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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 March 11, 2026 has been entered.
DETAILED ACTION
The amendment filed March 11, 2026 in response to the Office Action of September 11, 2025 is acknowledged and has been entered.
Claims 1, 5, and 7 have been amended.
Claims 11, 16, 21, 22, 24 and 25 have been cancelled.
Claims 26-31 have been added.
Claims 1, 3, 5, 7-10, and 26-31 are pending and under consideration.
In view of claim amendments and applicant’s arguments, the 103 rejections and Double Patenting rejections are hereby withdrawn.
NEW REJECTION
Claim Rejections - 35 USC § 112
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 7, 27, 28, 30, and 31 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.
Claim 7 recites “the method of claim 1 further comprising obtaining a sample from the human and identifying the obtained sample as having the mutation…”. The method of claim 1 already comprise a step of “identifying a sample from the human as having a mutation …”. It is not clear whether the step of identifying mutation in claim 7 is the same as the step of identifying mutation in claim 1, or the step of identifying mutation in claim 7 is an additional step of identifying mutation, besides the step of identifying mutation recited by claim 1.
Claim 7 recites “a molecular smoking signature” which renders the claim indefinite. It is unclear whether “a molecular smoking signature” refers to the molecular smoking signature recited by claim 1. Amending “a molecular smoking signature” to “the molecular smoking signature” would overcome the rejection.
Claim 27 recites “a molecular smoking signature” which renders the claim indefinite. It is unclear whether “a molecular smoking signature” refers to the molecular smoking signature recited by claim 1. Amending “a molecular smoking signature” to “the molecular smoking signature” would overcome the rejection.
Claim 28 recites “a molecular smoking signature” which renders the claim indefinite. It is noted that claim 28 depends on claim 1 indirectly. It is unclear whether “a molecular smoking signature” refers to the molecular smoking signature recited by claim 1. Amending “a molecular smoking signature” to “the molecular smoking signature” would overcome the rejection.
Claim 30 recites “a molecular smoking signature” which renders the claim indefinite. It is unclear whether “a molecular smoking signature” refers to the molecular smoking signature recited by claim 5. Amending “a molecular smoking signature” to “the molecular smoking signature” would overcome the rejection.
Claim 31 recites “a molecular smoking signature” which renders the claim indefinite. It is noted that claim 31 depends on claim 5 indirectly. It is unclear whether “a molecular smoking signature” refers to the molecular smoking signature recited by claim 5. Amending “a molecular smoking signature” to “the molecular smoking signature” would overcome the rejection.
Claim Rejections - 35 USC § 102
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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(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.
It is noted that the amended claims does not limit the mutation in ARID1A. Thus, identifying any mutation in ARID1A gene would read on the rejected claims. In view of the claim amendments, the 102 rejections set forth in the previous Office Action of 01/23/2025, which were withdrawn in the Office Action of 09/11/2025, are reestablished in this Office Action.
Claims 1, 3-5, 7-10, 26, and 29 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Marcrom (Marcrom et al., Clin Sarcoma Res, (2017) 7:14, Publication Date: 07/14/2017, of record), as evidenced by Core Biopsy (downloaded from: https://www.cancer.org/cancer/types/breast-cancer/screening-tests-and-early-detection/breast-biopsy/core-needle-biopsy-of-the-breast.html, on 1/16/2025, of record).
Marcrom teaches treating a young woman with clear cell sarcoma (CCS) with anti-PD1 checkpoint blockade with pembrolizumab (the elected species) with standard fractionation radiotherapy (reads on radiation therapy of instant claim 10) (§ Abstract – Case presentation).
Marcrom teaches identifying the young woman having a mutation in an Arid1A nucleic acid sequence: a frameshift mutation of ARID1A was identified with a 405 gene panel (page 2, col. 1, para. 3).
Regarding claims 3 and 4, Marcrom performed a core biopsy to test for the ARID1A mutation (page 2, col. 1, para. 3). A core biopsy would have cancer cells, as evidenced by CoreBiopsy (figure on page 1).
Marcrom teaches that 6 doses of pembrolizumab were administered after detecting the frameshift mutation of ARID1A, the patient remained disease-free after a complete radiographic response to the combination of pembrolizumab and radiation (Fig. 1 and the bridging paragraph of pages 2-3), which reads on “wherein the number of cancer cells present within said human is reduced”.
Response to Arguments
For the rejection under 35 U.S.C. 102 over Marcrom, Applicant argues in the Remarks of July 23, 2025:
Marcrom is a case presentation of one patient diagnosed with a specific type of cancer, clear cell sarcoma. The mutation found in this one and only patient was a frameshift mutation. See, pg. 2, col. 1, last paragraph. Nothing in either of the cited documents state or otherwise suggest a molecular smoking signature. However, without acquiescing to the validity of the current rejection and solely in the interest of expediting prosecution of the instant application, Applicant has amended claims 1 and 5 to recite that the molecular smoking signature comprises cytosine (C) to adenosine (A) transversions (C>A transversions).
Applicant’s arguments have been fully considered but they are not persuasive. As noted above, the amended claims does not limit the mutation in ARID1A to the molecular smoking signature. Accordingly, identifying any mutation in ARID1A gene would read on the rejected claims. Thus, the method of Marcrom, even though on one patient with a specific cancer, would still anticipate the claimed method.
Claims 1, 3-5, 7-10, 26, and 29 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Yauch (Yauch et al., WO 2017/214373 A1, Publication Date: 12/14/2017, of record).
Yauch teaches that about 20% of human cancers are associated with somatic mutations in subunits of the SWI/SNF complex, which includes a subunit ARID1A (page 1, lines18-25).
