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 CON of PCT/CN2021/091093 (04/29/2021) which has PRO 63/112,087 (11/10/2020), PRO 63/059,095 (07/30/2020), and PRO 63/017,878 (04/30/2020).
Status
Applicant amended the claims such that the prior rejections not reiterated here are withdrawn.
Following the amendment, claims 1, 2, 4, 5, 10, 12, 27, 33, 34, 36, 37, 40, 42, 44, 47, 48, 67, 68 and 71 are pending.
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, 2, 4, 5, 10, 12, 27, 33, 34, 36, 37, 40, 42, 44, 67, 68 and 71 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of use of a scope compounds similar to instant claim 48, does not reasonably provide enablement for the full scope of claim 1. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Claims 1, 2, 4, 5, 10, 12, 27, 33, 34, 36, 37, 40, 42, 44, 67 are to a scope of compounds having utility only as a protease inhibitor of SARS-CoV-2. Claims 68 and 71 are to a method of “treating or preventing a SARS-CoV-2 infection in a patient”, and “method of inhibiting a protease of SARS-CoV-2” with a compound of claim 1. The scope of claim 1 is very broad and claim 1’s Formula (X) which includes variable groups such as heteroaryl, heterocycloalkyl, aryl, cycloalkyl, all of which can be “optionally substituted” which is further defined in the specification as including an expansive scope including cycloalkyl, aryl, heteroaryl, heterocycloalkyl, etc. (Spec., p. 106-107 at [00202]).
The nature of the claimed invention is to a novel virus that was not well characterized and did not have known treatments or inhibitors at the time of filing. Although the level of skill in the art is very high, the level of predictability in the art is very low, particularly with respect to a virus that was novel and not characterized at the time of filing.
The specification provides very little guidance with respect to support for the methods of claims 68 and 71. Although the Specification has in vitro biological examples on page 180-185
of Compounds INSCoV- 110, 501, 502, 503, 504, 505, 507,508, 514, 515, 516, 517, 520, 523, 531, 534, 535, 536, 537, 538, 539, 549, 557, 558, 559, 560, 570, 571, 537(2), 574, 575, 576, 600, 601, 612, 614, 615, 616, 618, 620, 704, these compounds are all very similar in structure and do not represent the large structural variations encompassed by claim 1’s Formula (X) which includes variable groups such as heteroaryl, heterocycloalkyl, aryl, cycloalkyl, all of which can be “optionally substituted” which is further defined in the specification as including an expansive scope including cycloalkyl, aryl, heteroaryl, heterocycloalkyl, etc. (Spec., p. 106-107 at [00202]). In addition, while there are in vivo studies with a small subset of the above in vitro compounds, none of the studies relate to efficacy for treating or preventing SARS-CoV-2 infection in a patient or an in vivo method of inhibiting a protease of SARS-CoV-2, but are instead only to plasma stability or ADME studies. Furthermore, there are no working examples provided in the disclosure with respect to the methods of claims 68 and 71.
There was also a significant amount of experimentation required to practice the claimed invention because it was a novel virus and disease that was not well understood or characterized at the time of filing. As stated in the Specification on page 2, there are no known treatments for SARS-CoV-2. Similarly, at the time of filing, there were no known SARS-CoV-2 protease inhibitors. Thus, one of skill in the art would need to synthesize and screen each of the species within the broad scope of claim 1 and furthermore test each candidate with an in vivo model for efficacy which would be an enormous burden.
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. Thus, the claims are not enabled for the full scope of the claims.
Response to Remarks - 35 USC § 112 Enablement
Applicant amended the claims and argued that the current form of the claims are more commensurate with the exemplified compounds of table 1.
This argument is not persuasive for the reasons provided above. In addition, as stated above, the disclosure lacks support for the asserted utility of treating SARS-CoV-2 and the presented relevant data to this utility is very narrow with respect to scope of compounds, of limited significance with in vitro cell assays at micromolar levels greater than other therapeutics, and a lack of connection between the demonstrations and the expected therapeutic utility, particularly given the limited information regarding successful treatment of SARS-CoV-2 at the time of filing. The rejection is maintained.
