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 .
Current Status of 18/717,962
This Office Action is responsive to the amended claims and Applicant remarks of 08/27/2026. Claims 1-16, 18-21, 43, 46-49, 51, 53-54, and 57-61 are pending and have been examined on the merits.
Priority
The instant application is a national stage entry of PCT/US2022/052740, filed 12/13/2020, which claims priority to U.S. Provisional Patent Application No. 63/290,509, filed 12/16/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 08/27/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Arguments
Applicant has amended claims 43 and 51 to recite methods of inhibiting 5-LOX and 15-LOX comprising administering an effective does of the compounds of Formulae (I) or (Ia). These amendments render the previous rejection under 35 U.S.C. §112(a) moot as the newly amended claims are enabled by the disclosure. The rejection is withdrawn.
Applicants have amended claim 1 to recite the limitations of claim 17, which further requires that the compounds of Formulae (I) and (Ia) possess inhibitory activity against the group consisting of TNF, IL-6, IL-1b, IFNg, Lox5, Lox15, IL-10 and combinations thereof. These amendments render the previous rejection moot. Reference Blanco discloses chromenic phytocannabinoid compounds that overlap with the instantly claimed compounds; however, the reference is silent on the compounds possessing the required inhibitory activity of the amended claims. The previous rejection is withdrawn.
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 60 and 61 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.
Claims 60 and 61 recite the limitation "[t]he method of claim 57" in line one of the claims. There is insufficient antecedent basis for this limitation in the claim. Claim 57 is drawn to a compound and depends directly from claim 1, which is drawn to a compound. The claims do not recite a method.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 59 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The factors to be considered in determining whether a disclosure meets the enablement requirements of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 858 F.2d 731, 8 USPQ2d 1400 (Fed. Cir., 1988). The court in Wands states, “Enablement is not precluded by the necessity for some experimentation, such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is ‘undue’, not ‘experimentation’” (Wands, 8 USPQ2sd 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations” (Wands, 8 USPQ2d 1404). Among these factors are: (1) the nature of the invention; (2) the breadth of the claims; (3) the state of the prior art; (4) the predictability or unpredictability of the art; (5) the relative skill of those in the art; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. While all of these factors are considered, a sufficient amount for a prima facie case is discussed below.
(1) The nature of the invention and (2) the breadth of the claims:
The claims are drawn to a method of treating ameliorating, or preventing the recurrence of a cancer or dermatomyositis comprising administering an effective dose of a composition comprising a compound of Formula (I) or Formula (Ia). Thus, the claims taken together with the specification imply that the administration of any compound of Formula (I) or (Ia) is capable of treating or preventing the recurrence of any form of cancer or dermatomyositis when administered at an effective dose.
(3) The state of the prior art and (4) the predictability or unpredictability of the art:
The state of the prior art is that in-vitro cellular activity is not reliably predictive of therapeutic efficacy in vivo. Eastman (Eastman, Alan. "Improving anticancer drug development begins with cell culture: misinformation perpetrated by the misuse of cytotoxicity assays." Oncotarget 8.5 (2016): 8854.) teaches that the majority of anticancer drugs entering clinical trials provide little or no therapeutic benefit and identifies poor pharmacokinetics, limited bioavailability, unexpected toxicity, lack of efficacy, and the poor predictive value of preclinical models as significant barriers to successful translation of preclinical results to patients. The reference further explains that drug concentrations and exposure conditions employed in vitro frequently differ substantially from those achievable in patients and that testing only a limited number of cell lines can misrepresent the potential therapeutic efficacy of a compound.
The state of the prior art demonstrates that therapeutic efficacy in dermatomyositis is unpredictable and cannot reliably be inferred merely from inhibition or modulation of inflammatory mediators implicated in the disease. Iannone et al. (Iannone, Florenzo, et al. "Use of etanercept in the treatment of dermatomyositis: a case series." The Journal of rheumatology 33.9 (2006): 1802-1804.) evaluated etanercept, a TNF-a inhibitor, in five patients with active dermatomyositis. Despite targeting an inflammatory cytokine associated with the disease, all five patients experienced an exacerbation of dermatomyositis and the treatment was discontinued. The authors concluded that TNF-a inhibition was not effective for the treatment of dermatomyositis.
The instant disclosure provides only limited in vitro PBMC cytokine-secretion assays, recombinant 5-LOX and 15-LOX enzyme assays, cell-viability assays, and CB1/CB2 agonist assays for a small number of compounds. At most, these assays establish selected biochemical or cellular activities under the specific experimental conditions employed. They do not demonstrate that compounds of Formulae (I) and (Ia) are capable of treating, ameliorating, or preventing the recurrence of cancer or dermatomyositis in a subject as claimed. The disclosed activities do not provide a reasonable basis for extrapolating the therapeutic efficacy across the broad claimed compound genus across the diverse array of diseases encompassed by the instant claims.
(5) The relative skill of those in the art:
The level of ordinary skill in the art is high. The artisan would have substantial knowledge of medicinal chemistry, pharmacology, inflammatory signaling pathways, and therapeutic drug development, including experience interpreting cytokine, enzyme, receptor, and cell-based assays and evaluating whether these results are predictive of in-vivo therapeutic efficacy.
However, despite the high level of skill in the art, the artisan would not be able to predict which compounds of Formulae (I) and (Ia) would be therapeutically effective for the claimed methods of treatment based solely on the limited in-vitro assay data disclosed.
(6) The amount of direction or guidance presented and (7) the presence or absence of working examples:
The specification has provided guidance for in-vitro PBMC cytokine-secretion assays, recombinant 5-LOX, and 15-LOX enzyme assays, cell-viability assays, and CB1/CB2 agonist assays for a limited number of disclosed compounds. These assays merely characterize selected biological activities in a small subset of compounds and do not provide sufficient guidance to enable the treatment, amelioration, or prevention of recurrence of the claimed diseases using the full scope of compounds encompassed by Formulae (I) and (Ia).
However, the specification does not provide guidance for which compounds embraced by broadly claimed genus are therapeutically effective for the claimed method of treatment. The specification does not provide any working examples demonstrating treatment of any form of the claimed diseases nor does it disclose that the in-vitro assay results are reasonably predictive of therapeutic efficacy for these conditions. The specification provides no guidance demonstrating that the administration of the claimed compounds are capable of preventing the recurrence of cancer or dermatomyositis as claimed.
(8) The quantity of experimentation necessary:
Considering the state of the art as discussed by the references above, particularly with regards to the lack of reliable extrapolation from the disclosed inhibitory activities to therapeutic efficacy and the high unpredictability in the art as evidenced therein, and the lack of guidance provided in the specification, one of ordinary skill in the art would be burdened with undue experimentation to practice the invention commensurate in the scope of the claims.
Conclusion
Claims 1-16, 18-21, 43, 46-49, 51, and 53-58 are allowed.
Claims 59-61 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 CONNOR KENNEDY ENGLISH whose telephone number is (571)270-0813. The examiner can normally be reached Monday Friday, 8 a.m. 5 p.m. ET..
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/C.K.E./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
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