Yauch teaches methods for identifying a patient having a cancer who may benefit from treatment including one or more inhibitors of H3K27 methylation, optimizing therapeutic efficacy for treatment of a patient having cancer, predicting responsiveness of a patient having a cancer to treatment including one or more inhibitors of H3K27 methylation, and selecting a therapy for a patient having a cancer, including an immunotherapy, comprising a step of identify one or more genes encoding a nucleosome remodeling protein, including ARID1A (page 44, para. 3; and claims 47-50 and 85).
Yauch teaches that samples obtained from the patient is a cell sample, e.g. a tumor cell sample, a tissue sample e.g. a tumor tissue sample (last paragraph of page 4, first paragraph of page 5, last paragraph of page 31; claims 51-53), which would comprise at least one cancer cell.
Yauch teaches that the method includes administering to a patient from a cancer having a mutation in one or more genes encoding SWI/SNF complex, including ARID1A an inhibitor of H3K27 methylation (e.g. an H3K27 inhibitor; or an EXH2 inhibitor) (page 46, para. 5).
Yauch teaches that ARID1A mutation is identified by determining a nucleic acid sequence (e.g. a DNA sequence or an RNA sequence) in a sample obtained from a patient and comparing the sequence to a reference sequence (e.g. a wildtype sequence) (page 43, paras. 2 and 3).
Yauch teaches once a patient responsive or sensitive to treatment with an inhibitor of H3K27 methylation has been identified, treatment with the inhibitor of H3K27, alone or in combination with other therapeutic agents can be carried out. Such treatment may result in a reduction in tumor size (the bridging paragraph of pages 48-49).
Yauch teaches that administration of one or more inhibitors of H3K27 methylation can have the therapeutic effect. For example, an effective response can be reduced tumor size (e.g. reduce tumor size by 90% or more) (page 47, para. 2), which reads on reduced cancer cells in the patient.
Yauch teaches that H3K27 inhibitors include antibodies or antibody fragment (page 48, § Inhibitors of H3K27 methylation for use in the Methods of the invention), which reads on immunotherapy.
Regarding claims 3 and 4, the sample obtained from the patient is a tumor tissue sample (page 19, lines 18-39; claims 51 and 53), which comprises at least one cancer cell.
Regarding claims 8-10, Yauch teaches that an inhibitor of H3K27 methylation can be administered in combination with ipilimumab (page 53, para. 1). Given BRI, the combination therapy of an H3K27 methylation inhibitor + ipilimumab would read on the claim 8-10.
In addition, Yauch teaches treatment with the combination of an inhibitor of H3K27 methylation and at least one additional therapeutic agent preferably results in an additive, more preferably synergistic (or greater than additive), therapeutic benefit to the patient (the bridging paragraph of pages 48-49; and page 51 § Combination Therapy). In some instance, the method includes administering an anti-cancer agent, such as a chemotherapeutic agent (page 51, para. 4).
Response to Arguments
For the rejection under 35 U.S.C. 102 over Yauch, Applicant argues in the Remarks of July 23, 2025:
However, without acquiescing to the validity of the current rejection and solely in the interest of expediting prosecution of the instant application, Applicant has amended claims 1 and 5 to recite that the molecular smoking signature comprises cytosine (C) to adenosine (A) transversions (C>A transversions).
Applicant’s arguments have been fully considered but they are not persuasive. As noted above, the amended claims does not limit the mutation in ARID1A to the molecular smoking signature. Accordingly, identifying any mutation in ARID1A gene would read on the rejected claims. Thus, the method of Yauch would anticipate the claimed method.
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.
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.
Claims 1, 3-5, 7, and 26-31 are rejected under 35 U.S.C. 103 as being unpatentable over Shen (Shen et al., Nature Medicine, Vol. 24, 556-562, Publication Date: 05/07/2018, of record) in view of Anderson News (downloaded from: Preclinical MD Anderson study suggests ARID1a may be useful biomarker for immunotherapy | UT MD Anderson , Publication Date: 05/07/2018) and Wiegand (Wiegand et al., N Engl J Med, 2010; 363: 1532-1543, Publication Date: 09/08/2010, of record).
Examiner’s note: The specification does not give a clear definition of “a molecular smoking signature”. Thus, given Broadest Reasonable Interpretation (BRI), any cytosine (C) to adenosine (A) transversion in ARID1A gene would read the “molecular smoking signature” recited by claims 5, 30 and 31. Given the indefiniteness of claims 27 and 28, any cytosine (C) to adenosine (A) transversion in ARID1A gene would read the “molecular smoking signature” recited by claims 27 and 28.
Shen teaches that ARID1A interacts with mismatch repair (MMR) protein MSH2. ARID1A recruits MSH2 to chromatin during DNA replication and promoted MMR. Conversely, ARID1A inactivation compromised MMR and increased mutagenesis (Abstract). In The Cancer Genome Atlas (TCGA) datasets, ARID1A was substantially mutated in 26 of the 32 cancer types, with a high mutation rate in uterine corpus endometrial carcinoma, stomach adenocarcinoma, and urothelial bladder carcinoma (15-44%; Fig. 1a and Supplementary Table 1). We conducted a proteomic analysis and identified a key MMR protein, MSH2, as a binding partner of ARID1A (Fig. 1b,c and Supplementary Table 2). Also see the bridging paragraph of cols. 1-2 on page 556.
Shen teaches that tumor formed by an ARID1A-deficient ovarian cancer cell line in mice displayed increased mutation load, elevated numbers of tumor-infiltrating lymphocytes, and PD-L1 expression. Notably, treatment with anti-PD-L1 antibody reduced tumor burden and prolonged survival of mice bearing ARID1A-deficient but not ARID1A-wild-type ovarian tumors (Abstract).
Shen teaches that in human ARID1A-deficient tumors also exhibited remarkable increase in CD8 and PD-L1 (Fig. 4e).
