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 .
Election/Restrictions
Applicant’s election of the following species without traverse in the reply filed on 5/26/2026 is acknowledged;
A single species of non-small cell lung cancer, as recited in dependent claim 17,
An epidermal growth factor receptor mutation, corresponding to (a) in dependent claim 38,
The BRG1 loss of function mutation is in the ATPase catalytic domain of the protein, such as in dependent claim 36,
A PD-1 inhibitor as a single type of immunotherapy, such as in dependent claim 6,
The immunotherapy as a single type of anticancer therapy, such as in dependent claims 42, 44, and 47, and
The chemotherapeutic or cytotoxic agent is a MEK inhibitor which is selumetinib, such as in dependent claims 44 and 47.
Since, the applicant elected a single disclosed species in each category as explained above, therefore, based on that species election, claims 23, 27, 29, 31, and 33, are withdrawn as being drawn to a non-elected species.
Claims 1-3, 6, 12, 15, 17, 34-36, 38, 42, 44-47, and 49 are under consideration in this office action and will be examined on the merits.
Status of Claims
Claims 1-3, 6, 12, 15, 17, 23, 27, 29, 31, 33-36, 38, 42, 44-47, and 49 are pending. There are no amended, canceled or new claims.
Claims 1-3, 6, 12, 15, 17, 34-36, 38, 42, 44-47, and 49 are under consideration in the instant office action.
Information Disclosure Statement
The information disclosure statement (IDS/s) submitted on 1/06/2025 and 5/26/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claims 1, 6, 12, 34-36, and 38 are objected to because of the following informalities:
-In claim 1 and 34-36, the abbreviations/acronyms; BRM and/or BRG1 are not spelled out.
-In claim 6, the abbreviations/acronyms; PD-1, CTLA-4, a PD-L1 and CD- 161 are not spelled out.
-In claim 12, the abbreviations/acronyms; BAF are not spelled out.
-In claim 38, the abbreviations/acronyms; KRAS, GNAQ, GNA11, PLCB4, CYSLTR2, BAP1, SF3B 1, EIF1AX, TFE3, TFEB, MITF, EZH2, SUZ12, and/or EED are not spelled out.
Appropriate corrections are required.
Claim Rejections - 35 USC § 102
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.
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.
Claims 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Centore et al. (“METHODS OF TREATING CANCERS”, WO 2020/106915; Pub. Date: May 28, 2020) herein referred to as Centore.
Regarding claim 1, Centore teaches a method of treating cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of an agent that reduces the level and/or activity of BRM (a method of treating cancer in a subject in need thereof, including administering to the subject an effective amount of an agent that reduces the level and/or activity of BRM; page 2, lines 5-10) and an effective amount of an immunotherapy (the method can be used in combination with an additional therapeutic agent an immunoglobulin-based biologic that is a monoclonal antibody that agonizes a target to stimulate an anti-cancer response, i.e., the immunotherapy, dosages of the compounds when combined should provide a therapeutic effect; page 43, lines 15-25; page 45, lines 1-10). Furthermore, Centore teaches the method further includes administering to the subject or contacting the cell with an anticancer therapy, e.g., a chemotherapeutic or cytotoxic agent, immunotherapy (Summary of the invention, para 18: line 2).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived 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(a) are summarized as follows:
1. Applicant Claims
2. Determining the scope and contents of the prior art.
3. Ascertaining the differences between the prior art and the claims at issue, and 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 2, 3, 6, 12, 15, 17, 34-36, 38, 42, 44-47 and 49 are rejected under 35 U.S.C. 103(a) as being unpatentable Centore et al. (“METHODS OF TREATING CANCERS”, WO2020106915; Pub. Date: May 28, 2020) herein referred to as Centore in view of Vaswani et al. (“COMPOUNDS AND USES THEREOF”, WO 2020/160180 Al; Pub. Date: August 6, 2020) herein referred to as Vaswani.
Regarding claim 2, Centore teaches a method of treating cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of an agent that reduces the level and/or activity of BRM (a method of treating cancer in a subject in need thereof, including administering to the subject an effective amount of an agent that reduces the level and/or activity of BRM; page 2, lines 5-10) and an effective amount of an immunotherapy as explained above.
However, Centore does not explicitly teach the claimed compound having the structure
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or a pharmaceutically acceptable salt thereof.
