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 .
Claim 7 has undergone amendments. Thus, Claims 1-10, submitted on 13 April 2026, represent all claims currently under consideration.
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.
Response to Arguments
The 35 U.S.C. § 102(a)(1) rejection of Claims 1-3, 5-7, and 9-10 over Verdine is withdrawn. Verdine does not demonstrate that these compounds non-covalently inhibit the target protein, but rather demonstrate covalent binding to KRAS, which is not the function which is claimed in the examined application. Verdine only demonstrates that these compounds bind to KRAS, but does not demonstrate that the compound inhibits KRAS.
The 35 U.S.C. § 103 rejection of Claims 1-6 over McCarthy is withdrawn. Applicant argues that the structure of McCarthy’s compounds and the structures of the examined application are not similar, and that there was no articulation as to why the structural differences between Compound 11 and linked Compound A170 would be obvious. The Examiner finds this argument persuasive. The compounds of McCarthy are structurally disparate from those linked in the examined application.
The 35 U.S.C § 103 rejection of Claims 1-10 over Verdine is withdrawn for the reasons discussed previously.
The non-statutory patenting rejection of Claims 1-10 over U.S. Patent No. 11,793,074 is withdrawn. The Examiner had a typographic error, and this patent was erroneously referred to as 11,793,074. However, the patent was provided in the IDS, and was referred to as being cited in the IDS in the Office Action. A new rejection is made over U.S. Patent 11,739,074 using the same rejection as the prior office action.
The remaining non-statutory patenting rejections are each maintained. Each of these patents refers to compounds which are either directly identified in the linking table, or are structurally similar to those of the linking table. The specifications and/or claims for each of these patents states that these compounds are non-covalent inhibitors of RAS. Specific compounds which are either identical to, or similar to compounds of the linking table, are referenced (the means), and are shown or described as non-covalent inhibitors of RAS (the function).
The provisional non-statutory patenting rejection of Claims 1-10 over co-pending application 19/257,383 is withdrawn. There was a typographic error, and this application is 19/357,383. The claims are rejected over this application for the reasons described in the previous office action.
The provisional non-statutory patenting rejections of Claims 1-10 over the ‘266, ‘721, and ‘349 applications are each maintained. As described previously, each of these rejections either reference a compound identical to one found in the linking table, or one structurally similar to these compounds (a means), and reference the specification of these applications where the inhibitory function of these compounds, and their ability to form complexes are described (a function).
The remaining provisional non-statutory patenting rejections are each maintained as they are not the only rejections remaining.
Claim Interpretation
The following is a quotation of 35 U.S.C. 112(f):
(f) Element in Claim for a Combination. – An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The following is a quotation of pre-AIA 35 U.S.C. 112, sixth paragraph:
An element in a claim for a combination may be expressed as a means or step for performing a specified function without the recital of structure, material, or acts in support thereof, and such claim shall be construed to cover the corresponding structure, material, or acts described in the specification and equivalents thereof.
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art. The broadest reasonable interpretation of a claim element (also commonly referred to as a claim limitation) is limited by the description in the specification when 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is invoked.
As explained in MPEP § 2181, subsection I, claim limitations that meet the following three-prong test will be interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph:
(A) the claim limitation uses the term “means” or “step” or a term used as a substitute for “means” that is a generic placeholder (also called a nonce term or a non-structural term having no specific structural meaning) for performing the claimed function;
(B) the term “means” or “step” or the generic placeholder is modified by functional language, typically, but not always linked by the transition word “for” (e.g., “means for”) or another linking word or phrase, such as “configured to” or “so that”; and
(C) the term “means” or “step” or the generic placeholder is not modified by sufficient structure, material, or acts for performing the claimed function.
Use of the word “means” (or “step”) in a claim with functional language creates a rebuttable presumption that the claim limitation is to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites sufficient structure, material, or acts to entirely perform the recited function.
Absence of the word “means” (or “step”) in a claim creates a rebuttable presumption that the claim limitation is not to be treated in accordance with 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph. The presumption that the claim limitation is not interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, is rebutted when the claim limitation recites function without reciting sufficient structure, material or acts to entirely perform the recited function.
Claim limitations in this application that use the word “means” (or “step”) are being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action. Conversely, claim limitations in this application that do not use the word “means” (or “step”) are not being interpreted under 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph, except as otherwise indicated in an Office action.
