DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicants’ arguments and amendments, filed June 12, 2026, have been fully considered and they are persuasive in-part. The following rejections are either reiterated or newly applied as necessitated over the amendment. They constitute the complete set of rejections presently being applied to the instant application.
Status of the Claims
Claims 1-8, 10-15, and 17-20 are under examination.
Claim Interpretation
2. Instant claim 17 recites “using the mutation spectrum in a trained model to identify HRD; and treating the patient with a PARP inhibitor upon identification of HRD” The phrase “upon identification” indicates that this step is a contingent limitation. According to the MPEP §2111.04 (II) states, “The broadest reasonable interpretation of a method (or process) claim having contingent limitations requires only those steps that must be performed and does not include steps that are not required to be performed because the condition(s) precedent are not met. “ In other words, the step of “treating the patient with a PARP inhibitor upon identification of HRD” is not required to be performed.
Claim Rejections - 35 USC § 101
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 therefore, subject to the conditions and requirements of this title.
Claims 17-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more.
Claims 17-20 are directed to method of identifying homologous recombination deficiency (HRD). As described in Alice Corp. Pty. Ltd. V. CLS Bank Int’l, 573 U.S._, 134 S. Cr. 2347, 110 U.S.P.Q.2d 1976 (2014), a two-step analysis is required in considering the patent eligibility of the claimed subject matter. The first step requires determining if the claimed subject matter is directed to a judicial exception. The instant claims require the steps of generating a mutational spectrum from omics data and using the mutational spectrum in a trained model to identify HRD in the omics data from the tumor sample. However, these steps are drawn to mathematical steps. Dependent claims 18-20 are drawn to additional mathematical steps or to the data to be used in the mathematical algorithm. The courts have found mathematical algorithms to be drawn to the judicial exception of an abstract idea (In re Grams, 888 F.2d 835, 12 U.S.P.Q.2d 1824 (Fed. Cir. 1989)). Thus, the instant claims are drawn to a judicial exception.
This judicial exception is not integrated into a practical application. The instant claims do not recite an element that reflects an improvement in the functioning of a computer or other technology, an element that applies the judicial exception to effect a particular treatment, an element that implements the judicial exception with a particular machine, or an element that effects a transformation of a particular article to a different state or thing. The instant claims recite a step of obtaining omics data from a tumor sample that includes whole genome sequence data. However, this is an extra solution data gathering step. Extra solution activity does not integrate a judicial exception into a practical application. In addition, while instant claim 17 recites treating a patient with a PARP inhibitor, this step is written as a contingent limitation. As a contingent limitation, the step of treating the patient with a PARP inhibitor in claim 1 is not required. Thus, the instant claim does not recite a particular treatment.
The second part of the analysis requires determining if the claims include additional elements that are sufficient to amount to significantly more than the judicial exception. The instant claims recite the additional step of omics data from a tumor sample that includes whole genome sequence data. However, obtaining omics data from a tumor sample that includes whole genome sequence data is well-understood, conventional and routine (Kane et al. “Characterization, Detection, and Treatment Approaches for Homologous Recombination Deficiency in Cancer”, Trends in Molecular Medicine (2017) Vol. 23, Number 12, pages 1121-1137, esp. page 1127). Reciting such well-understood, routine, and conventional data gathering steps do not transform a judicial exception into patent eligible subject matter. In addition, the recitation of specific types of data, to be used in the judicial exception does not transform the abstract idea into a non-abstract idea. (See buySAFE, Inc. v Google, Inc. 765 F.3d 1350, 112 U.S.P.Q.2d 1093 (Fed.Cir.2014)). Furthermore, the elements taken as a combination are also well-understood, routine, and conventional, since the elements are merely specifying the types of data for a data gathering step. Thus, the instant claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
Response to Arguments
4. Applicants have responded to this rejection by amending claims 1 and 10 to require a step of treating a patient with a PARP inhibitor. This rejection is withdrawn as it was applied to claims 1-8 and 10-15. However, as explained above, instant claim 17 recites the step of treating a patient as a contingent limitation and does not require treating a patient as a limitation. This rejection is maintained and modified as necessitated by amendment as it was applied to claims 17-20.
