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 .
DETAILED ACTION
Claims 19-36 are pending and are under consideration in the instant office action.
Election/Restrictions
Applicant’s election without traverse of invention II (Claims 19-36) and the following species in their response dated 05/22/2026 is acknowledged.
Specie 1: Applicants elect compound of formula Ia shown below.
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Specie 2: N/A
Specie 3:. Applicant elect compound of formula IIa, specie shown below
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Specie 4: Applicants elect metastatic brain tumor. Upon further consideration, this specie requirement is withdrawn and the claims are examined to include all types of cancer.
Examination of the claims are conducted to the extent they read on the elected species. Applicants cancelled non-elected claims 1-18 in their amendment dated 5/22/2026.
Claims 19-36 are under examination and the requirement for restriction is made final.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/26/2024 and 4/10/2024 complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, it has been placed in the application file and the information therein has been considered as to the merits. See attached copy of the PTO-1449.
Priority
This application claims the benefit of priority from U.S. Provisional Application 63/427,731, filed November 23, 2022.
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, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 19-36 are rejected under 35 U.S.C. 103(a) as being unpatentable over by Guo et al. (US 2022/0389029, priority date 9/21/2020) , Sun et al. (US 12,338,246, priority date of 3/2/2020) and Shojaei et al. (US 12,390,469, priority date 5/5/2021) in view of Taylor et al. (US 10,934,302, Priority date of 3/21/2018)
Instant claims are drawn to a method of treating cancer in a subject, comprising administering to the subject having a tumor an effective amount of a combination comprising an amount of a Kirsten Rat Sarcoma oncogene homologue G12C (KRAS) inhibitor and an amount of a SH2- containing protein tyrosine phosphatase 2 (SHP2) inhibitor, wherein the KRAS inhibitor is a compound of Formula Ia, or a pharmaceutically acceptable salt thereof, and the SHP2 inhibitor is a compound of Formula IIa, or a pharmaceutically acceptable salt thereof, shown below
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Guo et al. discloses the instantly claimed compound of formula Ia as Compound 29A or 29B
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( Last compound on page 153 and 484, [ preparation method 1169) as KRAS inhibitor (abstract) [0001] and they teach pharmaceutical . compositions comprising their compounds with one or more pharmaceutically acceptable carriers [0088]. They disclose a method of preventing or treating disease related to KRAS-G12C including cancer such as non-samll cell lung cancer, colon cancer or pancreatic cancer (claim 27), comprising administering to a patient in need thereof a pharmaceutically effective amount of compound (reference claims 26-27 ). They further exemplify the activity of compound 29B in their studies showing the body weight and tumor volume changes after administration of compound 29B (Fig 1 and Fig 2). They disclose the effective concentration or the dosage of their compounds can be determined by conventional methods in combination with conventional influencing factors (e.g., mode of administration, pharmacokinetics of the compound, severity and duration of the disease, medical history of the individual, health status of the individual, degree of response of the individual to the drug, etc.) [0131] and teach a dosage of 1 mg/kg to mice in their experiment [2116] or dosage of 10 mg/kg, 30 mg.kg or 100 mg/kg [2118]
Sun e al. discloses the instantly claimed compound of formula IIa as a protein tyrosine phosphatase 2 (SHP2) inhibitor (abstract), col.20, lines 45-50, claim 6, col.153, lines 1-10)
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They teach treatment of non-receptor protein tyrosine phosphatase-mediated or dependent diseases or disorders, comprising the steps of: administration of a therapeutically effective amount of their inventive compound to in patient in need thereof (col.4, lines 332-40, lines 55-60) which includes cancers of different types including said cancer may be breast cancer, endometrial cancer, head and neck cancer, skin cancer, lung cancer, liver cancer, leukemia, ovarian cancer, cervical cancer, prostate cancer, bile duct cancer, esophageal cancer, pancreatic cancer, colorectal cancer, glioma, leiomyoma, fallopian tube tumor, kidney cancer, myeloma, bone cancer etc (col.25, line 55 to col.26, line 2). They also disclose combinations of their inventive compounds with an additional therapeutic agent for the prevention of the said diseases (col.26 , lines 52-60). Sun et al. teaches that , As is well known to those skilled in the art, the dose of a drug depends on a variety of factors, including but not limited to the following: the activity of the specific compounds used, or the age of the patient, or the weight of the patient, or the health status of the patient, or the diet of the patient, time of administration, mode of administration, rate of excretion, combination of drugs, etc.; in addition, the optimal treatment method such as the mode of treatment, the daily dosage of the general compound (I) or the types of pharmaceutically acceptable salt can be verified according to the conventional treatment regimens (col. 25, lines 23-33).
