DETAILED ACTION
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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 11/12/2025 has been entered.
Response to Amendment
The amendments received 11/12/2025 have been entered. Claims 1-2, 12-15, 17-19, and 23-28 are pending. Applicant’s amendments to the claims have overcome each and every rejection previously set forth in the Office Action mailed 05/16/2025. Applicant’s arguments are therefore considered moot.
New grounds of rejection are set forth herein as necessitated by amendments to the claims.
Priority
Examiner acknowledges that, according to the Filing receipt received 11/29/2022, that the instant application 18/054,527 filed 11/10/2022 claims domestic benefit of US provisional application 63/263,882 filed 11/10/2021.
In the Office Action mailed 10/26/2023, Examiner indicated that the instant claims were awarded the effective filing date of 11/10/2021. However, upon further consideration, Examiner has determined that the limitations of the instant claims are not adequately supported or enabled in the manner provided by 35 U.S.C. 112(a) or pre-AIA U.S.C. 112, first paragraph by 63/263,882. More specifically, the limitations of the following structure are not taught or suggested in their entirety.
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As such, instant claims 1-2, 12-15, 17-19, and 23-27 have been awarded the effective filing date of 11/10/2022. Claim 28 has been awarded the effective filing date of 11/10/2021.
Information Disclosure Statement
The Information Disclosure Statement filed on 11/12/2025 is in compliance with the provisions of 37 CFR 1.97 and has been considered in full. A signed copy of list of references cited from the IDS is included with this Office Action.
Claim Objections
Claims 1, 25, and 28 are objected to because of the following informalities:
Claim 1 ends in a semicolon and a period;
Claim 25 does not end in a period;
Claim 28: “a N-desmethyltamoxifen” should read “N-desmethyltamoxifen”.
Appropriate correction is required.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2, 17-18, and 24 are rejected under 35 U.S.C. 102(a)(1) as being unpatentable over Williams et al. (BMJ Case Reports; 2010; previously cited) as evidenced by Gamboa da Costa et al. (Chemical Research in Toxicology; 2003; previously cited).
Williams et al. discloses a method of alleviating pain in a subject due to osteoarthritis by administering tamoxifen to the subject (p. 1, cols. 1-2).
As evidenced by Gamboa da Costa et al., tamoxifen has the following structure (p. 2, scheme 1).
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Therefore, tamoxifen inherently has a structure of the formula of instant claims 1 and 2, wherein R1 and R2 are alkyl, R3 and R4 are hydrogen, R5 is an alkyl, and R6 is hydrogen when there are single bonds between Cα-Cβ and Cγ-Cδ and a double bond between Cβ-Cγ.
Claim(s) 1-2, 14-15, 17-18, and 24 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Maeda et al. (Rheumatology; 2000) as evidenced by Gamboa da Costa et al. (Chemical Research in Toxicology; 2003; previously cited).
Maeda et al. teaches a method of treating painful joints in a patient with arthralgia due to pachydermoperiostosis comprising administering to the patient oral tamoxifen citrate at a dose of 20 mg daily, wherein after a few days of treatment the patient experienced an improvement in pain (p. 1158, cols. 1-2). Maeda et al. teaches that pachydermoperiostosis is a primary hypertrophic osteoarthropathy associated with elevated cytosolic estrogen receptors, which may benefit from reduction in serum estrogen levels (p. 1158, col. 1).
As evidenced by Gamboa da Costa et al., tamoxifen has the structure as above. The structure of tamoxifen is within the scope of the claims, as are its pharmaceutically acceptable salts.
Claim(s) 1-2, 12, 14-15, 17-19, and 23-27 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by McCollum et al. (Cell Reports; August 2022; IDS filed 01/04/2024).
McCollum et al. discloses a method of treating osteoarthritic pain in a mouse model comprising local injection of 50 μM N-desmethyltamoxifen (0.002 mg/kg) into the knee joint (intra-articular injection) of mice which inhibited knee hyperalgesia (p. 6, p. e3). McCollum et al. discloses that N-desmethyltamoxifen has the following structure (Figure 3).