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 conflicting claims 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2 of U.S. Patent No. 11,608,346 (Patent Date: 21 March 2023) (‘346).
Claim 1 of ‘346 (See IDS, 7 October 2025) claims compounds A18, A25, A268, A280, A384, A385, A549, and A595. Claim 2 of ‘346 claims pharmaceutical compositions comprising a compound or pharmaceutically acceptable salt of Claim 1. The specification of ‘346 states that the claimed compounds are Ras inhibitors. The approach described herein entails formation of a high affinity three-component complex between a synthetic ligand and two intracellular proteins which do not interact under normal physiological conditions: the target protein of interest (e.g., Ras), and a widely expressed cytosolic chaperone in the cell (e.g., cyclophilin A) (Column 1, Line 64- Column 2, Line 3). The Linking Table submitted on 7 October 2025 of the examined application states that compounds 384 and 385, for example, are exemplified structures and/or materials and/or acts disclosed in the application as filed and thus, compositions of these compounds inherently perform the functions of Claims 1-10 of the examined application.
Claims 1-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2 of U.S. Patent No. 11,739,074 (Patent Date: 29 August 2023) (‘074).
Claim 1 of ‘074 (See IDS, 7 October 2025) claims several compounds which have similar structure to the compounds cited in the Linking Table, and thus, will similar properties to these cited compounds and will inherently perform the functions of Claims 1-10 of the examined application. Claim 2 claims a pharmaceutical composition comprising a compound of the invention and a pharmaceutically acceptable excipient. The specification states that the claimed compounds are Ras inhibitors. The approach described herein entails formation of a high affinity three-component complex between a synthetic ligand and two intracellular proteins which do not interact under normal physiological conditions: the target protein of interest (e.g., Ras), and a widely expressed cytosolic chaperone in the cell (e.g., cyclophilin A) (Column 1, Line 64- Column 2, Line 3).
Claims 1-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2 of U.S. Patent No. 11,566,007 (Patent Date: 31 January 2023) (‘007).
Claim 1 of ‘007 (See IDS, 7 October 2025) claims a compound selected from a group of compounds which are structurally similar to those of the linking table, and thus, will have similar properties to the cited compounds and will inherently perform the functions of Claims 1-10 of the examined application. Claim 2 claims a pharmaceutical composition comprising a compound of the invention and a pharmaceutically acceptable excipient. The specification states that the claimed compounds are Ras inhibitors. The approach described herein entails formation of a high affinity three-component complex between a synthetic ligand and two intracellular proteins which do not interact under normal physiological conditions: the target protein of interest (e.g., Ras), and a widely expressed cytosolic chaperone in the cell (e.g., cyclophilin A) (Column 1, Line 64- Column 2, Line 3).
Claims 1-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2 of U.S. Patent No. 11,690,915 (Patent Date: 4 July 2023) (‘915).
Claim 1 of ‘915 (See IDS, 7 October 2025) is directed to a compound selected from a group of compounds which are structurally similar to those of the linking table, and thus, will have similar properties to the cited compounds and will inherently perform the functions of Claims 1-10 of the examined application. Claim 2 claims a pharmaceutical composition comprising a compound of the invention and a pharmaceutically acceptable excipient. The specification states that the claimed compounds are Ras inhibitors. The approach described herein entails formation of a high affinity three-component complex between a synthetic ligand and two intracellular proteins which do not interact under normal physiological conditions: the target protein of interest (e.g., Ras), and a widely expressed cytosolic chaperone in the cell (e.g., cyclophilin A) (Column 1, Line 64- Column 2, Line 3).
Claims 1-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9 and 10 of U.S. Patent No. 12,252,497 (Patent Date: 18 March 2025) (‘497).
Claim 9 of ‘497 (See IDS, 25 October 2025) is directed to specific compounds such as
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which is structurally similar to the compounds cited in the linking table, and thus will have similar properties to these cited compounds and will inherently perform the functions of Claims 1-10 of the examined application. Claim 10 is directed towards a pharmaceutical composition comprising a compound of the invention and a pharmaceutically acceptable excipient. The specification states that the claimed compounds are Ras inhibitors. The approach described herein entails formation of a high affinity three-component complex between a synthetic ligand and two intracellular proteins which do not interact under normal physiological conditions: the target protein of interest (e.g., Ras), and a widely expressed cytosolic chaperone in the cell (e.g., cyclophilin A) (Column 1, Line 64- Column 2, Line 4).
