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
This application is a national stage entry of PCT/US2021/045455 filed on 08/11/2021 which claims priority to U.S. Provisional Application No. 63/186,689 filed on 05/10/2021; U.S. Provisional Application No. 63/153,521 filed on 02/25/2021; and U.S. Provisional Application No. 63/064,149 filed on 08/11/2020.
Election/Restrictions
Applicant’s election without traverse of Group II (claims 1-5, 9-12 and 15-17) drawn to a pharmaceutical composition comprising an FKBP ligand and an antiviral agent; FK1706 as a species of a FKBP ligand and remdesivir as a species of an antiviral agent in the reply filed on March 2, 2026 is acknowledged.
Claims 1-5, 9-12, 15-17, 26 and 27 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group or species, there being no allowable generic or linking claim.
Claims 18-23 are being examined as they read on the elected species.
Drawings
The replacement drawings were received on February 11, 2023. These drawings are acceptable.
Specification Objection
The use of the several terms including Tamiflu®, Prezcobix® , Avigan® and Triazavirin® which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 18-23 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “substantially” in claim 18 is a relative term which renders the claim indefinite. The term “substantially” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The only definition of substantially found in the instant specification is “The phrase “do not suppress an immune response” as used herein means that, upon administration of the composition, the subject's immune system is not substantially suppressed, is not significantly suppressed (e.g., compared to other subjects receiving the composition), or is not totally suppressed.” (paragraph [0095] of printed application). However, this is insufficient to provide a standard for ascertaining the requisite degree. The term "substantially" is often used in conjunction with another term to describe a particular characteristic of the claimed invention. It is a broad term. In re Nehrenberg, 280 F.2d 161, 126 USPQ 383 (CCPA 1960). The court held that the limitation "to substantially increase the efficiency of the compound as a copper extractant" was definite in view of the general guidelines contained in the specification. In re Mattison, 509 F.2d 563, 184 USPQ 484 (CCPA 1975). However, in the instant case there are no guidelines provided in the instant specification to determine what is meant by “does not substantially suppress an immune response of the subject.” For example, how much of the immune response can be suppressed in order to be considered substantial. Thus claim 18 and all claims dependent upon claim 18 (claims 19-23) are rejected. For the sake of compact prosecution, the claims are being interpreted as the subject's immune system is not suppressed, and examined herewith.
Claim 20 contains the trademarks/trade names Tamiflu®, Prezcobix® , Avigan® and Triazavirin®. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe certain formulations and, accordingly, the identification/description is indefinite. Thus, claim 20 is further indefinite.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claims 18-23 are rejected under 35 U.S.C. 103 as being unpatentable over Naoumov et al. U.S. Publication No. 2016/0082074 A1 in view of Price et al. (European Journal of Pharmacology 509 (2005) 11–19) and Brown et al. (Antiviral Research, Volume 169, September 2019, 104541, pages 1-10).
Claims 18-23 of the instant application claim a pharmaceutical composition comprising an FKBP ligand or a derivative thereof such as FK1706; and an antiviral agent such as remdesivir, wherein administration of the pharmaceutical composition to a subject does not substantially suppress an immune response of the subject.
Naoumov et al. teaches that a recent study performed a genome-wide SARS-CoV yeast-two-hybrid interaction screen with human cDNA libraries and identified human immunophilins (including cyclophilins [Cyps] and FK506-binding proteins [FKBPs] as interaction partners of CoV non-structural protein 1 [Nsp1] [0006]. Naoumov et al. further teaches that FK506 inhibits the replication of SARS-CoV, HCoV-NL63 and HCoV-229E and the dependence of HCoV-NL63 on FKBP1A/B [0006]. Naoumov et al. teaches that replication of human coronaviruses SARS-CoV, HCoV-NL63 and HCoV-229E is inhibited by the drug FK506 [0006]. Thus Naoumov et al. teaches that inhibition of the immunophilin FK506-binding proteins [FKBPs] inhibits replication of coronavirus.
Naoumov et al. teaches that it was demonstrated that, by using Alisporivir, NIM811 and a series of newly synthesized Cyclosporine A and FK506 derivatives, inhibition of HCoV-NL63 replication independent of the immunosuppressive character of the compounds [0008].
