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 .
Applicant’s amendment
Applicant’s preliminary amendment filed 7/11/2022 has been received and entered. Claims 1-13 have been amended, claims 14-19 have been cancelled and claims 20-26 have been added.
Claims 1-13, 20-26 are pending.
Priority
This application filed 4/29/2022 is a divisional of 15/319253 filed 12/15/2016, now US Patent 11,328794, which is a 371 National stage filing of PCT/US2015/036250 filed 6/17/2015 which claims benefit to US provisional application 62/013743 filed 6/18/2014.
Examiner note: this application is indicated to be a divisional, and in reviewing the prosecution of the parent application a restriction requirement was made and that the present claims are directed to non-elected group I.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 4/29/2022 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. See for example page 7 of 28 last full paragraph. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
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 1-13, 20-26 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Claim analysis
Claim 1 has been amended and is generally directed to a method for genotyping genomic DNA. More specifically, the claims have been amended to recite calculating LD scores for ‘a set of two or more polymorphic sites’ and genotyping of the preamble is accomplished in the final step by preparing a compilation of scores obtained in the calculation of LD. Dependent claims set forth the source of the DNA data (claim 2, being ‘human’ in claim 24) and types of polymorphic sites being analyzed (claims 4-8) and what platform is used to obtain the sequences which provide a variety of number of sites to be analyzed. The claims comprise a method where a sample analyzed using polymorphisms to determine the presence of LD and calculating a compilation of scores which represents a genotype. For determining LD in an unknow sample, the specification teaches:
“Two loci are in linkage disequilibrium (LD) if their alleles are not randomly
associated [11]. This non-random association implies that observing the allelic state of one
locus provides some information about the state of the other. Similarly, our approach is based on the idea that observations made in one sample should not provide information about bases
5in another sample if the two individuals are unrelated. In other words, the probability of observing one combination of alleles at linked loci should be dependent on the allele
frequencies if the two alleles originate from different chromosomes. However, if they both observations are made from the same chromosome, the probability of the observation is the
frequency of that haplotype. 10In our approach, we explicitly model allele and haplotype frequencies using a reference panel of phased haplotypes that represent the population from which our samples were drawn. We consider pairs of SNPs within close physical proximity of each other where a base has been observed. We compare the probabilities of observing the first base given the 15observation of the second under two simple models. The first represents the case where the two bases have been drawn from independent chromosomes, so the probability of the
observation is the frequency of the base in the population and is independent of the first base.
The second model represents the case where the two bases where drawn from the same
diploid individual, where there is an equal chance the two bases come from the same
20chromosome or independent chromosomes. The two models are compared as a log-likelihood
ratio (LLR). We aggregate the LLRs for pairs of SNPs by sampling pairs from sliding windows
across each chromosome to avoid the effects of linkage and to mitigate the influence of
heavily sampled regions.” (detailed at page 16).
It is noted that the passage references number 11 which is Slatkin M, Linkage disequilibrium--understanding the evolutionary past and mapping the medical future. Nat Rev Genet 2008, 9:477-85 and provides for a similar overview. In summary, the basis of the inventions is based in part on the teachings at pages 2-3 for:
“The majority of positions in the genome will not have any observations in a single low coverage library. Comparing two low-coverage 2WO 2015/195816 PCT/US2015/036250libraries compounds this problem, as very few positions will have observations in both libraries. This limits direct comparisons of alleles in different libraries to a very small number of informative sites.”
and the application of comparing informative polymorphisms/SNPs/genotype/alleles at pages 8-9 teaching:
“Since majority of these positions will not be observed in a low-coverage library, our method does not rely on direct comparison of SNP alleles but instead uses a likelihood model to examine pairs SNPs in linkage disequilibrium to determine whether the observations are consistent with a single individual.”
For step 1 of the 101 analysis, the claims are found to be directed to a statutory category of a process.
For step 2A of the 101 analysis, the judicial exception of the claims are the steps of obtaining, calculating LD and preparing a score based on possicle sequences representing polymorphisms to obtain linkage disequilibrium information/values if present in the data that is obtained. In view of the guidance of the specification and the art of record, polymorphisms are either indicated in the data or empirically determined relative and based on a reference, and given the presence or absence of the polymorphism the linkage of any given polymorphism would be established. To practice the steps, either the polymorphic sites are provided and linkage is provided, or alternatively the step requires aligning and comparing sequence to arrive at the identification of possible linkages to provide for an LD score. The claim requires computing LD based on the broad steps of the data that is received, and determine a potentially relatedness of the score for genotyping. The judicial exception is a set of instructions for analysis of sequence data appears to fall into the category of Mental Processes, that is concepts performed in the human mind (including an observation, evaluation, judgment, opinion), and mathematical concepts to the extent that the claims require calculating a score and correlating the score to relatedness of two samples. There is no requirement to the amount or complexity of the data that is required for step b) the calculation and determination of a score, and the breadth appears consistent with evaluations set forth in Fig 3, direct PCR/MPS analysis of alleles of interest, or low coverage reads of a genome as set forth in the specification. Dependent claims that set forth the type of polymorphism appear to be descriptive and do not appear to effect the evaluation or calculation or how a final score is calculated.