Claims 1-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 5 and 6 of U.S. Patent No. 12,202,845 (Patent Date: 21 January 2025) (‘845).
Claim 5 of ‘845 (See IDS, 7 October 2025) is drawn to a pharmaceutical composition comprising a compound of the structure
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. Claim 6 is drawn to a pharmaceutical composition comprising a compound of structure
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. These compounds are structurally similar to the compounds cited in the linking table, and thus will have similar properties to these cited compounds and will inherently perform the functions of Claims 1-10 of the examined application. The specification states that the claimed compounds are Ras inhibitors. The approach described herein entails formation of a high affinity three-component complex between a synthetic ligand and two intracellular proteins which do not interact under normal physiological conditions: the target protein of interest (e.g., Ras), and a widely expressed cytosolic chaperone in the cell (e.g., cyclophilin A) (Column 1, Lines 53-59).
Claims 1-10 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3 and 4 of U.S. Patent No. 11,952,352 (Patent Date: 9 April 2024) (‘352).
Claim 3 of ‘352 (See IDS, 7 October 2025) is directed to a pharmaceutical composition comprising a compound of the structure
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. Claim 4 is directed to a pharmaceutical composition comprising a compound of structure
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. The specification states that the claimed compounds are Ras inhibitors. The approach described herein entails formation of a high affinity three-component complex between a synthetic ligand and two intracellular proteins which do not interact under normal physiological conditions: the target protein of interest (e.g., Ras), and a widely expressed cytosolic chaperone in the cell (e.g., cyclophilin A) (Column 1, Line 64- Column 2, Line 4).These compounds are structurally similar to the compounds cited in the linking table, and thus will have similar properties to these cited compounds and will inherently perform the functions of Claims 1-10 of the examined application.
Claims 1-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3 and 4 of U.S. Patent No. 12,280,113 (Patent Date: 22 April 2025) (‘113).
Claim 3 of ‘113 (See IDS, 7 October 2025) is directed to a pharmaceutical composition comprising a compound of structure
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. Claim 4 of ‘113 is directed to a pharmaceutical composition comprising a compound of structure
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. The specification states that the compounds claimed are Ras inhibitors. These Ras inhibitors target, that is, selectively bind to or inhibit, Ras(ON) (e.g., selective over the GDP-bound, inactive state of Ras). The approach described herein entails the formation of a high affinity three-component complex between a synthetic ligand and two intracellular proteins which do not interact under normal physiological conditions: the target protein of interest (e.g., Ras), and a widely expressed cytosolic chaperone in the same cell (e.g., cyclophilin A) (Column 2, Lines 5-13). These compounds are structurally similar to the compounds cited in the linking table, and thus will have similar properties to these cited compounds and will inherently perform the functions of Claims 1-10 of the examined application.
Claims 1-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 12,384,750 (Patent Date: 12 August 2025) (‘750).
Claim 1 of ‘750 (See IDS, 7 October 2025) is directed to a method of treating lung cancer in a subject in need thereof, wherein the lung cancer comprises a KRAS G12C mutation, the method comprising administering to the subject a therapeutically effective amount of a compound of the structure
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. This compound is structurally similar to the compounds of the examined application, and thus would be expected to have similar properties and will inherently perform the claimed functions. The specification states that the claimed compounds are Ras inhibitors. The approach described herein entails formation of a high affinity three-component complex between a synthetic ligand and two intracellular proteins which do not interact under normal physiological conditions: the target protein of interest (e.g., Ras), and a widely expressed cytosolic chaperone in the cell (e.g., cyclophilin A) (Column 1, Line 64- Column 2, Line 4). ‘808 does not state that the compounds are formulated in a pharmaceutical composition, but it would be obvious to one of ordinary skill in the art to formulate these in the form of a composition as this is standard practice in the pharmaceutical arts.
Claims 1-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 3 of U.S. Patent No. 12,403,196 (Patent Date: 2 September 2025) (‘196).
