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 .
DETAILED ACTION
Preliminary amendment filed on 09/02/2022 is acknowledged. Claims 1-23 were canceled and claims 24-43 were newly added. Claims 24-43 are pending in the instant application and are examined on the merits herein.
Priority
This application is a National Stage Application of PCT/CN2021/078875, filed on 03/03/2021 and claims benefit of provisional application 62/984,771 filed on 03/03/2020.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 112(a) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 62/984,771, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The provisional application No. 62/984,771 teaches a composition comprising vardenafil for treating coronavirus infection in a subject, but fails to provide support for treating a viral infection wherein the vardenafil composition is used specifically as a monotherapy. The provisional application No. 62/984,771 teaches a composition comprising one or more compounds selected from Lopinavir, Ritonavir, Atazanavir, Indinavir Sulfate, Nelfinavir Mesylate, Ceftaroline fosamil, Leucal ( or called Leucovorin), Aztreonam, Cangrelor, Vardenafil, Fludarabine, Eltrombopag, Tedizolid, Macitentan, Cobicistat, and/or Lifitegrast, and any derivatives thereof, but fails to provide support for treating a viral infection wherein the vardenafil composition also comprises the broader term “antiviral agent”. The provisional application No. 62/984,771 teaches a composition comprising vardenafil for treating coronavirus that may be SARS-CoV-2, but does not support treating a coronavirus that is SARS-CoV-2 that has one or more spike protein mutations or a variant of SARS-CoV-2. The provisional application No. 62/984,771 teaches the composition may comprise vardenafil, fails to provide support for wherein vardenafil is in the form of vardenafil hydrochloride or vardenafil hydrochloride trihydrate.
Accordingly, claims 25-28, and 31-43 are not entitled to the benefit of the prior application and receive the filing date of 03/03/2021, which is the filing date of CN2021/078875 which provides support for these claims.
Information Disclosure Statement
The information disclosure statement (IDS) dated 09/02/2022 complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609, except where noted. Accordingly, the IDS document has been placed in the application file and the information therein has been considered as to the merits.
Claim Objections
Claims 31 and 40 are objected to because of the following informalities: the phrase “a D614G mutation in its spike protein” is repeated twice in lines 3 and 11 of the claims. Appropriate correction is required.
Claim 34 is objected to because of the following informalities: there is extra spacing between the phrases “vardenafil hydrochloride” and “trihydrate.” Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Claim 24-29 and 31-34 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.
Claim 24 recites the phrase, “use of vardenafil for the manufacture of a medicament for treating a coronavirus infection”, which merely recites a use without any active, positive steps delimiting how this use is actually practiced. Applicant is requested to clearly distinguish a category of invention under 35 USC 101 for each claim. For purposes of applying prior art, the examiner will interpret claim 24 as a method of treating a coronavirus infection in a subject using a composition comprising vardenafil.
Claims 25-29 and 31-24 recite the phrase, “The use according to claim 24”, which merely recites a use without any active, positive steps delimiting how this use is actually practiced. Applicant is requested to clearly distinguish a category of invention under 35 USC 101 for each claim. For purposes of applying prior art, the examiner will interpret “The use according to claim 24” as “The method according to claim 24”.
Claim 30 recites the phrase, “The method of claim 24”. There is insufficient antecedent basis for this limitation in the claim as claim 24 does not recite a method claim.
Claim Rejections - 35 USC § 101
Claims 24-29 and 31-34 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claims do not fall clearly into at least one of the four categories of patent eligible subject matter because a use claim is not considered a method for lack of distinct steps. Rather, the claims as presented can be interpreted to two distinct categories of invention: composition of matter and method. Further, "use" claims that do not clearly purport to claim a process, machine, manufacture, or composition of matter fail to comply with 35 U.S.C. 101. In re Moreton, 288 F.2d 708, 709, 129 USPQ 227, 228 (CCPA 1961) ("one cannot claim a new use per se, because it is not among the categories of patentable inventions specified in 35 U.S.C. § 101"). See MPEP §2173.05(q). For the purposes of applying prior art, the examiner will interpret claims 24-29 and 31-34 as a method of treating a coronavirus infection in a subject using a composition comprising vardenafil.
