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 .
It is noted that the present application has been transferred to a new Examiner, Terra C. Gibbs of Art Unit 1635.
DETAILED ACTION
This Office Action is a response to Applicant’s Amendment and Remarks filed March 12, 2026.
Claim 34 has been canceled. New claim 37 is acknowledged. Claims 1, 16 and 35 have been amended.
Claims 1-4, 13-16, 30-33 and 35-37 are pending in the present application.
Claims 1-4, 13-16, 30-33 and 35-37 have been examined on the merits as detailed below:
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Information Disclosure Statement
Applicant’s information disclosure statement (IDS) filed March 12, 2026 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Response to Amendment
This Official Action considers Applicant’s Amendment and Remarks filed March 12, 2026. The Amendments and Arguments filed therein are sufficient to overcome the previous rejection under 35 U.S.C. 103 as being unpatentable over Njar et al (US20180147216) in view of Erlander et al (US20150139946) and Lennerz et al (The Oncologist Vol.20:e8-e9, 2015).
After careful reconsideration of the pending claims and the invention as a whole, a new ground of rejection is made of record as detailed below:
Claim Rejections - 35 USC § 103
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.
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 pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4.Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-4, 13-16, 30-33 and 35-37 are rejected under 35 U.S.C. 103 as being unpatentable over US 2018/289683 A1 (MCCORMICK FRANK ET AL) 11 October 2018 (2018-10-11) (submitted and made of record on the IDS filed April 5, 2023).
The claims are drawn to a method of treating a subject who has a cancer containing an oncogenic KRAS mutant, the method comprising administering to the subject a therapeutically effective amount of an inhibitor of a KRAS expression factor (KRAS-EF), wherein the inhibitor is an antagonist of Androgen Receptor (AR) that has direct androgen receptor antagonistic activity and the cancer is a solid tumor with a mutation in KRAS at G12. The present Specification discloses that in some embodiments, the direct inhibitor is a small molecule antagonist of Androgen Receptor (AR), e.g., a non-steroidal antagonist (e.g., bicalutamide, nilutamide, flutamide).
NOTE: Applicant’s Disclosure does not define, “a therapeutically effective amount of an inhibitor of a KRAS expression factor”. With no expressed definition, the phrase takes its ordinary meaning as understood in the art. The Examiner will interpret the phrase to mean any amount sufficient to achieve the purpose stated in the claim. For further explanation, see MPEP 2111 as it relates to broadest reasonable interpretation.
MCCORMICK is relevant and relied upon in its entirety. The reference teaches methods and compounds for inhibiting K-Ras and for treating cancer. More specifically, MCCORMICK teaches KRAS modulators for reducing the level of activity of a KRAS protein including oncogenic mutants ([0005], [0008], [0009]), optionally in combination with further anti-cancer agents including the direct AR inhibitors (antiandrogens) bicalutamide, nilutamide, flutamide ([0139]).
MCCORMICK also teach that anti-cancer agents include progestins (e.g., megestrol acetate or medroxyprogesterone acetate). It is noted that both megestrol acetate and medroxyprogesterone acetate are direct AR inhibitors as evidenced by David G. McLeod, M.D., J.D. (Cancer, 1993 Volume 71, Issue S3 pp. 1046-1049).
MCCORMICK teaches identifying subjects having a cancer containing an oncogenic KRAS mutation, including the G12 mutation. For example, MCCORMICK explicitly discloses:
The disease is a disease related to (e.g. caused by) a Ras. In some embodiments, the disease is a disease related to (e.g. caused by) a K-Ras (e.g. K-Ras G12C, G13C, G12D, G12V, G12S, or G13D) or aberrant K-Ras signaling pathway activity (e.g. lung cancer, breast cancer, colon cancer, colorectal cancer, pancreatic cancer, leukemia).
MCCORMICK teaches the methods of their invention include administration of one or more additional therapies, for example cancer therapies such as chemotherapy or immunotherapy.
Before the effective filing date of the claimed invention, a method of treating a subject who has a cancer containing an oncogenic KRAS mutant comprising administering an antagonist of AR that has direct AR antagonistic activity, and the cancer is a solid tumor with a mutation in KRAS at G12 was taught and suggested in the prior art.
A person of ordinary skill in the art would have been motivated and expected reasonable success to devise the methods of the claimed invention using the disclosures of MCCORMICK. The reference is explicit in teaching, “the certain methods presented herein successfully treat cancer by decreasing the incidence of cancer and or causing remission of cancer.”
