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.The Applicant’s response to the office action filed on August 10, 2026 is acknowledged.
Status of the Application
2. Claims 1-4, 7, 10-11 are pending under examination. Claim 41 and new claims 42-47 are withdrawn from further consideration as being drawn to nonelected group. The Applicant’s arguments have been fully considered and found persuasive in-part for the following reasons.
Response to Arguments:
3. With reference to the rejection of claims under 35 USC 101, the Applicant’s arguments and the amendment have been fully considered and found unpersuasive. With reference to the Applicant’s arguments drawn to eligibility of claims drawn to a device for cardiac monitoring citing the case Cardionet, LLC v.InfoBionic, Inc, 955 F.3d 1358 (Fed.Cir.202), the arguments have been fully considered and found unpersuasive. In the instant context, the claims as presented are drawn to a method as opposed to a device. Use of one or more processors of next generation sequencing device to process sequence reads is known in the art. As discussed in the rejection, processing sequence reads using one or more processors to identify sequences reads of a set of alleles that are distinct from others in subsets represents metal steps, an abstract idea. The claims as presented do not add anything significantly more to the sequencing process because sequence data gathering, executing and outputting the sequence read data merely use of known sequencing processor technology, which does not add anything more to transform or alter the abstract idea, the judicial exception. Further, the method as claimed recites determining the MSI based on allele distribution differences in the sequence reads and said determining correlates with the presence of the MSI in a sample, said correlation or association represents judicial exception. The rejection has been maintained and restated to address the amendment.
4. The rejection of claims under 35 USC 103 as being obvious over Ryan in view of Venn has been withdrawn in view of the amendment.
New Rejections necessitated by the Amendment
Claim Rejections - 35 USC § 103
5. 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 1-4, 7 and 10-11 are rejected under 35 U.S.C. 103 as being unpatentable over Matsuguchi et al. (US 2018/0089373) in view of Niu et al. (Bioinformatics, Vol. 30(7), p. 1015-1016, (2014).
Matsuguchi et al. teach a method of claim 1, comprising receiving by one or more processors from next-generation sequencing device:
(i) a plurality of cell-free DNA sequence (cfDNA) read-pairs derived a subject, each cfDNA sequence read from the plurality of cfDNA sequence reads includes a forward or reverse unique molecular identifier (UMI) (unique identifier tags) (para 0014-0016, 0125, 0150-0153, 0233); and
(ii) a plurality of WBC (buffy coat)-derived sequence read-pairs from the subject (para 0014-0016, 0233);
identifying, by one or more processors, a first subset of the plurality of cfDNA sequence read-pairs and a second subset of the plurality of WBC-derived sequence read-pairs each read in the first and the second subset corresponds to the SNP alleles; identifying a set of alleles from the first and second subset, each allele of the set of alleles having a distinct sequence (para 0014-0016, 0150-0153, 0233-0234);
determining, by the one or more processors, for each allele of the set of alleles, a number of cfDNA sequence reads that include the allele and a number of WBC-derived sequence reads, that includes the allele, determining absolute difference based on the number of cfDNA sequence reads and the number of WBC-derived sequence reads for the allele; determining for each allelic locus from the plurality of loci, a distance based sum of absolute differences in the set of alleles (para 0014-0016,0150-0153, 0233-0234);
generating, the one or more processors, a first distribution indicating a number of allelic loci having distances within a group of distinct distance intervals and a second distribution indicating a number of allele variant loci having distances within a group of distinct distance intervals, the second distribution is from a reference sample (para 0014-0016, 0233-0234);
executing by one or more processors, a classifier using the first and second distribution to determine a threshold distance metric (para 0019-0029-0034, 0047-0048, 0129-0143, 0150-0153, 0172);
detecting by one or more processors, a number of loci in the first distribution above a threshold distance metric is greater than a number of loci in the second distribution to detect a presence of allelic variant loci (polymorphic loci or short tandem repeat loci) in the subject and above the threshold metric (0014-0016, 0183, 0233-0234, 0241).
With reference to claims 2-3, Matsuguchi et al. teach normalizing each allele of the set of alleles for the number of cfDNA and WBC-derived sequence reads, and the sum absolute difference associated with the alleles between the normalized sequence reads of cfDNA (para 0014-0016, 0163-0165).
With reference to claim 4, Matsuguchi et al. teach that the subject suffers from or is at risk of bladder, brain, gastric colorectal, or lung cancer (para 0083).
With reference to claim 7, Matsuguchi et al. teach that determining the presence or absence of at least one mutation in AKT, BRAF or APC, BAT25 (para 0008-0016, 0040, 0091, 0168-0172).
With reference to claim 10, Matsuguchi et al. teach that the cfDNA is from serum, plasma, urine or body fluids (para 0089).
