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 .
Claims Status
Claims 4, 5, 9, 11, 13, 14, 19, 22, 24, 26, 27, 29, and 30 are cancelled.
Claims 1-3, 6-8, 10, 12, 15-18, 20, 21, 23, 25, 28, and 31-33 are pending.
Claims 1-3, 6-8, 10, 12, 15-18, 20, 21, 23, 25, 28, and 31-33 are examined.
Priority
The instant application is a national stage application of PCT/US20/54722, filed 10/08/2020, which claims priority to provisional US application No. 62/913045, filed 10/09/2019, and claims priority to provisional US application No. 62/938505, filed 11/21/2019. Therefore, the Effective Filing Date (EFD) assigned to each of the claims 1-3, 6-8, 10, 12, 15-18, 20, 21, 23, 25, 28, and 31-33 is the provisional filing date of application No. 62/913045, filed 10/09/2019.
Information Disclosure Statement
The Information Disclosure Statements filed 06/17/2022, and 05/26/2023 are in compliance with the provisions of 37 CFR 1.97 and have therefore been considered. Signed copies of the IDS documents are included with this Office Action.
Drawings
The drawings filed 04/01/2022 are accepted.
Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objections
Claims 1, 2, 6, 7, 16-18, 20, 21, 23, 25, 28 are objected to because of the following informalities:
In claims 1, 2, 6, 7, 16-18, 20, 21, 23, 25, and 28, the reference to the steps “a), b), c), and d)” is inconsistent with the manner they are cited in the steps of the independent claims. While the steps of the independent claims are denoted as “a)”, “b)”, etc. the claims refer to these steps as “(a)”, “(b)”, etc.
In claim 20, “at each at each genomic locus” should read “at each
Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-3, 6-8, 10, 12, 15-18, 20, 21, 23, 25, 28, and 31-33 are rejected under 35 U.S.C. 101 because the claimed inventions are directed to an abstract idea of mental steps, mathematic concepts, or a natural law without significantly more.
The MPEP at MPEP 2106.03 sets forth steps for identifying eligible subject matter:
(1) Are the claims directed to a process, machine, manufacture or composition of
matter?
(2A)(1) Are the claims directed to a judicially recognized exception, i.e. a law of nature,
a natural phenomenon, or an abstract idea?
(2A)(2) If the claims are directed to a judicial exception under Prong One, then is the
judicial exception integrated into a practical application?
(2B) If the claims are directed to a judicial exception and do not integrate the judicial
exception, do the claims provide an inventive concept?
With respect to step (1): Yes, the claims recite methods.
With respect to step (2A)(1): The claims recite abstract ideas of mental processes.
“Claims directed to nothing more than abstract ideas (such as a mathematical formula or equation), natural phenomena, and laws of nature are not eligible for patent protection” (MPEP 2106.04). Abstract ideas include mathematical concepts (mathematical formulas or equations, mathematical relationships and mathematical calculations), certain methods of organizing human activity, and mental processes (procedures for observing, evaluating, analyzing/judging and organizing information (MPEP 2106.04(a)(2)). Laws of nature or natural phenomena include naturally occurring principles/relations that are naturally occurring or that do not have markedly different characteristics compared to what occurs in nature (MPEP 2106(b)).
