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 .
Status
Applicant's request for reconsideration of the finality of the rejection of the last Office action is persuasive and, therefore, the finality of that action is withdrawn. This is a new NON-FINAL action.
Claims 1-43 are cancelled.
Claims 48-51, 56, and 57 are withdrawn.
Claims 44-48, 52-55, and 58-65 are under examination.
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.
Claim 44 recites the limitation "the selected dinucleotide" in part (a) (i) and there is not previous reference to a selected dinucleotide. There is insufficient antecedent basis for this limitation in the claim.
Claims 44-48, 52-55, and 58-65 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.
Claim 44 is indefinite because it is not clear from the claim how a method of rephasing is achieved. The method recites part (a), (b), and (c) and then states “thereby rephasing the sequencing primers in the clonal population of the DNA templates.” The active method steps of the claims stop at unblocking the second blocking group. It is not clear how this achieves rephasing. The specification describes “Method 2: Dinucleotide-Frequency Rephasing (DFR) with Run-Forward” that comprises several rounds allowing the sequencing to “run-forward” until the sequencing on all strands stops at the same base. This is achieved by adding a blocked base that stops sequencing. Then a next base further down the sequence is selected which stops sequencing allowing all the sequences to “catch-up.”
This selection of a base (and repeat) that is farther down the sequence that allows for all the strands to reach the same blocked base is not described in the claims. The active method steps described in the claims is to add a blocked base, unblock it and then add the next blocked base and unblock it. It is not clear in step (iii) that the same type of blocking of the same base is achieved like it is described in step (ii).
Part (iii) also recites “treating the sequencing primers from step (ii) with…” however there are no sequencing primers recited in step (ii).
Claims 53-55 require removing five to fifty bases from the 3’ end of each of the sequencing primers. It is not clear if the process is removing the sequence being created or the primer. It is not clear how the sequencing can begin again if the primer is removed or how the cycles can be repeated multiple times if the removal of bases always goes back to the primer.
Claims 45-48, 52-55, and 58-65 require the limitations of claim 44 and do not overcome the rejection.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 44, 45, 47, 52, 58-60, and 65 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Glezer et al. (US 2021/0189481 A1, provisional filing date of 18 December 2019).
Regarding claims 44 and 59, Glezer et al. teach a method of alternating series of sequencing cycles and dark extension cycles allowing longer read lengths and addressing disadvantages of traditional nucleic acid sequencing protocols. (abstract).
Glezer et al. teach multiple cycles of extending and detecting sequencing primers that are hybridized to a clonal population of DNA templates being sequenced. (claim 1 (a), [0039] stating the template nucleic acid can be any desired nucleic acid).
Glezer et al. teach performing one or more dark cycles. (claim 1 (b), [0065]). Dark cycles are performed by incorporating nucleotides without a detection event. (claim 1 (b)). Furthermore, the dark cycles incorporate nucleotides without a reversible terminator moiety, i.e. unblocked. (claim 2 (b), claim 10). After the dark cycles, sequencing cycles with reversible terminators are resumed. (claim 1 (c), claim 2 (c)).
Glezer et al. teach that the reversible terminators are attached to the 3’ end of the incorporating strand to the temporarily halt the polymerase reaction until the reversible terminator is cleaved. [0004].
Regarding step (a)(i), Glezer et al. teach that during the dark cycles, nucleotides are incorporated that do not have a reversible terminator but a dark cycle can include the incorporation of one or more nucleotides that are identified, i.e. labeled with a reversible terminator. [0065, 0082, 0102-103].
Regarding step (a)(ii), Glezer et al. teach that to continue with the sequencing cycle the reversible terminator is cleaved, or unblocked. [0004].
Regarding step (a)(iii), Glezer et al. teach that the dark cycles can be repeated with a same or different nucleotide [0065, 0082, 0102-103].
Glezer et al. state that a detection event (including a nucleotide with a label and reversible terminator) can occur during the dark cycles to check for synchronization of a cluster. [0102-103].
