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 .
Status of the Claims
This Office Action is in response to Applicant's Restriction Requirement remarks filed on June 13, 2025. Claim(s) 1, 5-11, and 21-32 are pending. Claim(s) 7, 10, and 21-28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant's election of species of VS-6063 (FAK Inhibitor), co-stimulatory antibody (anti-4-1BB) (immunotherapeutic agent), and non-small cell lung cancer (cancer) without traverse of the restriction requirement in the reply is acknowledged. The requirement is deemed proper and is therefore made FINAL. Claim(s) 1, 5, 6, 8, 9, 11, 29, and 30-32 are examined herein insofar as they read on the elected invention and species.
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 claims at issue 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); and 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
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Claims 1, 5, 6, 8, 9, 11, 29, and 30-32 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-27 of U.S. Patent No. 10,532,056. Although the conflicting claims are not identical, they are not patentably distinct from each other because the instant claims are to a method for treating a human subject suffering from cancer, comprising administering a FAK inhibitor in combination with an immunotherapeutic agent or procedure, including an anti-PD antibody. Dependent claims are drawn to specific FAK inhibitors including VS-4718, VS-5095, VS-6062, VS-6063, BI 853520, or GSK2256098 (claim 9) and cancers including mesothelioma; neurofibromatosis, renal cancer; lung cancer, non-small cell lung cancer; liver cancer, thyroid cancer, ovarian, breast cancer, a nervous system tumor, schwannoma, meningioma, schwannomatosis, neuroma acoustic, adenoid cystic carcinoma, ependymoma, or ependymal tumors (claims 5-6), colorectal, leukemia, adenocarcinoma (claim 7). The patented claims teach treating a human subject suffering from cancer comprising administering to the subject an effective amount of VS-6063 or a pharmaceutically acceptable salt thereof, in combination with an anti-PD-1 antibody, wherein the cancer is selected from the group consisting of mesothelioma, lung cancer, non-small cell lung cancer, ovarian cancer, colorectal cancer, and pancreatic cancer. The two inventions overlap greatly in scope.
Claims 1, 5, 6, 8, 9, 11, 29, and 30-32 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 11,564,927. Although the conflicting claims are not identical, they are not patentably distinct from each other because the instant claims are to a method for treating a human subject suffering from cancer, comprising administering a FAK inhibitor in combination with an immunotherapeutic agent or procedure, including an anti-PD antibody. Dependent claims are drawn to specific FAK inhibitors including VS-4718, VS-5095, VS-6062, VS-6063, BI 853520, or GSK2256098 (claim 9) and cancers including mesothelioma; neurofibromatosis, renal cancer; lung cancer, non-small cell lung cancer; liver cancer, thyroid cancer, ovarian, breast cancer, a nervous system tumor, schwannoma, meningioma, schwannomatosis, neuroma acoustic, adenoid cystic carcinoma, ependymoma, or ependymal tumors (claims 5-6), colorectal, leukemia, adenocarcinoma (claim 7). The patented claims are drawn to a method for treating a human subject suffering from cancer, comprising administering an effective amount of a FAK inhibitor selected from VS-6063 and VS-4718, or a pharmaceutically acceptable salt thereof, in combination with an anti-PD-1 antibody, wherein the cancer is selected from the group consisting of mesothelioma, neurofibromatosis, renal cancer, lung cancer, non-small cell lung cancer, liver cancer, thyroid cancer, ovarian cancer, breast cancer, schwannoma, meningioma, schwannomatosis, acoustic neuroma, adenoid cystic carcinoma, ependymoma, and ependymal tumors. The two inventions overlap greatly in scope.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 5, 6, 8, 9, 11, 29, and 30-32 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for the treatment of mesothelioma, neurofibromatosis, renal cancer, lung cancer, non-small cell lung cancer, liver cancer, thyroid cancer, ovarian, breast cancer, schwannoma, meningioma, schwannomatosis, neuroma acoustic, adenoid cystic carcinoma, ependymoma comprising administering FAK inhibitors VS-4718 or VS-6063 in combination with an anti-4-1BB antibody, does not reasonably provide enablement for the treatment of all cancers with the combination of any immunotherapeutic agent and any immunotherapeutic agent or procedure. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims. The specification does not provide sufficient information that all cancers are treatable with the combination of any FAK inhibitor and any immunotherapeutic agent or procedure as described in the methods claimed.
The instant specification fails to provide information that would allow the skilled artisan to fully practice the instant invention without undue experimentation. Attention is directed to In re Wands, 8USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547, the court recited eight factors:(1) the nature of the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary.
(1). The Nature of the Invention: All of the rejected claims are drawn to an invention which pertains to a method of treating a human subject with the combination of any FAK inhibitor and any immunotherapeutic agent or procedure for the treatment of any cancer. The nature of the invention is extremely complex in that it encompasses the treatment of all types of cancers any FAK inhibitor and any immunotherapeutic agent or procedure.
(2). Breadth of the Claims: The complex nature of the subject matter of this invention is greatly exacerbated by the breadth of the claims. The claims encompass treatment of any number of cancers by a combination of FAK inhibitor and any immunotherapeutic agent or procedure.