Claim 3 of ‘196 (See IDS, 7 October 2025) is directed to a pharmaceutical composition comprising a compound selected from
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and a pharmaceutically acceptable excipient. The specification states that states that these compounds are Ras inhibitors, and selectively bind to or inhibit Ras(ON) (e.g., selective over the GDP-bound, inactive state of Ras). The approach described herein entails formation of a high affinity three component complex between a synthetic ligand and two intracellular proteins which do no interact under normal physiological conditions: the target protein (e.g., Ras), and a widely expressed chaperone protein in the cell (e.g., cyclophilin A) (Page 2, Lines 2-7).
Claims 1-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2 of U.S. Patent No. 12,465,643 (Patent Date: 11 November 2025) (‘643).
Claim 1 of ‘643 is directed to a compound of structure
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. Claim 2 is directed to a pharmaceutical composition comprising a compound of Claim 1 and a pharmaceutically acceptable excipient. The specification states that states that these compounds are Ras inhibitors, and selectively bind to or inhibit Ras(ON) (e.g., selective over the GDP-bound, inactive state of Ras). The approach described herein entails formation of a high affinity three component complex between a synthetic ligand and two intracellular proteins which do no interact under normal physiological conditions: the target protein (e.g., Ras), and a widely expressed chaperone protein in the cell (e.g., cyclophilin A) (Page 2, Lines 2-7).
Claims 1-10 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 12,409,225 (Patent Date: 9 September 2025) (‘225) .
Claims 1-3 of ‘225 (See IDS, 7 October 2025) are directed to compounds of structure of Formula Ib
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. Claim 4 is directed to a pharmaceutical composition comprising a compound of Claim 3 and a pharmaceutically acceptable excipient. The specification states that states that these compounds are Ras inhibitors, and selectively bind to or inhibit Ras(ON) (e.g., selective over the GDP-bound, inactive state of Ras). The approach described herein entails formation of a high affinity three component complex between a synthetic ligand and two intracellular proteins which do no interact under normal physiological conditions: the target protein (e.g., Ras), and a widely expressed chaperone protein in the cell (e.g., cyclophilin A) (Page 2, Lines 2-7).
Claims 1-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 33 and 34 of copending Application No. 19/044,266 (Amended Claims of 25 August 2025) (‘266).
Claim 33 of ‘266 claims a compound of Table 1 or Table 2, which includes the compound A170. All other compounds are presumed to have the same inherent function as compound A170 due to the similar structure, and thus, will perform the same function. Claim 34 claims a pharmaceutical composition comprising a compound of the invention. The specification states that these compounds are Ras inhibitors, and the approach described herein entails formation of a high affinity three-component complex between a synthetic ligand and two proteins which do not interact under normal conditions: the target protein of interest (Ras) and a widely expressed cytosolic chaperone in the cell (cyclophilin A) (Page 1, Lines 33-36).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 18, 19, 21-23, 33, 35, and 37 of copending Application No. 18/479,500 (Amended Claims of 20 February 2024) (‘500).
Claim 1 of ‘500 is directed to 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. Claim 18 claims the method of claim 1 wherein the RAS comprises an amino acid substitution at G12, G13, Q61, or a combination thereof. Claim 19 is directed to the method of claim 18 wherein the amino acid substitution is selected from G12C, G12D, G12V, G13C, G13D, or Q61L. Claim 21 is directed to the method of claim 1 wherein the RAS is KRAS, NRAS, HRAS, or a combination thereof. Claim 22 is directed to the method of Claim 21, wherein the KRAS comprises or further comprises an amino acid substitution at G12, G13, Q61, Y96, A146, KL117, L19, Q22, V14, A59, or a combination thereof. Claim 23 is directed to the method of Claim 22 wherein the KRAS 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. Claim 33 is directed to compounds of Table A1 or A2, which are structurally similar to the compounds cited in the examined application. Claim 35 is directed to a compound of Table B1 or B2, which are structurally similar to the compounds of the examined application. Claim 37 is directed to a compound of Table C1 or C2, which are structurally similar to the compounds of the examined application. The compounds of this application are non-covalent inhibitors of GTP bound RAS, including wild type and mutant KRAS, and due to their structural similarity to the compounds of the examined application, would be expected to perform similarly. ‘500 does not state that the compounds are formulated in a pharmaceutical composition, but it would be obvious to one of ordinary skill in the art to formulate these in the form of a composition as this is standard practice in the pharmaceutical arts.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5, 6, 8, and 9 of copending Application No. 18/518,027 (Amended Claims of 8 April 2024) (‘027).