Recent guidance from the office requires that the judicial exception be evaluated under a second prong to determine whether the judicial exception is practically applied. In the instant case, the claims do not have an additional element. The judicial exception of the claims requires steps recited at high level of generality and if practiced on a computer would only be stored on a non-transitory, and is not found to be a practical application of the judicial exception as broadly set forth. To the extent that step (a) is a physical method step of obtaining the sequence data, this step appears separate from the analysis and is broad and only necessary for the evaluation of the sequence data and would require a priori knowledge of polymorphisms or further empirical abstract analysis.
For step 2B of the 101 analysis, to the extent that step (a) can be interpreted to be a physical step of obtaining sequence read data and is directed to an additional element, it is found to be a step of obtaining sequence data in particular for SNPs which would be considered well known and conventional as provided by Li et al (2009-of record), as noted on page 7 of the specification providing a general listing common sequencing techniques. A review of the specification does not indicate that any special sequencing technique would be required, and appears to encompass only small parts of the genome for analysis (see claim for fragments and specification at page 8). In view of the specification and art of record, the analysis would only be informative with ‘mapped polymorphisms’ which requires prior knowledge relative to a database or previous studies for their identification. As such, the claims do not provide for any additional element to consider as significantly more under step 2B.
As indicated in the summary of the judicial exception above and in view of the teachings of the specification, the steps are drawn to analysis of sequence data. While the instruction can be implemented or stored on a medium and could be implemented on a computer, together the steps do not appear to result in significantly more than a means to compare sequences. The judicial exception of the method as claimed can be performed by hand and in light of the previous claims to a computer medium and in light of the teaching of the specification on a computer. In review of the instant specification the methods do not appear to require a special type of processor and can be performed on a general purpose computer.
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.
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.
Claims 1-13, 20-26 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al (2013) and Li et al (2009).
Claim 1 requires obtaining sequence data which comprises polymorphic sites, calculating linkage disequilibrium of sites and providing a compilation score based on the various sites and LD scores that can be made with the data. At the time identifying and evaluating SNP data from the genome for genotyping was known. For example, Li et al. (2013) teach that one crucial step for the successful application of genomic data analysis obtained using MPS (claim 9) is variant detection and genotype calling at detected variant loci. Li et al. provides a detailed discussion of methods to detect SNPs and/or perform genotype calling at detected SNPs, and methods that detect SNPs or estimate allele frequencies without individual-level genotype calls, and those that generate individual-level genotype calls with use and a focus will be on single-sample (SS), multi-sample single-site (MS-SS), and multi-sample linkage disequilibrium (LD) based (MS-LD) in determining genotype. Li et al do not specifically teach to prepare a compilation of scores, but clearly provide for analyzing multiple sites and use LD in the assessment of the genotype making obvious claim 1. Li et al (2009) provides further teaching and evidence that SNPs can be detected using MPS techniques and that read data from samples can be assessed to distinguish between true SNPs or methodological errors that are introduced in final read data being analyzed to be able to use read data reliably. Li et al. provides a detailed discussion of methods to detect SNPs and/or perform genotype calling at detected SNPs, and methods that detect SNPs or estimate allele frequencies. With respect to other dependent claims for the number and/or size of reads, % of genome and sample source of the DNA, these limitations describe the data that is analyzed and does not appear to materially affect how the claimed method is practiced, and given the teaching of both Li et al it would be obvious to use any source of DNA as a sample and provide the necessary coverage of the genome and use any number of polymorphic sites/SNPs as needed to be informative of a genotype. Given the review and specific teachings it would have been prima facie obvious to one having ordinary skill in the art at the time the invention was made to analyze portions or the whole genome as necessary to obtain a proper genotype of the sample. One having ordinary skill in the art would have been motivated to use MPS read data for genotyping as both Li et al provide and specifically analyze the necessary amount of data representing the genome to be sufficiently informative. Given the level of skill in the art, the review of both Li et al references, here would have been a reasonable expectation of success to identify and evaluate SNPs and provide an assessment of LD between them which would provide the basis of the genotype represented in the sample.
Thus, the claimed invention as a whole was clearly prima facie obvious.
Conclusion
No claim is allowed.
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/Joseph Woitach/Primary Examiner, Art Unit 1687
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