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
This office action is in reply to the application filed on 17 November 2023. Claims 1, 3, 9-11, 14, 16-17, 21, 35-36, 41, 44, 46, 48, 50, 52, 54 and 57 are amended. Claims 2, 4-8, 12-13, 15, 18-20, 22-34, 37-40, 42-43, 45, 47, 49, 51, 53, 55-56, 58-61 and 63 are canceled. Currently, claims 1, 3, 9-11, 14, 16-17, 21, 35-36, 41, 44, 46, 48, 50, 52, 54, 57 and 62 are pending.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 05 March 2024, 17 September 2024, 27 November 2024, 17 January 2025, 29 April 2025 and 17 October 2025, was filed after the mailing date of the application on 17 November 2023. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
The Examiner notes that due to the voluminous nature of the IDS submissions, there is a possibility that one or more relevant references may have been overlooked. The Examiner respectfully requests that Applicant kindly highlight the references they believe are the most relevant to the claimed subject matter.
Claim Objections
Claim 3 is objected to because of the following informalities: the word ‘administered’ is misspelled. Appropriate correction is required.
Claim Rejections - 35 USC § 102
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 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, 3, 21, and 35-36 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Huang et al. (Pharmaceutical formulation containing active metabolites of remdesivir for inhalation, WO 2021/231361 A1, Published November 18, 2021).
Huang discloses the use of the drug remdesivir and one or more active metabolites in a pharmaceutical formulation that is suitable for administration by soft mist inhalation, or nebulization inhalation, as compared to claim 3 (abstract), with the invention providing a means of treating viral infections in patient including the vaccinia virus, such as poxviridae, chordopoxvirinae, and orthopoxvirus, as compared to claims 1, 21, and 35-36 (pg. 7, para. 37). It is noted that Applicant acknowledges that the compound of instant Formula Ia is remdesivir (See specification filed on November 17, 2023 at page 4, paragraph 21).
As such, claims 1, 3, 21, and 35-36 are anticipated by Huang and rejected.
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.
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 non-obviousness.
Claims 1, 3, 9-11, 14, 16, 21, 35-36, 57, and 62 are rejected under 35 U.S.C. 103 as being unpatentable over Huang et al. (Pharmaceutical formulation containing active metabolites of remdesivir for inhalation, WO 2021/231361 A1, 2021) in view of T. Cihlar (Remdesivir treatment methods, US 11,975,012 B2, filed 28 May 2021, published 23 December 2021, entered in IDS on 17 September 2024).
Huang discloses the administration of remdesivir as a soft mist or nebulization inhalation as a means to treat viral infections including the vaccinia virus.
Huang does not, however, disclose the administration of remdesivir to human patients orally, parenterally, once daily, at a dosage of 5 mg to 300 mg, or at a dosage of 0.1 mg/kg to 15 mg/kg, or as a kit comprising remdesivir.
Cihlar rectifies this deficiency by teaching that remdesivir can be administered in any route appropriate to the condition to be treated including oral, rectal nasal, pulmonary, topical vaginal and parenteral (including subcutaneous, intramuscular, intravenous, intradermal, intrathecal, and epidural) and implants, as compared to claims 9 and 10 (col. 17). Cihlar also teaches the administration of remdesivir once daily or twice daily, as compared to claim 11 (col. 17), in a dose of 150-250 mg on day 1 and 50-150 mg on subsequent days for varying lengths of time, as compared to claim 14 (col. 17). The human patient is estimated to weigh at least 40 kg, giving a dosage range of 3.75 mg/kg to 6.25 mg/kg in the first dose range and 1.25 mg/kg to 3.75 mg/kg in the second dose range, as compared to claims 16 and 57 (col. 17). A prima facie case of obviousness necessarily exists when the prior art range overlaps or touches a claimed range, such as in the instant rejection. MPEP §2144.05. Lastly, Cihlar teaches the use of a kit, comprising a compound or composition disclosed, including remdesivir, a label and/or instructions for using, as compared to claim 62 (col. 32, section IV. Kits).