Mental processes recited in claim 1:
b) from the sequence reads, quantifying a linked reference allele and quantifying a linked alternative allele, thereby generating allele quantifications for a linked genomic locus
c) generating a set of genotype likelihoods for a target reference allele and a target alternative allele at the target genomic locus according to 1) a probability of the allele quantifications in b), given a particular genotype at the target genomic locus, and 2) a probability of a genotype at the target genomic locus based on prior probabilities of the target reference allele and the target alternative allele
generating a genotype at the target genomic locus based on the set of genotype likelihoods
Mental processes recited in claim 16:
b) for a haplotype group comprising a target genomic locus and a plurality of linked genomic loci, quantifying a linked reference allele and quantifying a linked alternative allele for each linked genomic locus in the group according to the sequence reads generated in a), thereby generating allele quantifications for each linked genomic locus in the haplotype group
c) generating a haplotype pair likelihood set for the haplotype group according to i) the allele quantifications in b), and ii) a probability of each haplotype pair
d) generating a genotype at the target genomic locus based on the haplotype pair likelihood set in c)
Dependent claims 2, 3, 6-8, 10, 12, 15, 17, 18, 20, 21, 23, 25, 28, and 31-33 recite additional steps that either are directed to abstract ideas or further limit the judicial exceptions in independent claim 1, and as such, are further directed to abstract ideas. Hence, the claims explicitly recite numerous elements that individually and in combination constitute abstract ideas. The relevant recitations are:
Claim 2: “the probability in (c)(1) is generated according to (i) a probability of observing the linked reference allele at the linked genomic locus, given a target reference allele at the target genomic locus, and/or (ii) a probability of observing the linked reference allele at the linked genomic locus, given a target alternative allele at the target genomic locus”
Claim 3: “the probability in (i) is based, in part, on a measure of linkage disequilibrium for the linked reference allele and the target reference allele, and the probability in (ii) is based, in part, on a measure of linkage disequilibrium for the linked reference allele and the target alternative allele, wherein the measure of disequilibrium is based on a haplotype frequency”
Claim 6: “the probability in (c)(2) is based, in part, on haplotype frequencies for (i) the target reference allele and the linked reference allele, (ii) the target reference allele and the linked alternative allele, (iii) the target alternative allele and the linked reference allele, and (iv) the target alternative allele and the linked alternative allele”
Claim 7: “(b) comprises quantifying a plurality of linked reference alleles and quantifying a plurality of linked alternative alleles, thereby generating a plurality of allele quantifications for a plurality of linked genomic loci”
Claim 8: “wherein (i) a plurality of genotype likelihood sets for the target genomic locus is generated according to the plurality of allele quantifications for the plurality of linked genomic loci, wherein the genotype at the target genomic locus is generated based on the plurality of genotype likelihood sets”
Claim 10: “a composite genotype likelihood is generated for each genotype from the plurality of genotype likelihood sets, wherein the genotype at the target genomic locus is generated based on the composite genotype likelihoods”
Claim 12: “generating a plurality of genotypes at a plurality of target genomic loci for the test sample, wherein each genotype in the plurality of genotypes is generated independently from the other genotypes in the plurality of genotypes, and identifying a subject based on the plurality of genotypes generated for the test sample”
Claim 15: “generating the genotype at the target genomic locus does not comprise generating a haplotype for two or more target genomic loci”
Claim 17: “the haplotype pair likelihood set for the haplotype group is generated in (c) according to a Bayesian probability”
Claim 18: “the haplotype group is generated in (c), given the allele quantifications in (b), according to i) a probability of the allele quantifications in (b) given each haplotype pair, and ii) a probability of each haplotype pair, wherein the probability in (i) is determined according to which genotype is most likely observed at each genomic locus across the haplotype group, given a particular haplotype pair”
Claim 20: “calculating the probability of the allele quantifications in (b) at each genomic locus and generating a product across all genomic loci in the haplotype group”
Claim 21: “the probability of each haplotype pair in (c)(ii) is determined, in part, according to haplotype frequencies, wherein the probability of each haplotype pair in (c)(ii) is determined, in part, according to haplotype frequencies for (i) a target reference allele and the linked reference allele, and (ii) a target reference allele and the linked alternative allele, (iii) a target alternative allele and the linked reference allele, and (iv) a target alternative allele and the linked alternative allele”
