DETAILED ACTION
All rejections and objections not mentioned below have been withdrawn.
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
PNG
media_image1.png
149
411
media_image1.png
Greyscale
Applicant’s election without traverse of compound WX001 (shown below), in the reply filed on 08/27/2025 is acknowledged.
Claims 1, 11, 13, and 17-20 read on the elected species.
In light of this species election, a search of compound WX001 was conducted. The compound WX001 was found to be free of the art. The scope was expanded to claim 19 which was found to be free of the art. The scope was then expanded to claim 18 which was found to be free of the art. The scope was next expanded to claim 1 which was found to be obvious over the prior art.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. CN202010187846.6, filed on 03/17/2020.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 12/07/2022, 05/30/2023, 02/13/2024 are being considered by the examiner.
Claim Rejections - 35 USC § 103 -New Due to Amendments
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.
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.
Claim(s) 1, 11, 17, 18, 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over LUO ( LUO et al., US 11905276 B2, effective filing date 2019-09-12) in view of Chamberlain (Chamberlain et al., Development of targeted protein degradation therapeutics, Nature Chemical Biology | VOL 15 | OCTOBER 2019 | 937–944).
The reference Luo teaches the following compounds (column 15):
PNG
media_image2.png
127
246
media_image2.png
Greyscale
The reference Luo teaches these compounds as well as the for the purpose of use in the manufacture of a medicament for treating diseases related to a CRBN receptor [column 1] as well as the concept of using similar drugs to degrade specific targets “It has been confirmed that the protein Cereblon (CRBN) was the target protein of thalidomide teratogenesis. Thalidomide combines with CRBN, DNA damage binding protein DDB1 (Damaged DNA Binding Protein 1), CUL4A (Cullin-4a) and Cullins 1 regulator (ROC1) to form E3 ubiquitin ligase complex, which ubiquitinates a variety of substrate proteins and forms ubiquitination chains, so that substrate proteins can be recognized and hydrolyzed by proteasome. Domide drugs are called Immunomodulatory Drugs (IMiDs), which activate the ubiquitination of transcription factors IKZF1 and IKZF3 resulting from E3 ubiquitin ligase complex formed with CRBN, and then the above ubiquitinated transcription factors IKZF1 and IKZF3 are recognized and degraded by proteasome, thus producing toxic effects on Multiple Myeloma. The deletion of these two transcription factors would stop the growth of myeloma. At present, domide drugs such as lenalidomide and pomadomide are the first-line drugs for treating multiple myeloma” [column 1]. The reference also teaches the pharmaceutically acceptable compositions of the compounds[column 36] and “At present, there is an urgent need to develop CRBN modulators with no teratogenicity, less peripheral neuropathy, stronger immunomodulation and higher anti-tumor activity, so as to improve the clinical treatment effect, reduce clinical side effects and benefit patients for long-term use”[column 2].
This helps to teach claim 1, 11, 17, 18, 20.
The reference Luo does not specifically teach attaching ULM via a linker to a PTM.
The reference Chamberlain teaches “Targeted protein degradation as a therapeutic modality has seen dramatic progress and massive investment in recent years because of the convergence of two key scientific breakthroughs: optimization of first-generation peptidic proteolysis-targeted chimeras (PROTACs) into more drug-like molecules able to support in vivo proof of concept and the discovery that clinical molecules function as degraders by binding and repurposing the proteins cereblon and DCAF15. This provided clinical validation for the general approach through the cereblon modulator class of drugs and provided highly drug-like and ligand-efficient E3 ligase binders upon which to tether target-binding moieties. Increasingly rational and systematic approaches including biophysical and structural studies on ternary complexes are being leveraged as the field advances. In this Perspective we summarize the discoveries that have laid the foundation for future degradation therapeutics, focusing on those classes of small molecules that redirect E3 ubiquitin ligases to non-native substrates”(abstract) and “The mechanistic findings for CELMoDs [cereblon E3 ligase modulating drugs] helped advance the field of targeted protein degradation in several ways: they provided clinical validation for targeted protein degradation by demonstrating that efficacious drugs already operated through this mechanism; they proved that low-molecular-weight therapeutics with excellent drug-like properties could efficiently trigger assembly of the ligase substrate-ligand ternary complex; they showed that it could be possible to degrade proteins from families assumed to be undruggable or even unligandable due to a lack of appropriate binding sites; and finally they provided highly efficient chemical scaffolds that could be used in a new generation of heterobifunctional ligands. Indeed, it was rapidly demonstrated that, with the appropriate linker, it is possible to link target-binding moieties to the thalidomide moiety to recruit the CRL4CRBN E3 ligase, resulting in robust protein degradation of BRD4 and FKBP12 (Fig. 1b)36,37. Subsequent efforts have demonstrated that this approach is broadly applicable with numerous proteins now reported to have been degraded in this manner, including BTK, BCR-Abl, FKBP12, BRD9, and CDK6 (refs. 36,38–41)”(page 938).
This helps to teach claim 1, 11, 17, 18, 20.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention to have modified Luo with Chamberlain because both discuss the topic of compounds for the purpose of use in the manufacture of a medicament for treating diseases related to a CRBN receptor as well as the concept of using drugs that modulate the CRBN receptor to degrade specific targets. Thus it would have been obvious to attach the compound of Luo via its alkyl chain as a linker, as discussed by Chamberlain, to tether target-binding moieties. One would be motivated to do so as to degrade specific other targets by a tethered directing group to treat alternative diseases, and to discover more targeted drugs to help fill the urgent need to develop CRBN modulators with no teratogenicity, less peripheral neuropathy, stronger immunomodulation and higher anti-tumor activity, so as to improve the clinical treatment effect, reduce clinical side effects. One would have a reasonable expectation of success because as taught by Chamberlain heterobifunctional molecules with a linker attaching a PTM-L-ULM is a standard and common approach.
Allowable Subject Matter
Claims 13 and 19 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Response to Arguments
Applicant’s arguments, see pages 1-3, filed 05/07/2026, with respect to the 103 rejection(s) have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of LUO ( LUO et al., US 11905276 B2, effective filing date 2019-09-12) in view of Chamberlain (Chamberlain et al., Development of targeted protein degradation therapeutics, Nature Chemical Biology | VOL 15 | OCTOBER 2019 | 937–944).
Conclusion
Claims 1, 11, 17, 18, 20 are rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALISON AZAR HASTINGS whose telephone number is (703)756-4584. The examiner can normally be reached Mon-Thurs 7:30am-5pm EST Friday 7:30-4pm EST (every other Friday off).
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, Kortney Klinkel can be reached at (571) 270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/A.A.H./ Examiner, Art Unit 1627
/Kortney L. Klinkel/ Supervisory Patent Examiner, Art Unit 1627
Prosecution Insights