DETAILED ACTION
Status of Claims
The amendment submitted April 16, 2026 has been entered.
Claims 1-2,4-5,10,12-13,18-19,21-23,25-26,28-40 and 42-43 are pending and under consideration.
Claims 2, 4-5, 10, 12-13, 18, 21-22, 25, 28, 30-40, 42-43 are amended by Applicant.
Claims 3, 6-9, 11, 14-17, 20, 24, 27, 41, and 44-45 are cancelled by Applicant.
Claims 31-33, 36-39 are withdrawn as explained below in the Election/Restrictions section.
Claims 1-2, 4, 5, 10, 12-13, 18-19, 21-23, 25-26, 28-30, 34-35, 40, 42-43 are under consideration and the subject of this office action as explained below in the Election/Restrictions section.
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 .
Election/Restrictions
Applicant’s election of RM-018 as a species of RAS(ON) inhibitor (shown below), MRTX849(adagrasib) as a species of RAS(OFF) and non-small cell lung cancer as a species of cancer without traverse in the reply filed on April 16, 2026 is acknowledged.
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The elections read on claims 1-2, 4, 5, 10, 12-13, 18-19, 21-23, 25-26, 28-30, 34-35, 40, 42-43.
For the purposes of compact prosecution, the search was expanded; however, Applicant should not assume search has been expanded to the full scope of the claims.
Claims 31-33, 36-39 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on April 16, 2026.
Claims 1-2, 4, 5, 10, 12-13, 18-19, 21-23, 25-26, 28-30, 34-35, 40, 42-43 are under consideration and the subject of this Office Action.
Information Disclosure Statement
Three information disclosure statements (IDS) submitted on March 20, 2024; November, 25, 2024 and April 16, 2026 are acknowledged.
The information disclosure statement filed March 20, 2026 fails to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because multiple Non-Patent Literature Documents are illegible (see Cite No. A, D, E, and G).
It has been placed in the application file, but the references as lined through have not been considered as to the merits. Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a).
Specification
Abstract Objections
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
The abstract of the disclosure is objected to because the abstract is less than 50 words. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Claim Rejections - 35 USC § 112(b)
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 35 is 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 35 recites “wherein the RAS(ON) inhibitor is selected from a compound of Table B1 or Table B2, or a pharmaceutically acceptable salt thereof.”
Claims 35 recites references to tables.
As per MPEP 2173.05(s), “where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table "is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience." Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).”
Therefore, claim 35 is rejected as being indefinite.
Claim Rejections - 35 USC § 102
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.
Claims 1-2, 4, 5, 10, 12-13, 18-19, 21-23, 25-26, 28-30, 40, 42-43 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Jin et al (WO 2020/132597 A1).
The applied reference has a common Applicant with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Regarding claim 1, Jin teaches “A method of treating cancer in a subject in need thereof, wherein the cancer comprises a mutation in RAS and the cancer is resistant to treatment with a RAS(OFF) inhibitor, the method comprising administering to the subject a RAS(ON) inhibitor.”
Specifically, Jin teaches “In an aspect, the disclosure features a method of treating a KRAS G12C protein-related disorder in a subject in need thereof, the method including administering to the subject an effective amount of a compound of the present invention or any pharmaceutical composition comprising such a compound. In an aspect, the disclosure features a method of treating a KRAS G13C protein-related disorder, an NRAS G12C protein-related disorder, an NRAS G13C protein-related disorder, an HRAS G12C protein-related disorder, or an HRAS G13C protein-related disorder, in a subject in need thereof, the method including administering to the subject an effective amount of a compound of the present invention or any pharmaceutical composition comprising such a compound (page 25, lines 16-23).”
Jin further teaches “In an aspect, the invention discloses a method of treating a disease or disorder that is characterized by aberrant RAS activity due to a RAS mutant. In some embodiments, the disease or disorder is a cancer. In some embodiments, the cancer is pancreatic cancer, colorectal cancer, non-small cell lung cancer, small cell lung cancer, acute myeloid leukemia, multiple myeloma, thyroid gland adenocarcinoma, a myelodysplastic syndrome, or squamous cell lung carcinoma. In some embodiments, the aberrant RAS activity is due to a RAS G12C mutation. In some embodiments, the aberrant RAS activity is due to a RAS G13C mutation. In some embodiments, the aberrant RAS activity is due to a KRAS G12C mutation. In some embodiments, the aberrant RAS activity is due to a KRAS G13C mutation. In some embodiments, the aberrant RAS activity is due to an HRAS G12C mutation. In some embodiments, the aberrant RAS activity is due to an HRAS G13C mutation. In some embodiments, the aberrant RAS activity is due to an HRAS G12C mutation. In some embodiments, the aberrant RAS activity is due to an HRAS G13C mutation…. In some embodiments, the aberrant RAS activity is due to a RAS G12C mutation. In some embodiments, the aberrant RAS activity is due to a RAS G13C mutation. In some embodiments, the aberrant RAS activity is due to a KRAS G12C mutation. In some embodiments,the aberrant RAS activity is due to a KRAS G13C mutation. In some embodiments, the aberrant RAS activity is due to an NRAS G12C mutation. In some embodiments, the aberrant RAS activity is due to an NRAS G13C mutation. In some embodiments, the aberrant RAS activity is due to an HRAS G12C mutation. In some embodiments, the aberrant RAS activity is due to an HRAS G13C mutation (page 57, lines 4-29).”