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.
Claims 24, 25, 29, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Suri et al. (WO 2018/231759 A1, published December 20, 2018, see IDS dated 09/02/2022).
Suri is drawn to a composition for inducing an immune response in a subject comprising an effector module. The effector module comprises a stimulus response element (SRE) and at least one payload, which is attached, appended, or associated with said SRE, wherein said SRE comprises a destabilizing domain (DD), said DD comprising, in whole or in part, the cGMP-specific 3',5'-cyclic phosphodiesterase (hPDE5; SEQ ID NO. l) (claim 1). The stimulus is a small molecule could be vardenafil (claim 39). Suri teaches that various infectious agents such as MERS coronavirus (MERS-CoV) and SARS-CoV may be treated with pharmaceutical compositions such as effector modules including their SREs or payloads (paragraph 0658). Suri teaches that the composition may be administered to a subject using any amount and any route of administration effective for treating a clinical condition such as an infection disease (paragraph 0547). Suri defines a “subject” to include animals such as humans (paragraph 0753). Although Suri does not use the specific term “monotherapy”, Suri teaches that the pharmaceutical composition may be used to treat infectious diseases and does not teach any required additional agents which would meet the limitations of instant claim 25 (paragraph 0654).
It would have been prima facie obvious to use a composition comprising vardenafil to treat a coronavirus such as MERS and SARS-CoV in a subject that is human and wherein the administration is done as a monotherapy before the effective filing date of the claimed invention to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to modify the composition taught by Suri to comprise vardenafil and apply it to treat SARS-CoV or MERS in a human because Suri teaches a composition comprising vardenafil that may treat SARS-CoV and MERS in a human. Further, Suri does not teach that the composition comprising vardenafil must be administered with any additional co-therapies, therefore the administration of the composition would necessarily meet the requirements of a monotherapy. One of ordinary skill in the art would have a reasonable expectation of success because Suri teaches a composition comprising vardenafil for treatment of SARS-CoV and MERS in a human.
Claim 24, 26, 29, 30, 35, 38, 39 is rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (WO 2018/231759 A1, published February 8, 2018, see PTO-892).
Chen is drawn to methods, pharmaceutical compositions and kits directed to antiviral therapy (abstract). Chen teaches a method of anti-viral treatment comprising administering to a subject that has a viral infection or is at risk of the viral infection administering the pharmaceutical composition of the invention (claim 86). Chen claims a kit that contains instructions to administer the pharmaceutical composition of the invention to a subject (claim 85 and claim 86). The pharmaceutical composition may include an antiviral and a phosphodiesterase inhibitor (paragraph 0099). The phosphodiesterase inhibitor may be phosphodiesterase 5 inhibitor such as vardenafil. Chen teaches co-administering the phosphodiesterase 5 inhibitor to a subject (paragraph 0058). Chen teaches co-administering an antiviral to a subject (paragraph 0057). Chen defines the term “subject” to include humans (paragraph 00192). Chen teaches that the virus may be any virus known to be a human or animal pathogen including human corona viruses (e.g. 229E, OC43, NL63, and HKUl), SARS-CoV and Middle East respiratory
syndrome coronavirus (paragraph 0054).
It would have been prima facie obvious to select and use a composition comprising vardenafil to treat a coronavirus such as SARS-CoV and MERS in a human in combination with an antiviral agent before the effective filing date of the claimed invention to arrive at the claimed invention. It would have been prima facie obvious for a person of ordinary skill in the art to select a composition comprising a phosphodiesterase 5 inhibitor such as vardenafil and an antiviral agent because Chen teaches that the method for treatment of SARS-CoV and MERS in a human by administering a composition comprising phosphodiesterase 5 inhibitor such as vardenafil and co-administering an antiviral agent. One of ordinary skill in the art would have a reasonable expectation of success because Chen teaches the method for treatment of SARS-CoV and MERS in a human by administering a composition comprising a phosphodiesterase 5 inhibitor such as vardenafil and co-administering an antiviral agent.
