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 is a 371 of PCT/US2023/018272 (04/12/2023).
This application has PRO 63/330,051 (04/12/2022).
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.
Claims 1-21 are rejected under 35 U.S.C. 103 as being unpatentable over Sengupta et al. (US20220079952) in view of Harbeson et al. (Annual Reports in Medicinal Chemistry, Vol 46, Ch 24, 2011, Pages 403-417), Li (“Bioisosteres”, in Medicinal Chemistry for Practitioners, Ch 4, 2020 (Published 2020-04-16), p. 225-304), and Gill et al. (US20150274679).
Sengupta et al. (US20220079952) teaches the following compound, KRM-II-08, as an anti-cancer agent (claim 7):
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Regarding claims 1-11 and 21, Sengupta does not teach a deuterium substitution at the lactam methyl group or R2 and R3 as deuterons as per instant claim 1 Formula I.
Li teaches that deuterium is a well-known and common isostere of hydrogen (p. 232) which is useful for optimization of metabolism and pharmacokinetics (p. 233-234). Li provides several examples of success including FDA-approved deuterium isostere drugs (p. 234), for example dextromethorphan-d6, deuterated ruxolitinib, and deuterated apremilast (p. 234-235).
Harbeson teaches the successful substitution of deuterium for hydrogen in drug discovery and development with several well-known examples including sildenafil which maintained activity when the N-methylpiperazine group was fully and partially deuterated (Table 1, p. 409):
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Gill teaches anticancer structurally related benzodiazepinone compounds wherein a -CD3 moiety is on the lactam nitrogen (a compound of Formula (1), wherein R3 is -CD3; [0023], [0025]).
One of ordinary skill in the art following the teaching of Sengupta would have considered utilizing the well-known technique of deuterium isostere optimization in view of the success demonstrated by Li and Harbeson as well as the teaching of related anti-cancer compounds as per Gill. One of ordinary skill in the art would have considered modifying the hydrogens on Sengupta’s compound to deuterium using the well-known and routine experimentation as taught by Li and Harbeson to improve the pharmacokinetic and metabolic properties of the compound. One of ordinary skill in the art would have had a reasonable expectation of success in the modification because of the numerous successful demonstrations in a wide range of pharmaceuticals and well-known success of the technique as taught by Li and Harbeson. It would have been prima facie obvious for one of ordinary skill in the art to modify Sengupta’s compound and iteratively deuterate at each hydrogen and arrive at the claimed invention.
Regarding claim 12, Sengupta teaches the compound is useful for treating melanoma (claim 3, [0021]).
Regarding claims 13-15, Sengupta teaches systemic administration, including oral and injection ([0038], [0055]).
Regarding claims 16-19, Sengupta teaches combination therapies including atezolizumab ([0049]-[0051]).
Regarding claim 20, Sengupta teaches a dose of 50 mg/kg/day ([0028]).
With each of the claims, the level of skill in the art is very high such that one of ordinary skill in the art would consider routine the combination of elements from the teaching of the art. One of ordinary skill in the art would have recognized that the results of the combination would be predictable due to the well-known nature and optimizations routinely performed in the art. Thus, one of ordinary skill in the art would have arrived at the invention as claimed before the effective filing date with a reasonable expectation of success. Therefore, the claims are rejected as prima facie obvious.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT H HAVLIN whose telephone number is (571)272-9066. The examiner can normally be reached 9am - 6pm.
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/ROBERT H HAVLIN/Primary Patent Examiner, Art Unit 1626
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