Claim Rejections - 35 USC § 103
5. 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.
6. Claims 1-4, 7, 10, 11, 13-15, 17, 18, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Abkevich et al. (US 2017/0283879 A1) in view of Kane et al. (“Characterization, Detection, and Treatment Approaches for Homologous Recombination Deficiency in Cancer”, Trends in Molecular Medicine (2017) Vol. 23, Number 12, pages 1121-1137).
Regarding claim 1, Abkevich et al. teach a method of treating a tumor (abstract, cancer treatment) that has homologous recombination deficiency (HRD) (abstract) score indicating significant HRD events (paragraph [0054], a number of score exceeding such reference indicates homologous recombination deficiency), comprising: obtaining omics data (paragraph [0093], whole genome, whole transcriptome, or whole exome sequencing can be done to determine genotypes at millions or even billions of base pairs; paragraph [0368], SNP data) from a tumor sample, (paragraph [0149]), assessing samples (e.g. cancer cells), and generating a mutational spectrum (paragraph [0151], mutation within a gene from a HDR pathway; paragraph [0088] Table 1, Selected HDR Pathway Genes) from omics data (paragraph [0093], whole genome, whole transcriptome, or whole exome sequencing can be done to determine genotypes at millions or even billions of bas pairs; paragraph [0368]], SNP data) using the mutational spectrum (paragraph [0012], mutation within a gene from a HDR pathway; paragraph [0088] Table 1, Selected HDR Pathway Genes) in a trained model (paragraph [0015], a computer sub-system programmed to calculated based on the plurality of signals, paragraph [0368], SNP data was analyzed using an algorithm) to identify HRD (paragraph [0015], to detect (a) HRD or likelihood of HRD (e.g., and HRD signature) in the sample) in the omics data (paragraph [0093], whole genome, whole transcriptome, or whole exome sequencing can be done to determine genotypes at millions or even billions of base pairs; paragraph [0368], SNP data) from the tumor sample (paragraph [0149], assessing samples e.g. cancer cells); identifying the cancer as likely responsive to treatment (paragraph [0015], an increased likelihood that the cancer patient will respond to a cancer treatment regimen) with a PARP inhibitor (paragraph [0015]) upon determination of HRD (paragraph [0015] an HRD signature); and administering a PARP inhibitor treatment (paragraph [0015] treatment regimen comprising PARP inhibitor) for the tumor upon determination of a high HRD score (paragraph [0009]. HRD is based on a score).
However, Abkevitch et al. do not teach where the omics data comprises whole genome sequence data generating a mutational spectrum from the omics data.
Kane et al. teach a method that includes using whole genome sequence data to generate a mutational spectrum (HRD signature) (page 1127).
Regarding claim 2, Abkevich et al. teach where the PARP inhibitor is selected from the group consisting of Olaparib or Veliparib (paragraph [0086]).
Regarding claim 3, Abkevich et al. teach where the treatment further comprises platinum-based chemotherapy (paragraph [0104]).
Regarding claim 4, Abkevich et al. teach where the trained model is generated using machine learning algorithm (paragraph [0092] and [0142]).
Regarding claim 7, Abkevich et al. teach where the omics data are from breast cancer sample (paragraph [0021]).
Regarding claim 10, Abkevich et al. teach a method of predicting likely treatment success of a cancer (paragraph [0015]) with a PARP inhibitor (paragraph [0015]), comprising: obtaining omics data (paragraphs [0093] and [0368]) from a tumor sample (paragraph [0149]) and generating a mutational spectrum (paragraphs [0151] and [0088]) from omics data (paragraphs [0093] and [0368]); using the mutational spectrum (paragraphs [0012] and [0088]) in a trained model (paragraphs [0015] and [0368]) to identify HRD (paragraph [0015]) in the omics data (paragraphs [0093] and [0368]) from the tumor sample (paragraph [0015]), identifying the cancer as likely responsive to treatment (paragraph [0015]) upon determination of HRD (paragraph [0015]), and treating the patient (paragraph [0009]).