Shen teaches that in both orthotopic and intraperitoneal ovarian cancer mouse models, ARID1A-deficient tumors showed a remarkable response to anti-PD-L1 antibody and ARID1A-deficient tumors are sensitive to immune checkpoint blockade targeting the PD1/PD-L1 pathway (Fig. 4g, h and Suppl. Fig. 11h; page 561, col. 2, para. 2). As shown in Suppl. Fig. 11j and k, the tumor size is significantly smaller after treatment than the size before treatment in only ARID1A deficient cancer.
Shen teaches the clinical relevance of this finding in TCGA tumors. The mutation load was significantly elevated in ARID1A mutant tumors (Fig. 3a and Supplementary Table 4). Furthermore, there was a negative association between ARID1A protein and mRNA expression level and mutation load (Fig. 3b,c). Also see page 561, col. 1, para. 2.
Shen teaches patients with ARID1A mutations in uterine corpus endometrial carcinoma tumors had better prognoses (Fig. 3h), which was consistent with the observation that patients with MSI tumors have better survival rates than patients with
MSS tumors (Fig. 3i). Also see page 561, col. 1, para. 4.
Shen teaches that based on data analysis of human tumors in TCGA, ARID1A mutations may be either a cause or a consequence of MMR deficiency in different genetic contexts (Supplementary Fig. 8; and page 561, col. 1, para. 3).
Shen teaches that in ovarian cancer patient specimens, ARID1A-deficient tumors also exhibited remarkable increase in CD8 and PD-L1 (Fig. 4e). Analysis of TCGA tumors using two independent TIL signatures showed that tumors with an increased-TIL transcriptome signature had significantly reduced ARID1A expression (Fig. 4f and Supplementary Fig. 10a–d). Furthermore, genes involved in ARID1A-associated enhancer-mediated regulation did not overlap with TIL signature genes, suggesting that the altered TIL signature was not due to transcriptional control through ARID1A-associated enhancer activity (Supplementary Fig. 10e). These findings raised the possibility that immune checkpoint blockade would restore antitumor immunity in ARID1A-deficient tumors and thereby limit tumor growth.
Shen teaches that immune checkpoint blockade is among the most promising emerging approach in cancer treatment. However, it benefits only a limited subpopulation of patients. Therefore, there is an urgent clinical need to identify molecular tumor subtypes that are likely to benefit from specific immunotherapies. Our results suggest ARID1A status as a potential predictor of response to inhibitors of the PD1/PD-L1 immune checkpoint pathway. The study may provide a mechanistic basis for broadening the application of immune checkpoint blockade to patients with SWI/SNF-pathway mutant tumors (page 561, col. 2, para. 3).
Shen teaches as set forth above. However, Shen does not explicitly teach identifying a sample from human as having a mutation in an ARID1A nucleic acid sequence and administering a cancer immunotherapy to the human.
Anderson News teaches that Shen’s study demonstrated that ARID1A deficiency has a causative relationship with MMR deficiency (page 2, para. 1); and ARID1A is essential to normal MMR function (page 2, para. 2).
Anderson News teaches that tumors with deficiencies in MMR are known to accumulate large numbers of genetic mutations and corresponding mutant proteins, or neoantigens, as the disease progresses. These neoantigens are thought to stimulate an immune response, making them more susceptible to checkpoint blockade therapy. Tumors with ARID1a mutations indeed carried higher mutational loads. Further, ARID1a mutations were more common in tumors with microsatellite instability (MSI), another marker for MMR dysfunction (page 2, paras. 3-4). TCGA data revealed that tumors with ARID1a mutations exhibited an activation of the immune system, according to gene expression levels of immune marker (page 2, para. 6).
Anderson News teaches that MMR deficiency is a marker for the use of checkpoint-blockade immunotherapy (page 2, para. 5).
Anderson News teaches that the data can contribute to clinical studies testing ARID1A as a new biomarker for checkpoint blockade therapies (the bottom paragraph on page 2).
Wiegand teaches method of detecting mutation in an ARID1A nucleic acid sequence from ovarian cancer samples: e.g. ovarian carcinoma (§ Method – PATIENTS AND SAMPLES; and § Method – TARGETED EXON RESEQUENCING OF ARID1A AND MUTATION VALIDATION).
Wiegand teaches that several C to A transversions have been identified in ovarian cancer samples, including C1680A (Y560*), C645A (Y215*) and C1687A (Q563*) (stars denote a stop codon) (Fig. 1). One of ordinary skill in the art would have expected that these nonsense mutations would lead to a deficiency of functional ARID1A.
Wiegand teaches that C1680A (Y560*) leads to negative expression of BAF250a which is the protein encoded by ARID1A gene (Table 1, and Supplemental Table 3).
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to identify ovarian cancer patient (human) population that are likely to benefit from specific immunotherapies, e.g. anti-PD1 or anti-PD-L1 therapy based on ARID1A status (e.g. a mutation diminishing ARID1A function), as taught by Shen and Anderson News, and to incorporate a step of obtaining and identifying a cancer tissue from the patients with mutation comprising a C to A transversions (such as C1680A (Y560*), C645A (Y215*) and C1687A (Q563*)) in an ARID1A nucleic acid sequence, because Shen and Anderson News teaches that 1) the immune checkpoint blockade is more effective to cancers with ARID1A mutations in two mouse models; 2) in human ARID1A-deficient tumors also exhibited remarkable increase in CD8 and PD-L1; 3) in human, ARID1A deficiency has a causative relationship with MMR deficiency and ARID1A is essential to normal MMR function; 4) in human, tumors with an increased-TIL transcriptome signature had significantly reduced ARID1A expression (Fig. 4f and Supplementary Fig. 10a–d); and 5) ARID1A status can be used as a potential predictor of response to inhibitors of the PD1/PD-L1 immune checkpoint pathway in clinical setting. In addition, these mutations were detected in ovarian cancer samples and these mutations lead to truncated proteins and negative expression of ARID1A, as taught by Wiegand. The motivation would have been to apply a well-established method to the checkpoint blockade therapies and there is a need to apply checkpoint blockade therapies to select suitable patient population, and patients with the C to A mutations in ARID1A genes taught by Wiegand would be deficient in functional ARID1A and be more responsive to anti-PD-L1 therapy as taught by Shen and Anderson News. Because the methods of detecting mutation in a nucleic acid sequence have been well known in the art, as evidenced by Wiegand, one of ordinary skill in the art would have had a reasonable expectation of success to reach the claimed methods.
