DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 9/1/26 has been entered.
The new rejections below are necessitated by applicant’s amendments filed 4/13/26.
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 . 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.
Withdrawn Rejections
The rejection of claims 1, 3-8 and 12-14 under 35 U.S.C. 103 as being unpatentable over Lei et al (WO 2021/185291; translated as *US 20230158152; cited in the IDS mailed 4/3/24) in view of Crew et al (US 2020/0095205; cited in the IDS mailed 4/3/24) is withdrawn in light of applicant’s amendments.
New Rejections
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.
Claims 9-11 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 9 is dependent on cancelled claim 1. Thus, the dependency of claim 9 is unclear. For purposes of examination, claim 9 will be interpreted as an independent claim.
Claims 10-11 are rejected as being dependent on rejected base claim 9 and not remedying the deficiencies of claim 9.
Claim Rejections - 35 USC § 103
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.
Claims 9-11 are rejected under 35 U.S.C. 103 as being unpatentable over Lei et al (WO 2021/185291; translated as *US 20230158152; cited in the IDS mailed 4/3/24) in view of Crew et al (US 2020/0095205; cited in the IDS mailed 4/3/24).
*For purposes of the rejection, the translation US ’152 will be cited and referred to in the rejection below.
Regarding claim 9, Lei et al suggest a compound or a pharmaceutically acceptable salt thereof (abstract; whole document); wherein PTM is selected from a drug that acts on AR targeted proteins (paragraph 0032). The compound of Lei et al is represented by PTM-L-ULM (paragraph 0007). ULM is selected from
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(paragraph 0029) and L is selected from
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(paragraph 0136).
Lei et al do not suggest a compound of formula II or a pharmaceutically acceptable salt thereof wherein PTM is
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.
Crew et al teach bifunctional compounds or proteolysis targeting chimeric compounds, which find utility as modulators of targeted ubiquitination of a variety of polypeptides and other proteins including androgen receptors, which are then degraded and/or otherwise inhibited by the bifunctional compounds (paragraph 0012). The bifunctional compounds are depicted as PTM-L-CLM, wherein L is a chemical linker moiety, PTM is a protein/polypeptide targeting moiety, such as AR binding moieties, and CLM is a cereblon E3 ubiquitin ligase binding moiety (paragraphs 0016-0017, 0021). Such compounds include androgen binding moieties that bind to androgen receptors (paragraph 0228), which Crew et al note are critical drivers of tumorigenesis in many forms of prostate cancers (paragraph 0010). Among these androgen binding moieties is
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(Compound 406, pg. 210 of 285; pg. 39).
Therefore, it would have been obvious to an artisan of ordinary skill before the effective filing date of the claimed invention to formulate the compounds of Lei et al with PTM as the androgen binding moiety,
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depicted in Crew et al. One would have been motivated to do so since Lei et al teach PTM is selected from drugs that act on AR and Crew et al suggest bifunctional compounds in the form of PTM-L-CLM with cereblon E3 ubiquitin ligase and AR binding moieties. Thus, a skilled artisan would have a reasonable expectation of success to select the specific AR binding moiety disclosed in Crew et al depending on the desired protein/polypeptide targeting moiety and the intended treatment of the bifunctional compounds.
Regarding claim 10, the combined teachings of Lei et al and Crew et al teach wherein PTM is
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(Compound 406, pg. 210 of 285; pg. 39 of Crew et al), L1 is selected from
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(paragraph 0136 of Lei et al).
and ULM is
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(paragraph 0029 of Lei et al).
Regarding claim 11, Lei et al do not teach administering its compounds or a pharmaceutically acceptable salt thereof to a subject in need of treatment for prostate cancer.
See the disclosure of Crew et al discussed above.
Therefore, it would have been obvious to an artisan of ordinary skill before the effective filing date of the claimed invention to administer the rendered obvious compounds of Lei et al and Crew et al to subjects in need of treatment for prostate cancer. Since a skilled artisan would have been motivated to utilize the androgen binding moiety
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of Crew et al as PTM in the bifunctional compounds of Lei et al, a skilled artisan would have a reasonable expectation of success to administer such compounds to subjects with prostate cancer since Crew et al teach its PTM moieties eliminate AR proteins, which provide a therapeutically beneficial response in prostate cancer.
Response to Arguments
Applicant's arguments filed 4/13/26 have been fully considered but they are not persuasive.
Applicant argues that the specific PTM substitution in claim 9 leads to unexpectedly superior pharmacokinetic properties, which would not have been predictable to a person of ordinary skill in the art before the effective filing date. Applicant notes that WX016 and WX017 (see Test Example 6, Table 13 in the specification) with the instant PTM have oral bioavailability values of 49.3% and 48.1%, respectively. In contrast Lei's compound WX001 has an oral bioavailability of only 11.7% as reported in Test Example 4, Table 4. Applicant submits the claimed compound achieves an approximately 4-fold (300%) increase in oral bioavailability relative to Lei's compound. Applicant further argues that Crew does not teach or suggest that replacing the PTM in Lei's compound would produce any particular pharmacokinetic benefit, let alone a 300% improvement in oral bioavailability.
However, such results are not persuasive for the following reasons. In comparing the compounds of WX016 and WX017 versus Lei's WX001, the only variable with respect to the comparison of the compounds should be PTM. In this case, Lei's compound, WX001, has a different ULM and L group than instant compounds WX016 and WX017 recited in claim 9. Thus, the results do not necessarily indicate that the improvement in oral bioavailability is due to the instant PTM. In this case, applicant must compare the claimed subject matter with the closest prior art to be effective to rebut a prima facie case of obviousness. In re Burckel, 592 F.2d 1175, 201 USPQ 67 (CCPA 1979) and MPEP 716.02(e). “A comparison of the claimed invention with the disclosure of each cited reference to determine the number of claim limitations in common with each reference, bearing in mind the relative importance of particular limitations, will usually yield the closest single prior art reference.” In re Merchant, 575 F.2d 865, 868, 197 USPQ 785, 787 (CCPA 1978) (emphasis in original).
Conclusion
Claims 9-11 are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RACHAEL E BREDEFELD whose telephone number is (571)270-5237. The examiner can normally be reached 8:00-5:00 Monday-Friday.
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/RACHAEL E BREDEFELD/ Supervisory Patent Examiner, Art Unit 3786
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