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 February 22, 2022 cancelling claims 1-20, amending claims 23-24 and adding new claims 27-28 is acknowledged.
Claims 21-28 are pending and will be examined.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on February 22, 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) 21-28 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Robins et al. (US Patent 9,371,558; June 2016).
With regard to claim 21, Robins teaches a method of measuring abundance values among a plurality of polynucleotides, the method comprising:
obtaining a plurality of polynucleotides in a sample, the sample comprising:
a first synthetic polynucleotide comprising a first PCR-free quantitation tag, the first PCR-free quantitation tag positioned between cut sites of a restriction enzyme (Abstract, Example 5, where synthetic template was added, where 4-5 molecules of each sequence of a synthetic template composition and where the synthetic template was detected through detection of barcode sequences; see also Fig 1, col. 19, line 22-24; col. 41 "Restriction Enzyme Sites" heading to col. 42, line 3; col. 45, line 55-65 where nucleic acid is cut);
and a second synthetic polynucleotide comprising a second PCR-free quantitation tag, the second PCR-free quantitation tag positioned between cut sites of a restriction enzyme (Abstract, Example 5, where synthetic template was added, where 4-5 molecules of each sequence of a synthetic template composition and where the synthetic template was detected through detection of barcode sequences; see also Fig 1, col. 19, line 22-24; col. 41 "Restriction Enzyme Sites" heading to col. 42, line 3; col. 45, line 55-65 where nucleic acid is cut);
digesting the first synthetic polynucleotide to liberate the first PCR-free quantitation tag (Fig 1, col. 19, line 22-24; col. 41 "Restriction Enzyme Sites" heading to col. 42, line 3; col. 45, line 55-65 where nucleic acid is cut);
digesting the second synthetic polynucleotide to liberate the second PCR-free quantitation tag (Fig 1, col. 19, line 22-24; col. 41 "Restriction Enzyme Sites" heading to col. 42, line 3; col. 45, line 55-65 where nucleic acid is cut);
sequencing the first PCR-free quantitation tag and the second PCR-free quantitation tag; and measuring the abundance of the first PCR-free quantitation tag and the second PCR-free quantitation tag (Abstract, Example 5, where the number of template products were divided by the number of unique synthetic template sequences to arrive at an amplification factor; see also col. 8, lines 36-49; col. 12 63 to col. 13, line 11; col. 50, line 19-24, where the diversity of nucleic acids is described and measured).
With regard to claim 22, Robins teaches a method of claim 21 further comprising comparing the abundance of the first PCR-free quantitation tag and the abundance of the second PCR-free quantitation tag; and determining the relative abundance of the first synthetic polynucleotide and the second synthetic polynucleotide (Abstract, Example 5, where the number of template products were divided by the number of unique synthetic template sequences to arrive at an amplification factor; see also col. 8, lines 36-49; col. 12 63 to col. 13, line 11; col. 50, line 19-24, where the diversity of nucleic acids is described and measured).
With regard to claim 23, Robins teaches a method of claim 21 or claim 22 wherein the first PCR-free quantitation tag is positioned between cut sites of the same restriction enzyme as the restriction enzyme whose cut sites the second PCR-free quantitation tag is positioned (Abstract, Example 5, where synthetic template was added, where 4-5 molecules of each sequence of a synthetic template composition and where the synthetic template was detected through detection of barcode sequences).
With regard to claim 24, Robins teaches a method of claim 21 or claim 22 wherein:
the first PCR-free quantitation tag is positioned between cut sites of a first restriction enzyme; and the second PCR-free quantitation tag is positioned between cut sites of a second restriction enzyme that differs from the first restriction enzyme (Abstract, Example 5, where synthetic template was added, where 4-5 molecules of each sequence of a synthetic template composition and where the synthetic template was detected through detection of barcode sequences).
