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
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 Feb. 11, 2026 has been entered.
Claim Status
Claims 66-76 are currently pending and subject to examination.
Claim Rejections – 35 USC § 103 – New Grounds of Rejection
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) 66-76 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lawrence et al. (WO 2017/220446 A1) in view of Chiang & Honore (WO2008057930A2), Hernandez-Pedro et al. (Prevention Research, Volume 68, Issue 9 Supplement, May 1, 2008), and Avery et al. (WO2020061636A1, priority date 28 Sept. 2019).
Claim 66 recites:
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Lawrence teaches crystalline BOBA-001 for the treatment of peripheral neuropathy:
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Lawrence, Specification, p. 6;
Another aspect of the present invention pertains to a method of treatment comprising administering to a subject in need of treatment a therapeutically effective amount of a crystalline form of BHBA-001 (e.g., Form 4), or BHBA-001 as obtained from a crystalline form of BHBA-001 (e.g., Form 4), as described herein, preferably in the form of a pharmaceutical composition….
In one embodiment, the treatment is treatment of, for example… peripheral neuropathy.
Lawrence, Specification, p. 8;
The term "treatment," as used herein in the context of treating a condition, pertains generally to treatment and therapy, whether of a human or an animal (e.g., in veterinary applications), in which some desired therapeutic effect is achieved, for example, the inhibition of the progress of the condition, and includes a reduction in the rate of progress, a halt in the rate of progress, alleviation of symptoms of the condition, amelioration of the condition, and cure of the condition. Treatment as a prophylactic measure (i.e., prophylaxis) is also included. For example, use with patients who have not yet developed the condition, but who are at risk of developing the condition, is encompassed by the term "treatment" (that is, treatment of condition encompasses reducing the risk of that condition)
Lawrence, Specification, p. 57.
Lawrence teaches that the compound BOBA-001 (BHBA-001) is a “a (selective) retinoic acid receptor beta (RARβ) (e.g., RARβ2) agonist” which can be used “to (selectively) activate RARβ (e.g., RARβ2), to cause or promote neurite development, neurite outgrowth, and/or neurite regeneration, and in the treatment of diseases and conditions that are mediated by RARβ (e.g., RARβ2), that are ameliorated by the activation of RAR3 (e.g., RARβ2), etc., including, e.g., neurological injuries such as spinal cord injuries.” (Lawrence, Specification, p. 1).
While Lawrence does not specifically teach that the symptom of neuropathy is neuropathic pain, one of ordinary skill in the art would have a reasonable expectation of success to ameliorate neuropathic pain by administering BOBA-001 to a patient in need thereof because retinoic acid receptor (RAR) agonists are known in the art to alleviate neuropathic pain.
For example, Chiang teaches “methods for treating neuropathic pain in mammals by administering a therapeutically effective amount of an RAR agonist compound.” (Chiang, Specification, p. 12). Hernandez-Pedro demonstrates this effect in a mouse model of chemotherapy induced neuropathic pain and finds that the retinoic acid receptor agonist all-trans retinoic acid reversed hyperalgesia as well as promoted nerve regeneration:
Peripheral neuropathy is a common side effect of several anticancer drugs, the effectiveness of these compounds are limited due to the toxic side effects related with the therapy. There are several chemotherapy agents used to treat cancer that are well known by their neurotoxic effects such as cisplatin and paclitaxel. Experimental animal models of chemotherapy-induced peripheral neuropathy have been developed for cisplatin, vincristine and paclitaxel, showing a decreased threshold for pain and temperature. The Neural Growth Factor (NGF) has been investigated as a potential treatment in several neurological diseases, previous reports have shown that retinoic acid (RA) induces differentiation in diverse neuronal cell lines in vivo and in vitro, stimulating the production of NGF and of its receptor. Methods: A total of 60 male wistar rats were randomly divided into 6 groups. Group A (control), B and C were treated with paclitaxel (5mg/kg daily during 6 days) and groups D and E received cisplatin (3mg/kg two times a week every 7 days, during 30 days), group F received all-trans retinoic acid exclusively. Additional all-trans retinoic acid (20mg/kg) p.o. was administered to groups B and D. Two conduct tests were used to asses temperature perception changes hot plate and pain threshold with monolfilaments of nylon, von Frey. The reverse transcriptase and Real time PCR (Applied Biosystem) was used to determine retinoic acid beta receptor expression in nerve biopsy. Levels of NGF in serum were obtained though ELISA analysis. Results: The test for temperature and pain sensation were not affected in the groups treated with RA, however, RA reverted pain and temperature sensation changes in animals treated with chemotherapy. The NGF was decreased in the group of cisplatin and paclitaxel in nerve biopsy when compared with groups A(Control), D (Cisplatin + AR) and B (paclitaxel +AR). Retinoic Acid showed an increased expression of the retinoic acid receptor beta in groups D and B, that were treated with retinoic acid. Conclusion: Retinoic Acid is able to revert the changes in pain and temperature sensation induced by chemotherapy. As well as to promote nerve regeneration by an increased expression of NGF levels and retinoic acid receptor beta in sciatic nerve.