Claim 23: “identifying the most probable haplotype pair from the haplotype pair likelihood set, wherein the genotype at the target genomic locus is generated in (d) according to the most probable haplotype pair”
Claim 25: “aggregating the haplotype pair likelihoods across all haplotype pairs for the haplotype group, thereby generating aggregate likelihoods, wherein the genotype at the target genomic locus is generated in (d) according to the highest aggregate likelihood”
Claim 28: “wherein (b) comprises, for a plurality of haplotype groups each comprising a target genomic locus and a plurality of linked genomic loci, quantifying a linked reference allele and quantifying a linked alternative allele for each linked genomic locus in each group according to the sequence reads generated in (a), thereby generating allele quantifications for each linked genomic locus for each group in the plurality of haplotype groups, wherein a plurality of haplotype pair likelihood sets are generated in (c) according to the allele quantifications for each linked genomic locus for each group in the plurality of haplotype groups, wherein a plurality of genotypes at a plurality of target genomic loci are generated in (d) based on the plurality of haplotype pair likelihood sets”
Claim 31: “wherein each genotype in the plurality of genotypes is generated independently from the other genotypes in the plurality of genotypes”
Claim 32: “identifying a subject based on the plurality of genotypes generated for the test sample”
Claim 33: “wherein generating the genotype at the target genomic locus does not comprise generating a haplotype group comprising two or more target genomic loci”
The abstract ideas in the claims are evaluated under Broadest Reasonable Interpretation (BRI) and determined herein to each cover mental processes because the claims recite no more than performing a statistical analysis of sequence information in order to identify a genotype.
With respect to step (2A)(2): The claims must therefore be examined further to determine whether they integrate that abstract idea into a practical application (MPEP 2106.04(d)). The claimed additional elements are analyzed alone or in combination to determine if the judicial exception is integrated into a practical application (MPEP 2106.04(d).I.; MPEP 2106.05(a-h)). If the claim contains no additional elements beyond the judicial exception, the claim fails to integrate the abstract idea into a practical application (MPEP 2106.04(d).III).
Claims 1 and 16 recite the following additional elements that are not abstract ideas:
for a test sample comprising nucleic acid, obtaining sequence reads aligned to a reference genome
The step of obtaining sequence reads is directed to data gathering as it gathers the data on which the judicial exceptions are performed. Data gathering does not impose any meaningful limitation on the abstract idea, or how the abstract idea is performed. Data gathering steps are not sufficient to integrate an abstract idea into a practical application (MPEP 2106.05(g)).
None of the dependent claims recite additional elements.
Lastly, the claims have been evaluated with respect to step (2B): Because the claims recite an abstract idea, and do not integrate that abstract idea into a practical application, the claims lack a specific inventive concept. Under said analysis, Applicant is reminded that the judicial exception alone cannot provide that inventive concept or practical application (MPEP 2106.05). Identifying whether the additional elements beyond the abstract idea amount to such an inventive concept requires considering the additional elements individually and in combination to determine if they provide significantly more than the judicial exception (MPEP 2106.05.A i-vi).
With respect to the instant claims, the additional elements described above do not rise to the level of significantly more than the judicial exception. As set forth in the MPEP at 2106.05(d)(I), determinations of whether or not additional elements (or a combination of additional elements) may provide significantly more and/or an inventive concept rests in whether or not the additional elements (or combination of elements) represents well-understood, routine, conventional activity. Said assessment is made by a factual determination stemming from a conclusion that an element (or combination of elements) is widely prevalent or in common use in the relevant industry, which is determined by either a citation to an express statement in the specification or to a statement made by an applicant during prosecution that demonstrates a well-understood, routine or conventional nature of the additional element(s); a citation to one or more of the court decisions as discussed in MPEP 2106(d)(II) as noting the well-understood, routine, conventional nature of the additional element(s); a citation to a publication that demonstrates the well-understood, routine, conventional nature of the additional element(s); and/or a statement that the examiner is taking official notice with respect to the well-understood, routine, conventional nature of the additional element(s).