Vaswani teaches compounds useful for the treatment of BAF complex-related disorders (Abstract). Vaswani teaches compounds useful for modulating BRG1- or BRM-associated factors (BAF) complexes (Background, page 1, lines 1-2). Vaswani teaches BRG1 is overexpressed in some cancer tumors and is needed for cancer cell proliferation. BRM, also known as probable global transcription activator SNF2L2 and/or ATP-dependent chromatin remodeler SMARCA2, is encoded by the SMARCA2 gene on chromosome 9 and has been shown to be essential for tumor cell growth in cells characterized by loss of BRG1 function mutations. Deactivation of BRG and/or BRM results in downstream effects in cells, including cell cycle arrest and tumor suppression (Background, page 1, para. 2; lines 6-11). Vaswani explicitly teaches the claimed compound having the structure:
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(Page 48, Compound # 725). Additionally, Vaswani teaches the method further includes administering to the subject or contacting the cell with an anticancer therapy, e.g., a chemotherapeutic or cytotoxic agent, immunotherapy, surgery, radiotherapy, thermotherapy, or photocoagulation (Page 64, lines 26-28 and claim 144, page 552).
It would have been obvious to a person having ordinary skill in the art to incorporate Vaswani compound # 725 to Centore’s method of treating cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of an agent that reduces the level and/or activity of BRM and/or BRG. One would have been motivated to do so in order to evaluate safety outcomes as well as better understand the effects of BRG1/BRM ATPase inhibitors on the growth of non-small cell lung cancer cells (NCIH1299) as taught by Vaswani (example 247, page 531).
Regarding claim 3, Centore and Vaswani teach the method of claim 2. Centore further teaches wherein the immunotherapy is administered (combination with an additional therapeutic that is a monoclonal antibody to stimulate an anti-cancer response; page 43, lines 15-25; page 45, lines 1-10) concurrently with the agent or compound (the delivery of the two or more agents is simultaneous or concurrent and the agents may be co-formulated; page 18, lines 25-30).
Regarding claim 6, Centore and Vaswani teach the method of claim 2. Centore further teaches a PD-1 inhibitor (examples include nivolumab and pembrolizumab; Summary of the invention, para 22: lines 6, 7)
Regarding claim 12, Centore and Vaswani teach the method of claim 2. Centore further teaches that the cancer has and/or has been identified as having a BRG1 loss of function mutation, a BRM loss of function mutation (Summary of the invention, para 21: lines 1-2) and the cancer is resistant or has failed to respond to dacarbazine, temozolomide, cisplatin, treosulfan, fotemustine, IMCgp100, a CTLA-4 inhibitor (e.g., ipilimumab), a PD-1 inhibitor (immunotherapy) (e.g., Nivolumab or pembrolizumab), a PD-L1 inhibitor (e.g., atezolizumab, avelumab, or durvalumab), a mitogen-activated protein kinase (MEK) inhibitor (e.g., selumetinib, binimetinib, or tametinib), and/or a protein kinase C (PKC) inhibitor (e.g., sotrastaurin or LXS196, also known as IDE196) (Summary of the invention, para 22: lines 5-9).
Regarding claim 15, Centore teaches a method of treating cancer in a subject as discussed above.
However, Centore does not explicitly teach the effective amount of the compound is: (a) an amount effective to increase the level of activated T-cells in the subject; and/or (b) an amount effective to increase the level of activated T-cells in the tumor microenvironment.
Vaswani teaches compounds useful for the treatment of BAF complex-related disorders (Abstract). Vaswani teaches compounds useful for modulating BRG1- or BRM-associated factors (BAF) complexes (Background, page 1, lines 1-2). Vaswani explicitly teaches administering the exact claimed compound (Page 48, Compound # 725). Additionally, Vaswani teaches a method of treating a BAF complex-related disorder in a subject in need thereof, the method comprising administering to the subject an effective amount of a compound of claim 115 (any one of compounds 1-776 in Table 1) or a pharmaceutical composition of claim 118 (A pharmaceutical composition comprising a compound of any one of claims 1 to 117 and a pharmaceutically acceptable excipient) (Page 550, claim 121). An amount effective to increase the level of activated T-cells in the subject is inherently taught as administering an effective amount of the claimed compound results in the claimed biological response. The dosage of the compounds of the invention, and/or compositions comprising a compound of the invention, can vary depending on many factors, such as the pharmacodynamic properties of the compound; the mode of administration; the age, health, and weight of the recipient; the nature and extent of the symptoms; the frequency of the treatment, and the type of concurrent treatment, if any; and the clearance rate of the compound in the animal to be treated. One of skill in the art can determine the appropriate dosage based on the above factors. The compounds of the invention may be administered initially in a suitable dosage that may be adjusted as required, depending on the clinical response as taught by Vaswani (page 83, lines 19-25).