Hernandez-Pedro, Abstract (emphasis added).
Chiang teaches that the retinoic acid receptor is specifically implicated from animal models of neuropathic pain including spinal nerve ligation (Chiang, Specification, p. 13). One of ordinary skill in the art would reasonably expect to achieve similar results across neuropathic pain associated with trigeminal neuralgia, neuropathic pain associated with occipital neuralgia; neuropathic pain associated with painful radiculopathy; neuropathic pain associated with rheumatoid arthritis; neuropathic pain associated with a thyroid hormone disorder; neuropathic pain associated with lower back pain; or neuropathic pain associated with carpal tunnel syndrome because all of these conditions are associated with nerve damage and nerve impingement and can be treated in a similar way.
For example, Avery teaches that “neuropathic (nerve) pain is caused by damage, injury or dysfunction of nerves due to trauma, surgery, disease or chemotherapy. It is often described as burning, painful, cold or akin to electric shocks and may manifest with tingling, pins and needles, numbness or itching. Neuropathic pain can be the primary symptom of a particular condition or disease state, such as cancer, complex regional pain syndrome or post herpetic neuralgia.” (Avery, Specification, p. 14-15) and includes peripheral neuropathic pain caused by chemotherapy, hypothyroidism, entrapment neuropathies such as carpel tunnel syndrome, sciatic pain (lumbar radiculopathy), neuropathic pain associated with back pain, rheumatoid arthritis, trigeminal neuralgia and neuropathic pain associated with nerve compression (Avery, Specification, p. 15-16). Avery demonstrates that spinal nerve ligation is a model for these types of painful neuropathies (Avery, Specification, p. 20).
Therefore, claim 66 was prima facie obvious at the time of filing.
Claims 67-76 merely recites types of neuropathic pain associated with a thyroid hormone disorder, rheumatoid arthritis or nerve compression and are therefore prima facie obvious for the reasons given in the rejection of claim 66.
Given the above teachings, the invention as a whole was prima facie obvious at the time of filing.
Nonstatutory Double Patenting – New Grounds of Rejection
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 66-76 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 10,752,616 B2 (herein ‘616) in view of Lawrence et al. (WO 2017/220446 A1) , Chiang & Honore (WO2008057930A2), Hernandez-Pedro et al. (Prevention Research, Volume 68, Issue 9 Supplement, May 1, 2008), and Avery et al. (WO2020061636A1, priority date 28 Sept. 2019).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are directed towards a method of treating neuropathic pain with BOBA-001 and the claims of ‘616 are directed towards the treatment of neuropathy BOBA-001. One of ordinary skill in the art would have a reasonable expectation of success to apply BOBA-001 to the treatment of neuropathic pain because it is known in the art that BOBA-001 is an RAR agonist and RAR agonists are known in the art for the treatment of neuropathic pain. The rejection of claims 66-67 as obvious over Lawrence in view of Chiang, Hernandez-Pedro and Avery is incorporated herein by reference.
Claims 66-76 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-38 of U.S. Patent No. 10,385,044 B2 (herein ‘044) in view of Lawrence et al. (WO 2017/220446 A1), Chiang & Honore (WO2008057930A2), Hernandez-Pedro et al. (Prevention Research, Volume 68, Issue 9 Supplement, May 1, 2008), and Avery et al. (WO2020061636A1, priority date 28 Sept. 2019).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are directed towards a method of treating neuropathic pain with BOBA-001 and the claims of ‘044 are directed towards the treatment of nerve injury with BOBA-001. One of ordinary skill in the art would have a reasonable expectation of success to apply BOBA-001 to the treatment of neuropathic pain because it is known in the art that BOBA-001 is an RAR agonist and RAR agonists are known in the art for the treatment of neuropathic pain. The rejection of claims 66-67 as obvious over Lawrence in view of Chiang, Hernandez-Pedro and Avery is incorporated herein by reference.
Claims 66-76 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims25-26 of U.S. Patent No. 11,401,265 B2 (herein ‘265) in view of Chiang & Honore (WO2008057930A2), Hernandez-Pedro et al. (Prevention Research, Volume 68, Issue 9 Supplement, May 1, 2008), and Avery et al. (WO2020061636A1, priority date 28 Sept. 2019).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are directed towards a method of treating neuropathic pain BOBA-001 and the claims of ‘265 are directed towards the treatment of a condition or disorder mediated by activation RARβ wherein the condition is caused by a neurological injury or neuropathy with compounds with BOBA-001. One of ordinary skill in the art would have a reasonable expectation of success to apply BOBA-001 to the treatment of neuropathic pain because RAR agonists are known in the art for the treatment of neuropathic pain. The rejection of claims 66-67 as obvious over Lawrence in view of Chiang, Hernandez-Pedro and Avery is incorporated herein by reference.
Conclusion
No claim is found to be allowable.
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/HEATHER DAHLIN/Examiner, Art Unit 1629