Naoumov et al. teaches non-immunosuppressive cyclosporin analogues which bind to cyclophilins, which are cyclophilin inhibitors, in particular to their pharmaceutical use in the treatment of infection with Coronaviurs (CoV) (abstract and [0002]). Naoumov et al. teaches that surprisingly it has been found that non-immunosuppressive cyclophilin inhibitors, in particular alisporivir and NIM811, have antiviral properties against Coronavirus that can be used effectively in the treatment of CoV infections [0011]. In particular, it has been found that the non-immunosuppressive cyclophilin inhibitors alisporivir and NIM811 inhibit CoV replication independent of the immunosuppressive character of the compounds [0011]. Thus Naoumov et al. teaches new anti-CoV treatments using alisporivir and NIM811 [0011]. Naoumov et al. further teaches methods for the treatment of CoV and CoV-co-infections comprising administering an effective amount of a non-immunosuppressive cyclophilin inhibitor, in particular alisporivir and/or NIM811, either alone or in combination with another antiviral agent such as ribavirin [0012]. Naoumov et al. further teach the preparation of a pharmaceutical composition comprising alisporivir and/or NIM811 in combination with a direct antiviral agent that inhibits Coronavirus growth [0015] and [0037].
Naoumov et al. further specifically demonstrates that a non-immunosuppressive FK506 analogue 6 with different properties regarding the inhibition of drug-Cyp/FKBP complexes, also inhibits coronavirus infection similarly to the cyclophilin inhibitors and the FKBP inhibitor FK506 ([0052], [0056]-[0057], figure 3B and Table 2). Naoumov et al. teaches that the main goal of the study was to test and compare the inhibitory effect of cyclosporines ALV and NIM811, however they found that the FK506 derivative 6 provided a first indication of the feasibility of expanding the concept of antiviral non-immunosuppressive CypA inhibitors into the field of FKBP inhibitors [0062]. Naoumov et al. teaches that the marked inhibition of HCoV-NL63 replication by the non-immunosuppressive derivatives of CsA and of FK506 highlights the functional relevance of host cell cyclophilins and FKBPs as antiviral targets [0069].
Naoumov et al. does not specifically teach combining an FKBP ligand with an antiviral agent. Naoumov et al. does not teach FK1706. Naoumov et al. does not teach remdesivir.
Although Naoumov et al. does not specifically teach combining an FKBP ligand with an antiviral agent, Naoumov et al. specifically teaches a pharmaceutical composition comprising a non-immunosuppressive cyclophilin inhibitor, in particular alisporivir and/or NIM811, either alone or in combination with another antiviral agent such as ribavirin for use in a method for treating coronavirus infection and a package comprising said pharmaceutical composition in combination with instructions to administer said composition is described ([0037]-[0038] and claims 1-8). Naoumov et al. further teaches as detailed above that like the non-immunosuppressive cyclophilin inhibitors, a non-immunosuppressive FK506 analogue 6 also inhibits coronavirus infection which indicates the feasibility of expanding the concept of antiviral non-immunosuppressive CypA inhibitors into the field of FKBP inhibitors [0062]. Naoumov et al. teaches that the marked inhibition of coronavirus replication by the non-immunosuppressive derivatives of CsA and of FK506 highlights the functional relevance of host cell cyclophilins and FKBPs as antiviral targets [0069].
Accordingly, prior to the effective filing date of the claimed invention, it would have been obvious to a person of ordinary skill in the art to treat coronavirus infections comprising the administration of a non-immunosuppressive FKBP inhibitor alone or in combination with an additional antiviral agent such as ribavirin based on the teachings of Naoumov et al. since it is demonstrated therein that a non-immunosuppressive FKBP inhibitor can inhibit coronavirus replication similarly to the non-immunosuppressive cyclophilin inhibitor. Thus, an ordinary skilled artisan would have been motivated to combine the non-immunosuppressive FKBP inhibitor with other antiviral agents with a reasonable expectation of providing an improved treatment for coronavirus infection.
A reference is good not only for what it teaches by direct anticipation but also for what one of ordinary skill in the art might reasonably infer from the teachings. (In re Opprecht 12 USPQ 2d 1235, 1236 (Fed Cir. 1989); In re Bode 193 USPQ 12 (CCPA) 1976).
"[I]n considering the disclosure of a reference, it is proper to take into account not only specific teachings of the reference but also the inferences which one skilled in the art would reasonably be expected to draw therefrom." In re Preda, 401 F.2d 825, 826, 159 USPQ 342, 344 (CCPA 1968); In re Lamberti, 545 F.2d 747, 750, 192 USPQ 278, 280 (CCPA 1976).
