DETAILED ACTION
This office action is in response to the applicant’s filing dated December 18th, 2025.
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 .
Priority
This application has a PRO of 63/366,484 filed on June 16th, 2022.
Status of Claims
Claims 1-59 and 62-87 are pending in the instant application. Acknowledgement is made of Applicant’s remarks and amendments filed on December 18th, 2025.
Election/Restrictions
Applicant’s election of Group I and species N-(6-((1H-Pyrazol-1-yl)methyl)-4-methoxy-benzo[d]isoxazol-3-yl)-3-(7-(((3S)-1-(2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindolin-5-yl)-pyrrolidin-3-yl)methyl)-2,7-diazaspiro[3.5]nonan-2-yl)-2,6-dimethoxybenzenesulfonamide (herein referred to as CAS RN: 3024119-94-3) shown below in the reply filed on December 18th, 2025 is acknowledged:
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CAS RN: 3024119-94-3 is a compound of instantly claimed Formula (I) wherein PTM is represented by the Formula (IA)
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, specifically R1 and R3 are H; R2 is –(C(R8)2)n-(5-membered heteroaryl), R8 is H and n is 1, and the 5-membered heteroaryl is pyrazole; R4 is C1-alkoxy; A is C6-aryl, R5 is C1-alkoxy and m is 2, forming 2,6-dimethoxybenzene; wherein Y is a chemical moiety linking PTM(**) and ULM(*) represented by the formula
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, specifically L1 is a bond, A1 is a 5-membered heterocycle that is pyrrolidine, L2 is (C(R10)2)p, R10 is H and p is 1, A2 is a 9 membered diazaspiroalkyl that is 2,7-diazaspiro[3.5]nonan-2-yl, and L3 is a bond; and wherein ULM is represented by the formula
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, specifically X3 and X4 are CO and R15 is H. CAS RN: 3024119-94-3 is the 5th compound listed on page 19 in claim 70.
Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 4, 9, 12-15, 20-21, 23-25, 27-28, 43-46, 55, 57, 59, 64-67, 69, and 73-87 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on December 18th, 2025.
A prior art search was conducted for the elected species of CAS RN: 3024119-94-3. This search retrieved prior art. Therefore, the Examiner’s search will not be extended unnecessarily to additional species in/for/during this Office action.
Claims 1-3, 5-8, 10-11, 16-19, 22, 26, 29-42, 47-54, 56, 58, 62-63, 68 and 70-72 read on the elected species and will be examined herein.
Claim Objections
The numbering of claims is not in accordance with 37 CFR 1.126 which requires the original numbering of the claims to be preserved throughout the prosecution. When claims are canceled, the remaining claims must not be renumbered. When new claims are presented, they must be numbered consecutively beginning with the number next following the highest numbered claims previously presented (whether entered or not).
Claims 60-61 were never entered in the original claim set. Misnumbered claims 62-87 should have been numbered claims 60-85.
Claim Rejections - 35 USC § 103
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 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 for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-3, 5-8, 10-11, 16-19, 22, 26, 29-42, 47-54, 56, 58, 62-63, 68 and 70-72 are rejected under 35 U.S.C. 103 as being unpatentable over Lee et al (US 12,122,763 B2); in view of Stupple et al (WO 2022/013369 A1); as evidenced by Handa et al (Pharmacology & Therapeutics, (2019), 202, 132-139), cited for evidentiary purposes only.
Regarding claims 1-3, 5-8, 10-11, 16-19, 22, 26, 29-42, 47-54, 56, 58, 62-63, 68 and 70-72, Lee teaches an Androgen Receptor (AR) degrading compound (page 3, Technical Field, second paragraph; page 4, column 3, lines 38-45) Example 126 shown below (page 99, column 193):
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which is a compound of Chemical Formula I taught by Lee (page 3, column 2, line 35) comprising an AR targeting moiety to the left of linker L in Chemical Formula I (page 4, column 3, lines 44-45); wherein linker L is
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(page 10, column 16, line 10); and wherein E is a cereblon (CRBN) ligand with a structure that binds to E3 ubiquitin ligase, namely thalidomide (CAS RN: 50-35-1)
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(page 4, column 3, lines 40-45; page 9, column 14, line 25); and can exist in the form of a pharmaceutical salt (page 16, column 70, lines 59-64). Lee teaches that the AR targeting moiety can be modified to achieve target optimization (page 4, column 3, lines 45-51). Lee therefore teaches that the target binding portion of the degrader scaffold may be altered while retaining the CRBN binding ligand and linker structure. Lee further teaches a pharmaceutical composition comprising Example 126 and a pharmaceutically acceptable carrier or excipient (page 17, column 30, lines 16-20); disclosing the use of Example 126 in concentrations of 0.01µM, 0.1µM and 1µM in AR degradation testing (page 168, column 331, Table 6). Moreover, Lee teaches that Example 126 is useful in treating cancer, especially prostate and breast cancer (page 17, column 29, lines 29-30).
It is noted linker L and CBRN binding ligand, thalidomide, E in Example 126 of Lee (as highlighted in the above image) is identical to the linker and CBRN binding ligand of the instantly claimed and elected compound, CAS RN: 3024119-94-3.
Handa et al, cited for evidentiary purposes only, teaches it is a well-established strategy in medicinal chemistry to manipulate CRBN activity in order to degrade various proteins, specifically by linking a CRBN-binding drug to another protein targeting compound (page 137, right column, first paragraph).
Lee does not teach a protein degrading compound comprising a KAT6 targeting moiety.
Stupple teaches Compound C (CAS RN: 2569009-58-9) shown below:
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which is a potent and selective catalytic inhibitor of KAT6 histone acetyltransferases KAT6A and KAT6B (page 4, lines 15-18; page 5, first compound). Stupple discloses that Compound C has anticancer properties when administered as a monotherapy, achieving 50% tumor growth inhibition against breast cancer cells at nanomolar concentration (page 110, lines 25-26 and 28-30), and when combined with another anticancer agent a synergistic effect was observed (page 110, lines 30-32; page 111, lines 4-9). Stupple teaches that KAT6A has an important role in gene regulation of ERa required for growth of ER+ breast cancer cells as well as prostate cancer (page 2, lines 31-32; page 3, lines 6-7). It is noted that Compound C of Stupple is identical to the KAT6 targeting moiety of the instantly claimed and elected compound, CAS RN: 3024119-94-3.
It would have been prima facie obvious to a person of ordinary skill in the art to incorporate the known potent KAT6 targeting moiety of Stupple into the known CBRN recruiting protein degradation compound of Lee, while retaining Lee’s linker L and CBRN binding ligand thalidomide. Lee teaches the target binding moiety of the degrader may be modified to optimize target engagement, thereby suggesting substitution of alternative protein targeting ligands with the same degrader scaffold. Stupple teaches that Compound C is a potent and selective inhibitor of KAT6, and further teaches that inhibition of KAT6 exhibits anticancer activity against breast and prostate cancers. Such a modification would have represented a predictable use of known elements according to their established functions. One would have had a reasonable expectation of success in producing a KAT6 targeting degrading compound for the treatment of breast and prostate cancers.
“[T]he rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395.
Taken together, all of this would result in the compound and composition of instant claims 1-3, 5-8, 10-11, 16-19, 22, 26, 29-42, 47-54, 56, 58, 62-63, 68 and 70-72 with a reasonable expectation of success.
Conclusion
Claims 1-3, 5-8, 10-11, 16-19, 22, 26, 29-42, 47-54, 56, 58, 62-63, 68 and 70-72 are rejected.
Claims 62-87 are objected to.
No claim is allowed.
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/C.L.J./Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691