Claim 1 of ‘027 is directed to a method of treating cancer in a subject in need thereof, wherein the cancer comprises a first RAS mutation that is G12C and a second RAS mutation, or a first RAS mutation at G12, wherein the cancer is resistant to treatment with a RAS(OFF) inhibitor, the method comprising administering to the subject a RAS(ON) inhibitor. Claim 5 is directed to the method of Claim 1 wherein the RAS mutation is selected from a KRAS mutation, NRAS mutation, and HRAS mutation. Claim 6 claims the method of Claim 1 wherein the RAS(ON) inhibitor is an inhibitor selective for RAS G12C, G13D, or G12D. Claim 8 is directed to the method of Claim 1 wherein the RAS(ON) inhibitor is a tri-complex RAS(ON) inhibitor. Claim 9 is directed to the method of Claim 1 wherein the RAS(ON) inhibitor is a compound of Formula A1
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. These compounds are structurally similar to the compounds of the examined application, and thus would be expected to have similar properties and will inherently perform the claimed functions. ‘027 does not state that the compounds are formulated in a pharmaceutical composition, but it would be obvious to one of ordinary skill in the art to formulate these in the form of a composition as this is standard practice in the pharmaceutical arts.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 27 and 28 of copending Application No. 18/591,721 (Amended Claims of 18 October 2024) (‘721).
Claim 27 of ‘721 is directed to a compound of Table 1 or Table 2. These compounds are structurally similar to the compounds of the examined application, and thus would be expected to have similar properties and will inherently perform the claimed functions. Claim 28 is directed to a pharmaceutical composition comprising a compound of the invention. The specification states that states that these compounds are Ras inhibitors, and selectively bind to or inhibit Ras(ON) (e.g., selective over the GDP-bound, inactive state of Ras). The approach described herein entails formation of a high affinity three component complex between a synthetic ligand and two intracellular proteins which do no interact under normal physiological conditions: the target protein (e.g., Ras), and a widely expressed chaperone protein in the cell (e.g., cytophilin A) (Page 2, Lines 2-7).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 27 and 28 of copending Application No. 18/591,721 (Amended Claims of 18 October 2024) (‘721).
Claim 27 of ‘721 is directed to a compound of Table 1 or Table 2. These compounds are structurally similar to the compounds of the examined application, and thus would be expected to have similar properties and will inherently perform the claimed functions. Claim 28 is directed to pharmaceutical compositions comprising a compound of the invention. The specification states that states that these compounds are Ras inhibitors, and selectively bind to or inhibit Ras(ON) (e.g., selective over the GDP-bound, inactive state of Ras). The approach described herein entails formation of a high affinity three component complex between a synthetic ligand and two intracellular proteins which do no interact under normal physiological conditions: the target protein (e.g., Ras), and a widely expressed chaperone protein in the cell (e.g., cytophilin A) (Page 2, Lines 2-7).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, and 6 of copending Application No. 18/634,034 (Amended Claims of 12 July 2024) (‘034).
Claim 1 of ‘034 is directed to a crystalline solid form of compound A
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. Claim 2 is directed to the solid form of Claim 1 wherein the compound is selected from Form 1, 2, 3 or 4. Claim 6 is directed to a pharmaceutical composition comprising the crystalline forms of compound A of Claim 2 and a pharmaceutically acceptable excipient. This compound is structurally similar to the compounds of the examined application, and thus would be expected to have similar properties and will inherently perform the claimed functions.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, and 10 of copending Application No. 18/634,289 (Amended Claims of 12 July 2024) (‘289).
Claim 1 of ‘289 is directed to a crystalline solid form of Compound A
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. Claim 2 is directed to the solid form of Claim 1 wherein Compound A is selected from Form 1, 2, 3, 4, 5, 6, 7, or 8. Claim 10 is directed to a pharmaceutical composition comprising a compound of Claim 2 and a pharmaceutically acceptable excipient. This compound is structurally similar to the compounds of the examined application, and thus would be expected to have similar properties and will inherently perform the claimed functions.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/762,805 (Amended Claims of 21 January 2025) (‘805).