With respect to claims 1 and 16: The additional element of for a test sample comprising nucleic acid, obtaining sequence reads aligned to a reference genome does not rise to the level of significantly more than the judicial exception. As referenced in the MPEP at 2106.05(d).II. with respect to Genetic Techs. Ltd., 818 F.3d at 1377; 118 USPQ2d at 1546, analyzing DNA to provide sequence information or detect allelic variants is a well-understood, routine, and conventional activity. As such, it is recognized that these additional limitations are routine, well understood, and conventional in the art. These limitations do not improve the functioning of a computer, or comprise an improvement to any other technical field, they do not require or set forth a particular machine, they do not affect a transformation of matter, nor do they provide a non-conventional or unconventional step. As such, these limitations fail to rise to the level of significantly more.
The claims have all been examined to identify the presence of one or more judicial exceptions. Each additional limitation in the claims has been addressed, alone and in combination, to determine whether the additional limitations integrate the judicial exception into a practical application. Each additional limitation in the claims has been addressed, alone and in combination, to determine whether those additional limitations provide an inventive concept which provides significantly more than those exceptions. Individually, the limitations of the claims and the claims as a whole have been found lacking.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claims 1-3, 6, and 15 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Wong et al. (US 8,428,886 B2, patented April 2013, IDS reference).
Regarding claim 1, Wong et al. teaches a method for generating a genotype for a target genomic locus for a test sample, comprising:
a) for a test sample comprising nucleic acid, obtaining sequence reads aligned to a reference genome (column 10, line 10; column 10, line 27);
b) from the sequence reads, quantifying a linked reference allele and quantifying a linked alternative allele, thereby generating allele quantifications for a linked genomic locus (column 14, line 25);
c) generating a set of genotype likelihoods for a target reference allele and a target alternative allele at the target genomic locus according to 1) a probability of the allele quantifications in (b), given a particular genotype at the target genomic locus, and 2) a probability of a genotype at the target genomic locus based on prior probabilities of the target reference allele and the target alternative allele (column 14, line 35); and
d) generating a genotype at the target genomic locus based on the set of genotype likelihoods (column 13, line 26).
Regarding claim 2, the claim is directed to the probability in (c)(1) being generated according to (i) a probability of observing the linked reference allele at the linked genomic locus, given a target reference allele at the target genomic locus, and/or (ii) a probability of observing the linked reference allele at the linked genomic locus, given a target alternative allele at the target genomic locus. Wong et al. teaches the method of claim 1. Wong et al. also teaches generating genotype likelihoods according to the probability of observing the linked reference allele given a target alternative allele at the target genomic locus (column 14, line 35).
Regarding claim 3, the claim is directed to the probability in (i) being based, in part, on a measure of linkage disequilibrium for the reference allele and the target reference allele, and the probability in (ii) being based, in part, on a measure of linkage disequilibrium for the linked reference allele and the target alternative allele, wherein the measure of disequilibrium is based on a haplotype frequency. Wong et al. teaches the method of claim 2. Wong et al. teaches a measure of linkage disequilibrium for the reference and target alleles (column 14, line 55) and the measure of disequilibrium being based on a haplotype frequency (column 14, line 57).
Regarding claim 6, the claim is directed to the probability in (c)(2) being based, in part, on haplotype frequencies for (i) the target reference allele and the linked reference allele, (ii) the target reference allele and the linked alternative allele, (iii) the target alternative allele and the linked reference allele, and (iv) the target alternative allele and the linked alternative allele. Wong et al. teaches the method of claim 1. Wong et al. also teaches the probability of a genotype based on prior probabilities being based in part on haplotype frequencies for the target, reference and linked alleles (column 14, line 57).
Regarding claim 15, the claim is directed to generating the genotype at the target genomic locus not comprising generating a haplotype for two or more target genomic loci. Wong et al. teaches the method of claim 1. Wong et al. teaches generating a genotype for one target genomic loci (column 13, line 26), and thus not two or more target genomic loci.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claims 7, 8, 10, 12, 16, 17, 18, 20, 21, 23, 25, 28, and 31-33 are rejected under 35 U.S.C. 103 as being unpatentable over Wong et al., as applied to claims 1-3, 6, and 15 in the 102 rejection above, in view of Ball et al. (US 2017/0262577 A1, published September 2017).
