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/CN2022/109599 (08/02/2022)
and claims foreign priority to CHINA 202110882817.6 (08/02/2021)
PCTCN2021128089 (11/02/2021).
Status
Claims 1-13 are pending.
Rejections not reiterated are withdrawn.
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.
Claims 1-13 are rejected under 35 U.S.C. 112(a) as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Claim 1 to a scope of compounds of formula (I), including “isomer mixture thereof”, where the isomers include positional isomers, where the compounds are to a genus including P1 and P3 as including 5-10-membered heteroaryl, P2 forming various cyclic structures, and R1-R3 to various alkyl and aryl groups, all of which may be substituted according to the definitions in the specification. The instant disclosure does not contain sufficient information regarding the subject matter of the claims as to enable one skilled in the pertinent art to make and use the claimed invention upon consideration of the factors set forth in In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1998), as follows. See also MPEP § 2164.01(a) and § 2164.04.
The breadth of the claims – the claims are to a large genus of compounds each claim in excess of millions of compounds.
The nature of the invention – the nature of the claimed invention is the compounds are alleged to be 3CL inhibitors of SARS-CoV-2 for treating or preventing coronavirus infection.
The state of the prior art – there are few known successful 3CL protease inhibitors that are therapeutic and Applicant cites no known successful demonstrations of the approach.
The level of one of ordinary skill – the level of skill in the art is high as evidenced by Tsai et al. (J. Med. Chem. 2006, 49, p. 3485-3495), Cherkasov et al. (J. Med. Chem. 2014, 57, p. 4977−5010) and Dearden et al. (SAR and QSAR in Environ. Res. 2009, 20, 241– 266).
The level of predictability in the art – the art is highly unpredictable due to the complex nature of the disease and the mode of action of the compounds used. The particular art is also unpredictable because there is no known or articulated rationale for how the compounds are alleged to induce therapeutic effect. Furthermore, as evidenced by Tsai et al. (J. Med. Chem. 2006, 49, p. 3485-3495) compounds of similar structure unpredictably vary from inactive to active as inhibitors. In addition, as evidenced by Cherkasov and Dearden, predicting pharmacological activity fails, for example, when based on data lacking in chemical structure space.
The amount of direction provided by the inventor – the primary guidance provided by the inventor is given in the Example apparently evaluating some in vitro activity of 37 compounds with many of the compounds not having all data reported. Each of the compounds evaluated are all of very similar structure and does not map large chemical structure space compared to the scope of the claims. There is no apparent or reported correlation between the structure of the compounds within the claims and those tested. This lack of supporting data and explanation would cause one of skill in the art to question whether the examples support enablement of the full scope of the claims. There are no statistical measures associated with the data leading to the conclusion that the data has questionable statistical significance.
The existence of working examples – there are no working examples of the claimed compounds being effective for the asserted utility as indicated above.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure – given the high level of unpredictability in the art, the lack of working examples, and the limited guidance provided in the examples, there would be a tremendous amount of experimentation required before one of skill in the art would consider being enabled to make and use the full scope of the claims for the asserted utility.
In view of the specification and evidence of record, one of skill in the art would be required to perform an undue amount of experimentation to test each of the compounds of the claims using an appropriate model select candidates for further development in vivo, perform testing to determine dosing, and finally efficacy testing. Thus, one of skill in the art would be required to start ab initio and develop any compound within the scope of the claims. Such a level of experimentation is undue. Weighing the above factors by a preponderance of the evidence results in the conclusion that the claims are not enabled for the asserted utility with the full scope of the claims.
Response to Remarks - 35 USC § 112(a)
Applicant argues the claims as amended are significantly narrowed by amending the definitions of P1 and P2 in a manner that is structurally very close to the 37 example compounds synthesized and tested, and therefore the claims are enabled.
This argument is not persuasive as the amended claims continue to encompass a scope that would require an undue amount of experimentation considering the example compounds are limited to species where P1 is pyridyl while R1 are all at the 5-position are are one of Br, CF3, CH3, OCH3, CN, oxadiazole, pyrazole; and P1 is isoquinolnyl only substituted at the 5-position by R1 of F. In addition, the claims also include the expansive scope of optical and geometric isomers, prodrugs, and metabolites without any supporting disclosure. Based on the limited disclosure and the high level of unpredictability in the art, one of skill in the art would not have an expectation that all of the compounds within the scope of the claims would share the same utility and would require undue experimentation to practice the full scope of claimed invention. Rejection maintained.
New 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 1-13 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Arnold et al. (WO2023044171, EFD 2021-09-20).
Arnold teaches compounds, including compound 109 (p. 50):
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276
425
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corresponding to claim 1’s formula (I) where P1 is isoquinolinyl; P2 forms a 3-membered cyclopropyl substituted by two methyls; and P3 is the first alternative where R2 is t-butyl, X is -C(O)-, and R3 is trifluoromethyl. Arnold teaches administering the compounds in a method of treating disease including SARS-CoV-2 (claim 55).
Conclusion
No claims allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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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