Claim 1 of ‘805 is directed to a compound having the structure
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. The specification states that these compounds are Ras inhibitors, and the approach described herein entails formation of a high affinity three-component complex between a synthetic ligand and two proteins which do not interact under normal conditions: the target protein of interest (Ras) and a widely expressed cytosolic chaperone in the cell (cyclophilin A) (Page 1, Lines 33-36). These compounds are structurally similar to the compounds of the examined application, and thus would be expected to have similar properties and will inherently perform the claimed functions. ‘805 does not state that the compounds are formulated in a pharmaceutical composition, but it would be obvious to one of ordinary skill in the art to formulate these in the form of a composition as this is standard practice in the pharmaceutical arts.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22 and 23 of copending Application No. 18/769,009 (Amended Claims of 13 February 2025) (‘009).
Claim 22 is directed to a compound selected from a large group of compounds which are structurally similar to the compounds cited in the examined application. Claim 23 is directed to a pharmaceutical composition comprising a compound of the invention and a pharmaceutically acceptable excipient. The specification states that these compounds are Ras inhibitors, and the approach described herein entails formation of a high affinity three-component complex between a synthetic ligand and two proteins which do not interact under normal conditions: the target protein of interest (Ras) and a widely expressed cytosolic chaperone in the cell (cyclophilin A) (Page 1, Lines 33-36). These compounds are structurally similar to the compounds of the examined application, and thus would be expected to have similar properties and will inherently perform the claimed functions.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/771,135 (Amended Claims of 25 October 2024) (‘134).
Claim 1 of ‘134 is directed to a method of treating a pancreatic cancer in a subject comprising administering 10 to 500 mg of compound A
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. This compound is structurally similar to the compounds of the examined application, and thus would be expected to have similar properties and will inherently perform the claimed functions. ‘135 does not state that the compounds are formulated in a pharmaceutical composition, but it would be obvious to one of ordinary skill in the art to formulate these in the form of a composition as this is standard practice in the pharmaceutical arts.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/795,852 (Amended Claims of 21 March 2025) (‘852).
Claim 1 of ‘852 is directed to a method of treating lung cancer in a human subject in need thereof, comprising administering 50 to 600 mg of Compound A
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wherein the lung cancer comprises a RAS G12C mutation. This compound is structurally similar to the compounds of the examined application, and thus would be expected to have similar properties and will inherently perform the claimed functions. ‘852 does not state that the compounds are formulated in a pharmaceutical composition, but it would be obvious to one of ordinary skill in the art to formulate these in the form of a composition as this is standard practice in the pharmaceutical arts.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 137 and 138 of copending Application No. 18/913,242 (Amended Claims of 6 May 2025) (‘242).
Claim 137 of ‘242 is directed to a pharmaceutical composition comprising a compound of structure
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and a pharmaceutically acceptable excipient. Claim 138 is directed to a pharmaceutical composition comprising a compound of structure
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and a pharmaceutically acceptable excipient. The specification states that these compounds are Ras inhibitors, and the approach described herein entails formation of a high affinity three-component complex between a synthetic ligand and two proteins which do not interact under normal conditions: the target protein of interest (Ras) and a widely expressed cytosolic chaperone in the cell (cyclophilin A) (Page 1, Lines 33-36).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 18/947,833 (Amended Claims of 14 November 2024) (‘833).
Claim 1 of ‘833 is directed to a method of treating cancer comprising a KRAS G12D mutation in a subject comprising administering a therapeutically effective amount of a compound
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. The specification states that these compounds are Ras inhibitors, and the approach described herein entails formation of a high affinity three-component complex between a synthetic ligand and two proteins which do not interact under normal conditions: the target protein of interest (Ras) and a widely expressed cytosolic chaperone in the cell (cyclophilin A) (Page 1, Lines 33-36). ‘833 does not state that the compounds are formulated in a pharmaceutical composition, but it would be obvious to one of ordinary skill in the art to formulate these in the form of a composition as this is standard practice in the pharmaceutical arts.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2, 6, and 53 of copending Application No. 18/973,320 (Amended Claims of 19 May 2025) (’320).