(3). Guidance of the Specification: The guidance given by the specification as to how one would administer the claimed compounds to a subject in order to treat any type of cancer cell is limited. All of the guidance provided by the specification is directed toward effectiveness of the combination of VS-6063 or VS-4718 and an anti-PD-1 and anti-4-1BB antibodies in decreasing colon tumor volumes.
(4). Working Examples: Applicant provides in vitro examples of the cytotoxicity of the combination of VS-6063 or VS-4718 and anti-4-1BB antibodies, and its effectiveness in colon tumor cell lines.
(5). State of the Art. While the state of the art is relatively high with regard to treating specific cancers, the state of the art with regard to treating cancer, generally, is underdeveloped. In particular, there is no known anticancer agent that is effective against all cancers. There are compounds that treat a range of cancers, but no one has ever been able to figure out how to get a compound to be effective against cancer generally, or even a majority of cancers. Thus, the existence of such a "silver bullet" is contrary to our present understanding in oncology. This is true in part because cancers arise from a wide variety of sources, such as viruses (e.g. EBV, HHV-8, and HTLV-1), exposure to chemicals such as tobacco tars, genetic disorders, ionizing radiation, and a wide variety of failures of the body's cell growth regulatory mechanisms. Different types of cancers affect different organs and have different methods of growth and harm to the body, and different vulnerabilities. Even those that affect a single organ are often not generally treatable. For example, the main types of lung cancer are small cell (oat cell), giant cell, clear cell, adenocarcinoma of the lung, squamous cell cancer of the lung, and mesothelioma.
In the instant case, Schwock (Expert Opinion Therapeutic Targets, 2010) describes small molecule inhibitors of the focal adhesion kinase (FAK) should be examined in further clinical studies and combinations with existing therapies need to be explored. More efforts are required to identify markers which predict response towards FAK inhibition (abstract).
There is no such thing as a treatment of these generally because of their diversity. Thus, it is beyond the skill of oncologists today to get an agent to be effective against cancers generally, evidence that the level of skill in this art is low relative to the difficulty of such a task.
(6). Predictability of the Art. The invention is directed to inhibiting cancer cells in general. It is wellestablished that "the scope of enablement various inversely with the degree of unpredictability of the factors involved," and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839 (1970). Cancers are especially unpredictable due to their complex nature. The treatment of one type of cancer could not be necessarily the same for the other type.
(7). The Quantity of Experimentation Necessary. In order to practice the claimed invention, one of skill in the art would have to first envision a combination of an appropriate pharmaceutical carrier, a dosage for each compound, the duration of treatment, route of treatment, etc. and, in the case of human treatment, an appropriate animal model system for one of the claimed compounds. One would then need to test the combination in the model system to determine whether or not the combination is effective for inhibiting cancer cells. If unsuccessful, which is likely given the lack of significant guidance from the specification or prior art regarding treatment of any cancer with the combination of FAK inhibitor and any immunotherapeutic agent or procedure, one of skill in the art would have to then either envision a modification of the first combination of pharmaceutical compound, compound dosage, duration of treatment, route of administration, etc. and appropriate animal model system, or envision an entirely new combination of the above and test the system again. If again unsuccessful, which is likely given the lack of significant guidance from the specification or prior art regarding treatment of any cancer with the combination of FAK inhibitor and any immunotherapeutic agent or procedure, the entire, unpredictable process would have to be repeated until successful. In order to practice Applicant's invention, it would be necessary for one to conduct the preceding experimentation for each type of cancer because, there is no known drug effective for inhibiting all types of cancer. Therefore, it would require undue, unpredictable experimentation to practice the claimed invention to treat any cancer in a mammal by administration of the combination of the claims. Genentech, 108 F.3d at 1366 states that "a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion" and "[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable." Therefore, a method for treating any cancer, generally, by administering the combination of FAK inhibitor and any immunotherapeutic agent or procedure of the claims is not considered to be enabled by the instant specification.
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.
Claim 1, 5, 6, 29, and 32 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 pre-AIA the applicant regards as the invention.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). By way of example, claim 1 recites the broad recitation of a disease or disorder, and the claim also recites “abnormal cell growth, e.g., cancer (e.g., a cancer described herein)”, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Amending the claims by deleting the terms (e.g., … or i.e., …) would obviate the rejection.
Claim Rejections - 35 USC § 103
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 of this title, 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.
Claims 1, 5, 6, 8, 9, 11, 29, and 30-32 are rejected under 35 U.S.C. 103 as being unpatentable over Garmey (US 2014/0105891) and Moskalenko (US 2004/0197312).
