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 .
Status of the Claims
Claims 1-20 are under examination.
Claim Objections
2. Claims 9 and 16 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claim. See MPEP § 608.01(n). Accordingly, the claims 9 and 16 have not been further treated on the merits.
Claim Interpretation
3. Instant claim 1 recites “identifying the cancer as likely responsive to treatment with a PARP inhibitor upon determination of HRD, and administering a PARP inhibitor treatment for the tumor upon determination of a high HRD score.” Instant claim 10 recites “identifying the cancer as likely responsive to treatment with a PARP inhibitor upon determination of HRD.” The phrase “upon determination” indicates that these steps are 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 steps of “identifying the cancer as likely responsive to a treatment with a PARP inhibitor” and “administering a PARP inhibitor treatment for the tumor” are not required to be performed.
Claim Rejections - 35 USC § 112
4. The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-9 and 14 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “high HRD score” in claim 1 is a relative term which renders the claim indefinite. The term “high HRD score” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Dependent claims 2-9 are also rejected for depending from claim 1.
Claim 5 recites the limitation "the machine learning algorithm" in line 1. There is insufficient antecedent basis for this limitation in the claim. This term was not recited previously in the claim or the parent claim. It is unclear to what the term refers.
Claim 6 recites the limitation "the expected mutations indication HRD" in line 2. There is insufficient antecedent basis for this limitation in the claim. This term was not recited previously in the claim or the parent claim. It is unclear to what the term refers. Furthermore, the it is unclear to what mutations are included in the expected mutations indication HRD. The metes and bound of the claim are unclear.
Claim 14 recites the limitation "the patient" in line 1. There is insufficient antecedent basis for this limitation in the claim. This term was not recited previously in the claim or the parent claim. It is unclear to what the term refers.
Claim Rejections - 35 USC § 101
5. 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 1-8, 10-15, and 17-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception without significantly more.
Claims 1-8, 10-13, and 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 4-8, 11-13, and 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. 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 1 recites administering a PARP inhibitor, this step is written as a contingent limitation. As a contingent limitation, the step of administering 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 obtaining omics data. However, obtaining omics data is well-understood, conventional and routine. 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 the 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.
Claim Rejections - 35 USC § 102
6. 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)(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 1-4, 7, 10, 11, 13-15, 17, 18, and 20 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Abkevich et al. (US 2017/0283879 A1).
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).
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 (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]), and identifying the cancer as likely responsive to treatment (paragraph [0015]) upon determination of HRD (paragraph [0015]).
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 PARP inhibitor (paragraph [0086]).
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]).
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]).
Claim Rejections - 35 USC § 103
7. 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.
8. Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Abkevich et al. (US 2017/0283879 A1) 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. is applied as above.
Abkevich et al. does 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. 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. 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 Abkevich et al.
9. Claims 5, 12 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Abkevich et al. (US 2017/0283879 A1) 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. is applied as above.
Abkevich et al. does 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. 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. 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.
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 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. and Vaske et al. are applied as above.
Abkevich 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., Vaske et al. and Lin et al. The motivated to combine Abkevich 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. 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. and Vaske et al.
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.
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, Olivia Wise can be reached at (571) 272-2249. 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.
/JERRY LIN/Primary Examiner, Art Unit 1685