In the instant case, a skilled artisan would reasonably infer from the teachings of Naoumov et al. that non-immunosuppressive FKBP inhibitors also inhibit coronavirus replication and thus one would specifically combine said inhibitors with ribavirin or other antiviral compounds to form a pharmaceutical composition for treating coronavirus infection as taught in Naoumov et al. Thus Naoumov et al. renders obvious a pharmaceutical composition comprising an FKBP ligand or a derivative thereof; and an antiviral agent, wherein administration of the pharmaceutical composition to a subject does not suppress an immune response of the subject as claimed in instant claim 18.
Although Naoumov et al. does not teach FK1706, Naoumov et al. specifically teaches that a non-immunosuppressive FK506 analogue 6 compound was successful in inhibiting coronavirus replication and thus the inhibition of coronavirus replication by inhibitors of FK506 is independent of any immunosuppressive activity.
Price teaches FK1706 is a novel non-immunosuppressive immunophilin ligand characterized by binding to FK506 binding proteins (FKBPs) (title and abstract). Price et al. teaches that FK1706, a derivative of FK506, showed similarly high affinity for two FKBP subtypes, FKBP-12 and FKBP-52, but inhibited T cell proliferation and interleukin-2 cytokine production with much lower potency and efficacy than FK506 (abstract). Price et al. teaches that because FK1706 did not dramatically inhibit lymphocyte proliferation or interleukin-2 production demonstrates that this compound is not immunosuppressive (page 18).
Accordingly, prior to the effective filing date of the claimed invention, it would have been obvious to a person of ordinary skill in the art to combine the teachings of Naoumov et al. which teaches as detailed above that like the non-immunosuppressive cyclophilin inhibitors, non-immunosuppressive FK506 analogue compounds also inhibits coronavirus replication and thus are useful in the treatment of coronavirus infection, with the teachings of Price et al. which teaches that FK1706, a derivative of FK506, is a novel non-immunosuppressive immunophilin ligand characterized by binding to FK506 binding proteins (FKBPs). Thus since FK1706 is a non-immunosuppressive FK506 analogue compounds, a person of ordinary skill in the art would have been motivated to use FK1706 in the method of Naoumov et al. for treating coronavirus infection combined with another antiviral drug with a reasonable expectation of predictable results. It is prima facie obvious to substitute one known element for another known element to obtain predictable results. Thus preparing a pharmaceutical formulation comprising FK1706 and an antiviral agent for the treatment of coronavirus infection is rendered obvious in view of the cited prior art teachings.
Although Naoumov et al. does not teach remdesivir, Naoumov et al. specifically teaches combining the immunophilin ligand with a direct antiviral agent that inhibits Coronavirus growth such as ribavirin which is an RNA polymerase inhibitor. Thus claims 20 and 21 of the instant application are rendered obvious.
In addition, prior to the effective filing date of the claimed invention remdesivir was known in the art to inhibit coronavirus growth. Brown et al. teaches that Remdesivir (RDV, GS-5734) is a monophosphoramidate prodrug of an adenosine analog with potent activity against an array of RNA virus families including Filoviridae, Paramyxoviridae, Pneumoviridae, and Orthocoronavirinae, through the targeting of the viral RNA dependent RNA polymerase (RdRp) (abstract). Brown et al. specifically shows potent antiviral activity of RDV against coronavirus (abstract and throughout).
Accordingly, prior to the effective filing date of the claimed invention it would have been obvious to a person of ordinary skill in the art to combine a non-immunosuppressive immunophilin such as FK107 as taught by Price et al. with a direct antiviral agent that inhibits Coronavirus growth such as remdesivir as taught by Brown et al. based on the teachings of Naoumov et al. which specifically teaches combining a non-immunosuppressive immunophilin ligand with a direct antiviral agent that inhibits Coronavirus growth for the treatment of coronavirus infection. Since remdesivir is a direct antiviral agent that inhibits Coronavirus growth, an ordinary skilled artisan would have been motivated to combine it with a non-immunosuppressive FK506 analogue compound such as FK1706 with a reasonable expectation of providing an improved treatment for coronavirus infections. Furthermore, since two compounds are being combined for the treatment of coronavirus infections, using dosages lower than necessary for each individual compound is rendered obvious. Thus claim 22 is rendered obvious in view of the cited prior art teachings.
Thus the cited claims of the instant application are rendered obvious in view of the cited prior art teachings.
Conclusion
Claims 1-5, 9-12, 15-17, 26 and 27 are withdrawn. Claims 18-23 are rejected. Claims 6-8, 13-14, 24-25, 28 and 29 are canceled. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARA R. MCMILLIAN whose telephone number is (571)270-5236. The examiner can normally be reached Tuesday-Friday 12:00 PM-6:00 PM.
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/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623
KRM
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