Claim 2 of ‘320 is directed to a compound of structure of Formula 1b
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. Claim 6 is directed to a compound of structure of Formula 1e
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. Claim 53 is directed to a pharmaceutical composition comprising a compound of Claim 6 and a pharmaceutically acceptable excipient. The specification states that these compounds are Ras inhibitors, and selectively bind to or inhibit Ras(ON) (e.g., selective over the GDP-bound, inactive state of Ras). The approach described herein entails formation of a high affinity three component complex between a synthetic ligand and two intracellular proteins which do no interact under normal physiological conditions: the target protein (e.g., Ras), and a widely expressed chaperone protein in the cell (e.g., cytophilin A) (Page 1, Lines 32-37). These compounds are structurally similar to the compounds of the examined application, and thus would be expected to have similar properties and will inherently perform the claimed functions.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 13 of copending Application No. 19/003,004 (Amended Claims of 14 August 2025) (‘004).
Claim 13 of ‘004 is directed to a compound having the structure of formula III
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. The specification states that states that these compounds are Ras inhibitors, and selectively bind to or inhibit Ras(ON) (e.g., selective over the GDP-bound, inactive state of Ras). The approach described herein entails formation of a high affinity three component complex between a synthetic ligand and two intracellular proteins which do no interact under normal physiological conditions: the target protein (e.g., Ras), and a widely expressed chaperone protein in the cell (e.g., cytophilin A) (Page 1, Lines 32-35). These compounds are structurally similar to the compounds of the examined application, and thus would be expected to have similar properties and will inherently perform the claimed functions. ‘004 does not state that the compounds are formulated in a pharmaceutical composition, but it would be obvious to one of ordinary skill in the art to formulate these in the form of a composition as this is standard practice in the pharmaceutical arts.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 19/196,471 (Amended Claims of 1 May 2025) (‘471).
Claim 1 of ‘471 is directed to a method of treating lung cancer in a subject comprising administering a therapeutically effective amount of a compound having the following structure
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. The specification states that states that these compounds are Ras inhibitors, and selectively bind to or inhibit Ras(ON) (e.g., selective over the GDP-bound, inactive state of Ras). The approach described herein entails formation of a high affinity three component complex between a synthetic ligand and two intracellular proteins which do no interact under normal physiological conditions: the target protein (e.g., Ras), and a widely expressed chaperone protein in the cell (e.g., cyclophilin A) (Page 2, Lines 2-7). ‘471 does not state that the compounds are formulated in a pharmaceutical composition, but it would be obvious to one of ordinary skill in the art to formulate these in the form of a composition as this is standard practice in the pharmaceutical arts.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-10 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 19/196,483 (Amended Claims of 9 July 2025) (‘483).
Claim 1 of ‘483 is directed to a method of treating pancreatic cancer in a subject comprising administering a therapeutically effective amount of a compound having the following structure
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. The specification states that states that these compounds are Ras inhibitors, and selectively bind to or inhibit Ras(ON) (e.g., selective over the GDP-bound, inactive state of Ras). The approach described herein entails formation of a high affinity three component complex between a synthetic ligand and two intracellular proteins which do no interact under normal physiological conditions: the target protein (e.g., Ras), and a widely expressed chaperone protein in the cell (e.g., cytophilin A) (Page 2, Lines 2-7). ‘483 does not state that the compounds are formulated in a pharmaceutical composition, but it would be obvious to one of ordinary skill in the art to formulate these in the form of a composition as this is standard practice in the pharmaceutical arts.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 19/219,571 (Amended Claims of 27 May 2025) (‘571).
Claim 1 of ‘571 is directed to a method of treating pancreatic cancer in a subject comprising administering a therapeutically effective amount of a compound having the following structure
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. This compound is structurally similar to the compounds disclosed in the examined application and thus will be expected to have similar properties, and will inherently perform the functions of Claims 1-10. ‘571 does not state that the compounds are formulated in a pharmaceutical composition, but it would be obvious to one of ordinary skill in the art to formulate these in the form of a composition as this is standard practice in the pharmaceutical arts.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, and 21 of copending Application No. 19/230,256 (Amended Claims of 6 June 2025) (‘256).