Response to Arguments
For the rejection under 35 U.S.C. 103 over Shen and Wiegand, Applicant argues in the Remarks of July 23, 2025:
The cited documents do not disclose results with human patients. Thus, Shen et al. reports a certain syngeneic mouse model which is recognized to have very poor translational success.
Applicant’s arguments have been fully considered but they are not persuasive. Contrary to Applicant’s arguments, Shen’ teachings are not limited to a certain syngeneic mouse model. As set forth above, Shen and Anderson News teaches that 1) the immune checkpoint blockade is more effective to cancers with ARID1A mutations in two mouse models; 2) in human ARID1A-deficient tumors also exhibited remarkable increase in CD8 and PD-L1; 3) in human, ARID1A deficiency has a causative relationship with MMR deficiency and ARID1A is essential to normal MMR function; 4) in human, tumors with an increased-TIL transcriptome signature had significantly reduced ARID1A expression (Fig. 4f and Supplementary Fig. 10a–d); and 5) ARID1A status can be used as a potential predictor of response to inhibitors of the PD1/PD-L1 immune checkpoint pathway in clinical setting. Based on data in both human and mouse, one of the ordinary skill in the art would have a reasonable expectation that cancers with mutation comprising a C to A transversions (such as C1680A (Y560*), C645A (Y215*) and C1687A (Q563*)) in an ARID1A nucleic acid sequence (taught by Wiegand) would be suitable for checkpoint inhibitor (such as PD-L1 antibody) therapy.
In addition, in the field of biological field, no invention has absolute certainty of success before experimental tests. Thus, only a reasonable expectation of success (not absolute) would have motivated an artisan to treat a human having cancer as claimed. Given the teachings from references, an ordinary skilled in the art would have would have had a reasonable expectation of success that the method would be suitable for human cancer patients with ARID1A mutations.
In addition, the specification discloses human data on a specific cancer: NSCLC and specific immunotherapy: checkpoint inhibitor therapy (see Examples). However, the claims are not limited to NSCLC and/or checkpoint inhibitor therapy. Thus, the example is not commensurate in scope with the claimed invention and is not probative on the non-obviousness of the claimed invention.
Furthermore, Shen is concerned with C>T transversions. Other transversions such as C>A, C>G, T>A, T>C, and T>G were seen at low percentages in various tumor cells. See, for example, FIG. 3D. Based on these data, one of ordinary skill in the art would not have any motivation to identify any transversion other than C>T transversions.
Applicant respectfully disagrees. Weigand requires truncated ARID1A or negative expression of ARID1A. Indeed, the cited C>A transversions cited by the Office appear to be stop codons, resulting in peptides which would have lengths of either 215 amino acids (Y215*), or 560 amino acids (Y560*), 563 amino acids (0563*). In contrast Applicant teaches a smoking signature having at least 20 mutations…. The combination of Shen and Weigand requires deficient and truncated ARID1A peptides wherein the C>A transversions are stop codons. Indeed, Weigand states that the ARID1A mutations were mostly truncating mutations which were evenly distributed across the gene.
Applicant’s arguments have been fully considered but they are not persuasive. As noted above, the amended claims does not limit the mutation in ARID1A to the molecular smoking signature as cited by claim 1. Accordingly, identifying any mutation in ARID1A gene would read on the rejected claims. In addition, given BRI, any cytosine (C) to adenosine (A) transversion in ARID1A gene would read the “molecular smoking signature” recited by claims 5, 30 and 31. Given the indefiniteness of claims 27 and 28, any cytosine (C) to adenosine (A) transversion in ARID1A gene would read the “molecular smoking signature” recited by claims 27 and 28. Thus, the mutations taught by Weigand would not only read on a mutation in an ARID1A nucleic acid sequence, but also read on “a smoking molecular signature (as evidenced by instant claim 5)”, because “a mutational load of at least twenty mutations comprising cytosine (C) to adenosine (A) (C>A) transversions” is optional limitation for amended claim 1.
Claims 8-10 are rejected under 35 U.S.C. 103 as being unpatentable over Shen (Shen et al., Nature Medicine, Vol. 24, 556-562, Publication Date: 05/07/2018, of record) in view of Anderson News (downloaded from: Preclinical MD Anderson study suggests ARID1a may be useful biomarker for immunotherapy | UT MD Anderson , Publication Date: 05/07/2018) and Wiegand (Wiegand et al., N Engl J Med, 2010; 363: 1532-1543, Publication Date: 09/08/2010, of record), as applied to claims 1, 3-5, 7, and 26-31 above, and further in view of Marcrom (Marcrom et al., Clin Sarcoma Res, (2017) 7:14, Publication Date: 07/14/2017, of record).
As set forth above, Shen, Anderson News and Wiegand teach method of claim 1. Although Shen and Wiegand teaches identifying cancer patients with ARID1A mutation comprising C to A transversion for anti-PD1 or anti-PD-L1 therapy, Shen, Anderson News and Wiegand does not teach antibodies recited by claim 8, e.g. pembrolizumab (the elected species), or combination therapy of claims 9 and 10.
Marcrom teaches that the combination of pembrolizumab and radiation are effective to Clear Cell Sarcoma with a mutated ARID1A (Fig. 1 and the bridging paragraph of pages 2-3). Marcrom teaches that the ARID1A mutation is a frame shift mutation (page 2, col. 1, para. 3). One of ordinary skill in the art would recognize that a ARID1A frame-shift mutation would lead to ARID1A deficiency.