However, Abkevitch et al. do not teach where the omics data comprises whole genome sequence data generating a mutational spectrum from the omics data.
Kane et al. teach a method that includes using whole genome sequence data to generate a mutational spectrum (HRD signature) (page 1127).
Regarding claim 11, Abkevich et al. teach where the omics data are whole genome sequencing data (paragraph [0093]).
Regarding claim 13, Abkevich et al. teach where the omics data is from breast cancer (paragraph [0021]).
Regarding claim 14, Abkevich et al. teach treating the patient with platinum-based chemotherapy (e.g. cisplatin, carboplatin or oxalapatin) (paragraphs [0086] and [0103]).
Regarding claim 15, Abkevich et al. teach where the PARP inhibitor is selected from the group consisting of Olaparib or Veliparib (paragraph [0086]).
Regarding claim 17, Abkevich et al. teach identifying homologous recombination deficiency (HRD) (paragraph [0054]) in omics data (paragraph [0093] and [0368]), comprising: generating a mutational spectrum (paragraphs [0151] and [0088]) from omics data; using the mutational spectrum in a trained model (paragraphs [0015] and [0368]) to identify HRD (paragraph [0015]), and treating the patient (paragraph [0009]).
However, Abkevitch et al. do not teach where the omics data comprises whole genome sequence data generating a mutational spectrum from the omics data.
Kane et al. teach a method that includes using whole genome sequence data to generate a mutational spectrum (HRD signature) (page 1127).
Regarding claim 18, Abkevich et al. teach where the omics data are whole genome sequencing data (paragraph [0093]).
Regarding claim 20, Abkevich et al. teach where the omics data is from breast cancer (paragraph [0021]).
It would have been obvious for one of ordinary skill in the art, at the time of filing, to combine the teachings of Abkevich et al. and Kane et al. Abkevich et al. teach detecting a HRD signature in a sample (paragraph [0015]). Kane et al. teach determining HRD signatures in a whole genome (page 1127). One of ordinary skill in the art would have been motivated to use the method of Kane et al. with Abkevich et al. in order to gain the benefit of analyzing a whole genome for HRD signatures. Furthermore, one of ordinary skill in the art would have had a reasonable expectation of success in combining the teaching, because the data from Kane et al. may be readily incorporated in the method of Abkevich et al.
Response to Arguments
7. Applicants have responded to the rejection made under 35 U.S.C. §102 in view of Abkevich et al. by amending the claims to recite that the omics data comprises whole genome sequence data to generate a mutation spectrum from the omics data. The reference by Kane et al. is applied to address this limitation. This rejection is necessitated by amendment.
8. Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Abkevich et al. (US 2017/0283879 A1) in view of Kane et al. (“Characterization, Detection, and Treatment Approaches for Homologous Recombination Deficiency in Cancer”, Trends in Molecular Medicine (2017) Vol. 23, Number 12, pages 1121-1137) as applied to claims 1-4, 7, 10, 11, 13-15, 17, 18, and 20 above, and further in view of Lin et al. (US 2016/0010159 A1).
Abkevich et al. and Kane et al. and applied as above.
Abkevich et al. and Kane et al. do not teach where the omics data do not have germline mutations in BRCA1/BRCA2, CHEK2, PALB2 or ATM (signature 3 negative) and have a HRD mutation signature.
Lin et al. teach where a gene signature generated from germline BRCA1/2-mutated ovarian cancer is not inextricably linked to HR repair deficiency (paragraph [0067]).
It would have been obvious for one of ordinary skill in the art, at the time of filing, to combine the teachings of Lin et al., Kane et al. and Abkevich et al. Lin et al. teach that a gene signature generated from germline BRCA1/2-mutated ovarian cancers are not inextricably linked to HR repair deficiency. One of ordinary skill in the art would have been motivated to combine the teachings of Lin et al., Kane et al. and Abkevich et al. to create a more accurate predictor of HR repair deficiency. Furthermore, one of ordinary skill in the art would have a reasonable expectation of success because the data of Lin et al. can be incorporated with the data of Kane et al. and Abkevich et al.