Regarding claim 2, 4-5, Jin teaches “wherein the RAS(ON) inhibitor and the RAS(OFF) inhibitor are administered simultaneously or sequentially,” “wherein the RAS(ON) inhibitor and the RAS(OFF) inhibitor are administered as a single formulation or in separate formulations,” and “the RAS(OFF) inhibitor is administered for a first period of time; and the RAS(ON) inhibitor is administered for a second period of time, wherein the first period of time and the second period of time do not overlap and the first period of time precedes the second period of time.”
Specifically, Jin teaches “In some embodiments, two or more compounds may be administered simultaneously; in some embodiments, such compounds may be administered sequentially; in some embodiments, such compounds are administered in overlapping dosing regimens (page 37, lines 10-14).”
Additionally, Jin teaches “ A compound of the present invention and an additional therapy, such as an anti-cancer agent, may be administered together, such as in a unitary pharmaceutical composition, or separately and, when administered separately, this may occur simultaneously or sequentially. Such sequential administration may be close or remote in time (page 59, lines 39-41 and page 60, lines 1-4).”
Jin additionally teaches “That is, a compound described herein and any of the agents described herein can be formulated together in the same dosage form and administered simultaneously. Alternatively, a compound of the invention and any of the therapies described herein can be simultaneously administered, wherein both the agents are present in separate formulations. In another alternative, a compound of the present disclosure can be administered and followed by any of the therapies described herein, or vice versa. In some embodiments of the separate administration protocol, a compound of the invention and any of the therapies described herein are administered a few minutes apart, or a few hours apart, or a few days apart (page 73, lines 15-22).”
Regarding claim 10, Jin teaches “wherein the subject has been treated with a RAS(OFF) inhibitor.”
Jin specifically teaches “The two or more anti-cancer agents can be used in a cocktail to be administered in combination or administered separately. Suitable dosing regimens of combination anti-cancer agents are known in the art and described in, for example, Saltz et al., Proc. Am. Soc. Clin. Oncol. 18:233a (1999), and Douillard et al., Lancet 355(9209) :1041 -1047 (2000),” and additionally, that “In some embodiments, an anti-cancer agent is an additional Ras inhibitor (e.g., AMG 510, MRTX1257, MRTX849, JNJ4699157, LY3499446, ARS-3248, or ARS-1620), or a Ras vaccine, or another therapeutic modality designed to directly or indirectly decrease the oncogenic activity of Ras (page 65, lines 36-41 and page 66 lines 1-2).”
Regarding claim 12, Jin teaches “wherein the cancer has a RAS pathway reactivation, the mutation in RAS is an amplification of RAS, or the mutation in RAS is an acquired mutation in RAS, or a combination thereof.
As aforementioned, Jin teaches “In an aspect, the invention discloses a method of treating a disease or disorder that is characterized by aberrant RAS activity due to a RAS mutant(page 57 lines 4-5). “
Regarding claims 18-30, and 40, Jin teaches “wherein the RAS comprises an amino acid substitution at G12, G13, Q61, or a combination thereof,” “wherein the amino acid substitution is selected from G12C,G12D, G12V, G13C, G13D, or Q61L,” “wherein the RAS is KRAS, NRAS, or a combination thereof,” “wherein the KRAS comprises or further comprises an amino acid substitution at G12, G13, Q61, Y96, A146, K117, L19, Q22, V14, A59, or a combination thereof, ”wherein the KRAS amino acid substitution is selected from G12D, G12V, G12C, G13D, G12R, G12A, Q61H, G12S, A146T, G13C, Q61L, Q61R, K117N, A146V, G12F, Q61K, L19F, Q22K, V14I, A59T, A146P, G13R, G12L, G13V, or a combination thereof,”“wherein the NRAS comprises or further comprises an amino acid substitution at G12, G13, Q61, P185, A146, G60, A59, E132, E49, T50, or a combination thereof,” “wherein the NRAS amino acid substitution is selected from Q61R, Q61K, G12D, Q61L, Q61H, G13R, G13D, G12S, G12C, G12V, G12A, G13V, G12R, P185S, G13C, A146T, G60E, Q61P, A59D, E132K, E49K, T501, A146V, A59T, or a combination thereof,” “wherein the HRAS comprises or further comprises an amino acid substitution at G12, G13, Q61, K117, A59, A18, D119, A66, A146, or a combination thereof,” “wherein the HRAS amino acid substitution is selected from Q61R, G13R, Q61K, G12S, Q61L, G12D, G13V, G13D, G12C, K117N, A59T, G12V, G13C, Q61H, G13S, A18V, D119N, G13N, A146T, A66T, G12A, A146V, G12N, G12R, or a combination thereof and “wherein the RAS(ON) inhibitor is an inhibitor selective for RAS G12C, G13D, or G12D,” and “wherein the RAS(OFF) inhibitor selectively targets RAS G12C.”
