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 .
The preliminary amendment filed March 10, 2022, canceling claims 1-14 and 22-26 is acknowledged. Claims 15-21 and 27-38 are pending and will be examined.
Claims 15-21 and 27-38 are pending.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on March 10, 2022 was filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 102
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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(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) 15-18, 27-29 and 32-35 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nadeau et al. (US PgPub 20090131647; May 2009).
With regard to claim 15, Nadeau teaches a reaction mixture for analyzing, quantitating or detecting one or more alleles or polymorphisms in a target nucleic acid,
wherein the reaction mixture comprises a first allele-specific primer, which is specific for a first allele, comprising a first 5'-universal tail which comprises a binding site for a first universal FRET-based reporter primer (UFP), wherein the first UFP comprises a first fluorophore and at least a first quencher moiety (see for example, p 13, Example 5 and Table 1 where primers specific for specific SNPs are included);
and a second allele-specific primer which is specific for a second allele, comprising a second 5'-universal tail which comprises a binding site for a second UFP, wherein the second UFP comprises a second fluorophore and at least a second quencher moiety (see for example, p 13, Example 5 and Table 1 where primers specific for specific SNPs are included);
wherein the first fluorophore and the second fluorophore are different and the first quencher moiety and the second quencher moiety are the same or different (paragraph 39-40 and Fig 1A where a reporter probe includes a donor and quencher).
With regard to claim 16, Nadeau teaches a reaction mixture of claim 15, wherein the first fluorophore and the second fluorophore are located at the 5'-end of the first UFP and the second UFP respectively, and the at least first quencher moiety and the at least second quencher moiety are located at an internal nucleotide of the first UFP and the second UFP respectively (paragraph 39-40 and Fig 1A where a reporter probe includes a donor and quencher).
With regard to claim 17, Nadeau teaches a reaction mixture of claim 15, further comprising a locus specific primer (see for example, p 13, Example 5 and Table 1 where primers specific for specific SNPs are included).
With regard to claim 18, Nadeau teaches a reaction mixture of claim 15, further comprising one or more nucleic acid polymerases (Abstract, legend to Fig 2A and paragraph 4).
With regard to claim 27, Nadeau teaches an oligonucleotide comprising an allele-specific portion and a 5'-universal tail, wherein the 5'-universal tail comprises a binding site for a universal FRET-based reporter primer and the universal tail is not complementary to the target nucleic acid sequence (paragraph 39-40 and Fig 1A where a reporter probe includes a donor and quencher).
With regard to claim 28, Nadeau teaches an oligonucleotide of claim 27, wherein the 5'-universal tail comprises a nucleotide sequence that is identical to the sequence of a universal FRET-based reporter primer (paragraph 39-40 and Fig 1A where a reporter probe includes a donor and quencher).
With regard to claim 29, Nadeau teaches an oligonucleotide of claim 27, wherein the 5'-universal tail comprises a nucleotide sequence that is complementary to the sequence of a universal FRET-based reporter primer (paragraph 39-40 and Fig 1A where a reporter probe includes a donor and quencher).
With regard to claim 32, Nadeau teaches a kit for analyzing, quantitating or detecting one or more alleles or polymorphisms in a target nucleic acid (see for example, p 13, Example 5 and Table 1 where primers specific for specific SNPs are included).
wherein the kit comprises a first allele-specific primer, which is specific for a first allele, comprising a first 5'-universal tail which comprises a binding site for a first universal FRET-based reporter primer (UFP), wherein the first UFP comprises a first fluorophore and at least a first quencher moiety (paragraph 39-40 and Fig 1A where a reporter probe includes a donor and quencher);
and a second allele-specific primer which is specific for a second allele, comprising a second 5'-universal tail which comprises a binding site for a second UFP, wherein the second UFP comprises a second fluorophore and at least a second quencher moiety (paragraph 39-40 and Fig 1A where a reporter probe includes a donor and quencher);
wherein the first and second fluorophore are different and the at least first quencher moiety and the at least second quencher moiety are the same or different (paragraph 39-40 and Fig 1A where a reporter probe includes a donor and quencher).
With regard to claim 33, Nadeau teaches a kit of claim 32, wherein the first fluorophore and the second fluorophore are located at the 5'-end of the first UFP and the second UFP respectively, and the at least first quencher moiety and the at least second quencher moiety are located at an internal nucleotide of the first UFP and the second UFP respectively (?).
