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/CN2021/132748 (11/24/2021)
and claims foreign priority to CHINA 202011334883.1 (11/24/2020).
Status
Claims 1-11, 13-14, 16-22 are pending.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-6, 11, 13, 16-20 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sampson et al. (US10501474, published 2019-12-10).
Sampson teaches the following compound (claim 1):
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as well its preparation (cols. 37-38) in an amount of 2.28 g of the HCl salt (“Representative Examples A1: 4-amino-5-(6-(4-methylpiperazin-1-yl)-1H-benzo[d]imidazol-2-yl)thieno[2,3-b]pyridin-6(7H)-one”). A calculation of the number of molecules in the prior art sample is:
MW 380.1 g/mol (free base) + 36.5 g/mol (HCl) = 416.6 g/mol
2.28 g / 416.6 g/mol = 5.47x10-3 mol
5.47x10^-3 mol x 6.022x10^23 molecules/mol = 3.29 x 10^21 molecules
The numerical natural occurrence of n deuterons in molecules = (1.5 x 10^-4)^n.
Thus, in the prior art sample there would multiple molecules where there were 5 deuterons simultaneously. Therefore, claims 1-6, 11, 13, 16-20 each requiring five or less deuterons are anticipated.
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 1-11, 13-14, 16-22 are rejected under 35 U.S.C. 103 as being unpatentable over Sampson et al. (US10501474, published 2019-12-10) in view of Harbeson et al. (Annual Reports in Medicinal Chemistry, Vol 46, Ch 24, 2011, Pages 403-417) and Li (“Bioisosteres”, in Medicinal Chemistry for Practitioners, Ch 4, 2020 (Published 2020-04-16), p. 225-304).
Sampson teaches the following compound (claim 1) useful as an HPK1 inhibitor pharmaceutical for treating tumors including with in vitro and in vivo demonstrations of activity (cols 89-94):
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.
Sampson does not teach replacement of hydrogens with deuterium in the molecule.
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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One of ordinary skill in the art following the teaching of Sampson would have considered utilizing the well-known technique of deuterium isostere optimization in view of the success demonstrated by Li and Harbeson. One of ordinary skill in the art would have considered modifying the hydrogens on Sampson’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 Sampson’s compound and iteratively deuterate at each hydrogen and arrive at the claimed invention.
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.
Regarding claim 21, Sampson teaches the combination of the compound with a second anti-cancer agent (col 94, lines 43-46).
Regarding claim 22, Sampson teaches administering the compound to a subject to treat a HPK1 regulated disease (col 2, lines 55-58).
Thus, the claims are rejected as prima facie obvious.
Conclusion
No claims allowed.
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/ROBERT H HAVLIN/Primary Patent Examiner, Art Unit 1626