Jin specifically teaches “In some embodiments, the aberrant RAS activity is due to a RAS G12C mutation. In some embodiments, the aberrant RAS activity is due to a RAS G13C mutation. In some embodiments, the aberrant RAS activity is due to a KRAS G12C mutation. In some embodiments, the aberrant RAS activity is due to a KRAS G13C mutation. In some embodiments, the aberrant RAS activity is due to an HRAS G12C mutation. In some embodiments, the aberrant RAS activity is due to an HRAS G13C mutation. In some embodiments, the aberrant RAS activity is due to an HRAS G12C mutation. In some embodiments, the aberrant RAS activity is due to an HRAS G13C mutation (page 57, lines 8-15).”
Jin additionally teaches “The present disclosure features compounds (e.g., macrocyclic compounds) of Formula I capable of modulating biological processes, for example through binding to a presenter protein that is a member of the cyclophilin A (“CYPA”) family and a target protein that is a mutated RAS protein in which the mutation replaces an amino acid in the wild-type amino acid sequence with a cysteine, e.g., KRAS G12C, KRAS G13C, NRAS G12C, NRAS G13C, HRAS G12C and HRAS G13C (page 1, lines 34-38),” and “ In an aspect, the disclosure features a method of treating a KRAS G12C protein-related disorder in a subject in need thereof, the method including administering to the subject an effective amount of a compound of the present invention or any pharmaceutical composition comprising such a compound. In an aspect, the disclosure features a method of treating a KRAS G13C protein-related disorder, an NRAS G12C protein-related disorder, an NRAS G13C protein-related disorder, an HRAS G12C protein-related disorder, or an HRAS G13C protein-related disorder, in a subject in need thereof, the method including administering to the subject an effective amount of a compound of the present invention or any pharmaceutical composition comprising such a compound (page 25, lines 16-23).”
Regarding claims 42-43, Jin teaches “wherein the RAS(OFF) inhibitor is selected from sotorasib (AMG 510), adagrasib (MRTX849), MRTX1257, JNJ-74699157 (ARS- 3248), LY3537982, LY3499446, ARS-853, ARS-1620, GDC-6036, JDQ443, BPI-421286, and JAB-21000.”
As aforementioned, Jin specifically teaches “The two or more anti-cancer agents can be used in a cocktail to be administered in combination or administered separately. Suitable dosing regimens of combination anti-cancer agents are known in the art and described in, for example, Saltz et al., Proc. Am. Soc. Clin. Oncol. 18:233a (1999), and Douillard et al., Lancet 355(9209) :1041 -1047 (2000),” and additionally, that “In some embodiments, an anti-cancer agent is an additional Ras inhibitor (e.g., AMG 510, MRTX1257, MRTX849, JNJ4699157, LY3499446, ARS-3248, or ARS-1620), or a Ras vaccine, or another therapeutic modality designed to directly or indirectly decrease the oncogenic activity of Ras.”
Regarding claim 43, Jin teaches “wherein the cancer is selected from colorectal cancer, non-small cell lung cancer, small-cell lung cancer, pancreatic cancer, appendiceal cancer, melanoma, acute myeloid leukemia, small bowel cancer, ampullary cancer, germ cell cancer, cervical cancer, cancer of unknown primary origin, endometrial cancer, esophagogastric cancer, GI neuroendocrine cancer, ovarian cancer, sex cord stromal tumor cancer, hepatobiliary cancer, bladder cancer, appendiceal cancer, endometrial cancer, and melanoma.”
As aforementioned Jin specifically teaches “In some embodiments, the disease or disorder is a cancer. In some embodiments, the cancer is pancreatic cancer, colorectal cancer, non-small cell lung cancer, small cell lung cancer, acute myeloid leukemia, multiple myeloma, thyroid gland adenocarcinoma, a myelodysplastic syndrome, or squamous cell lung carcinoma (page 25, lines 24-28).”
Therefore, Claims 1-2, 4, 5, 10, 12, 18-19, 21-23, 25-26, 28-30, 40, 42-43 are rejected as being anticipated by Jin.
Allowable Subject Matter
Claims 13 and 34 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
Claims 1-2, 4, 5, 10, 12, 18-19, 21-23, 25-26, 28-30, 40, 42-43 are under consideration and are rejected.
Claim 13 and 34 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAROLYN L. LADD whose telephone number is (703)756-5313. The examiner can normally be reached M-Th, 7:00 am to 5:30 pm EST.
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/C.L.L./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
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