It would have been obvious to a person having ordinary skill in the art to incorporate Vaswani compound # 725 to Centore’s method of treating cancer in a subject in need thereof, the method comprising administering to the subject an effective amount of an agent that reduces the level and/or activity of BRM and/or BRG. One would have been motivated to do so in order to evaluate safety outcomes as well as better understand the effects of BRG1/BRM ATPase inhibitors on the growth of non-small cell lung cancer cells (NCIH1299) as taught by Vaswani (example 247, page 531).
Regarding claim 17, Centore and Vaswani teach the method of claim 2. Centore further discloses wherein the cancer is non-small cell lung cancer (the cancer is non-small cell lung cancer, inhibition of cell proliferation of non-small cell lung cancer cell line by a BRM inhibitor is shown in figure 5; page 29, lines 15-20; page 58, lines 20-25; figure 5).
Regarding claims 34, Centore and Vaswani teach the method of claim 2. Centore further discloses the cancer expresses BRG1 and/or BRM protein and/or the cell or subject has been identified as expressing BRG1 and/or BRM, the cancer expresses BRG1 protein and/or the cell or subject has been identified as expressing BRG1 and the cancer expresses BRM protein and/or the cell or subject has been identified as expressing BRM (Summary of the invention, para 14: lines 1-4).
Regarding claims 35, Centore and Vaswani teach the method of claim 2. Centore further discloses the subject or cancer has and/or has been identified as having a BRG1 loss of function mutation (Summary of the invention, para 21: line 1).
Regarding claims 36, Centore and Vaswani teach the method of claim 2. Centore further discloses the term “inhibiting BRG and/or BRM” refers to blocking or reducing the level or activity of the ATPase catalytic binding domain or the bromodomain of the protein (Definitions, para 25: lines 1-2). Centore further discloses exemplary BRG1 loss of function mutations include, but are not limited to, a homozygous BRG1 mutation and a deletion at the C-terminus of BRG1 (Definitions, para 6: lines 3-4).
Regarding claims 38, Centore and Vaswani teach the method of claim 2. Centore further discloses the cancer harbors a mutation in GNAQ, the cancer harbors a mutation in GNA11, the cancer harbors a mutation in PLCB4, the cancer harbors a mutation in CYSLTR2, the cancer harbors a mutation in BAP1, the cancer harbors a mutation in SF3B1, the cancer harbors a mutation in EIF1AX, the cancer harbors a TFE3 translocation, the cancer harbors a TFEB translocation, a MITF translocation, the cancer harbors an EZH2 mutation, the cancer harbors a SUZ12 mutation and/or the cancer harbors an EED mutation (Summary of the invention, para 17: lines 1-7).
Regarding claims 42, Centore and Vaswani teach the method of claim 2. Centore further discloses the anticancer therapy, e.g., a chemotherapeutic or cytotoxic agent, immunotherapy (Summary of the invention, para 18: line 2).
Regarding claims 44-47 and 49, Centore and Vaswani teach the method of claim 2. Centore further discloses the anticancer therapy, e.g., a chemotherapeutic or cytotoxic agent (Summary of the invention, para 18: line 2). Centore discloses the agent that reduces the level and/or activity of BRG1 and/or BRM is used in combination with another anti-cancer therapy such as a MEK inhibitor, and/or a PKC inhibitor (Summary of the invention, para 16: lines 1-2). Centore discloses the cancer is resistant or has failed to respond to a protein kinase C (PKC) inhibitor (e.g., sotrastaurin or LXS196, also known as IDE196; Summary of the invention, para 20: lines 8-9). Centore further discloses the second agent is a mitogen-activated protein kinase (MEK) inhibitor (e.g., selumetinib, binimetinib, or tametinib) and/or a protein kinase C (PKC) inhibitor (e.g., sotrastaurin) (Combination Therapies, para 5-6; lines 3 and 1 respectively).
Conclusion
Claims 1-3, 6, 12, 15, 17, 34-36, 38, 42, 44-47 and 49 are rejected.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAHAR INAM whose telephone number is (571)272-0821. The examiner can normally be reached 7:30 am-5:00 pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James H Alstrum-Acevedo can be reached at (571) 272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SAHAR INAM/
Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/
Supervisory Patent Examiner, Art Unit 1622
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