DETAILED ACTION
This office action is in response to the Applicant’s filing dated June 29th, 2026.
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 .
Priority
This application has a PRO of 63/459,493 filed on April 14th, 2023.
Status of Claims
Claims 1-13 are pending in the instant application.
Election/Restrictions
Applicant's election with traverse of Group I in the reply filed on June 29th, 2026 is acknowledged. The traversal is on the grounds that ABX-1431 is not a compound of Formula (I), and because claim 10 requires the administration of a compound of Formula (I) the method cannot be practiced with ABX-1431. The applicant contends the same argument for doxorubicin in relation to claims 11-13. This is not found persuasive because as ABX-1431 is not a compound of Formula (I), it is in fact a materially different product. Claim 10 is drawn to a method of inhibiting enzymatic activity against MAGL, and ABX-1431 is a known MAGL inhibitor. Therefore, the method can be practiced with a materially different product, which in this case is ABX-1431. As doxorubicin is not a compound of Formula (I), the same rationale applies to claims 11-13, which are drawn to a method of treating and/or preventing diseases or disorders related to MAGL, including cancer. See MPEP § 806.05(h).
The requirement is still deemed proper and is therefore made FINAL.
Claims 10-13 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected group, there being no allowable generic or linking claim. Applicant timely traversed the restriction requirement in the reply filed on June 29th, 2026.
Applicant’s election of species without traverse of Compound 1 shown below in the reply filed on June 29th, 2026 is acknowledged:
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355
594
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Which is a compound of Formula (I) wherein R1 is
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74
78
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; wherein m and p are 0; wherein Y is
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62
76
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; wherein A and D are N, and connected by a single bond; wherein E and Z are C; wherein R2 is halogen, specifically F; and wherein R3 is H.
A prior art search was conducted for the elected compound.
This compound was found free of prior art.
Therefore, the Examiner expanded search to encompass all compounds of Formula (I).
These compounds were found free of prior art.
Claims 1-9 are directed to an allowable product. Pursuant to the procedures set forth in MPEP § 821.04(B), claims 10-13, directed to the process of making or using an allowable product, previously withdrawn from consideration as a result of a restriction requirement, are hereby rejoined and fully examined for patentability under 37 CFR 1.104.
Because all claims previously withdrawn from consideration under 37 CFR 1.142 have been rejoined, the restriction requirement as set forth in the Office action mailed on May 4th, 2026 is hereby withdrawn. In view of the withdrawal of the restriction requirement as to the rejoined inventions, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
Claim Rejections - 35 USC § 112(b)
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.
Claim 8 is 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.
Regarding claim 8, the structures recited are of low enough resolution that they are illegible; thus, the metes and bounds of the claim are unclear.
Claim Rejections - 35 USC § 112(a)
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.
Claims 11-13 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for inhibiting Monoacylglycerol Lipase (MAGL) with compounds of Formula (I) in vitro on pages 105-108 in Example 41 and analgesic activity in a formalin induced pain model in rats with compounds of Formula (I) on pages 108-110 in Example 42, does not reasonably provide enablement for treating and/or preventing all diseases or disorders related to MAGL. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. This is a scope of enablement rejection.
To be enabling, the specification of the patent application must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fd. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated that:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996). As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is "undue", not "experimentation".
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
1- the quantity of experimentation necessary,
2- the amount of direction or guidance provided,
3- the presence or absence of working examples,
4- the nature of the invention,
5- the state of the prior art,
6- the relative skill of those in the art,
7- the predictability of the art, and
8- the breadth of the claims
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
1. The nature of the invention and breadth of the claims
The invention relates to a method of treating and/or preventing a disease or disorder related to MAGL.
Claims 11-13 are directed to a method of treating and/or preventing a subject having or susceptible to a disease or disorder related to MAGL. Thus, the claims are extremely broad with regards to the diseases to be treated as well as the possible compounds that can be utilized.
2. The state and predictability of the art, and relative skill of those in the art
The relative skill of those in the art is high, generally that of an M.D. or Ph.D. The artisan using Applicant’s invention would generally be a physician with a M.D. degree and several years of experience.
The factor is outweighed, however, by the unpredictable nature of the art. It is well established that “the scope of enablement varies with the degree of unpredictability of the factors involved” and physiological activity is considered to be an unpredictable factor. See In re Fisher, 166 USPQ 18, at 24 (In cases involving unpredictable factors, such as most chemical reactions and physiological activity, the scope of enablement obviously varies inversely with the degree of unpredictability of the factors involved); Nationwide Chemical Corporation, et. al. v. Wright, et. al., 192 USPQ 95 (one skilled in chemical and biological arts cannot always reasonably predict how different chemical compounds and elements might behave under varying circumstances); Ex parte Sudilovsky 21 USPQ2d 1702 (Applicant’s invention concerns pharmaceutical activity. Because there is no evidence of record of analogous activity for similar compounds, the art is relatively unpredictable); In re Wright 27 USPQ2d 1510 (the physiological activity of RNA viruses was sufficiently unpredictable that success in developing specific avian vaccine was uncertain).