Claims 24, 26-28 and 35-37 are rejected under 35 U.S.C. 103 as being unpatentable over Clarke et al. (US2017 /0071964 A1, published 03/16/2017, see PTO-892) and Chen et al. (WO 2018/231759 A1, published February 8, 2018, see PTO-892) and as evidenced by PubChem (https://pubchem.ncbi.nlm.nih.gov/compound/Remdesivir, accessed 08/16/2025, see PTO-892).
Clarke is drawn to methods for treating Coronaviridae virus infections (title). Clarke teaches a method of inhibiting a Coronaviridae RNA-dependent RNA polymerase and treating a viral infection caused by a Coronaviridae virus with a compound of Formula I or a pharmaceutically acceptable salt, solvate, and/or ester thereof (paragraphs 0110-0111). Clarke teaches a method of treating a Coronaviridae infection with the compound remdesivir (claims 39 and 62). As evidenced by Pubchem, the structure disclosed by Clarke in claim 62 is remdesivir. Clarke teaches that the methods of treatment include those for treating coronavirus infections in a human including infections caused by alpha coronaviruses 229E (HCo V-229E) and NL63 (HCoV-NL63, New Haven coronavirus), beta coronaviruses OC43 (HCoV-OC43), HKUl, SARS-CoV, and MERS-CoV, and HCoV-EMC (paragraph 0336). Clarke teaches that the method of treating a Coronaviridae infection in a human in need thereof may comprise administering a pharmaceutical composition comprising an effective amount of a Formula I compound such as remdesivir in combination with at least one additional therapeutic agent (paragraph 0106) and that the composition may contain an additional therapeutic agent (paragraph 0109).
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Compound exemplified by Clarke (claim 62) that is remdesivir as evidenced by PubChem.
Clarke does not teach a composition comprising vardenafil or the administration of a composition comprising vardenafil.
The teachings of Chen are discussed above.
It would have been prima facie obvious to combine the teachings of Clarke and Chen before the effective filing date of the claimed invention by including vardenafil, as taught by Chen, in the composition for treatment of coronavirus that comprises remdesivir and an additional therapeutic agent taught by Clarke to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to include vardenafil as the additional therapeutic agent because Chen teaches that the inclusion of a phosphodiesterase 5 inhibitor such as vardenafil may be used to treat coronavirus in a subject and Clarke teaches that the composition for treating coronavirus may include remdesivir, which inhibits RdRp, and an additional therapeutic agent. One of ordinary skill in the art would have a reasonable expectation of success because Clarke teaches a composition for treating SARS-CoV and MERS comprising remdesivir and an additional therapeutic agent, and Chen teaches that vardenafil may be used to treat SARS-CoV and MERS.
Claims 31-32 and 40-41 are rejected under 35 U.S.C. 103 as being unpatentable over Clarke et al. (US2017 /0071964 A1, published 03/16/2017, see PTO-892) and Chen et al. (WO 2018/231759 A1, published February 8, 2018, see PTO-892) as applied to claims 24, 29 and 35 above, and further in view of Reuschl et al. (bioRxiv preprint doi: https://doi.org/10.1101/2021.01.24.427991, published 02/04/2021, see PTO-892).
Claims 24, 26, and 35 are rejected as discussed above.
The combined teachings of Clarke and Chen are discussed above.
The combined teachings of Clarke and Chen do not teach the method of treating a SARs-CoV-2 with a mutation in the spike protein or is a variant B.1.1.7 as recited in the instant claims.
Reuschl is drawn to the study of the full-length B.1.1.7 variant virus of the SARS-CoV-2 infection (abstract). Reuschl teaches that remdesivir possesses similar antiviral activity against both the early-lineage SARS-CoV-2 and the B.1.1.7 variant (page 2). Reuschl also teaches that the B.1.1.7 variant contains spike protein mutations N501Y and P681H (Figure 1, page 3).
