DETAILED ACTION
This office action is in response to applicant’s filing dated November 13, 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 .
Status of claims
Claims 1 – 16 and 20 - 22 are pending in the instant application. Acknowledgment is made of Applicant’s amendments filed November 13, 2025.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1 - 16, drawn to a compound of general formula (I), B-L-K, where the bifunctional compound of formula (I) binds to both, targeted protein AR and E3 ubiquitin ligases, and acts as an androgen receptor (AR) degrader, in the reply filed on November 13, 2025 is acknowledged.
Claims 20 – 22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 November 13, 2025.
Applicant’s election without traverse of compound 97
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and B (
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), L (
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), K (
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) fragments of molecule B-L-K as single species in the reply filed on November 13, 2025 is acknowledged. Upon performing the search of prior art Examiner detected compounds related to non-elected species. Hence, the election of species has been withdrawn and examination will proceed to the full scope of claims 1 – 16, as claims related to the Group I invention.
Claims under consideration in the instant office action are claims 1 -16.
Priority
The present application is a 371 of PCT/CN2021/132803, filed November 24, 2021, which claims the benefits of priority of CN Application No. 202011329463.4 filed November 25, 2020, CN Application No. 202110006143.3 filed January 11, 2021, CN Application No. 202110123667.0 filed January 29, 2021 and CN Application No. 202110403688.8 filed April 16, 2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 08/02/2023 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Rejections - 35 USC § 112
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.
Claim 11 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.
The claim recites the term:”[…] “preferably” (line 19 and 29), which is equivalent to phrase “such as”, renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
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 – 16 are rejected under 35 U.S.C. 103 as being unpatentable over Andersen et al (WO 2020/198711 A1, hereinafter Andersen).
Instant claims are directed to a compound of general formula B-L-K, where the bifunctional compound of formula B-L-K binds to both, targeted protein AR and E3 ubiquitin ligases, and acts as an androgen receptor (AR) degrader. The compound of formula B-L-K has the following structural fragments:
B is androgen receptor (AR) binding moiety having a structure e.g.:
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,
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, where Rb11 is halogen, CF3 or NC; and Rb12 is H, OCH3, OCH2CH3 or OCH2CH2Cl; such as
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or
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L is a linker of structure e.g.:
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where Ak1, Ak2, Ak3 are each independently -CH2-, -OCH2-, - OCH2CH2-,
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-C(=O)-, -NRL- (RL is H); Cy1, Cy2, Cy3 and Cy4 are each independently selected from a bond or
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,
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,
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,
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. Such as L has a structure e.g.:
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,
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or
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.
K is a E3 ligase binding moiety of structure e.g.:
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,
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or
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.
One of the exemplary compounds of formula B-L-K are:
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,
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,
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,
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,
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. Instant claims are further drawn to a pharmaceutical composition comprising compound of formula B-L-K and pharmaceutically acceptable carrier.
Andersen teaches PROTAC compounds of formula : PLM-LI-PTC, where PLM is E3 ligase binding group, LI is a linker and PTC is androgen receptor binding group (page 6, [18] – [22]). Andersen teaches compounds where
PTC has a structure:
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(page 126, A109),
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(page 139, A214),
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(page 139, A213),
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(page 131, A145) or
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(page 128, A121).
LI has a structure of -LI-LII(q)-, where LI and LII is a bond or group, covalently bounded to PLM or PTC, and q >0 (page 45, [219]), such as -LI-LII(q)- is a polyethylene glycol chain from 1 to 12 polyethylene glycol units, -CH2-, -O-(CH2)i-, -(CH2)i-N-(CH2)i-, CO, C=C, C3-11 heterocyclyl, aryl, where i is 1 – 10. The exemplary linkers are:
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,
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,
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,
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(pages 48 – 50, Table 2).
PLM has a sturucture e.g.:
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,
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(page 216),
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, where R is an atom, covalently joined to a LI and n is 1 – 4 (pages 221 – 222).
One of the exemplary compounds of fromula PLM-LI-PTC, taught by Andersen is
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(page 296, example 53). Andersen is also teaching a pharmaceutical composition comprising compound of formula PLM-LI-PTC and a pharmaceutically acceptable carrier (page 14, [98]).
Thus, Andersen teaches bifunctional compounds, PROTACs, selectively degrading androgen receptor (AR) protein, where the compound consists of ligands binding AR and E3 ligase, connected via bivalent linker, where the structure of all the fragments is equivalent to the corresponding fragments of instantly claimed compounds. MPEP 2143.B states: it could be possible to view a claimed compound as consisting of two known compounds attached via a chemical linker. The claimed compound might properly be found to have been obvious if there would have been a reason to link the two, if one of ordinary skill would have known how to do so, and if the resulting compound would have been the predictable result of the linkage procedure. Thus, Office personnel should recognize that in certain situations, it may be proper to reject a claimed chemical compound as obvious even without identifying a single lead compound.
Thus, since prior art teaches compounds, whose chemical structure includes all the structural elements of instantly claimed compounds, and where the compounds taught by prior art are useful for the same purpose (targeted AR degradation), it would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present invention to combine the structural elements known in the art (E3 ligase binding ligand, AR binding ligand and appropriate linker), by known methods, with no change in their respective functions to yield heterobifunctional compound with predictable properties. The one of ordinary skills would be motivated to do so in search of an agent applicable for targeted AR degradation with improved desired properties, with the reasonable expectation of success.
Therefore, taking all together, taught by prior art, the invention as a whole is prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
Claims 1 -16 are rejected. No claim is allowed.
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/E.V.V./ Examiner, Art Unit 1691
/SAVITHA M RAO/ Primary Examiner, Art Unit 1691