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 .
Priority
The instant application is a CON of PCT/US2023/012660 filed February 9, 2023 which claims benefit to domestic provisional application No. 63/310,219 filed February 15, 2022.
Status of Claims
Acknowledgement is made of original (1-3, 5, 7, 11-14, 16-17, 19, 23, 25, 27-28), amended (4, 6, 8-10, 15, 18, 20-21, 24, 26, 30-32), previously presented (22), cancelled (29, 33-43), claims filed on October 25, 2024. Claims 1-28, 30-32 are pending in instant application.
Claim Rejections - 35 USC § 102
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.
Claim(s) 1-3, 6-8, 15-16, 18-19, 20-28, 30-32 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by WO 20211260090 A1 to Bezencon et. al.1
Regarding claims 1-2, 8, 15-16, 20-22, 24-25, 28 and compounds of Formula I, Bezencon teaches structures of instant Formula I, such as CAS# 2756581-81-2 (see Bezencon at p. 48 Example 47 and at claim 11, “1-(3-Difluoromethyl-bicyclo[1.1.1]pent-1-yl)-3-(3-trifluoromethyl-benzyl)-urea”), the same as instant compound 7.
Bezecon Example 47
CAS# 2756581-81-2
Instant
Formula I
Instant
Compound 7
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Regarding instant claims 1-3, 6-7, 15-16, 21-28, and a compound of Formula I, Bezecon teaches CAS# 2756581-57-2 (see Bezecon at p. 44 Example 23 and claim 11, “1-(3-Trifluoromethoxy-benzyl)-3-(3-trifluoromethyl-bicyclo[1.1.1]pent-1-yl)-urea”), the same as instant compound 2.
Bezecon Example 23
CAS# 2756581-57-2
Instant
Formula I
Instant
Compound 2
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252
686
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Regarding instant claims 18-19, Bezecon teaches CAS#2756581-46-9 (see Bezecon at p. 12 Example 42 and at claim 11, “1-(3-Difluoromethyl-bicyclo[1.1.1]pent-1 -yl)-3-[2-hydroxy-1-(3-trifluoromethyl-phenyl)-ethyl]-urea”). Similar to instant 31
Bezecon Example 16
CAS# 2756581-46-9
Instant
Formula I
Instant
Compound
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268
550
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Regarding claim 30 and a composition, Bezecon teaches compositions comprising a disclosed compound and a therapeutically inert excipient (see Bezecon claim 12).
Regarding claims 31-32 and a method of treatment of a Kv7.2 disease, disorder, or disability, Bezeconteaches the compounds act pharmacologically as Kv7 openers (see Bezecon at p. 4 lines 24-27) and teaches using the compounds for treating epilepsy (see Bezecon claim 14), such as instantly claimed encephalopathy (see Bezecon at p. 26 lines 8-19).
Claim Rejections - 35 USC § 103
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.
Claim(s) 4, 17 are rejected under 35 U.S.C. 103 as being unpatentable over Bezecon as applied to claims 1-3, 6-8, 15-16, 18-19, 20-28, 30-32 above in view of Meanwell.2
The prior art differs from the instant claims as follows, while Bezecon teaches instantly claimed compounds of Formula I, Bezecon does not specify i) R1 as F or ii) R2 or R3 as D.
However,
Regarding claim 4 and R1 is halogen, Meanwell teaches fluorine and hydrogen are bioisosteres, and substitution of hydrogen with fluorine can increase drug potency (see Meanwell at p. 285).
Bezecon also teaches CAS# 2756581-50-5 (see Bezecon at p. 43 Example 16 and at claim 11, “1-(3-Difluoromethyl-bicyclo[1.1.1]pent-1-yl)-3-(3-fluoro-5-trifluoromethyl-benzyl)-urea”).
Bezecon Example 16
CAS# 2756581-50-5
Instant
Formula I
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Regarding claim 17 and R2 and R3 are D, Meanwell also teaches hydrogen and deuterium are bioisosteres, and substitution with deuterium influences pharmacokinetic properties (see Meanwell at p. 342).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to arrive at the instantly claimed invention with a reasonable expectation of success in view of the prior art for at least the following reason(s):
Per MPEP § 2143(I)(D), a prima facie case of obviousness exists for applying a known technique to a known method or product ready for improvement to yield predictable results. It would have been obvious to an artisan to modify a known species (as taught by Bezecon) by an H for F or H for D substitution (as taught by Meanwell), because the prior art teaches these modifications can optimize drug properties (as taught by Meanwell). Moreover, an isomeric change to give R1 as F would be obvious, because Bezecon teaches a meta-fluorine substituent is suitable (as in CAS# 2756581-50-5), and an isomeric change of CF3’s position to R8 would give a species wherein R1 is fluorine and R8 is CF3. Per MPEP § 2144.09(I)-(II), “[a] prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities” because “[c]ompounds which are…isomers…are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties” (see, e.g., MPEP § 2144.09(I)-(II)), and the Court has stated that “[i]f a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability.” KSR, 127 S.Ct. at 1740. Here, the prior art teaches highly similar structural isomers of the instantly claimed invention, wherein such isomers have the same, exact utility as the instantly claimed compounds; accordingly, an artisan would readily appreciate that such compounds could be utilized in the treatment of epilepsy, exactly as taught and suggested in view of the prior art.
Furthermore, it is well-within the ordinary skill in art to incorporate deuterium or fluorine in lieu of hydrogen on a known compound.
Therefore, an artisan would arrive at the same invention as presently claimed for reasons taught in the prior art.
Allowable Subject Matter
Claims 9-14 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The closest prior art is Bezecon. Bezecon teaches compounds of instant Formula I, but does not contemplate R1 as a cyano group, or R1 and R5 forming the ring of claim 12. No suggestion or motivation was found in the prior art to make such changes to the compounds of Bezecon.
Conclusion
Claims 9-14 are objected to.
Claims 1-8, 18-28, 30-32 are rejected.
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/S.R./Examiner, Art Unit 1627
/JENNIFER A BERRIOS/ Primary Examiner, Art Unit 1613
1 Cite No. 2 in the IDS filed 9/27/24. Filed June 24, 2021. Hereinafter Bezencon.
2 Meanwell, N. A. "The Influence of Bioisosteres in Drug Design: Tactical Applications to Address Developability Problems" Tactics in Contemporary Drug Design, 2014, 9, 283-381. DOI:10.1007/7355_2013_29. Select pages. Hereinafter Meanwell.
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