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
1. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on August 11, 2025 has been entered.
Status of the Application
2. Claims 3-6, 8, 15, 22, 24, 59-60, 64, 67, 70-73 are pending under examination. New claims 74-75 are added. The Applicant’s arguments and the amendment have been fully considered and found persuasive in-part for the following reasons.
Claim Rejections - 35 USC § 112-Withdrawn
3. The rejection of claims 72-73 under 35 USC 112(b) has been withdrawn in view of the amendment.
Claim Rejections - 35 USC § 103-maintained
4. 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.
A. Claims 3-5, 8, 15, 24, 59, 60, 64, 67 and 71-75 are rejected under 35 U.S.C. 103 as being unpatentable over Wu et al. (US 2017/0327870) in view of Armes et al. (US 2012/0258456).
Wu et al. teach a method of claim 67, 15, 74-75, comprising: a) assembling a reaction mixture comprising, (i) a target molecule comprising a nucleic acid sequence of interest, (ii) a set of oligonucleotides comprising a 1st SW (selective wobble) (universal or unnatural nucleotide) primer comprising a 1st SW site, a 2nd SW primer comprising a 2nd SW site, a third primer (additional oligonucleotide or a blocker oligonucleotide) and a polymerase with 3’-5’exonuclease activity (para 0004-0028, 0064-0066, 0072-0076, primers comprise unnatural or universal nucleotides at SNP site, wherein the 3’-5’ exonuclease cleaves a phosphodiester bond linking molecular moiety to the primer(para 0082, 0121-0135);
b) conducting an amplification reaction of the target molecule comprising the nucleic acid sequence of interest using the reaction mixture (para 0082, 0121-0135);
c) detection amplified target nucleic acid comprising the nucleic acid sequence of interest nucleic acid of interest or variants thereof present in the target molecule (para 0082, 0121-0135);
wherein the 1st SW site and 2nd SW site are configured to enable non-disrupted nested amplification and quantitation of the target molecule of interest (para 0121-0135, 0076, 0079-0097);
wherein a 3’ end of the 1st and 2nd SW primer comprise a first molecular moiety and a second molecular moiety that are non-complementary to the target nucleic acid sequence of interest and wherein the 1st SW site and the first molecular moiety in the 1st SW primer are at different sites and the 2nd SW site and the second molecular moiety in the 2nd SW primer are at different sites; wherein the first and the second molecular moiety are configured to be cleaved prior to extension of the 1st and 2nd SW primer using the 3’-5’ exonuclease activity of the polymerase (para 0121-0135, 0072-0082).
With reference to claim 3-4, Wu et al. teach that the first and the second label comprises a fluorescent dye-quencher pair and the primer set comprises a first and second primer complementary to the target molecule comprising the nucleic acid of interest (para 0118-0119, 0164-0165).
With reference to claim 8, Wu et al. teach that the specific and/or quantitative detection comprises: annealing an amplification primer pair to both strands of the target molecule comprising nucleic acid sequence of interest, amplifying the target molecule with the primer pair in the presence of the polymerase, and detecting fluorescence emission (para 0121-0135).
With reference to claim 59, Wu et al. teach that the target is generated by a reverse transcription (para 0027, 0081, 0097, 0109).
With reference to claims 60, 64, Wu et al. teach that the molecular moiety comprises inosine, uracil, iso-dG, iso-dC (para 0121-0135, 0144-0145).
However, Wu et al. did not specifically teach a probe comprising attenuation site.
Armes et al. teach a method of 3-5, 8, 15, 24, 59, 60, 64, 67 and 71-75 for monitoring amplification reaction and detecting target nucleic acid wherein the amplification reaction comprises oligonucleotides (probe or primer) comprising a detectable label and one or more internal residues or abasic site mimics (attenuation site comprising one or more units), wherein the internal residue or abasic mimics comprise a spacer and a detectable dye pair, wherein the internal residue comprises a fluorophore , wherein the polymerase binding unit comprises an archaebacterial polymerase binding unit (para 0102-0104, 0110-0118, 0090-0096, 0026, 0062, 0072-0085).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to modify the method of Wu et al. with a probe comprising attenuation site as taught by Armes et al. to develop an improved method for amplifying target polynucleotide sequences in a sample. The ordinary person skilled in the art would have motivated to combine the method of Wu et al. with a probe comprising attenuation site of Armes et al. and have a reasonable expectation of
success that the combination would improve the amplification of specific target nucleic acids because Armes et al. explicitly taught that use of oligonucleotides comprising internal abasic site mimics or attenuation site that would improve the detection of different variants of the target nucleic acid and monitoring detection during amplification (para 0026, 0093) and such a modification of the method is considered obvious over the cited art.
