DETAILED ACTION
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 .
2. This action is in response to the papers filed June 25, 2026. Applicant’s remarks and amendments have been fully and carefully considered but are not found to be sufficient to put the application in condition for allowance. Any new grounds of rejection presented in this Office Action are necessitated by Applicant's amendments. Any rejections or objections not reiterated herein have been withdrawn. This action is made FINAL.
Claims 5 and 7 are currently pending and have been examined herein.
Claim Rejections - 35 USC § 103
3. 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.
Claims 5 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Wang (The Journal of Molecular Diagnostics, Vol 15 No 1 January 2013) in view of Kwok (Nucleic Acids Research Vol 8 No 4 1990 pages 999-1005).
Wang teaches a method for DNA mutation detection in cancer called AS-NEPB-PCR amplification. The method is shown in Figure 1.
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Further Table 1 provides primers for detecting the EGFR (L858R) mutation.
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Thus Wang teaches a method comprising performing a PCR, the PCR comprising:
(a) a primer composition for detecting a single-nucleotide variant (SNV), the composition comprising:
(i) a first forward primer that includes a nucleotide sequence complementary to a to-be-detected DNA fragment including a single nucleotide variant to be detected (the AS primer is complementary to the target mutation strain);
(ii) a second forward primer that includes the nucleotide sequence complementary to a wild-type DNA fragment that does not contain a single nucleotide variant, wherein the 3' terminal end is phosphorylated (NEP Blocker is complementary to the Target WT strain; and
(iii) a reverse primer;
(b) a DNA polymerase; and
(c) a to-be-detected DNA fragment (the target mutation strain).
Further Wang teaches that when there is a single-nucleotide variant in the to-be-detected DNA fragment, an amplification product by the polymerase chain reaction (PCR) is generated, and when there is no single-nucleotide variant in the to-be-detected DNA fragment, the amplification product by polymerase chain reaction (PCR) is not generated.
Wang does not teach a method wherein the first forward primer further comprises 2 to 6 nucleotide sequences that are not complementary to the to-be-detected DNA fragment at a terminal 3' end of the primer and the second forward primer further comprises 2 to 6 nucleotide sequences that are not complementary to the wild-type DNA fragment at the terminal 3' end of the primer. Additionally Wang does not teach a method wherein the PCR is performed using a DNA polymerase without 3'->5' exonuclease activity.
However Kwok investigated the effects of primer template mismatches on PCR. Kwok teaches that the presence of a mismatched T at the 3’ terminus allowed significant amplification even when coupled with an adjacent mismatch. Kwok teaches that even two mismatched T’s at the 3’ terminus allowed efficient amplification (abstract, page 1003). Kwok teaches PCR was performed with AmpliTaq which is a DNA polymerase without 3'->5' exonuclease activity (page 1001).
Accordingly, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of Wang by adding 2 “T” nucleotides that are not complementary to the to-be-detected DNA fragment at a terminal 3' end of the first forward primer and 2 nucleotides that are not complementary to the wild type DNA fragment at the terminal 3’ end of the second forward primer. In the instant case the prior art of Wang teaches that when detecting low frequency mutations, it is desirable to block amplification of the target wild type strain (abstract). Wang teaches one way to do this is to use a NEP blocker having a phosphate group at the 3’ end to block primer extension. One of skill in the art would have been motivated to add 2 nucleotides that are not complementary to the wild type DNA fragment at the terminal 3’ end of the NEP blocker for the benefit of having an extra way to block primer extension, since it would be expected that a NEP blocker with 3 mismatches at the 3’ terminal end would have reduced extension in comparison to the AS primer having only 2 mismatches at the 3’ terminal end. On the other hand, there was a reasonable expectation that the AS primer with 2 “T” nucleotides at the terminal 3’ end would still be able to amplify the target mutation strain since Kwok teaches that two mismatched T’s at the 3’ terminus allowed efficient amplification when AmpliTaq DNA polymerase was used (abstract, page 1003). One of skill in the art would have been motivated to add the additional 2 “T” to both the AS primer and the NEP blocker of Wang for the benefit of obtaining better allelic discrimination.
4. 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 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 date of this final action.
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/AMANDA HANEY/Primary Examiner, Art Unit 1682
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