Garmey teaches a method of treating a proliferative disorder, e.g., a cancer, in a subject [0003]. The method comprising administering a CDP-topoisomerase inhibitor in combination with an angiogenesis inhibitor, e.g., a VEGF pathway inhibitor,
e.g., a VEGF pathway inhibitor described herein, e.g., a VEGF inhibitor, e.g., a small molecule inhibitor, protein, e.g., a fusion protein (e.g., aflibercept) or an antibody against VEGF, e.g., bevacizumab; or a VEGF receptor inhibitor (e.g., a VEGF receptor 1 inhibitor or a VEGF receptor 2 inhibitor), e.g., a small molecule inhibitor, e.g., sorafenib, sunitinib, pazopanib or brivanib, or an antibody against VEGF receptor [0004].
Garmey teaches the cancer treatment, e.g., chemotherapeutic agent, other than the CDP-topoisomerase inhibitor, is a chemotherapeutic agent or a combination of chemotherapeutic agents described herein [0161].
Garmey teaches preferred cancers include breast cancer (e.g., metastatic or locally advanced breast cancer), prostate cancer (e.g., hormone refractory prostate cancer), renal cell carcinoma, lung cancer (e.g., small cell lung cancer and non-small cell lung cancer (including adenocarcinoma, squamous cell carcinoma, bronchoalveolar carcinoma and large cell carcinoma), pancreatic cancer, gastric cancer (e.g., gastroesophageal, upper gastric or lower gastric cancer), colorectal cancer, squamous cell cancer of the head and neck, ovarian cancer
(e.g., advanced ovarian cancer, platinum-based agent resistant or relapsed ovarian cancer), lymphoma (e.g., Burkitt's, Hodgkin's or non-Hodgkin's lymphoma), leukemia (e.g., acute myeloid leukemia) and gastrointestinal cancer [0031].
Garmey teaches the cancer is ovarian cancer, and the chemotherapeutic agent is selected from imatinib, docetaxel, cabazitaxel, niraparib, paclitaxel, carboplatin, cisplatin, votinostat, veliparib, topotecan, AZ2281, lenalidomide, doxorubicin, bevacizumab, bendamustine, N-acetylcysteine, olaparib, rucaparib, AZD0530, lovastatin, flutamide, SU5416, CP-4055, MORAb-003 (farletuzumab), sagopilone (ZK 219477), sorafenib, panitumumab, trabectedin, KHK2866, gemcitabine, catumaxomab, melphalan, celecoxib, aflibercept, and defactinib (VS-6063) [0162].
Garmey teaches the method further comprises administering one or more chemotherapeutic agents, e.g., one or more chemotherapeutic agent described herein, in combination with the CDP-topoisomerase inhibitor conjugate, particle or composition and the angiogenesis inhibitor. For example, in one embodiment, the method comprises administering CDP-topoisomerase inhibitor conjugate, particle or composition in combination with the angiogenesis inhibitor and a taxane (e.g., docetaxel, paclitaxel, larotaxel cabazitaxel) [0043].
Garmey teaches the method includes selecting a subject having
or at risk of becoming resistant to treatment with a chemotherapeutic agent,
e.g., the subject is at risk of developing hypoxia-induced resistance to a chemotherapeutic agent, for treatment with the, particle or composition [0048].
Garmey teaches the CDP-topoisomerase inhibitor conjugate, particle or composition is administered with at least one additional therapeutic agent, such as a chemotherapeutic agent [0947].
Garmey teaches the CDP-topoisomerase inhibitor conjugate, particle or composition is administered in combination with an immunosuppressive agent [0957].
Garmey teaches the pharmaceutical compositions may be administered orally, parenterally (e.g., via intravenous, subcutaneous, intracutaneous, intramuscular, intraarticular, intraarterial, intraperitoneal, intrasynovial, intrasternal, intrathecal, intralesional or intracranial injection), topically, mucosally (e.g., rectally or vaginally), nasally, buccally, ophthalmically, via inhalation spray (e.g., delivered via nebulization, propellant or a dry powder device) or via an implanted reservoir. Typically, the compositions are in the form of injectable or infusible solutions [0910].
Garmey teaches the combination with a number of antibodies.
Garmey does not specifically teach the antibody as a co-stimulatory antibody such as anti-4-1BB as required by the elected species.
Moskalenko teaches improved methods of cancer immunotherapy, comprising: administering the combination of a cytokine-expressing cellular vaccine and at least one additional cancer therapeutic agent selected from the group consisting of an anti-CTLA4 antibody, an anti-4-1BB antibody (claims 1 and 13) wherein the cancer is non-small cell lung (claim 9; [0054]), among others.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have employed VS-6063 in anti-proliferative treatments for non-small cell lung cancer further comprising immunotherapeutic agents such as antibodies as taught by Garmey and employed co-stimulatory antibody such as anti-4-1BB. The examiner respectfully points out the following from MPEP 2144.06: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose ....[T]he idea of combining them flows logically from their having been individually taught in the prior art.', In re Kerkhoven, 626 F.2d 846, 850,205 USPQ 1069, 1072 (CCPA 1980).
Thus, based on the foregoing reasons, the instant claims are deemed unpatentable over the cited reference.
Conclusion
Claims 1, 5, 6, 8, 9, 11, 29, and 30-32 are not allowed.
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/SAHAR JAVANMARD/Primary Examiner, Art Unit 1627