Regarding claim 7, the claim is directed to (b) comprising quantifying a plurality of linked reference alleles and quantifying a plurality of linked alternative alleles, thereby generating a plurality of allele quantifications for a plurality of linked genomic loci. Wong et al. teaches the method of claim 1. Wong et al. teaches quantifying a linked reference allele and a linked alternative allele (column 14, line 25)
Wong et al. does not teach the claim element of quantifying a plurality of linked reference alleles and quantifying a plurality of linked alternative alleles.
However, Ball et al. teaches haplotype phasing models. Ball et al. teaches a haplotype group comprising a plurality of linked alleles (paragraph [0021]).
Regarding claim 8, the claim is directed to (i) a plurality of genotype likelihood sets for the target genomic locus being generated according to the plurality of allele quantifications for the plurality of linked genomic loci, wherein the genotype at the target genomic locus is generated based on the plurality of genotype likelihood sets. Wong et al. teaches the method of claim 7 in view of Ball et al. Wong et al. teaches generating a genotype likelihood according to allele quantifications for the linked loci (column 14, line 35), wherein the genotype is generated according to the quantifications (column 13, line 26).
Ball et al. teaches generating likelihoods for all possible haplotypes (paragraph [0054]).
Regarding claim 10, the claim is directed to a composite genotype likelihood being generated for each genotype from the plurality of genotype likelihood sets, wherein the genotype at the target genomic locus is generated based on the composite genotype likelihoods. Wong et al. teaches the method of claim 8 in view of Ball et al. Wong et al. also teaches composite genotype likelihoods and generating a genotype at the target locus based on the composite genotype likelihoods (column 13).
Regarding claim 12, the claim is directed to generating a plurality of genotypes at a plurality of target genomic loci for the test sample, wherein each genotype in the plurality of genotypes is generated independently from the other genotypes in the plurality of genotypes, and identifying a subject based on the plurality of genotypes generated for the test sample. Wong et al. teaches the method of claim 1. Wong et al. teaches the test sample comprising genetic material from multiple individuals and the genotypes for each individual are generated independently (column 9, line 47).
Wong et al. does not teach the claim element of a plurality of genotypes at a plurality of target genomic loci, and identifying a subject based on the plurality of genotypes generated.
However, Ball et al. teaches that SNPs can serve as biomarkers for hereditary and disease studies, and that haplotypes are identified based on consecutive SNPs of varying length (paragraph [0004]). Thus, it would be obvious to one of ordinary skill in the art to use these haplotypes to identify family members or hereditary status of an individual using these methods because the SNPs serve as biomarkers.
Regarding claim 16, Wong et al. teaches a method for generating a genotype for a target genomic locus for a test sample, comprising:
a) for a test sample comprising nucleic acid, obtaining sequence reads aligned to a reference genome (column 10, line 10; column 10, line 27);
b) for a haplotype group comprising a target genomic locus and a plurality of linked genomic loci, quantifying a linked reference allele and quantifying a linked alternative allele for each linked genomic locus in the group according to the sequence reads generated in (a), thereby generating allele quantifications for each linked genomic locus in the haplotype group (column 14, line 25);
c) generating a haplotype pair likelihood set for the haplotype group according to i) the allele quantifications in (b), and ii) a probability of each haplotype pair; and
d) generating a genotype at the target genomic locus based on the haplotype pair likelihood set in (c) (column 13, line 26).
Wong et al. does not teach the claim elements of a haplotype group comprising a target genomic locus and a plurality of linked genomic loci, c) generating a haplotype pair likelihood set for the haplotype group according to i) the allele quantifications in (b), and ii) a probability of each haplotype pair, and d) generating a genotype based on the haplotype pair likelihood set in (c).
