicant argues Fu teaches the exact opposite, namely a method for enriching double-stranded nucleic acid sequences from a library that do not comprise a cleavable or excisable moiety. It is unclear what part of Fu is a teaching away because Fu et al. was not relied upon for teaching the double stranded nucleic acid with cleavable or excisable moieties. Fu does not teach reasons to not use cleavable excisable moieties.
Thus the rejection is maintained.
Conclusion
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 extension fee 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. Any inquiry concerning this communication or earlier communications from the examiner should be directed to KIMBERLY CHONG at (571)272-3111. The examiner can normally be reached Monday thru Friday 9-5 pm.
If attempts to reach the examiner by telephone are unsuccessful please contact the SPE for 1636 Neil Hammell at 571-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KIMBERLY CHONG/Primary Examiner, Art Unit 1636
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