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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 3/9/26 has been entered.
Withdrawn rejections
Rejection of claims 1, 13, 15-17, 21-22 and 27-28 under 35 USC 112(b) is withdrawn in view of amendments filed on 2/10/26.
Rejection of claims 1, 13, 15-17, 21-22 and 27-28 under 35 USC 102(a)(1) over Korthout et al is withdrawn in view of amendments limiting the claims to curative treatment of subjects.
New rejection
Claim Rejections - 35 USC § 112
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 1, 15, 16, 17, 21, 22, 27 and 28 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while being enabling for using the compounds of formula I where the compound id cannabidiolic acid, does not reasonably provide enablement for using the compounds with other definitions for substituents R1 – R3 and R5. The specification is not adequately enabled for the scope compounds that have diverse groups at R1-R3 and R5. Compounds made and tested represent the scope of claim 13, not claim 1. The specification does not enable any skilled pharmacologist or physician to use the invention commensurate in scope with these claims. The factors to be considered in making an enablement rejection have been summarized above.
a) Determining if any particular claimed compounds within the scope of claim 1 would be active would require synthesis of the substrate and subjecting it to testing with Applicants' AMPK inhibition assay. Considering the large number of compounds to be made this is a large quantity of experimentation.
b) The direction concerning the claimed compounds is found on pages 2-130, which merely states Applicants' intent to make and use such compounds.
c) In the instant case none of the working examples contains any compound other than CBDA. CBDA is the only compound depicted and tested for AMPK inhibitory activity. No examples showing synthesis or direction for how one might synthesize compounds within the scope of claim 1 are present.
d) The nature of the invention is inhibition of AMPK and treatment of NAFLD. This involves physiological activity. The nature of the invention requires an understanding of the AMPK, the binding activity of small ligands to ADaM pocket of AMPK, and the ability of those compounds to inhibit AMPK. In view of the unpredictability of receptor binding activity and claimed divergent substituents with varied polarity, size, and polarisability, the skilled physician would indeed question the inclusion of diverse moieties as R1-R3 and R4, commensurate in scope with these claims. Also see the MPEP § 2164.03 for enablement requirements in the structure sensitive arts of pharmacology and medicinal chemistry
e) The state of the art is detailed knowledge of the ADaM pocket of AMPK receptor is lacking. There is no analysis in the specification that describes which parts of CBDA are involved in the binding and therefore are responsible for the observed activity. There is no reasonable basis for the assumption that the myriads of compounds embraced the present formula (I) will all share the same biological properties. For example, R2 includes H and also includes geranyl 2,3-epoxide, and also cyclohexene containing groups. These groups are not known bioisosteres and there is no basis to consider them to impart the same physiological activity. In re Surrey 151 USPQ 724 (compounds actually tested which demonstrated the asserted psychomotor stimulatory and anti-convulsant properties were those having the 3,4-dichlorophenyl substituent at the 2-position on the thiazolidone nucleus not sufficient for enablement of any heterocyclic radical at the same position). In re Fouche, 169 USPQ 429 at 434 (a Markush group including both aliphatic and heterocyclic members not enabled for the use of those compounds within the claim having heterocyclic moieties.) In re CAVALLITO AND GRAY, 127 USPQ 202 (claims covering several hundred thousand possible compounds, of which only thirty are specifically identified in appellants' application, not enabled unless all of the thirty specific compounds disclosed had equal hypotensive potency because that fact would strongly indicate that the potency was derived solely from the basic structural formula common to all of them. A wide variation in such potency would suggest that it was due in part to the added substituents and might be eliminated or even reversed by many of the possible substituents which had not been tried.)
Compounds made and tested represent the scope of claim 13 not claim 1.
f) The artisan using Applicants' invention to treat NAFLD with the claimed compounds would be a physician with a MD degree and several years of experience. He would be unaware of how to predict a priori how a changing the substituents of CBDA would affect biological activity. In view of the divergent substituents at R1-R3 and R5, the skilled physician would indeed question the inclusion of all of the possible variations, commensurate in scope with claim 1.
g) Physiological activity, is well-known to be unpredictable, In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) (contrasting mechanical and electrical elements with chemical reactions and physiological activity). See also In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); In re Vaeck, 947 F.2d 488, 496, 20 USPQ2d 1438, 1445 (Fed. Cir. 1991). h) The breadth of the claims includes numerous compounds of formula (I). Thus, the scope is very broad. The present claims embrace various radicals, which are not art-recognized as equivalent. The specific compounds made are not adequately representative of the compounds embraced by the extensive Markush groups instantly claimed.
MPEP 2164.01(a) states, “A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557,1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).” That conclusion is clearly justified here. Thus, undue experimentation will be required to practice Applicants' invention.
Allowable subject matter
Claim 13 is allowed. Korthout et al (WO 2012/144892) teaches administration for treatment of atherosclerosis and diabetes by administration of CBDA. Art does not suggest treatment of NAFLD.
Conclusion
Claims 1, 13, 15, 16, 17, 21, 22, 27 and 28 are pending
Claims 1, 15, 16, 17, 21, 22, 27 and 28 are rejected
Claim 13 is allowed
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/YEVGENY VALENROD/Primary Examiner, Art Unit 1628