Marcrom further teaches that pembrolizumab and nivolumab are FDA-approved for a wide variety of cancers (page 3, col. 1, para. 4).
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to treat a human having a cancer having an inactivation mutation in ARID1A with anti-PD1 or anti-PDL1 therapy, as taught by Shen, Anderson News and Wiegand, and to modify the method by using pembrolizumab as the anti-PD1 therapeutics because Marcrom teaches pembrolizumab is effective for a cancer with ARID1A frame-shift mutations and pembrolizumab is FDA-approved for a wide variety of cancers. Given that pembrolizumab are widely used in cancer therapy, as evidenced by Marcrom, one of ordinary skill in the art would have had a reasonable expectation of success to reach the claimed invention. The motivation would have been to use a well-tested and FDA-approved antibody for a special subpopulation of cancer patients.
Regarding claims 9 and 10, Marcrom teaches using the combination of pembrolizumab and radiation for treating. Marcrom further teaches that anti-PD1 therapy can enhance local response to radiotherapy and promote abscopal effects with tumor regression at unirradiated sites. Preclinical data and early clinical observations support synergy between immune checkpoint blockade and radiotherapy across multiple tumor types (page 3, col. 2, para. 1). It would have prima facie been obvious to use additional radiotherapy to further enhance the efficacy of the anti-PD1 therapy. The motivation would have been to develop new treatment and to improve efficacy of anti-PD1 therapy. Given that both pembrolizumab and radiotherapy are widely-used in cancer treatment, one of ordinary skill in the art would have had a reasonable expectation of success to reach the claimed invention.
Response to Arguments
For the rejection under 35 U.S.C. 103 over Shen, Wiegand and Macrom, Applicant first reiterate the arguments for Shen and Wiegand set forth above and further argue that Macrom does not add anything that would obviate the instantly claimed invention.
Applicant’s arguments have been fully considered but they are not persuasive. As set forth above, Shen, Anderson News and Wiegand teach the method of claim 1. Macrom further teach that the combination of pembrolizumab and radiation are effective to Clear Cell Sarcoma with a mutated ARID1A (ARID1A deficient mutation). Thus, it would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to treat a human having a cancer having an inactivation mutation in ARID1A with anti-PD1 or anti-PDL1 therapy, as taught by Shen, Anderson News and Wiegand, and to modify the method by using pembrolizumab as the anti-PD1 therapeutics because Marcrom teaches pembrolizumab is effective for a cancer with ARID1A frame-shift mutations and pembrolizumab is FDA-approved for a wide variety of cancers. Given that pembrolizumab are widely used in cancer therapy, as evidenced by Marcrom, one of ordinary skill in the art would have had a reasonable expectation of success to reach the claimed invention. The motivation would have been to use a well-tested and FDA-approved antibody for a special subpopulation of cancer patients.
Regarding Applicant’s that Shen do not disclose results with human patients, as set forth above, contrary to the argument, Shen and Anderson News teaches that 1) the immune checkpoint blockade is more effective to cancers with ARID1A mutations in two mouse models; 2) in human ARID1A-deficient tumors also exhibited remarkable increase in CD8 and PD-L1; 3) in human, ARID1A deficiency has a causative relationship with MMR deficiency and ARID1A is essential to normal MMR function; 4) in human, tumors with an increased-TIL transcriptome signature had significantly reduced ARID1A expression (Fig. 4f and Supplementary Fig. 10a–d); and 5) ARID1A status can be used as a potential predictor of response to inhibitors of the PD1/PD-L1 immune checkpoint pathway in clinical setting. Thus, based on the teachings of references, one of ordinary skilled in the art would have a reasonable expectation of success to reach the claimed invention.
Claims 9 and 10 are alternatively rejected under 35 U.S.C. 103 as being unpatentable over Shen (Shen et al., Nature Medicine, Vol. 24, 556-562, Publication Date: 05/07/2018, of record) in view of Anderson News (downloaded from: Preclinical MD Anderson study suggests ARID1a may be useful biomarker for immunotherapy | UT MD Anderson , Publication Date: 05/07/2018) and Wiegand (Wiegand et al., N Engl J Med, 2010; 363: 1532-1543, Publication Date: 09/08/2010), as applied to claims 1, 3-5, 7, and 26-31 above, and further in view of Zamarin (Zamarin et al., Pharmacology & Therapeutics, 150 (2015) 23-32, Publication Date: 01/10/2015, of record).
As set forth above, Shen, Anderson News and Wiegand teach method of claim 1. Although Shen, Anderson News and Wiegand teaches identifying cancer patients with ARID1A mutation comprising C to A transversion for anti-PD1 or anti-PD-L1 therapy, or combination therapy such as chemotherapy (the elected species) of claims 9 and 10.
Zamarin teaches that PD-1/PD-L1 antibodies have been used to treat various cancers (page 25, col. 2, para. 2; and Fig. 1).
Zamarin teaches that combination therapies that can promote appropriate tumor immune activation may make tumors more receptive to concurrent or sequential immunotherapeutic interventions (page 26, col. 1, para. 1).
Zamarin teaches that combination therapies (including in combination with chemotherapy) have been developed for enhancing anti-tumor immune response (§ 4. Combination therapies).
Zamarin teaches that chemotherapies have been shown to demonstrate the release of antigens and DAMPs thus triggering immunogenic cell death; gemcitabine, 5-FU, and taxanes can reduce the number of tumor-infiltrating and splenic MDSCs; cyclophosphamide can selectively deplete of regulatory T cells (page 26, col. 2, para. 2).