B. Claim 6 and 70 are rejected under 35 U.S.C. 103 as being unpatentable over Wu et al. (US 2017 /0327870) in view of Armes et al. (US 2012/0258456) and further in view of Corman et al. (Euro Surveill, Vol. 25(3), page 1-8, January 2020).
Wu et al. in view of Armes et al. teach a method of amplifying a target nucleic acid as discussed above.
However, Wu et al. and Armes et al. did not specifically teach that the nucleic acid sequence of interest comprising SARS-CoV-2 sequence as claimed in claims 6 and 70.
Corman et al. teach a diagnostic method for detecting a SARS-CoV-2 nucleic acid sequence (2019-nCov) in a sample, wherein the method comprises performing a real-time RT-PCR for detecting SARS-CoV-2 in a sample (page 1, abstract, paragraphs under Methods section on page 2-3).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the invention to modify the method of Wu et al. and Armes et al. with SARS CoV-2 as a target nucleic acid for detection in a sample as taught by Corman et al. to develop an improved amplification method for detecting SARS CoV-2 target nucleic acids in a sample. The ordinary person skilled in the art would have motivated to combine the method of Wu et al. and Armes et al. with the target nucleic acid of SARS CoV-2 as taught by Corman et al. and have a reasonable expectation of success that the combination would result in an improved method for detecting SARS CoV-2 nucleic acid in a sample because Corman et al. explicitly taught diagnostic method for detecting the SARS CoV-2 in a sample (page 1, abstract) and such a modification of the method is considered obvious over the cited art.
Response to Arguments:
With reference to the rejection of claims 3-5, 8, 15, 22, 24, 59-60, 64, 67, 71-73 under 35 USC 103 as being unpatentable over Wu et al. in view of Armes et al. and the rejection of claims 6 and 70 under 35 USC103 as being unpatentable over Wu et al. in view of Armes et al. and further in view of Corman et al., and the declaration under CFR 1.132, the Applicant’s arguments, declaration and the amendment have been fully considered and found persuasive in-part. The amendment to the independent claims 15 and 67 recite ‘an attenuation site comprising a spacer and/or an abasic nucleotide’ and the amended claims also recite ‘the attenuation site comprises a polymerase binding nucleic acid units’. The declaration under CFR 1.132 indicates that the attenuation site comprising a spacer, which is not a nucleotide is not cleaved by the polymerase having 3’-5’ exonuclease activity. The arguments and the amendment have been found persuasive in-part for the attenuation site comprising abasic nucleotide and polymerase binding to nucleotide units. However the arguments were found unpersuasive for an attenuation site comprising a spacer, which is not a nucleotide. Further, the Applicant cited the paragraphs 0145, 0151, 0156 to support the amendment, clearly disclose nucleotide unit and the polymerase binding activity. However, said cited paragraphs do not relate the polymerase binding activity with a spacer (non-nucleotide). Thus, the rejection has been maintained for reciting an attenuation site comprising a spacer, which is one of the alternatives represented by ‘and/or’ which is within the scope of the rejection. The rejection of claim 22 is moot and withdrawn because the combination did not teach the limitations in claim 22. The rejection of claims 3-6, 8, 15, 24, 59, 60, 64, 67 and 70-73 has been maintained and restated as above to address the amendment.
New issues
Informalities
5. The following informalities are noted:
(i) claim 22 in the preamble of the claim recites ‘comprising a SW method comprising’. Amending the claim to delete ‘a SW method comprising’ is suggested.
(I) claim 15 step (A) (ii) recites ‘a 1st SW (selective wobble) primer’ and a 2nd SW primer’; claim 22 recites ‘1st SW’ and 2nd SW’. Amending the claim to recite ‘a first selective wobble (SW) primer’ and a second SW primer’ is suggested. Appropriate correction is required.
Claim Rejections - 35 USC § 112
6. 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 3-6, 8, 15, 22, 24, 59-60, 64, 67, 70-75 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. Claims 15 and 67 recite ‘wherein the attenuating site comprises a polymerase binding nucleotide unit’. The limitation is unclear and indefinite because the independent claims 15 and 67 recite ‘attenuating site comprises an abasic nucleotide and/or a spacer’, wherein a spacer is not a nucleotide and it is not clear how an attenuating site comprising a spacer can comprise a polymerase binding nucleotide unit.
Conclusion
Claim 22 is free of prior art.
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Suryaprabha Chunduru
Primary Examiner
Art Unit 1681
/SURYAPRABHA CHUNDURU/Primary Examiner, Art Unit 1681