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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.
Claim(s) 12-13, 19, 23, and 25-28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Maeda et al. (Rheumatology; 2000) as evidenced by Gamboa da Costa et al. (Chemical Research in Toxicology; 2003; previously cited) as applied to claims 1-2, 14-15, 17-18, and 24 above, and further in view of Tsai et al. (Life Sciences; 1992) and Lim et al. (Cancer Chemother Pharmacol; 2005; previously cited).
Maeda et al., as evidenced by Gamboa da Costa et al., discloses as above.
Maeda et al. does not disclose that the tamoxifen citrate is administered locally or via intra-articular injection. Maeda et al. does not disclose that the dose of tamoxifen citrate achieves a concentration within the subject of at least 1 nM. Maeda et al. does not disclose that the compound administered is N-desmethyltamoxifen. These limitations are obvious over Tsai et al. and Lim et al.
Tsai et al. discloses a method of treating estrogen-mediated osteoarthritis in rabbits comprising administering tamoxifen via intra-articular injection to the knees of the rabbits (p. 1944). Tsai et al. discloses that tamoxifen is an estrogen antagonist and blocks the receptor binding of sex hormones, thereby mediating the erosive effects of osteoarthritis (p. 1944, second paragraph).
Lim et al. teaches that the major metabolites of tamoxifen include N-desmethyltamoxifen and 4-hydroxytamoxifen, wherein 4-hydroxytamoxifen is considered the active metabolite of tamoxifen due to its potent anti-estrogen activity (p. 472, col. 1, par. 1). Lim et al. additionally teaches that endoxifen (4-hydroxy-N-desmethyl-tamoxifen) is a metabolite formed from N-desmethyltamoxifen via CYP2D6 (p. 472, col. 1, par. 2). Lim et al. teaches that endoxifen has similar anti-estrogenic potency compared to 4-hydroxytamoxifen (abstract).
It would have been prima facie obvious for one of ordinary skill in the art to administer the tamoxifen citrate of Maeda et al. via intra-articular injection (i.e., locally). One would have been motivated to do so, with reasonable expectation of success, in order to more directly treat the affected area. Tamoxifen, moreover, has been shown to treat estrogen-mediated osteoarthritic conditions via intra-articular injection as in Tsai et al.
It would have been prima facie obvious for one of ordinary skill in the art to substitute the tamoxifen citrate of Maeda et al. with 4-hydroxytamoxifen or N-desmethyltamoxifen. One would have been motivated to do so, with reasonable expectation of success, as 4-hydroxytamoxifen is an active metabolite of tamoxifen with potent anti-estrogen activity. Moreover, one would expect that N-desmethyltamoxifen would be metabolized into endoxifen following administration, wherein endoxifen has been shown by Lim et al. to be virtually equipotent compared to 4-hydroxytamoxifen.
Regarding achieving a concentration of tamoxifen within the subject of at least 1 nM, it would have been prima facie obvious to arrive at a dose of tamoxifen such that the concentration of the compound in the subject is at least 1 nM. One would have been motivated to do so via routine optimization, with reasonable expectation of success, in order to arrive at a dose of tamoxifen that effectively treats pain in the subject.
Claim(s) 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over McCollum et al. (Cell Reports; August 2022; IDS filed 01/04/2024) as applied to claims 1-2, 12, 14-15, 17-19, and 23-27 above.
McCollum et al. teaches as above.
While McCollum et al. does not teach achieving a concentration of N-desmethyltamoxifen within the subject of at least 1 nM, it would have been prima facie obvious to arrive at a dose of N-desmethyltamoxifen such that the concentration of the compound in the subject is at least 1 nM. One would have been motivated to do so via routine optimization, with reasonable expectation of success, in order to arrive at a dose of that effectively treats pain in the subject.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MADELINE E BRAUN whose telephone number is (703)756-4533. The examiner can normally be reached M-F 8:30am-5:00pm ET.
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/M.E.B./Examiner, Art Unit 1624 12/31/2025
/BRENDA L COLEMAN/Primary Examiner, Art Unit 1624
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