As such, it would have been prima facie obvious, to a person of ordinary skill in the art with a reasonable expectation of success, to consider the administration of remdesivir in manners described by Cihlar, including oral and parenteral, on a daily basis, in a dosing range for human patients between 5-300 mg and 0.1 mg/kg to 15 mg/kg, and to use a kit comprising remdesivir to treat the disease of interest.
Claim 17 is rejected under 35 U.S.C. 103 unpatentable over Huang et al. (Pharmaceutical formulation containing active metabolites of remdesivir for inhalation, WO 2021/231361 A1, 2021) in view of Harness et al. (Arylamide compounds for treatment and prevention of viral infections, WO 2021/248008 A1, 2021), U.S. Food & Drug Administration (Emergency use authorization 092, 27 October 2022), and Akazawa et al. (Potential anti-monkeypox virus activity of atovaquone, mefloquine, and molnupiravir, and their potential use as treatments, bioRxiv preprint, 2 August 2022, doi.org/10.1101/2022.08.02.502485).
Huang discloses the administration of remdesivir as a soft mist or nebulization inhalation as a means to treat viral infections including the vaccinia virus.
Huang does not, however, disclose administering to the patient a therapeutically effective amount of an additional therapeutic agent.
Harness overcomes this by teaching the use of brilacidin, a non-peptidic host defense peptide/protein mimetic, to treat SARS-CoV-2, in conjunction with remdesivir. In a Calu-3 cell line assay, Harness assesses the synergistic effects of brilacidin in combination with remdesivir or favipiravir. Brilacidin and favipiravir independently exerted up to 90% and 80% inhibition of viral titers, respectively, which did not increase over time. In a brilacidin/remdesivir combination, the viral infectious titer was inhibited by >99% (pg. 36, Example 4). This therapeutic combination was so effective, that the FDA agreed to Eli Lilly and Company’s issuance request for an emergency use authorization for the treatment of suspected or laboratory confirmed COVID-19 in certain hospitalized patients, demonstrating remdesivir’s potential application in other combinatorial therapies. In the case of monkeypox virus, a subset of orthopox virus, Akazawa identifies three approved-drugs including atovaquone, mefloquine, and molnupiravir that exhibit anti-monkeypox virus activity, with 50% inhibitory concentrations at 0.5 µM (abstract).
As such, it would have been prima facie obvious, to a person of ordinary skill in the art, at the time of filing, that remdesivir could be used synergistically as a combination therapy as had been previously demonstrated, and to consider approved drugs that had already shown efficacy to other poxviruses, i.e. monkeypox.
Allowable Subject Matter
Claims 41, 44, 46, 48, 50, 52, and 54 are objected to (see below) and recite allowable subject matter.
The following is a statement of reasons for the indication of allowable subject matter: a method of using remdesivir to treat infections caused by parapoxvirus, molluscipoxvirus, yatapoxvirus, capripoxvirus, suipoxvirus, leporipoxvirus, and avipoxvirus was not taught in the prior art in a 100% embodiment. The closest match is taught by Huang et al. (Pharmaceutical formulation containing active metabolites of remdesivir for inhalation, WO 2021/231361 A1, 2021) with the use of remdesivir to treat an infection caused by poxviridae, chordopoxvirinae, and orthopoxvirus.
Claims 41, 44, 46, 48, 50, 52, and 54 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Summary
Claim 3 is objected to under 35 U.S.C. 112(b). Claims 1, 3, 21, 35-36 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2). Claims 9-11, 14, 16-17, 57 and 62 are rejected under 35 U.S.C. 103. Claims 41, 44, 46, 48, 50, 52 and 54 are objected to and recite allowable matter.
Conclusion
Claims 1, 3, 9-11, 14, 16-17, 21, 35-36, 57 and 62 are rejected. Claims 3, 41, 44, 46, 48, 50, 52 and 54 are objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Allen Chao whose telephone number is (571)272-7001. The examiner can normally be reached Monday - Friday 0700-1300.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James H Alstrum-Acevedo can be reached at 571-272-5548. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ALLEN CHAO/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622