With reference to claim 11, Matsuguchi et al. teach that the method further comprises generating a statistical classifier that generates a decision boundary of data points representing the presence or absence of allelic marker loci, process the data points from the first and second distribution using classifier to determine whether the first distribution belongs to the first or second set and determining allelic loci to classify the first distribution belonging to the first set of data points that represent the presence of said loci (para 0014-0016, 0150-0153, 0233-0234).
Matsuguchi et al. did not specifically teach distinguishing microsatellite instability and microsatellite stability by executing the classifier.
Niu et al. teach a method of claims 1-4, 7, 10-11, for detecting microsatellite instability in a subject, wherein the method comprises MSIsensor classifier to distinguish microsatellite instability high (MSI-H), microsatellite instability low (MSI-L) and microsatellite stability (MSS) using sequence read paired sequence data (page 1016, paragraphs 3.1-3.2 under subheading ‘results’, Fig. 1).
It would be prima facie obvious to an ordinary person skilled in the art before the effective filing date of the invention to modify the method of Matsuguchi et al. with the method MSIsensor classifier as taught by Niu et al. to differentiate MSI from MSS in a biological sample of a subject. The ordinary person skilled in the art would have motivated to combine the references and have a reasonable expectation of success that the combination would result in improving the identification of microsatellite instability status because Niu et al. explicitly taught that MSIsensor classifier is an efficient and effective tool for detecting MSI status and distinguishing the MSI and MSS (page 1015, abstract and paragraph 3.2 on page 1016) and such a modification of the method is considered obvious over the cited prior art.
Claim Rejections - 35 USC § 101
6. 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 1-4, 7 and 10-11 are rejected under 35 U.S.C. § 101 because the claimed invention is directed to judicial exceptions (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more, in accordance with MPEP § 2106. Claims 1-4, 7, 10-11 are drawn to a process, a statutory subject matter. The instant amended claims correlate the detection of microsatellite instability (MSI) loci in a subject associated with a disease condition, said correlation of MSI exists in nature that represents law of nature, or natural phenomenon. Claims 1-4, 7, 10-11 also are directed to mental processes to determine and detect MSI by one or more processors based on sequence read-pairs in comparison to reference sequence read-pairs, mapping sequence variations to determine MSI with variants or mutations in the nucleic acid sequence, which recite mental processes, which represents abstract idea. Claims 1-4, 7, 10-11 are further analyzed to determine if the claims as a whole integrate the recited judicial exception into a practical application or not. These judicial exceptions do not integrate into a practical application because the claims do not recite an additional element that reflects an improvement to the technology or applies or uses the recited judicial exception to affect a particular outcome. Rather, the instant claims recite additional elements that amount to mere instructions to implement abstract ideas in a generic computing environment or mere instructions to apply the recited judicial exception. These additional elements do not reflect an improvement to the technology or use the recited judicial exception to modify or effect a particular outcome but are identified as computer implemented insignificant extra-solution activity that do not integrate into practical applications (MPEP § 2106.05(g)). The instant claims recite additional elements that amount to mere instructions (identifying MSI loci in cfDNA and WBC-derived sequence read-pairs by executing sequence data). These additional elements do not provide practical integration, as they are generically reciting computing components without improvement or particularity added to a machine, nor do they impose any meaningful limitation on the judicial exceptions (see MPEP 2106.05(a and b). These additional elements equate to steps of mere data gathering and organizing sequence data for input/output into the generic system (MPEP § 2106.05(g)) and so, merely inform the field of use of the invention without indication that these would affect or alter the judicial exception (see
MPEP § 2106.05(h)). The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims recite additional elements that equate to mere instructions to apply the recited exception in a generic way or in a generic computing environment. Alice Corp., 573 U.S. at 223, 110 USPQ2d at 1983. See also 573 U.S. at 224, 110 USPQ2d at 1984. These additional elements do not contribute significantly more to well-known and conventional genetic variant searches, which are routinely performed and utilized by persons with ordinary skill in the art of genetics and bioinformatics as of the effective filing date (Illumina Next-Gen sequencing (NGS) AND Salipante et al. (Clin Chem., Vol. 60(9), p. 1192-1199, (2014)); Matsuguchi et al. (US 2018/0089373); Niu et al. (Bioinformatics, Vol. 30(7), p. 1015-1016, (2014); Ryan et al. (US 2012/0122701); Venn (US 2017/0213008); which disclose NGS methodology regarding microsatellite instability analyses and status of microsatellite instability MSI and microsatellite stability MSS. These additional elements merely inform the field of use of the invention without any particularity of components or steps which do not transform the judicial exception. The additional elements do not transform the claimed judicial exception into a patent-eligible application of the judicial exception. Therefore, the claims do not amount to significantly more than the judicial exception itself. Furthermore, the additional elements evaluated in combination do not contribute to an inventive concept, i.e., do not amount to significantly more than the judicial exception(s).
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SURYAPRABHA CHUNDURU whose telephone number is (571)272-0783. The examiner can normally be reached 8.00am-4.30pm.
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/SURYAPRABHA CHUNDURU/Primary Examiner, Art Unit 1681
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