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to treat a human having a cancer having a mutation in ARID1A comprising C to A transversions with anti-PD1 or anti-PDL1 therapy, as taught by Shen, Anderson News and Wiegand, and to modify the method by further administering an additional chemotherapy because Zamarin teaches chemotherapy may further enhance antitumor activity of the anti-PD-L1 immunotherapy by enhance antigen presentation, MDSC depletion and Treg depletion (Fig. 1 and § 4.1.3. Chemotherapy). Given that both anti-PD-L1 therapy and chemotherapy are well known in the art, as evidenced by the references, one of ordinary skill in the art would have had a reasonable expectation of success to combine an anti-PD-L1 therapy with a chemotherapy for better efficacy. The motivation would have been to develop a more efficient treatment for the claimed patient.
Response to Arguments
For the rejection under 35 U.S.C. 103 over Shen, Wiegand and Zamarin, Applicant first reiterate the arguments for Shen and Wiegand set forth above and further argue:
Zamarin is directed to use of combination therapies in treatment of tumors. However, Zamarin is silent with respect to identifying tumors as having smoking signatures with a mutational load of at least twenty mutations comprising C to A transversions. Since the combination of Shen and Weigand does not teach, suggest, disclose or otherwise provide any guidance as per Applicant's instantly claimed invention. However, for the sake of advancing prosecution, Applicant has amended claim 1 to recite identifying a smoking signature having a mutational load of at least twenty mutations comprising C to A transversions. Accordingly, the combination of cited references fails to render the instantly claimed invention obvious
Applicant’s arguments have been fully considered but they are not persuasive. First, as noted above, the amended claim 1 does not limit the mutation in ARID1A to the molecular smoking signature. Accordingly, identifying any mutation in ARID1A gene would read on the rejected claims.
In response to applicant's arguments against the Zamarin individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). As set forth above, combining teachings of Shen, Anderson News, Wiegand Zamarin, one of ordinary skill in the art would have had a reasonable expectation of success to reach the claimed invention because Zamarin teaches chemotherapy may further enhance antitumor activity of the anti-PD-L1 immunotherapy by enhance antigen presentation, MDSC depletion and Treg depletion (Fig. 1 and § 4.1.3. Chemotherapy).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
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Patent No. 9,982,304
Claims 1, 3-5, 7, and 26-31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 9,982,304 (hereinafter Pat. 304, Appl. No.: 13/819,933, of record) in view of Shen (Shen et al., Nature Medicine, Vol. 24, 556-562, Publication Date: 05/07/2018, of record), Anderson News (downloaded from: Preclinical MD Anderson study suggests ARID1a may be useful biomarker for immunotherapy | UT MD Anderson , Publication Date: 05/07/2018), and Wiegand (Wiegand et al., N Engl J Med, 2010; 363: 1532-1543, Publication Date: 09/08/2010, of record).
The claims of Pat. 304 teach a method comprising: amplifying coding regions of ARID1A gene or cDNA in a biological sample of an individual, wherein the biological sample comprises ovarian cells; sequencing the amplified coding regions of ARID1A gene or cDNA; detecting a mutation, wherein the mutation is a frameshift or a stop codon in the gene or cDNA (claim 1).
The claims of Pat. 304 teach the method of claim 1, wherein the biological sample is selected from the group consisting of tissue, blood, serum, plasma, ascites, and urine (claim 2).
The claims of Pat. 304 teach the method of claim 1, wherein the individual is suspected of having ovarian cancer (claim 3).
The claims of Pat. 304 teach the method of claim 1, further comprising the step of obtaining the biological sample from the individual (claim 4).
The claims of Pat. 304 teach the method of claim 1, wherein the mutation is a stop codon caused by a nonsense mutation (claim 12); the method of claim 1 wherein the mutation is a frameshift mutation caused by an insertion or a deletion (claim 13).
Thus, the claims of Pat. 304 teach obtaining a sample (e.g. tissue) from an individual, and identifying a mutation (such as nonsense mutation) in an ARID1A nucleic acid sequence. However, the claims of Pat. 304 do not explicitly teach identifying a sample from human as having a mutation in an ARID1A nucleic acid sequence and administering a cancer immunotherapy to the human.
Shen and Anderson News teaches that 1) the immune checkpoint blockade is more effective to cancers with ARID1A mutations in two mouse models; 2) in human ARID1A-deficient tumors also exhibited remarkable increase in CD8 and PD-L1; 3) in human, ARID1A deficiency has a causative relationship with MMR deficiency and ARID1A is essential to normal MMR function; 4) in human, tumors with an increased-TIL transcriptome signature had significantly reduced ARID1A expression (Fig. 4f and Supplementary Fig. 10a–d); and 5) ARID1A status can be used as a potential predictor of response to inhibitors of the PD1/PD-L1 immune checkpoint pathway in clinical setting. Wiegand teaches that several C to A transversions (nonsense mutations) have been identified in ovarian cancer samples, including C1680A (Y560*), C645A (Y215*) and C1687A (Q563*) (stars denote a stop codon) (Fig. 1). Wiegand teaches that C1680A (Y560*) leads to negative expression of BAF250a which is the protein encoded by ARID1A gene (Table 1, and Supplemental Table 3). One of ordinary skill in the art would have expected that these nonsense mutations would lead to a deficiency of functional ARID1A.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to develop the method of identifying mutations of ARID1A taught by the claims Pat. 304, and to identify ovarian cancer patient (human) population that are likely to benefit from specific immunotherapies, e.g. anti-PD1 or anti-PD-L1 therapy based on ARID1A status (e.g. a mutation diminishing ARID1A function), as taught by Shen and Anderson News, and to incorporate a step of obtaining and identifying a cancer tissue from the patients with mutation comprising a C to A transversions (such as C1680A (Y560*), C645A (Y215*) and C1687A (Q563*)) in an ARID1A nucleic acid sequence, because Shen and Anderson News teaches that 1) the immune checkpoint blockade is more effective to cancers with ARID1A mutations in two mouse models; 2) in human ARID1A-deficient tumors also exhibited remarkable increase in CD8 and PD-L1; 3) in human, ARID1A deficiency has a causative relationship with MMR deficiency and ARID1A is essential to normal MMR function; 4) in human, tumors with an increased-TIL transcriptome signature had significantly reduced ARID1A expression (Fig. 4f and Supplementary Fig. 10a–d); and 5) ARID1A status can be used as a potential predictor of response to inhibitors of the PD1/PD-L1 immune checkpoint pathway in clinical setting. In addition, these mutations were detected in ovarian cancer samples and these mutations lead to truncated proteins and negative expression of ARID1A, as taught by Wiegand. The motivation would have been to expand the method of Pat. 304 to an effective treatment process and to develop a better treatment for cancer patients with ARID1A mutations. Given that the method of identifying ARID1A mutation and anti-PD1/anti-PD-L1 immunotherapy are well known and widely used in the art, one of ordinary skill in the art would have had a reasonable expectation of success to reach the claimed invention.
