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 .
Election/Restrictions
Applicant’s election without traverse of the invention of Group I (claims 1-15 drawn to method of detecting a target nucleic acid) in the reply filed on 03/11/2026 is acknowledged.
Claims 16-34 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 03/11/2026.
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.
Claim(s) 1-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Komori et al (WO 2016/103234) in view of Ng et al (1989).
Relevant to the methods of Claim 1, Komori et al teaches a method of detecting a target nucleic acid comprising contacting a sample with: a first oligonucleotide (i.e.: sequence conversion DNA or SC DNA) comprising, in the 5' to 3' direction, a signal DNA generation sequence, an endonuclease recognition site, and a sequence complementary a portion of the signal DNA generation sequence (i.e.: cover sequence) and a second complementary sequence that is complementary to the 3’ end of a target, where the oligonucleotide forms a hairpin structure (Figs 1-3); a polymerase; and a nicking endonuclease (e.g.: p.2-4).
Relevant to claims 7 and 8, Komori et al teaches (p.17-18) that the methods can be performed at constant temperatures, and temperatures from about 200C to about 420C.
Relevant to claims 9 and 10, Kimori et al teaches methods using enzymes with displacement activity, and without exonuclease activity (e.g.: p.15).
Relevant to claims 11 and 12, Kimori et al teaches methods applied to detection of miRNA and infections agents (e.g.: p.20).
Relevant to claim 15, Kimori et al teaches oligonucleotides comprising 3’-end modifications (e.g.: p.13-14, Fig. 3; p.23 – Example 1).
Further relevant to the instantly rejected claims, Komori et al teaches (p.13-14) that the oligonucleotide may comprise a modification, including abasic groups. Komori et al teaches modifications can reduce or eliminate the occurrence of any non-desired extension reactions, such as replication initiated from the 3 'end of the oligonucleotide that may lead to detection errors (e.g., false positives), and may prevent non-specific extension reactions arising from events such as binding between the oligonucleotide and a non-target sequence, binding between the oligonucleotide and a target sequence at an incorrect position, or non-templated de novo or ab initio DNA synthesis may also lead to detection errors.
Komori et al does not exemplify an oligonucleotide with at least one abasic moiety located between the 5' end and the 3' end of the second complementary sequence and is selected from a nucleotide position that is 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, nucleotides from the 5' end of the second complementary sequence. However, the effects of abasic sites in primers on the polymerase extension capabilities of the primer were known in the prior art and are taught by Ng et al.
Relevant to the rejected claims, Ng et al teaches abasic sites positions 5, 7, 9 and 11 in a 12-mer primer (e.g.: Fig 6), and demonstrates, by using the primers in a direct incorporation assay, that primers with abasic lesions at 12-mer positions 11 and 9 were unable to support incorporation, and primers with abasic lesions at 12-mer positions 5 and 7 showed decreased incorporation (Fig. 7).
It would have been prima facie obvious to someone with ordinary skill in the relevant art before the effective filing date of the rejected claims to have used the structures of Komori et al for the detection of a target nucleic acid, and to have included abasic sites in the oligonucleotide as suggested by Komori et al and exemplified by Ng et al. The skilled artisan would have been motivated put abasic sites in the oligonucleotide based on the expressed teachings of Komori et al that oligonucleotide modifications such as abasic groups may reduce or eliminate the occurrence of any non-desired extension reactions, and the expressed teaching of Ng et al that abasic groups at various positions in a primer may prevent or reduce polymerase-based primer extension. Where the claims recite particular positions of an abasic group, it is noted that such positions are recited in relation to the 5’-end of the second complementary sequence, and thus the position of the abasic group in relation to the 3’-end of the second complementary sequence may be different depending on the length of the second complementary sequence; nonetheless it is noted that Ng et al teaches the effectiveness of abasic sites that are 5, 7, 9, and 11 nucleotides from the 5-end of a primer (relevant to the limitations of claims 1 and 3). Ng et al does not exemplify the use of a plurality of abasic sites (relevant to claims 2, 4, 5, and 6), but where Ng et al teaches that abasic sites in a primer abrogate the binding of a polymerase to a template-primer structure, it would have been prima facie obvious to the skilled artisan to include a plurality of abasic sites in a primer to increase the effect of binding abrogation. Where Ng et al teaches that the positioning of abasic sites effects the disruption of polymerase binding, the use of multiple abasic sites, and particular abasic positioning would have been routine optimization for the skilled artisan practicing the methods of Komori et al in view of Ng et al. Similarly, with regard to the reduction in background signal amplification as recited in claim 13 and 14, where Ng et al teaches that different abasic positions have quantitatively different effects on nucleotide incorporation by a polymerase, and where Komori et al teaches that a goal of including oligonucleotide modifications is to reduce or eliminate the occurrence of any non-desired extension reactions, achieving any desired level of background signal would have been a matter of routine optimization to one of ordinary skill in the art.
Conclusion
No claim is allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Dean et al (US Pat 7,205,129) provides teachings related to primers with a plurality of abasic sites and the effect on extension reactions using the primers .
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Stephen Kapushoc
Primary Examiner
Art Unit 1683
/STEPHEN T KAPUSHOC/ Primary Examiner, Art Unit 1683
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