DETAILED ACTION
This Office action is in response to amendments filed February 3, 2026. Claims 1 and 8-10 are amended. Claims 12-14 are newly added.
Claims 1 and 3-14 are pending.
The new rejections below are necessitated by applicant’s amendments.
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Withdrawn Rejections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 1-10 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as being unpatentable over Lei et al (WO 2021/185291; translated as *US 20230158152; cited in the IDS mailed 4/3/24) is withdrawn in light of applicant’s amendments.
The rejection of claim 11 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20230158152; cited in the IDS mailed 4/3/24) in view of Crew et al (US 2020/0095205; cited in the IDS mailed 4/3/24) is withdrawn in light of applicant’s amendments.
Response to Arguments
Applicant's arguments filed 2/3/26 have been fully considered but they are not persuasive.
Applicant argues that Lei et al do not teach the structure of the newly amended PTM,
PNG
media_image1.png
59
174
media_image1.png
Greyscale
. However, such arguments are rendered moot. The rejection below necessitated by applicant’s amendments relies upon Crew et al to teach the PTM moiety,
PNG
media_image1.png
59
174
media_image1.png
Greyscale
. and renders obvious the addition of such a moiety to Lei’s compounds.
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 1 and 3-14 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 1, Lei et al suggest a compound of formula II 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
PNG
media_image2.png
137
153
media_image2.png
Greyscale
(paragraph 0029) and L is selected from
PNG
media_image3.png
71
215
media_image3.png
Greyscale
(paragraph 0136).
Lei et al do not suggest a compound of formula II or a pharmaceutically acceptable salt thereof wherein PTM is
PNG
media_image1.png
59
174
media_image1.png
Greyscale
.
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
PNG
media_image1.png
59
174
media_image1.png
Greyscale
(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,
PNG
media_image1.png
59
174
media_image1.png
Greyscale
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 3-4, Lei et al teach L is selected from
PNG
media_image4.png
111
176
media_image4.png
Greyscale
(paragraph 0253).
Regarding claims 5-6, Lei et al teach L is selected from
PNG
media_image3.png
71
215
media_image3.png
Greyscale
(paragraph 0136).
Regarding claim 7, Lei et al teach ULM is
PNG
media_image5.png
151
190
media_image5.png
Greyscale
(paragraph 0029).
Regarding claim 8, the combined teachings of Lei et al and Crew et al teach wherein PT is
PNG
media_image1.png
59
174
media_image1.png
Greyscale
(Compound 406, pg. 210 of 285; pg. 39 of Crew et al)
and ULM is
PNG
media_image5.png
151
190
media_image5.png
Greyscale
(paragraph 0029 of Lei et al).
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
PNG
media_image5.png
151
190
media_image5.png
Greyscale
(paragraph 0029) and L is selected from
PNG
media_image3.png
71
215
media_image3.png
Greyscale
(paragraph 0136).
Lei et al do not suggest a compound of formula II or a pharmaceutically acceptable salt thereof wherein PTM is
PNG
media_image1.png
59
174
media_image1.png
Greyscale
.
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
PNG
media_image1.png
59
174
media_image1.png
Greyscale
(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,
PNG
media_image1.png
59
174
media_image1.png
Greyscale
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
PNG
media_image1.png
59
174
media_image1.png
Greyscale
(Compound 406, pg. 210 of 285; pg. 39 of Crew et al), L1 is selected from
PNG
media_image3.png
71
215
media_image3.png
Greyscale
(paragraph 0136 of Lei et al).
and ULM is
PNG
media_image5.png
151
190
media_image5.png
Greyscale
(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 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
PNG
media_image1.png
59
174
media_image1.png
Greyscale
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.
Regarding claims 12-13, Lei et al teach L is selected from
PNG
media_image3.png
71
215
media_image3.png
Greyscale
(paragraph 0136).
Regarding claim 14, Lei et al teach ULM is
PNG
media_image5.png
151
190
media_image5.png
Greyscale
(paragraph 0029).
Conclusion
Claims 1 and 3-14 are rejected. No claims are allowed.
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 RACHAEL E BREDEFELD whose telephone number is (571)270-5237. The examiner can normally be reached 8:00-5:00 Monday-Friday.
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, Alford Kindred can be reached at (571)272-4037. 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.
/RACHAEL E BREDEFELD/ Supervisory Patent Examiner, Art Unit 3786