Claims 8-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 9,982,304 (hereinafter Pat. 304, Appl. No.: 13/819,933, of record) in view of Shen (Shen et al., Nature Medicine, Vol. 24, 556-562, Publication Date: 05/07/2018, of record), Anderson News (downloaded from: Preclinical MD Anderson study suggests ARID1a may be useful biomarker for immunotherapy | UT MD Anderson , Publication Date: 05/07/2018), and Wiegand (Wiegand et al., N Engl J Med, 2010; 363: 1532-1543, Publication Date: 09/08/2010), as applied to claims 1, 3-5, 7, and 26-31 above, and further in view of Marcrom (Marcrom et al., Clin Sarcoma Res, (2017) 7:14, Publication Date: 07/14/2017, of record).
The claims of Pat. 304 in view of Shen, Anderson News, Wiegand teach the method of instant claim 1, as set forth above. However, the references do not teach antibodies recited by claim 8, e.g. pembrolizumab (the elected species), or combination therapy.
As set forth above, Marcrom teaches that the combination of pembrolizumab and radiation are effective to CCS with ARID1A mutation (Fig. 1 and the bridging paragraph of pages 2-3). Marcrom further teaches that pembrolizumab and nivolumab are FDA-approved for a wide variety of cancers (page 3, col. 1, para. 4).
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to treat a human having a cancer having a mutation in ARID1A with anti-PD1 or anti-PDL1 therapy, as taught by the claims of Pat. 304, Shen, Anderson News and Wiegand, and to use pembrolizumab as the anti-PD1 therapeutics because Marcrom teaches pembrolizumab is effective for a cancer with ARID1A mutations and pembrolizumab is FDA-approved for a wide variety of cancers. Given that pembrolizumab are widely used in cancer therapy, as evidenced by Marcrom, one of ordinary skill in the art would have had a reasonable expectation of success to reach the claimed invention. The motivation would have been to use a well-tested and FDA-approved antibody for a special subpopulation of cancer patients.
Regarding claims 9 and 10, Marcrom teaches using the combination of pembrolizumab and radiation for treating. Marcrom further teaches that anti-PD1 therapy can enhance local response to radiotherapy and promote abscopal effects with tumor regression at unirradiated sites. Preclinical data and early clinical observations support synergy between immune checkpoint blockade and radiotherapy across multiple tumor types (page 3, col. 2, para. 1). It would have prima facie been obvious to use additional radiotherapy to further enhance the efficacy of the anti-PD1 therapy. The motivation would have been to develop new treatment and to improve efficacy of anti-PD1 therapy. Given that both pembrolizumab and radiotherapy are widely-used in cancer treatment, one of ordinary skill in the art would have had a reasonable expectation of success to reach the claimed invention.
Patent No. 11,959,142
Claims 1, 3-5, 7, and 26-31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 11,959,142 (hereinafter Pat. 142, Appl. No.: 16/610,772, of record) in view of Shen (Shen et al., Nature Medicine, Vol. 24, 556-562, Publication Date: 05/07/2018, of record), Anderson News (downloaded from: Preclinical MD Anderson study suggests ARID1a may be useful biomarker for immunotherapy | UT MD Anderson , Publication Date: 05/07/2018), and Wiegand (Wiegand et al., N Engl J Med, 2010; 363: 1532-1543, Publication Date: 09/08/2010, of record).
The claims of Pat. 142 teach a method for identifying the presence of circulating tumor DNA in a subject, and treating said subject comprising: detecting one or more genetic alterations in cell-free DNA in a biological sample isolated from the subject, wherein the step of detecting is performed when the subject is not known to harbor a cancer cell; and wherein the step of detecting one or more genetic alterations in cell-free DNA includes using a method comprising steps of: … vi) identifying sequence alterations using aligned sequences of multiple distinct molecules containing identical redundant changes; and, vii) identifying the presence of circulating tumor DNA when at least one of the detected genetic alterations in the cell-free DNA is a cancer cell mutations; and thereafter administering a therapeutic agent to the subject (claim 1).
The claims of Pat. 142 teach the method of claim 1, wherein the biological sample is selected from the group consisting of blood, plasma, urine, cerebrospinal fluid, saliva, sputum, broncho-alveolar lavage, bile, lymphatic fluid, cyst fluid, stool, ascites, and combinations thereof (claim 2).
The claims of Pat. 142 teach the method of claim 1, wherein the presence of circulating tumor DNA indicates the presence of a cancer cell (claim 3).
The claims of Pat. 142 teach he method of claim 1, wherein the cancer cell mutation is present in a gene selected from the group consisting of ARID1A, …, or combinations thereof (claim 4).
Thus, the claims of Pat. 142 teach diagnosing cancer cell in a subject and treat the subject identifying a sample from a subject having a mutated ARID1A nucleic acid sequence, and treating the subject with cancer with a therapeutic agent. However, the claims of Pat. 142 does not explicitly teach identifying a sample from human as having a mutation in an ARID1A nucleic acid sequence and administering a cancer immunotherapy to the human.