With regard to claim 34, Nadeau teaches a kit of claim 32, further comprising a locus specific primer (see for example, p 13, Example 5 and Table 1 where primers specific for specific SNPs are included).
With regard to claim 35, Nadeau teaches a kit of claim 32, further comprising one or more nucleic acid polymerases (Abstract, legend to Fig 2A and paragraph 4).
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.
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) 19-21 and 30-31 is/are rejected under 35 U.S.C. 103 as being unpatentable over Nadeau et al. (US PgPub 20090131647; May 2009) as applied over 15-18, 27-29 and 32-35 above and further in view of Xi et al. (US Patent 9,476,093; October 2016).
With regard to claim 19, Xi teaches a reaction mixture of claim 15, further comprising a pyrophosphorolysis enzyme (Abstract; col 1 and col. 4 and col. 7 where pyrophosphatase is included).
With regard to claim 20, Xi teaches a reaction mixture of claim 15, further comprising a polyphosphorolysis enzyme (Abstract, col. 1 where “activation by polyphosphorolysis (APP) reactions” is described).
With regard to claim 21, Xi teaches a reaction mixture of claim 20, further comprising one or more polyphosphorolyzing agents (Abstract, col. 1 where “activation by polyphosphorolysis (APP) reactions” is described).
With regard to claim 30, Xi teaches an oligonucleotide of claim 27, wherein the 3' end of the oligonucleotide comprises a blocking agent such that the blocked end is configured to be activated by a pyrophosphorolysis enzyme (Abstract; col 1 and col. 4 and col. 7 where pyrophosphatase is included).
With regard to claim 31, Xi teaches an oligonucleotide of claim 30 wherein the blocking agent is a dideoxynucleotide (ddN) (col. 7, where dideoxynucleotide is described).
With regard to claim 36, Xi teaches a kit of claim 32, further comprising a pyrophosphorolysis enzyme (Abstract; col 1 and col. 4 and col. 7 where pyrophosphatase is included).
With regard to claim 37, Xi teaches a kit of claim 32, further comprising a pyrophosphorolysis enzyme (Abstract; col 1 and col. 4 and col. 7 where pyrophosphatase is included).
With regard to claim 38, Xi teaches a kit of claim 37, further comprising one or more polyphosphorolyzing agents (Abstract, col. 1 where “activation by polyphosphorolysis (APP) reactions” is described).
It would have been prima facie obvious to one of ordinary skill in the art at the time the
invention was made to have adjusted the teachings of Nadeau to include the polyphorolysis and pyrophosphorolysis enzymes and activation as described by Xi to arrive at the claimed invention with a reasonable expectation for success. Both Nadeau and Xi are focused on detection of specific nucleic acid targets. Xi teaches “methods for polymerizing, amplifying, and/or sequencing a target nucleic acid from a test sample using activation by polyphosphorolysis (APP) reaction. Polyphosphorolysis refers to the removal of a non-extendable nucleotide from a nucleic acid (e.g., an oligonucleotide) in the presence of one or more polyphosphorolyzing agents and an enzyme that exhibits polyphosphorolyzing activity. APP may be used to polymerize and/or amplify and/or sequence nucleic acid molecules, including but not limited to ribonucleic acid (e.g., RNA) and/or deoxyribonucleic acid (e.g., DNA), or hybrids thereof. Other uses for the methods described herein will be readily understood by one of skill in the art. " (col. 5, lines 5-16). Xi also teaches “The methods are useful to, for example, detect minimal residual disease-causing agent(s) (e.g., rare remaining cancer cells during remission, especially mutations in the p53 gene or other tumor suppressor genes previously identified within the tumors), and/or measure mutation load (e.g., the frequency of specific Somatic mutations present in normal tissues, such as blood or urine)” (col. 1, line 37-43). Therefore, one of ordinary skill in the art at the time the invention was made would have been motivated to have adjusted the teachings of Nadeau to include the polyphorolysis and pyrophosphorolysis enzymes and activation as described by Xi to arrive at the claimed invention with a reasonable expectation for success.
Citation of Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Mokany et al. (Clin Chem, 2013, 59:2, 419-426).
Conclusion
No claims are allowed. All claims stand rejected.
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/STEPHANIE K MUMMERT/Primary Examiner, Art Unit 1681