Detailed Action
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 .
Priority
This application filed 08/21/2024 is a national stage application of PCT/US2023/062957, filed 02/21/2023, which claims the benefit of provisional application 63/312,568, filed 02/22/2022.
Information Disclosure Statement
The Information disclosure statement (IDS) filed 08/21/2024 was considered by the examiner.
Claim Objections
Claim 4 objected to because of the following informalities:
Claim 4 does not provide an abbreviation for homologous recombination deficiency, but in later claim 13, 14, and 16, references “HRD”.
Claim 4 states “… is at risk of having a homologous recombination deficiency”, should state, “… is at risk of having a homologous recombination deficiency (HRD)”.
Appropriate correction is required.
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.
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 1-18 rejected under 35 U.S.C. 103 as being unpatentable over Vogelstein (Bert Vogelstein et al., “Methods and Materials for Assessing and Treating Cancer”, WO 2019067092 A1, Pub. Date: 04/04/2019), in view of Setton (Jeremy Setton et al., “Homologous recombination deficiency: how genomic signatures are generated”, Current Opinion in Genetics and Development, Volume 66, Pgs. 93-100, Pub. Date: 01/18/2021).
Regarding Claims 1 and 2, Vogelstein teaches a method for identifying the presence of cancer in a subject by obtaining biological samples from a subject to test for the presence of genetic and protein biomarkers, comparing the detected levels of the protein biomarker to one or more protein biomarker references, and identifying the presence of cancer in a subject when one or more genetic biomarkers are detected and the detected levels of the protein biomarker is higher than the reference level (Pgs. 24-25, [29]).Vogelstein teaches that genetic biomarkers can include modifications in a tumor suppressant gene, such as insertions (Pg. 47, [109]).
Regarding Claims 1, 2, 10, and 11 Vogelstein teaches the method for identifying the presence of cancer in a subject includes administering one or more therapeutic interventions, and lists platinum compounds such as cisplatin and carboplatin, and poly (ADP)-ribose polymerase (PARP) inhibitors such as Olaparib, and rucaparib as examples of cancer treatments (Pg. 25, [29] and Pg. 694, [773]).
Regarding Claim 3, Vogelstein discloses “In some embodiments, the mutational analysis comprises Next Generation Sequencing” (Pg. 492, [557]).
Regarding Claim 5, Vogelstein teaches assessing the plurality of genes and/or gene products further comprises mutational analysis of IDH1 (Pg. 491-492, [557]).
Regarding Claim 6, Vogelstein teaches breast, ovary, prostate, and pancreatic cancer as types of cancer in a subject (Pg. 25, [29]).
Regarding Claim 7, Vogelstein teaches Stage I, II, III, and IV cancer as embodiments (Pg. 128, [200]).
Regarding Claim 9, Vogelstein teaches the target polynucleotide comprising 10 to 25 base pairs in length (Pg. 405, [508]).
Regarding Claim 12, Vogelstein teaches “methods provided herein for identifying the presence of cancer in a subject with high sensitivity and specificity are performed on a liquid sample(s) obtained from the subject (e.g., blood, plasma, or serum) (Pg. 51, [119]).
Regarding Claims 13 and 14, Vogelstein teaches “In other embodiments, the sequencing depth ranges from about 100-300 .sup.χ to detect a genomic S Ps/loci that is used to assess copy number gains/losses of genomic DNA or loss-of- heterozygosity (LOH)” (Pg. 577, [658]).
Regarding Claim 15, Vogelstein teaches detection of a genetic biomarker that includes a method for amplifying a nucleic acid, and discloses SBS3 and SBS8 as first and second capture primers (Pg. 414, [515]).
Regarding Claim 17, Vogelstein teaches “For example, methods provided herein can be used when a subject has not been diagnosed with cancer and/or when a subject is not known to harbor a cancer cell” (Pg. 158, [250]).
Regarding Claim 18, Vogelstein teaches “In some embodiments, any of the variety of methods disclosed herein can be performed on subjects who have previously undergone treatments for cancer” (Pg. 129, [203]).
Vogelstein does not teach templated insertions, or detecting the levels of templated insertions (TINS) in a biological sample, and comparing to a control sample.
Setton teaches “Cancer genomes provide a durable record of the genetic alterations that accumulate during carcinogenesis stemming from DNA damage and DNA repair defects (Pg. 93, Introduction).
Setton also teaches “This study has also found that HR-proficient breast tumors harboring loss-of-function alterations in this broad set of genes are enriched with MH-associated deletions and templated insertions (TINS)” (Pg. 94, Small insertion and deletions (indels)). Setton also teaches, “HR-deficient tumors are known to be vulnerable to specific cancer therapies, including platinum salts and inhibitors of the poly (ADP-ribose) polymerase (PARP)” (Pg. 93, Introduction).
It would have been prima facie obvious for one of ordinary skill in the art to take the method disclosed in Vogelstein for selecting a cancer patient for treatment by detecting insertions obtained from cancer patients, and administering platinum or PARP inhibitors for treatment and combine it with the method disclosed in Setton for administering PARP inhibitors/ platinum therapies to patients with high TINS because Setton teaches that high TINS is associated with carcinogenesis and administering the same drugs (PARP inhibitors/platinum) to the same patient population (cancer patients), would yield the same results. Although Setton does not disclose a threshold for high TINS diagnoses, it would have been obvious to establish a threshold for TINS characterization because Vogelstein teaches a threshold for protein biomarkers, it would be obvious for one of ordinary skill in the art to also establish a threshold for genetic biomarkers.
Vogelstein does not teach the HR pathway, BRCA1 or BRCA2 driver mutations, direct-repeat TINS or inverted TINS, or ID6 as an additional HRD signature.
Regarding Claims 4 and 5, Setton teaches “DNA repair defects that can be elucidated by examination of mutational signatures include those affecting the homologous recombination (HR) pathway, as exemplified by tumors harboring inactivation of BRCA1 or BRCA2.
Regarding Claim 8, Setton teaches TMEJ can produce two different classes of templated insertions at repair junctions: (i) direct repeats mapping to the opposing strand on the other side of the break, and (ii) inverse repeats mapping to the reverse complement of the same strand (also typically within 30 bp)
Regarding Claim 16, Setton teaches Tumors harboring defects in HR were noted to be enriched in indel signature 6 (ID6) which was characterized by ≥5 base pair (bp) deletions with associated microhomology.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date to take the method disclosed in Vogelstein for selecting a cancer patient for treatment by detecting insertions obtained from cancer patients, and administering platinum or PARP inhibitors for treatment and combine it with the method disclosed in Setton for administering PARP inhibitors/platinum therapies to patients with high TINS because both Setton and Vogelstein have the same patient population, and administering the same drug to the same patient population would yield the same results.
Conclusion
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/C.M.R./Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627
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