With regard to claim 25, Robins teaches a method for detecting sub-sampling error in a sample comprising a plurality of polynucleotides, the method comprising: obtaining a sample comprising at least a first sample polynucleotide and a second sample polynucleotide;
spiking the sample with at least one synthetic diversity standard designed to detect sub- sampling error (Abstract, Example 5, where synthetic template was added); amplifying polynucleotides in the spiked sample (Abstract, Example 5, for example, where multiplex primers were added);
sequencing a first sample polynucleotide, a second sample polynucleotide, and at least one synthetic diversity standard; measuring the diversity of unique sequences of the synthetic diversity standard polynucleotide (Abstract, Example 5, where the number of template products were divided by the number of unique synthetic template sequences to arrive at an amplification factor; see also col. 8, lines 36-49; col. 12 63 to col. 13, line 11; col. 50, line 19-24, where the diversity of nucleic acids is described and measured);
comparing the diversity of unique sequences of the synthetic diversity standard polynucleotide to an expected diversity of unique sequences of the synthetic diversity standard polynucleotide; and detecting and quantifying sub-sampling error in the sample if the measured diversity of the synthetic diversity standard is less than the expected diversity of the synthetic diversity standard polynucleotide (Abstract, Example 5, where the number of template products were divided by the number of unique synthetic template sequences to arrive at an amplification factor; see also col. 8, lines 36-49; col. 12 63 to col. 13, line 11; col. 50, line 19-24, where the diversity of nucleic acids is described and measured).
With regard to claim 26, Robins teaches a method of claim 25 wherein the at least one synthetic diversity standard comprises a set of synthetic diversity standards (col. 8, lines 36-49; col. 12 63 to col. 13, line 11; col. 50, line 19-24, where the diversity of nucleic acids is described and measured).
With regard to claim 27, Robins teaches a method of claim 22, wherein the first PCR-free quantitation tag is positioned between cut sites of the same restriction enzyme as the restriction enzyme whose cut sites the second PCR-free quantitation tag is positioned (Abstract, Example 5, where synthetic template was added, where 4-5 molecules of each sequence of a synthetic template composition and where the synthetic template was detected through detection of barcode sequences).
With regard to claim 28, Robins teaches a method of claim 22 wherein:
the first PCR-free quantitation tag is positioned between cut sites of a first restriction enzyme; and the second PCR-free quantitation tag is positioned between cut sites of a second restriction enzyme that differs from the first restriction enzyme (Abstract, Example 5, where synthetic template was added, where 4-5 molecules of each sequence of a synthetic template composition and where the synthetic template was detected through detection of barcode sequences).
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) 24 and 27 is/are rejected under 35 U.S.C. 103 as being unpatentable over Robins et al. (US Patent 9,371,558; June 2016) as applied over claims 21-23, 26 and 28 in view of Brenner et al. (US PgPub 20060211030A1; September 2006).
With regard to claim 24, Brenner teaches a method of claim 21 or claim 22 wherein:
the first PCR-free quantitation tag is positioned between cut sites of a first restriction enzyme; and the second PCR-free quantitation tag is positioned between cut sites of a second restriction enzyme that differs from the first restriction enzyme (Figure 1C, legend, where tags are released for detection, which is a PCR-free detection; paragraph 40).
With regard to claim 27, Brenner teaches a method of claim 22, wherein the first PCR-free quantitation tag is positioned between cut sites of the same restriction enzyme as the restriction enzyme whose cut sites the second PCR-free quantitation tag is positioned (Figure 1C, legend, where tags are released for detection, which is a PCR-free detection; paragraph 40).
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 Robins to include the PCR-free quantitation as taught by Brenner to arrive at the claimed invention with a reasonable expectation for success. Brenner teaches “After the metric tags are completely assembled, the binary tags and restriction fragment can be cleaved from fragments (159) to give metric tags (165), which may, for example, be replicated using a biotinylated primer, captured, and digested to release the single stranded metric tags to be separated using conventional techniques. (For example, the captured strands are digested with appropriate nicking and/or restriction endonucleases having recognition sites in primer binding sites (130) and (134)). After loading onto electrophoretic separation column (170), the metric tags are separated and counted to give the number of restriction fragments in the original sample.” (paragraph 40). Therefore, one of ordinary skill in the art at the time the invention was made would have adjusted the teachings of Robins to include the PCR-free quantitation as taught by Brenner 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. Kinumi et al (Eur J Mass Spectrom, 2009, 15:399-407). Donald et al. (J of Chrom. B, 2005, 217:173-182).
Conclusion
No claims are allowed. All claims stand rejected.
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/STEPHANIE K MUMMERT/Primary Examiner, Art Unit 1681