Claim 1 of ‘256 is directed to a method of treating a RAS protein-related disease in a subject in need thereof, comprising administering to the subject a RAS(ON) multi-selective inhibitor on an intermittent dosing regimen. Claim 2 is directed to the method of claim 1 wherein the subject has a mutation of RAS. Claim 21 claims the method of Claim 1 wherein the RAS(ON) inhibitor is selected from a group of several compounds, including
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. The compounds of Claim 21 are structurally similar to the compounds disclosed in the examined application and thus will be expected to have similar properties, and will inherently perform the functions of Claims 1-10. ‘256 does not state that the compounds are formulated in a pharmaceutical composition, but it would be obvious to one of ordinary skill in the art to formulate these in the form of a composition as this is standard practice in the pharmaceutical arts.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 31 of copending Application No. 19/269,349 (Amended Claims of 31 October 2025) (‘349).
Claim 1 of ‘349 is directed to a compound of formula I
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. Claim 31 is directed to a pharmaceutical composition comprising a compound of Claim 1 and a pharmaceutically acceptable excipient. The specification states that states that these compounds are Ras inhibitors, and selectively bind to or inhibit Ras(ON) (e.g., selective over the GDP-bound, inactive state of Ras). The approach described herein entails formation of a high affinity three component complex between a synthetic ligand and two intracellular proteins which do no interact under normal physiological conditions: the target protein (e.g., Ras), and a widely expressed chaperone protein in the cell (e.g., cyclophilin A) (Page 1, Lines 32-35). These compounds are structurally similar to the compounds disclosed in the examined application and thus will be expected to have similar properties, and will inherently perform the functions of Claims 1-10.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 19/388,266 (Amended Claims of 13 November 2025) (‘266).
Claim 1 of ‘266 is directed to a compound having the structure of formula Int-1
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. The specification states that states that these compounds are Ras inhibitors, and selectively bind to or inhibit Ras(ON) (e.g., selective over the GDP-bound, inactive state of Ras). The approach described herein entails formation of a high affinity three component complex between a synthetic ligand and two intracellular proteins which do no interact under normal physiological conditions: the target protein (e.g., Ras), and a widely expressed chaperone protein in the cell (e.g., cyclophilin A) (Page 1, Lines 32-35). ‘266 does not state that the compounds are formulated in a pharmaceutical composition, but it would be obvious to one of ordinary skill in the art to formulate these in the form of a composition as this is standard practice in the pharmaceutical arts.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 100 of copending Application No. 19/357,383 (Amended Claims of 14 October 2025) (‘383).
Claim 1 of ‘383 is directed to a compound of Formula Ia
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. Claim 100 is directed to a pharmaceutical composition comprising a compound of the invention and a pharmaceutically acceptable excipient. The specification states that states that these compounds are Ras inhibitors, and selectively bind to or inhibit Ras(ON) (e.g., selective over the GDP-bound, inactive state of Ras). The approach described herein entails formation of a high affinity three component complex between a synthetic ligand and two intracellular proteins which do no interact under normal physiological conditions: the target protein (e.g., Ras), and a widely expressed chaperone protein in the cell (e.g., cytophilin A) (Page 2, Lines 2-7). These compounds are structurally similar to the compounds disclosed in the examined application and thus will be expected to have similar properties, and will inherently perform the functions of Claims 1-10.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-10 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending Application No. 19/308,863 (Amended Claims of 25 August 2025) (‘863).
Claim 1 of ‘863 is directed to a compound selected from the group consisting of
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. The specification states that states that these compounds are Ras inhibitors, and selectively bind to or inhibit Ras(ON) (e.g., selective over the GDP-bound, inactive state of Ras). The approach described herein entails formation of a high affinity three component complex between a synthetic ligand and two intracellular proteins which do no interact under normal physiological conditions: the target protein (e.g., Ras), and a widely expressed chaperone protein in the cell (e.g., cyclophilin A) (Page 1, Lines 32-35). ‘873 does not state that the compounds are formulated in a pharmaceutical composition, but it would be obvious to one of ordinary skill in the art to formulate these in the form of a composition as this is standard practice in the pharmaceutical arts.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1-10 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PHILLIP MATTHEW RZECZYCKI whose telephone number is (703)756-5326. The examiner can normally be reached Monday Thru Friday 730AM-5PM EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew Kosar can be reached at 571-272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/P.M.R./Examiner, Art Unit 1625
/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625
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