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. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on September 25, 2025 has been entered.
Status of the Application
2. Claims 1-4, 7 and 10-11 are pending under examination. New claim 41 drawn to a non-transitory computer-readable storage method comprising instructions executable is a new method not related to the claims under examination and is withdrawn as a non-elected group. Claims 13, 15, 18-19, 22-24 and new claim 41 are withdrawn from further consideration as being drawn to non-elected group. Claims 5-6, 8-9, 12, 14, 16-17, 20-21 and 25-40 were canceled. The Applicant’s arguments and the amendment have been fully considered and found persuasive in-part for the following reasons.
Claim Rejections - 35 USC § 101-Maintained
3. 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 for use in a disease and/or therapy assessment or prognosis of a disease, 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 processor based on sequence reads in comparison to reference sequence reads, mapping sequence variations to determine MSI associations 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 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 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 reads). 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 effect 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)); Ryan et al. (US 2012/0122701) in view of Venn (US 2017/0213008) which disclose NGS methodology with regard to microsatellite instability analyses. 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 an inventive concept, i.e., do not amount to significantly more than the judicial exception(s).
Response to Arguments:
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. The amended claims while reciting detecting the presence of microsatellite instability in a subject, also recite correlating said microsatellite instability to a disease and said correlation is considered as a law of nature or judicial exception. Further, the recitation for sue in disease and/or therapy assessment’ is considered as an intended use. With reference to the arguments drawn to new claim 41, the arguments were found unpersuasive because the new claim 41 is drawn to a new method that is not related to claim 1 and withdrawn from further consideration as being drawn to nonelected group. The rejection is restated to address the amendment.
Claim Rejections - 35 USC § 103-Withdrawn
4. The rejection of claims under 35 USC 103 as being unpatentable over Kim et al. in view of Salipante et al. in view of the amendment and persuasive arguments drawn to WBC derived sequencing reads.
New Rejections
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 Ryan et al. (US 2012/0122701) in view of Venn (US 2017/0213008).
Note: Claims 1-4, 7, 10-11 recite ‘optionally’ which is interpreted as an optional limitation
which is not necessarily required by the claims. Claims also recite ‘for use in disease and/or therapy assessment’ which is considered as an intended use.
Ryan et al. teach a computer-implemented 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 comprising primers) (para 0258-0271, 0134-0135, 0152-0161, 0134, 0168-0170, 0085-0086, 0109-0114); and
(ii) a plurality of WBC-derived sequence read-pairs from the subject (para 0258-0271, 0134-0135);
identifying, by one or more processors, a first subset of the plurality of cfDNA sequence reads and a second subset of the plurality of WBC-derived sequence reads 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 0269-0271, 0134-0135, 0139-0152, 0176-187, 0135-0139, 0010-0012, 0062-0077);
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 (mapping) based sum of absolute differences in the set of alleles (para 0269-0271, 0176- 0187, 0139-0152, 0020-0029, 0010-0012, 0085-0098);
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 0176-0209, 0139-0152, 0010-0012, 0036-0041, 0085-0086);
detecting by the 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 and outputting the data by displaying the data on a display device (0010-0013, 0085-0086, 0173-0201, 0010, 0036-0048, 0135-0137, 0161, 0062).
With reference to claims 2-3, Ryan 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 0191-0205).
With reference to claim 10, Ryan et al. teach that the cfDNA is from serum, plasma, urine or body fluids (para 0048, 0058).
With reference to claim 11, Ryan 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 0176-0201, 0042-0043, 0060-0070).
Although Ryan et al. teach SNP allelic variation, Ryan et al. did not specifically teach detecting microsatellite instability (MSI) based on sequence reads comparison of sequencing reads of cfDNA with WBC DNA sequencing reads.
Venn teaches a method of claims 1-4, 7, 10-11, for detecting allelic variation or microsatellite instability in a subject suffering from or at risk for cancer determining at least one mutation in an exon of a cancer related gene includes ETS, TERT, BRAF, TGFBR2, comprising extracting DNA from white blood cells and cell free DNA from a subject, sequencing and comparing the sequencing data of DNA from WBC with fetal DNA sequencing data to detect microsatellite instability (para 0038-0040, 0176-0203, 0142-0154, 0171, 0009, 0045-0052, 0016).
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 Ryan et al. with the method of detecting MSI as taught by Venn to develop an improved sensitive method for detecting microsatellite instability in a biological sample. 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 because Venn explicitly taught that MSI detection using NGS of cfDNA and white blood cell DNA and detecting gene variation associated with a cancer (para 0176-0186) and such a modification of the method is considered obvious over the cited prior art.
Conclusion
No claims are allowable.
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Suryaprabha Chunduru
Primary Examiner
Art Unit 1681
/SURYAPRABHA CHUNDURU/Primary Examiner, Art Unit 1681