However, Ball et al. teaches haplotype phasing models. Ball et al. teaches a haplotype group comprising a plurality of linked alleles (paragraph [0021]),generating a likelihood for different possible haplotype pairs, and calling a haplotype genotype based on these likelihoods (paragraph [0069]).
Regarding claim 17, the claim is directed to the haplotype pair likelihood set for the haplotype group being generated in (c) according to a Bayesian probability. Wong et al. teaches the method of claim 16 in view of Ball et al. Wong et al. also teaches an allele likelihood being generated according to a Bayesian probability (column 12, line 40).
Furthermore, Ball et al. teaches generated haplotype pair likelihoods according to Bayesian probability (page 8, paragraph [0080]).
Regarding claim 18, the claim is directed to the haplotype pair likelihood set for the haplotype group being generated in (c), given the allele quantifications in (b), according to i) a probability of the allele quantifications in (b) given each haplotype pair, and ii) a probability of each haplotype pair, wherein the probability in (i) is determined according to which genotype is most likely observed at each genomic locus across the haplotype group, given a particular haplotype pair. Wong et al. teaches the method of claim 16 in view of Ball et al. Wong et al. teaches allele likelihoods being generated according to 1) a probability of the allele quantifications in (b), given a particular genotype at the target genomic locus, and 2) a probability of a genotype at the target genomic locus based on prior probabilities of the target reference allele and the target alternative allele (column 14, line 35).
Wong et al. does not teach the claim element of generating a haplotype pair likelihood.
However, Ball et al. teaches generating a haplotype pair likelihood given allele quantifications according to the allele quantifications given each haplotype pair and a probability of each haplotype pair (paragraphs [0031], [0051], [0052], [0054]).
Regarding claim 20, the claim is directed to calculating the probability of the allele quantifications in (b) at each genomic locus and generating a product across all genomic loci in the haplotype group. Wong et al. teaches the method of claim 18 in view of Ball et al. Wong et al. teaches quantifying a linked reference allele and quantifying a linked alternative allele, thereby generating allele quantifications for a linked genomic locus (column 14, line 25).
Wong et al. does not teach the claim element of a haplotype group.
However, Ball et al. teaches assigning quantifications for alleles (paragraph [0053]) and generating the probabilities across all genomic loci in the haplotype group by analyzing all possible haplotype likelihoods (paragraph [00054]).
Regarding claim 21, the claim is directed to the probability of each haplotype pair in (c)(ii) is determined, in part, according to haplotype frequencies, wherein the probability of each haplotype pair in (c)(ii) is determined, in part, according to haplotype frequencies for (i) a target reference allele and the linked reference allele, (ii) a target reference allele and the linked alternative allele, (iii) a target alternative allele and the linked reference allele, and (iv) a target alternative allele and the linked alternative allele. Wong et al. teaches the method of claim 16 in view of Ball et al. Wong et al. teaches quantifying a linked reference allele and quantifying a linked alternative allele, thereby generating allele quantifications for a linked genomic locus (column 14, line 25).
Wong et al. does not teach the claim element of a probability of specifically a haplotype pair.
However, Ball et al. teaches examining haplotype pair probabilities (paragraph [0054]).
Regarding claim 23, the claim is directed to (c) further comprising identifying the most probable haplotype pair from the haplotype pair likelihood set, wherein the genotype at the target genomic locus is generated in (d) according to the most probably haplotype pair. Wong et al. teaches the method of claim 16 in view of Ball et al.
Wong et al. does not teach the claim element of identifying the most probably haplotype pair.
However, Ball et al. teaches identifying the most probably haplotype pair, thus representing the most probable phased haplotype (paragraph [0069]).
Regarding claim 25, the claim is directed to (c) further comprising aggregating the haplotype pair likelihoods across all haplotype pairs for the haplotype group, thereby generating aggregate likelihoods, wherein the genotype at the target genomic locus is generated in (d) according to the highest aggregate likelihood. Wong et al. teaches the method of claim 16 in view of Ball et al.