Shojaei et al. discloses instantly claimed compound of formula IIa as SHP2 inhibitors useful in the method of treating cancer (abstract) and discloses the specific compound as compound 1a as follows.
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They teach the treatment of brain tumor and a dosage of 5, 10, 15, 20 or 25 mg/kg (reference claim 1, 3 and 16), they disclose the treatment to include cancers such as glioblastoma (col. 15, lines 38-29) and that it reduces the tumjor volume and tumor burden in the patient (col.15, lines 45-56. where that their method of treating cancer inhibits metastasis of the cancer in the patient. In some embodiments, metastasis is inhibited by at least about 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 100%.(col. 16. Lines 48-53). They disclose administration of their inventive compound with another anti-cancer therapy(col.17, lines 47-55).
The references above do not teach the specific combination of compound of formula Ia with that of formula IIa as claimed.
However, Taylor et al. discloses novel compounds and methods of inhibiting the activity of SHP2 phosphatase with the following compounds and compounds structurally similar to these and methods of treating disorders associated with SHP1 deregulation which includes cancers such as leukemia, breast cancer, lung cancer and colorectal cancer ( (abstract), col.3, lines 28-43, claims 3).
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They disclose synergistic inhibition of NCI-H23 (KRAS G12C mutant non-small cell lung cancer cells ) using ARS-1620 (KRAS G12C inhibitor) and a SHP2 inhibitor of their invention (Fig 2B, see col.4, lines 11-14).
Accordingly the instantly claimed compounds of formula Ia and IIa are individually known in the art as agents for treating cancers, whose efficacy when administered alone is well established for the treatment of a cancer. Taylor et al specifically teaches the synergistic properties of combining a KRAS inhibitor with SHP2 inhibitor in treatment of certain cancers. Accordingly it would have been obvious to a person of ordinary skill in the art to combine these two agents taught by Gua et al., Sun et al. and Shojaei et al. It would also have been obvious to test the utility of these agents in the treatment of brain cancer as instantly claimed there is a constant need for better treatment option for brain cancers.
One would have been motivated to do so because the cited prior art clearly and unequivocally teaches, suggests, and motivates the use of both the claimed compounds of formula Ia and IIa for the treatment of cancer both alone and in combination with other chemotherapeutic agents. It is generally 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. In re Kerkhoven, 205 U.S.P.Q. 1069 (CCPA 1980). The idea for combining said compositions flows logically from their having been individually taught in the prior art. In re Crockett, 126 U.S.P.Q. 186, 188 (CCPA 1960). Accordingly, to establish obviousness in such fact situations it is NOT necessary that the motivation come explicitly from the reference itself (although the Examiner believes it does, as discussed supra). The natural presumption that two individually known anticancer agents would, when combined, provide a third composition also useful for treating cancer flows logically from each having been individually taught in the prior art. Applicant has presented no evidence (e.g. unexpected results) to rebut this natural presumption.
In re Diamond and Kellman, 149 USPQ 562 (C.C.P.A. 1966), supports the obviousness of combining two drugs known to be useful for the same purpose. In Diamond, Appellants were claiming a combination of adenosine-5-monophosphate (A5MP) and a glucocorticoid. The Examiner cited prior art teaching that A5MP and glucocorticoids were known in the art to be useful for treating collagen diseases and that combining drugs for the treatment of disease is suggested by the prior art. Appellants argued that the combination of the two drugs is non-obvious since there is no teaching to combine these two out of all known anti-inflammatory agents. The Court was not persuaded by this argument, stating that: “...we think it clear that it is a standard practice in this art to combine ingredients.” One skilled in the art would have been imbued with at least a reasonable expectation that these two agents when combined would provide synergistic activity against different cancer types.
With regards to instant claims 27 and 35-36 claiming dosages of the compounds, As taught by Guo et al. and Sun et al. it would be obvious to a person of ordinary skill in the art to determine the effective dosages of each of these which gives the synergistic effect in combination through routine conventional methods. It is noted that "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Conclusion
Claims 19-36 are rejected. No claims are allowed
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAVITHA RAO whose telephone number is (571)270-5315. The examiner can normally be reached on Mon-Fri 7 am to 4 pm..
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor ,Renee Claytor can be reached on (571) 272-8394. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SAVITHA M RAO/Primary Examiner, Art Unit 1691
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