Shen and Anderson News teaches that 1) the immune checkpoint blockade is more effective to cancers with ARID1A mutations in two mouse models; 2) in human ARID1A-deficient tumors also exhibited remarkable increase in CD8 and PD-L1; 3) in human, ARID1A deficiency has a causative relationship with MMR deficiency and ARID1A is essential to normal MMR function; 4) in human, tumors with an increased-TIL transcriptome signature had significantly reduced ARID1A expression (Fig. 4f and Supplementary Fig. 10a–d); and 5) ARID1A status can be used as a potential predictor of response to inhibitors of the PD1/PD-L1 immune checkpoint pathway in clinical setting. Wiegand teaches that several C to A transversions (nonsense mutations) have been identified in ovarian cancer samples, including C1680A (Y560*), C645A (Y215*) and C1687A (Q563*) (stars denote a stop codon) (Fig. 1). Wiegand teaches that C1680A (Y560*) leads to negative expression of BAF250a which is the protein encoded by ARID1A gene (Table 1, and Supplemental Table 3). One of ordinary skill in the art would have expected that these nonsense mutations would lead to a deficiency of functional ARID1A.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to develop the method of identifying mutations of ARID1A taught by the claims Pat. 142, and to identify ovarian cancer patient (human) population that are likely to benefit from specific immunotherapies, e.g. anti-PD1 or anti-PD-L1 therapy based on ARID1A status (e.g. a mutation diminishing ARID1A function), as taught by Shen and Anderson News, and to incorporate a step of obtaining and identifying a cancer tissue from the patients with mutation comprising a C to A transversions (such as C1680A (Y560*), C645A (Y215*) and C1687A (Q563*)) in an ARID1A nucleic acid sequence, because Shen and Anderson News teaches that 1) the immune checkpoint blockade is more effective to cancers with ARID1A mutations in two mouse models; 2) in human ARID1A-deficient tumors also exhibited remarkable increase in CD8 and PD-L1; 3) in human, ARID1A deficiency has a causative relationship with MMR deficiency and ARID1A is essential to normal MMR function; 4) in human, tumors with an increased-TIL transcriptome signature had significantly reduced ARID1A expression (Fig. 4f and Supplementary Fig. 10a–d); and 5) ARID1A status can be used as a potential predictor of response to inhibitors of the PD1/PD-L1 immune checkpoint pathway in clinical setting. In addition, these mutations were detected in ovarian cancer samples and these mutations lead to truncated proteins and negative expression of ARID1A, as taught by Wiegand. The motivation would have been to expand the method of Pat. 304 to an effective treatment process and to develop a better treatment for cancer patients with ARID1A mutations. Given that the method of identifying ARID1A mutation and anti-PD1/anti-PD-L1 immunotherapy are well known and widely used in the art, one of ordinary skill in the art would have had a reasonable expectation of success to reach the claimed invention.
Claims 8-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 11,959,142 (hereinafter Pat. 142, Appl. No.: 16/610,772) in view of Shen (Shen et al., Nature Medicine, Vol. 24, 556-562, Publication Date: 05/07/2018, of record), Anderson News (downloaded from: Preclinical MD Anderson study suggests ARID1a may be useful biomarker for immunotherapy | UT MD Anderson , Publication Date: 05/07/2018), and Wiegand (Wiegand et al., N Engl J Med, 2010; 363: 1532-1543, Publication Date: 09/08/2010), as applied to claims 1, 3-5, 7, and 26-31 above, and further in view of Marcrom (Marcrom et al., Clin Sarcoma Res, (2017) 7:14, Publication Date: 07/14/2017, of record).
The claims of Pat. 142 in view of Shen, Anderson News and Wiegand teach the method of instant claims 1, as set forth above. However, the references do not teach antibodies recited by claim 8, e.g. pembrolizumab (the elected species), or combination therapy.
As set forth above, Marcrom teaches that the combination of pembrolizumab and radiation are effective to CCS with ARID1A mutation (Fig. 1 and the bridging paragraph of pages 2-3). Marcrom further teaches that pembrolizumab and nivolumab are FDA-approved for a wide variety of cancers (page 3, col. 1, para. 4).
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to treat a human having a cancer having a mutation in ARID1A with anti-PD1 or anti-PDL1 therapy, as taught by the claims of Pat. 142, Shen, Anderson News and Wiegand, and to use pembrolizumab as the anti-PD1 therapeutics because Marcrom teaches pembrolizumab is effective for a cancer with ARID1A mutations and pembrolizumab is FDA-approved for a wide variety of cancers. Given that pembrolizumab are widely used in cancer therapy, as evidenced by Marcrom, one of ordinary skill in the art would have had a reasonable expectation of success to reach the claimed invention. The motivation would have been to use a well-tested and FDA-approved antibody for a special subpopulation of cancer patients.
Regarding claims 9 and 10, Marcrom teaches using the combination of pembrolizumab and radiation for treating. Marcrom further teaches that anti-PD1 therapy can enhance local response to radiotherapy and promote abscopal effects with tumor regression at unirradiated sites. Preclinical data and early clinical observations support synergy between immune checkpoint blockade and radiotherapy across multiple tumor types (page 3, col. 2, para. 1). It would have prima facie been obvious to use additional radiotherapy to further enhance the efficacy of the anti-PD1 therapy. The motivation would have been to develop new treatment and to improve efficacy of anti-PD1 therapy. Given that both pembrolizumab and radiotherapy are widely-used in cancer treatment, one of ordinary skill in the art would have had a reasonable expectation of success to reach the claimed invention.
Response to Arguments
For the Double Patenting rejection, Applicant is reiterating the arguments set forth above. Thus for the reasons set forth above the rejection is maintained.
Conclusion
No claims are allowed.
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/CHENG LU/ Examiner, Art Unit 1642
/SAMIRA J JEAN-LOUIS/ Supervisory Patent Examiner, Art Unit 1642
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