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 .
Status of the Claims/Amendments
Claims 1-14, 45, and 46 are pending in the preliminary amendment filed 12/2/24.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/2/24 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
CB 113797341 A is not in English has been considered to the extent of the provided English abstract.
Further, it is noted that the listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered. Specifically, reference to PARP1 inhibitor documents on Page 7 of the specification (e.g. WO 2010/133647) are not on an IDS.
Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
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.
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.
Claim(s) 1-4, 6-14, 45, and 46 is/are rejected under 35 U.S.C. 103 as being unpatentable over GAY (US 2021/0062274 A1) in view of CHARRIER (WO 2011/163527 A1), PENNEY (WO 2019/13711 A1), BURAK (WO 2020/115548 A1), and PACKER (WO 2021/013735 A1, IDS 12/2/24).
The instant claims are drawn generally to a method of treating cancer with a combination of a selective PARP1 inhibitor and an ATR inhibitor.
Gay teaches, “Small cell lung cancer (SCLC) is an aggressive neuroendocrine malignancy with dismal long-term survival rates (Byers & Rudin, 2015). Despite recent advancements in the standard of care—most notably with the recent addition of immunotherapy to platinum-based frontline chemotherapy—the absolute improvements in progression-free survival (PFS) and overall survival (OS) are modest (Antonia et al., 2016; Chung et al., 2020; Horn et al., 2018; Chung et al., 2018; Paz-Ares et al., 2019). In contrast to non-small cell lung cancer (NSCLC), where patient selection for targeted and immune-based therapies has dramatically altered treatment approaches and patient outcomes (Zimmermann et al., 2018), a persistent challenge in optimizing therapy for SCLC patients remains a lack of prospectively validated biomarkers. As a result, clinical trials for SCLC patients have focused on unselected populations and have yielded predictably disappointing results. Better defining the subsets of SCLC that predict sensitivity, or govern resistance, to targeted and immune-based therapies represents a fundamental unmet need for this disease.” (para [0004]). Gay teaches classification of the patient small cell lung cancer and treatment with compounds including PARP inhibitors and ATR inhibitors (e.g. claim 5), and combinations thereof, and further exemplifies that the ATR inhibitor is AZD6738, aka ceralasertib (e.g. claim 5), as well as treatment of SCLC comprising administering a PARP inhibitor, a nucleoside analog, an anti-metabolite, or a Pt-chemotherapeutic (e.g. claim 34).
Charrier teaches ATR inhibitor pharmaceutical compositions (e.g. claim 50), and the use in treating cancer (e.g. claim 51). Charrier teaches that, “The present invention relates to pyrrolopyrazine compounds useful as inhibitors of ATR protein kinase…These compounds have unexpected ability to treat cancer as single agents. These compounds also show surprising synergy with other cancer agents, such as cisplatin, in combination therapies.” (para [0007]). Charrier teaches cancer includes oral, cardiac, lung, GI, GU, liver, bone, nervous system, gynecological, hematological, skin, thyroid, and adrenal glands, (para [0069]), providing specific examples of each cancer, e.g. breast, glioma, prostate (para [0069]). Charrier teaches the ATR compounds in pharmaceutical compositions (e.g. para [0077]+), in combination therapies (e.g. para [0081]), where the additional agent is an anti-cancer agent (e.g. para [0082], [0085]). Charrier contemplates inclusion of updated cancer therapies, citing NIH and FDA and The Merck Manual ([para [0087]).
Penney teaches treating cancer via administration of an ATR inhibitor in combination with a PARP inhibitor (e.g. claim 59) where the cancer is lung cancer, ovarian cancer, endometrial cancer, pancreatic cancer, head and neck cancer, esophageal cancer, breast cancer and colorectal cancer (e.g. claim 61). Penney additionally teaches an article of manufacture of the ATR inhibitor, comprising: (a) a packaging material; (b) an ATR inhibitor, or a pharmaceutically acceptable salt thereof; and (c) a label, a package insert, or directions for obtaining the label or the package insert, contained within the packaging material, wherein the label or package insert provides prescribing information based on level of CDKN1A activity, or based on the level of CDKN1A activity and TP53 mutations status, determined for the cancer in a patient. (e.g. claim 66). Penney additionally teaches that in some embodiments, “the ATR inhibitor is used in combination with a DNA damaging agent, a PARP inhibitor, and a Chkl inhibitor.” (e.g., para [0025]).