As illustrative of the state of the art, the examiner cites Gura et al (Science, New Series, (1997), 278(5340), 1041-1042), cited for evidentiary purposes, teaches that researchers face the problem of sifting through potential anticancer agents to find ones promising enough to justify human clinical trials. The reference further teaches that, since formal screening began in 1955, many thousands of drugs have shown activity in cell or animal models, but only 39 have actually been useful for chemotherapy (page 1041, first and second paragraphs). With regard to unpredictability in cancer, Johnson et al (British Journal of Cancer, (2001), 84(10), 1424-1431), also cited for evidentiary purposes, teaches that the in vivo activity of 39 different agents in a particular histology in a tumor model did not correlate with activity in the same human cancer (page 1426, Results). With regard to unpredictability in neurodegenerative disease, Sabbagh et al (Neurobiology of Aging, (2013), 34(1), 169-183), also cited for evidentiary purposes, teaches substantial resources and effort have been invested into the development of therapeutic agents for Alzheimer’s disease (AD) with mixed and limited success; research into the etiology of AD with animal models mimicking aspects of the disorder has substantially contributed to the advancement of potential therapies; although these models have shown utility in testing novel therapeutic candidates, large variability still exists in terms of methodology and how the models are utilized; no model has yet predicted a successful disease-modifying therapy for AD (abstract). Sabbagh teaches current pharmacological interventions for AD have symptomatic benefits but do not prevent or delay progressive neurodegeneration (page 169, left, 1st paragraph). With regard to unpredictability in MAGL inhibition, Deng et al (Acta Pharmaceutica Sinica B, (2020), 10(4),582-602,), also cited for evidentiary purposes, teaches “Although MAGL inhibition was disclosed to have the potential for cancer treatment, how MAGL affects the metabolism of cancer cells is not well understood, and studies about the role of MAGL in cancer are also contradictory. Therefore, further comprehensive and systematic investigation on the role of MAGL in cancer is still required. According to the preclinical studies, MAGL inhibitors may have some side effects such as inducing CB1R desensitization in a chronic use. To avoid these potential adverse effects, lowering the dose of currently available irreversible inhibitors to ensure that MAGL is not completely inhibited will be required” (page 598, right column, last paragraph).
“The amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability of the art” In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970).
Accordingly, the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statutory requirements. Furthermore, the mechanism of action of anticancer agents is often unknown or highly unpredictable, and the administration of such agents is frequently accompanied by undesirable side effects.
3. The amount of direction or guidance provided and the presence or absence of working examples
The specification provides data for inhibiting Monoacylglycerol Lipase (MAGL) with compounds of Formula (I) in vitro on pages 105-108 in Example 41 and analgesic activity in a formalin induced pain model in rats with compounds of Formula (I) on pages 108-110 in Example 42, but it is not sufficient to provide support for the full scope of compounds encompassed by the claims or for the full scope of diseases or disorders related to MAGL.
The specification provides no particular direction or guidance for determining the particular administration regimens (e.g. timing, administration routes, etc) necessary to treat and/or prevent diseases or disorders related to MAGL encompassed by the claims, particularly in humans. At best, an "effective amount" is exemplified as a dosage sufficient to inhibit MAGL. While experimentation is presented for analgesic activity in rats, there is no experimentation or mechanism or action presented or discussed in the specification regarding treatment or prevention of other MAGL related diseases or disorders such as neuroinflammation, neurodegenerative disease, cancer or psychiatric disorders.
4. The quantity of experimentation necessary
Because of the known unpredictability of the art (as discussed in supra) and in the absence of experimental evidence commensurate in scope with the claims, the skilled artisan would not accept that any compound of Formula (I) could be predictably used as treatment or preventative for all conditions or disorders related to MAGL.
Genentech Inc. vs. Nova Nordisk states, "[A] patent is not a hunting license. It is not a reward for a search but a compensation for its successful conclusion and 'patent protection' is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable" (42 USPQ 2d 1001, Fed. Circuit 1997). A review of the state of the art fails to reveal the mechanism of action or experimental data regarding the use of any claimed compounds to treat or prevent all diseases or disorders related to MAGL. Determining if any particular claimed compound would treat or prevent a disease or disorder related to MAGL would require synthesis of the compound, formulation into a suitable dosage form, and subjecting it to clinical trials or to testing in an assay known to correlate to clinical efficacy of such treatment. As noted in supra, even in vitro and in vivo assays do not always correlate to efficacy in humans and are not generally predictive of clinical efficacy. This is undue experimentation given the limited guidance and direction provided by Applicants.
Accordingly, the inventions of instant claims 11-13 do not comply with the scope of enablement requirement of 35 U.S.C 112, first paragraph, since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation with no assurance of success.
Conclusion
Claims 8 and 11-13 are rejected.
Claims 1-7 and 9-10 are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTOPHER L JOHNSON whose telephone number is (571)272-1672. The examiner can normally be reached Monday - Friday 08:00AM - 5:00PM EST with Flex on Fridays.
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/C.L.J./Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691
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