It is noted and the Examiner acknowledges that MCCORMICK teaches AR antagonists as optional combination partners alongside a KRAS inhibitor in methods of treatment of a cancer containing an oncogenic KRAS mutant. However, it is important to note that the claims recite “comprising” language. Applicant is reminded that:
The transitional term "comprising", which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See, e.g., >Mars Inc. v. H.J. Heinz Co., 377 F.3d 1369, 1376, 71 USPQ2d 1837, 1843 (Fed. Cir. 2004) ("like the term 'comprising,' the terms 'containing' and 'mixture' are open-ended.").< Invitrogen Corp. v. Biocrest Mfg., L.P., 327 F.3d 1364, 1368, 66 USPQ2d 1631, 1634 (Fed. Cir. 2003) ("The transition 'comprising' in a method claim indicates that the claim is open-ended and allows for additional steps."); Genentech, Inc. v. Chiron Corp., 112 F.3d 495, 501, 42 USPQ2d 1608, 1613 (Fed. Cir. 1997) ("Comprising" is a term of art used in claim language which means that the named elements are essential, but other elements may be added and still form a construct within the scope of the claim.); Moleculon Research Corp. v. CBS, Inc., 793 F.2d 1261, 229 USPQ 805 (Fed. Cir. 1986); In re Baxter, 656 F.2d 679, 686, 210 USPQ 795, 803 (CCPA 1981); Ex parte Davis, 80 USPQ 448, 450 (Bd. App. 1948) ("comprising" leaves "the claim open for the inclusion of unspecified ingredients even in major amounts"). >In Gillette Co. v. Energizer Holdings Inc., 405 F.3d 1367, 1371-73, 74 USPQ2d 1586, 1589-91 (Fed. Cir. 2005), the court held that a claim to "a safety razor blade unit comprising a guard, a cap, and a group of first, second, and third blades" encompasses razors with more than three blades because the transitional phrase "comprising" in the preamble and the phrase "group of" are presumptively open-ended. "The word 'comprising' transitioning from the preamble to the body signals that the entire claim is presumptively open-ended." Id.
Therefore, the presently claimed invention does not exclude the K-ras modulators plus AR antagonists for cancer treatment of MCCORMICK.
The Examiner also acknowledges that MCCORMICK discloses a long list of anti-cancer agents as cancer therapeutics. However, Applicant should note that a long list of combinations does not make any one of them less obvious (Merck v. Biocraft, Fed. Cir. 1989).
Therefore, the subject matter of claims 1-4, 13-16, 30-33 and 35-37 is obvious over MCCORMICK, absent some evidence to the contrary.
******
Claims 1-4, 13-16, 30-33 and 35-37 are rejected under 35 U.S.C. 103 as being unpatentable over US Patent No. 11141418 to University of Texas System.
The claims are as described above.
University of Texas System is relevant and relied upon in its entirety. The reference teaches methods and compositions for KRAS inhibitors. More specifically, University of Texas System teach KRAS modulators for reducing the level of activity of a KRAS protein including oncogenic mutants (Abstract), optionally in combination with further chemotherapeutic agents including “anti-hormonal agents” or “endocrine therapeutics”, including the direct AR inhibitors (anti-androgens) bicalutamide, nilutamide, flutamide.
University of Texas System also teach that chemotherapeutic agents include “anti-hormonal agents” or “endocrine therapeutics”, such as progestins (e.g., megestrol acetate or medroxyprogesterone acetate). It is noted that both megestrol acetate and medroxyprogesterone acetate are direct AR inhibitors as evidenced by David G. McLeod, M.D., J.D. (Cancer, 1993 Volume 71, Issue S3 pp. 1046-1049).
University of Texas System teach identifying subjects having a cancer containing an oncogenic KRAS mutation, including the G12C, G12D or G12V mutation. See Figure 3, for example.
University of Texas System teach the methods of their invention include administration of one or more additional therapies, for example combinations of two or more of the chemotherapeutic agents including “anti-hormonal agents” or “endocrine therapeutics”.
Before the effective filing date of the claimed invention, a method of treating a subject who has a cancer containing an oncogenic KRAS mutant comprising administering an antagonist of AR that has direct AR antagonistic activity, and the cancer is a solid tumor with a mutation in KRAS at G12 was taught and suggested in the prior art.