Claim Rejections - 35 USC § 102 – Carniato et al.
Claims 1, 2, 4, 5, 10, 20, 27, 36, 37, 40, 42, 44, 67 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Carniato et al. (US20110104162).
Carniato in claim 6 teaches compound 129:
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which corresponds to instant claim 1’s Formula (X) when
B,B1=bond; R1=halo acetyl; R3=heteroaryl (2-thiophenyl); R5=H;
R4=cycloalkyl; R11=C1-haloalkyl; R15a,b,c,d=H R16=H;
and anticipates each of claims 1, 2, 4, 5, 10, 20, 27, 36, 37, 40, 42, 44. Regarding claim 67, Carniato claim 8 teaches composition with and excipient.
Applicant amended the claims in a manner which narrowed R3 and avoids the cited art. This rejection is withdrawn.
New Claim Rejections Necessitated by Amendment
New Claim Rejection - 35 USC § 102 – St. John et al.
Claims 1, 2, 4, 5, 10, 27, 33, 34, 36, 37, 40, and 67 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by St. John et al. (US20170313685).
St. John teaches in claim 18 the following compound:
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which corresponds to instant claim 1’s Formula (X) when
B,B1=bond; R1=heterocyclo acetyl; R3=heteroaryl (pyridyl); R5=H;
R4=cycloalkyl; R11=alkyl (t-butyl); R15a,b,c,d=H R16=H;
and anticipates each of claims 1, 2, 4, 5, 10, 20, 27, 36, 37, 40, 42, 44. Regarding claim 67, St. John teaches a pharmaceutical composition comprising an excipient (claim 19).
New Claim Rejection - 35 USC § 102 – St. John et al.
Claims 1, 2, 4, 5, 10, 12, 27, 33, 34, 36, 37, 40, 42, 44, 47, 67 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tsuboi et al. (J. Am. Chem. Soc. 2011, 133, 16605–16616).
Tsuboi teaches compound 3 (Table 1)
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132
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which corresponds to instant claim 1’s Formula (X) when
B,B1=bond; R1=halo acetyl; R3=heteroaryl (pyridyl); R5=H;
R4=cycloalkyl; R11=halogen; R15a,b,c,d=H R16=H;
and anticipates each of the claims. Regarding claim 67, Tsubio teaches composition with and excipient (p. 16606-07: compound in DMSO).
New Claim Rejection - Double Patenting
Claims 1, 2, 4, 5, 10, 12, 27, 33, 34, 36, 37, 40, 42, 44, 47, 48, 67, 68 and 71 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 5-14, 19-27 of U.S. Patent No. 11731944 in view of St. John et al. (US20170313685). Although the claims at issue are not identical, they are not patentably distinct from each other because the patent claims species including
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(claim 5) which would anticipate the claims but for a methyl group instead of a hydrogen at the “R5” position as per instant claim 1, the patent also claims the same method of treatment/use. St. John teaches coronavirus protease inhibitor that are closely structurally related including the compound of claim 18 which has a hydrogen at the “R5” position. One of ordinary skill in the art following the teaching of the patent would have had a reasonable expectation that changing a methyl to a hydrogen would result in a compound with similar activity in view of the teaching of St. John in the same field of endeavor and affecting the same family of virus. Thus, the claims are prima facie obvious.
Claim 1, 2, 4, 5, 10, 12, 27, 33, 34, 36, 37, 40, 42, 44, 47, 48, 67, 68 and 71 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-62 of copending Application No. 18705742 (reference application) in view of St. John et al. (US20170313685). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference application is to a genus of compounds with species disclosed such as
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which would anticipate the claims but for a methyl group instead of a hydrogen at the “R5” position as per instant claim 1, the reference application also claims the same method of treatment/use. St. John teaches coronavirus protease inhibitor that are closely structurally related including the compound of claim 18 which has a hydrogen at the “R5” position. One of ordinary skill in the art following the teaching of the reference application would have had a reasonable expectation that changing a methyl to a hydrogen would result in a compound with similar activity in view of the teaching of St. John in the same field of endeavor and affecting the same family of virus. Thus, the claims are prima facie obvious.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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