It would have prima facie been obvious to combine the combined teachings of Clarke and Chen with the teachings of Reuschl to apply the composition comprising vardenafil and remdesivir to treat a SARS-CoV-2 infection from the B.1.1.7 variant as taught by Reuschl to arrive at the claimed invention. It would have been prima facie obvious for one or ordinary skill in the art to treat a SARS-CoV-2 infection from the B.1.1.7 variant with the composition comprising vardenafil and remdesivir taught by the combined teachings of Chen and Clarke because Reuschl teaches that remdesivir is still effective against the B.1.1.7 variant which contains the spike protein mutations N501Y and P681H. One of ordinary skill in the art would have a reasonable expectation of success because Reuschl teaches that remdesivir is as effective against the B.1.1.7 variant of SARS-CoV-2.
Claims 33-34 and 42-43 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (WO 2018/231759 A1, published February 8, 2018, see PTO-892) as applied to claims 24 and 35 above, and further in view of Serno et al (US 8,273,876 B2, published 09/25/2012, see PTO-892).
Claims 24 and 35 are rejected as discussed above.
Chen is discussed above.
Chen further teaches that the compounds and pharmaceutical compositions may be administered orally in tablets and pills and can be also be administered parenterally (paragraph 00190).
Chen is silent on the form of vardenafil.
Serno is drawn to medicaments containing vardenafil hydrochloride trihydrate. Serno teaches that vardenafil hydrochloride is unsuitable as an ingredient of medicaments in which the ingredient is to be present in solid form because different polymorphic forms may take up different amounts of water which results in different dissolving behavior and may change the bioavailability, maximum plasma concentration and time of appearance of the maximum plasma concentration. Serno teaches that vardenafil hydrochloride trihydrate can be obtained solid medicaments in uniform and reproducible forms (column 1, lines 27-45). Serno also exemplifies in example 5 the pharmacokinetics after administration of tablets containing vardenafil hydrochloride trihydrate and a solution containing vardenafil hydrochloride. The results showed that the tablets of the vardenafil hydrochloride trihydrate have a relative bioavailability of 93% compared with the aqueous solution. Therefore, similar results were seen with between the solid form of the vardenafil hydrochloride trihydrate and the aqueous form of the vardenafil hydrochloride when administered orally (column 7, lines 22-67).
It would have been prima facie obvious to combine the teachings of Serno and Chen before the effective filing date of the claimed invention by selecting vardenafil hydrochloride trihydrate as the form of vardenafil in the composition taught by Chen to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to select vardenafil hydrochloride trihydrate because Serno teaches that vardenafil hydrochloride is unsuitable as an ingredient in medicaments in which the ingredient is present in solid and Chen teaches that the composition comprising vardenafil may be administered orally in tablet form. One of ordinary skill in the art would have a reasonable expectation of success because Serno teaches that the vardenafil hydrochloride trihydrate form may be obtained in a uniform and reproducible form.
It would have been prima facie obvious to combine the teachings of Serno and Chen before the effective filing date of the claimed invention by selecting vardenafil hydrochloride as the form of vardenafil in a non-solid form in the composition taught by Chen to arrive at the claimed invention. It would have been obvious to one of ordinary skill in the art that in an aqueous formulation vardenafil hydrochloride may be used in a composition as the vardenafil because Serno shows that the solid form of vardenafil hydrochloride trihydrate and the aqueous form of vardenafil hydrochloride when administered orally have similar bioavailability. One of ordinary skill in the art would have a reasonable expectation of success because Serno shows similar pharmacokinetics between the solid form of vardenafil hydrochloride trihydrate and the aqueous form of vardenafil hydrochloride.
Conclusion
No claims allowed.
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/SAMANTHA LYNN SCHACHERMEYER/Examiner, Art Unit 1693 /SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693