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 .
Claim Status
Claims 16-17 have been canceled. Claims 15 and 18-29 are pending and under examination. Claim 15, 18, 20-21, and 24-29 have been amended. Claim 15 is the only dependent claim.
Response to Arguments
Objections Withdrawn
The objection to the specification for improperly demarcated trademarks is withdrawn following the applicants’ amendments.
Rejections Withdrawn
The rejection of claims 18, 20, and 25 under 35 USC 112(b) is withdrawn following the applicants’ amendments.
The rejection of claims 15-29 under 35 USC 102(a)(1) is withdrawn following the applicants’ amendments.
New Rejections
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.
Claims 15 and 18-29 are rejected under 35 U.S.C. 103 as being unpatentable over Zheng et al. (CN 107604045 A, published Jan. 19, 2018).
In regards to claims 15, Zheng teaches A primer combination for preparing an amplicon library for detecting the variation of a target gene, comprising: a forward outer primer F1, a forward inner primer F2, and a reverse primer R designed according to a target amplicon” (see pg. 1 ¶11); “wherein the forward outer primer F1 is sequentially composed of a sequencing adapter 1, a barcode sequence for distinguishing different samples, and a universal sequence” (see pg. 1, ¶12); “the forward inner primer F2 is sequentially composed of a universal sequence molecular tag sequence, and a forward specific primer sequence of the target amplicon” (see pg. 1, ¶13); “wherein the molecular tag sequence comprises 6-30 bases.” Zheng teaches the molecular tag is composed of 10-12 random bases and teaches the use of a specific base for sequencing fidelity (see pg. 2, ¶8). The use of 12 bases would encode for over a trillion different possible combinations and likely solve the same multiplexing problem as using a 6-30 base molecular tag. One of ordinary skill in the art would know to modify the length of the tag as needed for experimental design. Furthermore, 10-12 bases is within the range of 6-30 bases reading on the limitations of the instant claim. Zheng further teaches “at least one set of specific bases; wherein the specific bases are set in the random bases” (see pg. 1 ¶13, pg. 2 ¶6); and wherein the specific bases in each set are composed of 1-5 bases (see pg. 2 ¶6). Zheng teaches the use of 3 specific bases “GAT” which is in the range of 1-5 bases, reading on the limitations of the instant claim (see pg. 2 ¶6); and the reverse outer primer R is sequentially composed of a sequencing adapter 2 and a reverse specific primer sequence of the target amplicon (see pg. 2 ¶2). Therefore Zheng teaches all of the limitations of claim 15.
The applicant’s arguments (pg. 10 para. 3) that Zheng does not disclose a molecular tag sequence that comprises 6-30 bases and includes both random bases and at least one specific base is false, as pointed out by the applicant in the same paragraph “the molecular tag (NNNNNNNNNNGAT) disclosed by Zheng is only 10-12 random bases” however this range is between 6-30 bases and does disclose specific bases sequence of three bases with the random bases (see pg. 2 ¶6). These three bases are in the range of 1-5 as required by the claim. Zheng explicitly states “ The upstream primer F2 is composed of a universal sequence 1, a molecular tag, a specific base sequence, and an upstream specific primer sequence” (see pg. 1 last paragraph) and then states that the “[t]he specific base sequence is GAT” (see pg. 2, ¶6). The applicants’ remarks are improperly narrowing “set in” to require interspersion that the claim does not recite.
In regards to claims 18 and 25, Zheng teaches barcode sequence of 8-12 nucleotides with no continuous bases and a GC content of 40-60% and a universal sequence of 16-25 nucleotides, with a GC content of 35-65% no continuous bases and no obvious secondary structure (see pg. 2 ¶4-5).
In regards to claims 19 and 20, Zheng teaches using sequencing adapters that correspond to different sequencing platforms, and specifically cites using i5 and i7 for Illumina platforms and A and P for Ion Torrent platforms (see pg. 2 ¶10-12).
In regards to claim 21, Zheng teaches using the primers described above to perform a one-step PCR amplification (see pg.2 ¶9).
In regards to claims 22, 27, and 29, Zheng teaches utilizing blood, urine, cerebrospinal fluid, or tissue samples (see pg. 2 ¶18).
In regards to claim 23, Zheng teaches the forward inner primer F2 is sequentially composed of the universal sequence, a molecular tag sequence, and the forward specific primer sequence of the target amplicon (see pg. 1 ¶ 13). While Zheng’s primer description lists the specific base sequence separately, the instant application incorporates the specific base sequence into the molecular tag sequence. One of ordinary skill in the art would understand them to be functionally equivalent.
In regards to claim 26 and 28, Zheng teaches using their method to detect mutation rates following the steps of preparing an amplicon library, then diluting to generate a sequencing library, followed by sequencing (see pg. 3 ¶4-5).
Conclusion
No claim is allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Matthew H Raymonda whose telephone number is (703)756-5807. The examiner can normally be reached Monday - Friday 10:00 am - 4:00 pm.
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/MATTHEW HAROLD RAYMONDA/Examiner, Art Unit 1684
/AARON A PRIEST/Primary Examiner, Art Unit 1681