Response to Arguments
9. Applicants have responded to this rejection by amending the claims to recite that the omics data comprises whole genome sequence data to generate a mutation spectrum from the omics data. The reference by Kane et al. is applied to address this limitation. This rejection is necessitated by amendment.
10. Claims 5, 12 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Abkevich et al. (US 2017/0283879 A1) in view of Kane et al. (“Characterization, Detection, and Treatment Approaches for Homologous Recombination Deficiency in Cancer”, Trends in Molecular Medicine (2017) Vol. 23, Number 12, pages 1121-1137) as applied to claims 1-4, 7, 10, 11, 13-15, 17, 18, and 20 above, and further in view of Vaske et al. (US 2012/0041683 A1).
Abkevich et al. and Kane et al. are applied as above.
Abkevich et al. and Kane et al. do not teach using k-means clustering.
Vaske et al. teach a method of determining the probability that a patient’s diagnosis may be treated with a particular therapy (abstract) where the machine learning model uses K-means clustering to find and group optimal clusters in mutational spectra (paragraphs [0027] and [0047])
It would have been obvious for one of skill in the art, at the time of filing, to combine the teachings of Abkevich et al., Kane et al. and Vaske et al. Vaske et al. teach that k-means clustering may be used to determine pathway activities (paragraph [0027]). One of ordinary skill in the art would have been motivated to combine the teachings of Abkevich et al., Kane et al. and Vaske et al. to gain the benefit of determining these pathway activities. Furthermore, one of ordinary skill the art would have a reasonable expectation of success since the k-means clustering could be applied to the data of Abkevich et al. and Kane et al.
Response to Arguments
9. Applicants have responded to this rejection by amending the claims to recite that the omics data comprises whole genome sequence data to generate a mutation spectrum from the omics data. The reference by Kane et al. is applied to address this limitation. This rejection is necessitated by amendment.
10. Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Abkevich et al. (US 2017/0283879 A1) in view of Kane et al. (“Characterization, Detection, and Treatment Approaches for Homologous Recombination Deficiency in Cancer”, Trends in Molecular Medicine (2017) Vol. 23, Number 12, pages 1121-1137) in view of Vaske et al. (US 2012/0041683 A1) as applied to claims 1-5, 7, 10, 11-15, 17, 18, and 20 above, and further in view of Lin et al. (US 2016/0010159 A1).
Abkevich et al., Kane et al. and Vaske et al. are applied as above.
Abkevich et al., Kane et al. and Vaske et al. do not teach where the discovery of mutational spectrum show evidence of HRD but do not contain the expected mutations indication of HRD.
Lin et al. teach where a gene signature generated from germline BRCA1/2-mutated ovarian cancer is not inextricably linked to HR repair deficiency (paragraph [0067]).
It would have been obvious for one of skill in the art, at the time of filing, to combine the teachings of Abkevich et al., Kane et al., Vaske et al. and Lin et al. The motivated to combine Abkevich et al., Kane et al. and Vaske et al. are provided above. Lin et al. teach where a gene signature generated from germline BRCA1/2-mutated ovarian cancer is not inextricably linked to HR repair deficiency (paragraph [0067]). One of ordinary skill in the art would have been motivated to combine Lin et al. with Abkevich et al., Kane et al. and Vaske et al. to gain the benefit of being able to discover a mutational spectrum that does not contain the expected mutations that indicate HRD. Furthermore, one of ordinary skill the art would have a reasonable expectation of success since the data of Lin et al. could be incorporated into the method of Abkevich et al., Kane et al. and Vaske et al.
Response to Arguments
9. Applicants have responded to this rejection by amending the claims to recite that the omics data comprises whole genome sequence data to generate a mutation spectrum from the omics data. The reference by Kane et al. is applied to address this limitation. This rejection is necessitated by amendment.
Conclusion
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.
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JERRY LIN whose telephone number is (571)272-2561. The examiner can normally be reached T-F 7am-5pm.
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/JERRY LIN/Primary Examiner, Art Unit 1685
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