Wong et al. does not teach the claim element of generating or aggregating haplotype pair likelihoods.
However, Ball et al. teaches generating aggregate haplotype pair likelihoods across all the haplotype pairs and phasing the haplotype according to the highest likelihood (paragraph [0069]).
Regarding claim 28, the claim is directed to (b) comprising, for a plurality of haplotype groups each comprising a target genomic locus and a plurality of linked genomic loci, quantifying a linked reference allele and quantifying a linked alternative allele for each linked genomic locus in each group according to the sequence reads generated in (a), thereby generating allele quantifications for each linked genomic locus for each group in the plurality of haplotype groups, wherein a plurality of haplotype pair likelihood sets are generated in (c) according to the allele quantifications for each linked genomic locus for each group in the plurality of haplotype groups, wherein a plurality of genotypes at a plurality of target genomic loci are generated in (d) based on the plurality of haplotype pair likelihood sets. Wong et al. teaches the method of claim 16 in view of Ball et al. Wong et al. teaches quantifying a linked reference allele and quantifying a linked alternative allele, thereby generating allele quantifications for a linked genomic locus (column 14, line 25), generating a set of genotype likelihoods for a target reference allele and a target alternative allele at the target genomic locus according to 1) a probability of the allele quantifications in (b), given a particular genotype at the target genomic locus, and 2) a probability of a genotype at the target genomic locus based on prior probabilities of the target reference allele and the target alternative allele (column 14, line 35), and generating a genotype at the target genomic locus based on the set of genotype likelihoods (column 13, line 26).
Wong et al. does not teach the claim element of applying this method to a haplotype group.
However, Ball et al. teaches a haplotype group comprising a plurality of linked alleles (paragraph [0021]),generating a likelihood for different possible haplotype pairs, and calling a haplotype genotype based on these likelihoods (paragraph [0069]).
Regarding claim 31, the claim is directed to each genotype in the plurality of genotypes being generated independently from the other genotypes in the plurality of genotypes. Wong et al. teaches the method of claim 28 in view of Ball et al. Wong et al. also teaches generating genotypes for multiple samples independently (column 9, line 47).
Regarding claim 32, the claim is directed to identifying a subject based on the plurality of genotypes generated for the test sample. Wong et al. teaches the method of claim 28 in view of Ball et al.
Wong et al. does not teach the claim element of identifying a subject based on the plurality of genotypes generated for the test sample.
However, Ball et al. teaches that SNPs can serve as biomarkers for hereditary and disease studies, and that haplotypes are identified based on consecutive SNPs of varying length (paragraph [0004]). Thus, it would be obvious to one of ordinary skill in the art to use these haplotypes to identify family members or hereditary status of an individual using these methods because the SNPs serve as biomarkers.
Regarding claim 33, the claim is directed to generating the genotype at the target genomic locus not comprising generating a haplotype group comprising two or more target genomic loci. Wong et al. teaches the method of claim 16 in view of Ball et al. Wong et al. teaches generating a genotype without generating a haplotype group (column 13, line 26).
Furthermore, Ball et al. teaches generating a genotype comprising generating a haplotype group for one target genomic loci (paragraph [0007], column 2).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have incorporated the elements of generating haplotype groups and haplotype likelihoods of Ball et al. to the method of Wong et al. because Wong et al. is directed to calling genotypes (Abstract), including linked alleles affected by haplotypes (column 14, line 55), and Ball et al. is directed to genotyping haplotypes (paragraph [0007]). Thus, one of ordinary skill in the art would have a reasonable expectation of success of calling genotypes of a haplotype by combing the prior art references.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMILIE A NEULEN whose telephone number is (571)272-7543. The examiner can normally be reached 9am - 5pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Larry D Riggs can be reached at (571)270-3062. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/E.A.N./Examiner, Art Unit 1686
/LARRY D RIGGS II/Supervisory Patent Examiner, Art Unit 1686