Regarding claim 45, Glezer et al. state the following:
In embodiments, the methods of sequencing a template nucleic acid includes executing a plurality of sequencing cycles after a dark cycle, each sequencing cycle including (i) extending the complementary polynucleotide by incorporating a second nucleotide using a polymerase; and (ii) detecting a label that identifies the second nucleotide. In embodiments, the nucleotide is selected from one or more of dATP, dCTP, dGTP, and dTTP or analogue thereof. In embodiments, the nucleotide includes a detectable label. In embodiments, the detectable label is a fluorescent label. In other embodiments, the nucleotide includes a reversible terminator moiety. [0103].
Therefore, by stating one or more, the limitations of claim 45 are met.
Regarding claim 47, Glezer et al. teach the blocking groups are known in the art, and may be, for instance, a 3′-ONH2 reversible terminator, a 3′-O-allyl reversible terminator, or a 3′-O-azidomethyl reversible terminator. [0103]. Claim 47 does not state they must be different from each other.
Regarding claim 52, Glezer et al. teach a sequencing cycle that incorporates and identifies up to 100 nucleotides. [0106].
Regarding claim 58, Glezer et al. teach non-dark or regular cycles after the dark cycles. (claim 1).
Regarding claims 60 and 65, Glezer et al. teach that following a plurality of dark cycles a sequencing cycle can be reinstated and can be elongated for 500-1000 base pairs. [0154]. Glezer et al. states that the dark cycles can be anywhere from 1 to 50 cycles, for example. [0116].
Claim Rejections - 35 USC § 103
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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 46 is/are rejected under 35 U.S.C. 103 as being unpatentable over Glezer et al. (US 2021/0189481 A1, provisional filing date of 18 December 2019).
The teachings of Glezer et al. are applied to this claim as they are applied to claims 44, 45, 47, 52, 58-60, and 65 under 35 USC 102(a)(2).
Glezer et al. does not specifically teach where three bases have one blocking group and the fourth has a different blocking group. Glezer et al. does teach that blocking groups are known in the art, and may be, for instance, a 3′-ONH2 reversible terminator, a 3′-O-allyl reversible terminator, or a 3′-O-azidomethyl reversible terminator. [0103]. Therefore, one of ordinary skill in the art would be motivated to use different blocking groups in the method taught by Glezer et al. as a way to control the sequencing progression. Glezer et al. is interested in checking for synchronization of a cluster and could use different blocking groups to allow the polymerase on one strand to continue while the other do not.
Claim(s) 63 is/are rejected under 35 U.S.C. 103 as being unpatentable over Glezer et al. (US 2021/0189481 A1, provisional filing date of 18 December 2019) in view of Porreca (Nature Biotechnology, 2010).
The teachings of Glezer et al. are applied to this claim as they are applied to claims 44, 45, 47, 52, 58-60, and 65 under 35 USC 102(a)(2).
Glezer et al. does not specifically teach where the clonal population is a nanoball. Porreca teaches the benefits of sequencing on nanoballs: lower cost and throughput is driven by the speed of the camera and by how many spots can be packed into a single image. The combination lowers the cost of sequencing per base. Therefore, one of ordinary skill in the art would be motivated to use a DNA nanoball because it is overall cheaper to use in sequencing methods.
Claim(s) 64 is/are rejected under 35 U.S.C. 103 as being unpatentable over Glezer et al. (US 2021/0189481 A1, provisional filing date of 18 December 2019) in view of Ambardar et al. (Indian J Microbiol, 2016).
The teachings of Glezer et al. are applied to this claim as they are applied to claims 44, 45, 47, 52, 58-60, and 65 under 35 USC 102(a)(2).
Glezer et al. does not specifically teach where the clonal population of DNA templates is a cluster of DNA strands produced by bridge PCR in an emulsion droplet.
Ambardar et al. provide an overview of high throughput sequencing and include bridge PCR or emulsion PCR to amplify the anchored DNA fragments into millions of spatially template fragments before using the sequencing platform. (page 396). Therefore, it would have been obvious to one of ordinary skill in the art to use one of two known methods for generating DNA fragments for sequencing by synthesis methods. One of ordinary skill in the art would pick one of the two known methods as described by Ambardar et al.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MINDY G BROWN whose telephone number is (571)270-5605. The examiner can normally be reached Monday -Friday, 9:00 am - 5:00 pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Anne Gussow can be reached at (571) 272-6047. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MINDY G BROWN/Patent Examiner, Art Unit 1683
/ANNE M. GUSSOW/Supervisory Patent Examiner, Art Unit 1683