Burak teaches treating cancer with an ATR inhibitor in combination with a PARP inhibitor (e.g. claim 17), and the ATR inhibitor is selected from AZ20, AZD0156, AZD1390, AZD6738, BAY-1895344, EPT-46464, M3541, M4344, M6620 (formerly known as VE-922 or VX-970), NU6027, VE-821 , or an analog thereof (e.g. claim 23), and the cancer is breast cancer, non-small cell lung cancer, small cell lung cancer, pancreatic cancer, head and neck cancer, prostate cancer, colorectal cancer, sarcoma, adrenocortical carcinoma, neuroendocrine cancer, Ewing’s Sarcoma, multiple myeloma, or acute myeloid leukemia (e.g. claim 29).
Packer teaches that, “It is believed that PARP inhibitors having improved selectivity for PARP1 may possess improved efficacy and reduced toxicity compared to other clinical PARP1/2 inhibitors. It is believed also that selective strong inhibition of PARP1 would lead to trapping of PARP1 on DNA, resulting in DNA double-strand breaks (DSBs) through collapse of replication forks in S-phase. It is believed also that PARP1-DNA trapping is an effective mechanism for selectively killing tumor cells having HRD.” (page 1, lines 37-41). Futher, “An unmet medical need therefore exists for effective and safe PARP inhibitors. Especially PARP inhibitors having selectivity for PARP1…. Furthermore, azaquinolones described herein have surprisingly high selectivity for PARP1… [and] have advantageously low hERG activity.” (page 2, lines 5-12).
Packer teaches the compound AZD5305 (compound of instant claim 4) in example 4 (spanning page 15 and 16), and the genus of compounds (e.g. claim 1+). Packer teaches the compounds for the treatment of cancer (e.g. claim 18), where the cancer is breast, ovary, pancreas, prostate, hematological, GI, or lung (e.g. claims 25, 35, and 37).
While the art teaches treatment of cancer, such as SCLC, with ATR and PARP, and specifically PARP1 inhibitors, alone, and the combination of PARP and ATR to treat cancers, the art does not teach the combination of ATR and PARP1 inhibitors.
Taken as a whole, the art provides that ATR inhibitors surprisingly showed synergy with other anticancer agents, and that combinations with drugs, such as PARP inhibitors, were recognized for their ability to treat cancers, alone or in combination with one another. It would have been obvious to have used any ATR inhibitor, including ceralasertib, in a combination therapy, as it is one suggested by Burak (as AZD6738) and Gay, for treatment of SCLC. It would have been obvious to have selected a PARP1 compound such as AZD5305 to take advantage of the improved efficacy and reduced toxicity taught by Packer. As set forth in In re Kerkhoven, 205 USPQ 1069 (CCPA 1980), “It is prima facie obvious to combine two compositions each of which is taught by prior art to be useful for same purpose in order to form third composition that is to be used for very same purpose; the idea of combining them flows logically from their having been individually taught in prior art.” Here, both compounds are taught in the art to provide specific advantages such as increased synergy and improved efficacy and reduced toxicity, and are taught for treating various cancers, including lung cancers, such as SCLC, and thus in addition to simple substitution of the PARP1 inhibitor in the suggested combination therapy containing PARP, it would have been prima facie obvious to combine the ATR and PARP1 inhibitors, both taught for the very same purpose to make a combination with the very same purpose, and then use it for treating cancer, such as SCLC.