A person of ordinary skill in the art would have been motivated and expected reasonable success to devise the methods of the claimed invention using the disclosures and motivation of University of Texas System.
It is noted and the Examiner acknowledges that University of Texas System teach AR antagonists as optional combination partners alongside a KRAS inhibitor in methods of treatment of a cancer containing an oncogenic KRAS mutant. However, the claims recite open-ended “comprising” language as discussed supra. Therefore, the presently claimed invention does not exclude the KRAS inhibitors plus AR antagonists for cancer treatment of University of Texas System.
The Examiner also acknowledges that University of Texas System discloses a long list of the long list of chemotherapeutic agents including “anti-hormonal agents” or “endocrine therapeutics” as cancer therapeutics. However, Applicant should note that a long list of combinations does not make any one of them less obvious (Merck v. Biocraft, Fed. Cir. 1989).
Therefore, the subject matter of claims 1-4, 13-16, 30-33 and 35-37 is obvious over University of Texas System, absent evidence to the contrary.
******
Claims 1-4, 13-16, 30-33 and 35-37 are rejected under 35 U.S.C. 103 as being unpatentable over US20180147216 to Njar et al. (submitted and made of record in the Office Action filed February 20, 2025) in view of US 2018/289683 A1 (MCCORMICK FRANK ET AL) 11 October 2018 (2018-10-11) (submitted and made of record on the IDS filed April 5, 2023) or US Patent No. 11141418 to University of Texas System.
The claims are as described above.
Njar et al. is relevant and relied upon in its entirety. The reference teaches methods of treating pancreatic cancer, the method comprising administering an androgen receptor downregulating and/or degrading agent. See Abstract. Njar et al. teach the anti-androgen/AR blocker is bicalutamide, nilutamide, or flutamide, for example.
Njar et al. teach the methods of their invention can include a patient derived xenograft model harboring KRAS mutations, but do not necessarily teach the pancreatic cancer contains an oncogenic KRAS mutation, such as G12C, G12D or G12V.
As discussed above, both MCCORMICK and University of Texas System teach pancreatic cancer contains an oncogenic KRAS mutation, such as G12C, G12D or G12V.
For example, MCCORMICK explicitly discloses:
The disease is a disease related to (e.g. caused by) a Ras. In some embodiments, the disease is a disease related to (e.g. caused by) a K-Ras (e.g. K-Ras G12C, G13C, G12D, G12V, G12S, or G13D) or aberrant K-Ras signaling pathway activity (e.g. lung cancer, breast cancer, colon cancer, colorectal cancer, pancreatic cancer).
Njar et al. teach the methods of their invention are used in combination with further chemotherapeutic agents, but do not necessarily mention progestins (e.g., megestrol acetate or medroxyprogesterone acetate).
Both MCCORMICK and University of Texas System teach megestrol acetate or medroxyprogesterone acetate as additional therapeutics administered to treat a subject who has a cancer containing an oncogenic KRAS mutant.
Before the effective filing date of the claimed invention, a method of treating pancreatic cancer, the method comprising administering an androgen receptor downregulating and/or degrading agent was taught and suggested in the prior art of Njar et al.
Over 90% of pancreatic ductal carcinomas carry a KRAS mutation, including G12 mutations as evidenced by Lennerz et al. (The Oncologist Vol.20:e8-e9, 2015) (submitted and made of record in the Office Action filed February 20, 2025). It would have been obvious to modify the teachings of Njar et al. to include a subject who has a pancreatic cancer containing the oncogenic KRAS mutant in KRAS at G12 of either MCCORMICK or University of Texas System since both latter references teach KRAS-mutant cancers, including pancreatic cancer, can be treated with an AR antagonist paired with a KRAS-targeting agent.
A person of ordinary skill in the art would have been motivated and expected reasonable success to devise the methods of the claimed invention using Njar et al. successful treatment of difficult-to-treat pancreatic cancer.
Therefore, the subject matter of claims 1-4, 13-16, 30-33 and 35-37 is obvious over Njar et al. in view of either MCCORMICK or University of Texas System.
Conclusion
No claims are allowable at this time.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Terra C. Gibbs whose telephone number is 571-272-0758. The Examiner can normally be reached from 8 am - 5 pm M-F.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Ram Shukla can be reached on 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TERRA C GIBBS/Primary Examiner, Art Unit 1635