Further, with regards to the kit, it is additionally noted that with regards to the ‘instructions’, The MPEP states, “Where the only difference between a prior art product and a claimed product is printed matter that is not functionally related to the product, the content of the printed matter will not distinguish the claimed product from the prior art. In re Ngai, 367 F.3d 1336, 1339, 70 USPQ2d 1862, 1864 (Fed. Cir. 2004) (Claim at issue was a kit requiring instructions and a buffer agent. The Federal Circuit held that the claim was anticipated by a prior art reference that taught a kit that included instructions and a buffer agent, even though the content of the instructions differed.). See also In re Gulack, 703 F.2d 1381, 1385-86, 217 USPQ 401, 404 (Fed. Cir. 1983)("Where the printed matter is not functionally related to the substrate, the printed matter will not distinguish the invention from the prior art in terms of patentability …. [T ]he critical question is whether there exists any new and unobvious functional relationship between the printed matter and the substrate.").” Here, the combination is prima facie obvious to create, above, and the printed materials do not distinguish the product.
Further, it is noted that claims 8-14 limit one aspect of the larger Markush group to a subset, e.g. A, B, or C is A, B, or C’, however it does not require selection of said condition. For example, claim 13 limits brain cancer to glioma or glioblastoma, but it does not require that the treatment/patient be one with brain cancer- in contrast to a claim that recited: “wherein the cancer is a brain cancer, and the brain cancer is selected from…”
Claim(s) 1-4, 6-14, 45, and 46 is/are rejected under 35 U.S.C. 103 as being unpatentable over GAY (US 2021/0062274 A1) in view of CHARRIER (WO 2011/163527 A1), PENNEY (WO 2019/13711 A1), BURAK (WO 2020/115548 A1), and PACKER (WO 2021/013735 A1, IDS 12/2/24), and further in view of PACKER(2) (WO 2021/260092 A1, IDS 12/2/04).
The instant claims and teachings of Gay, Charrier, Penney, Burak, and Packer are above. The instant claims are further drawn to the PARP1 inhibitor being AZD9574.
Packer(2) teaches AZD9574 (e.g. claim 10), as a PARP1 selective inhibitor (spenoted by the instant specification to be found in example 20), along with the genus containing the compound (e.g. claim 1+), providing the same benefits and advantages of AZD5105 (e.g. page 1, lines 36-40, page 2, lines 1-11). The compounds of Packer(2) are suggested for use in treating cancers, e.g. glioma/glioblastoma, SCLC, and NSCLC (e.g. page 3, lines 29-39).
Taken as a whole, the art provides that ATR inhibitors surprisingly showed synergy with other anticancer agents, and that combinations with drugs, such as PARP inhibitors, were recognized for their ability to treat cancers, alone or in combination with one another. It would have been obvious to have used any ATR inhibitor, including ceralasertib, in a combination therapy, as it is one suggested by Burak (as AZD6738) and Gay, for treatment of SCLC. It would have been obvious to have selected a PARP1 compound such as AZD5305 to take advantage of the improved efficacy and reduced toxicity taught by Packer. As set forth in In re Kerkhoven, 205 USPQ 1069 (CCPA 1980), “It is prima facie obvious to combine two compositions each of which is taught by prior art to be useful for same purpose in order to form third composition that is to be used for very same purpose; the idea of combining them flows logically from their having been individually taught in prior art.” Here, both compounds are taught in the art to provide specific advantages such as increased synergy and improved efficacy and reduced toxicity, and are taught for treating various cancers, including lung cancers, such as SCLC, and thus in addition to simple substitution of the PARP1 inhibitor in the suggested combination therapy containing PARP, it would have been prima facie obvious to combine the ATR and PARP1 inhibitors, both taught for the very same purpose to make a combination with the very same purpose, and then use it for treating cancer, such as SCLC.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Andrew D Kosar whose telephone number is (571)272-0913. The examiner can normally be reached Monday-Friday, 7am-3:30pm.
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/Andrew D Kosar/ Supervisory Patent Examiner, Art Unit 1625
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