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
Pursuant to the amendment dated 09/29/2025, claims 1 and 18 are cancelled and claims 2, 6-8, and 14 are amended. Claims 2-17 are pending in the instant application and are examined on the merits herein.
Priority
This application is a National Stage Application of PCT/CN2021/092693, filed on 05/10/2021 and claims foreign priority to CHINA 202010158032.X filed on 03/09/2020.
Information Disclosure Statement
The information disclosure statement (IDS) dated 09/29/2025 complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, the IDS document has been placed in the application file and the information therein has been considered as to the merits.
Withdrawn Rejections
Applicant’s amendment, filed on 09/29/2025, with respect to the rejection of claim 2 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, has been fully considered and is persuasive. Applicant has cancelled 1 and amended claim 2 to be the independent claim. The rejection is hereby withdrawn.
Applicant’s amendment, filed on 09/29/2025, with respect to the rejection of claim 14 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, has been fully considered and is persuasive. Applicant has amended claim 14 to remove the relative term “severe”. The rejection is hereby withdrawn.
Applicant’s amendment, filed on 09/29/2025, with respect to the rejection of claims 2-5, 8-10 and 12-18 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement, has been fully considered and is persuasive. Applicant has amended claims 2 and 8 to remove the phrase “preventing”. The rejection is hereby withdrawn.
Applicant’s amendment, filed on 09/29/2025, with respect to the rejection of claim 1 under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Einav et al. (US 8,895,598 B2, published November 25, 2014, see PTO-892 dated 06/27/2025), has been fully considered and is persuasive. Applicant has canceled instant claim 1 rendering the rejection moot. The rejection is hereby withdrawn.
Applicant’s amendment, filed on 09/29/2025, with respect to the rejection of claims 1, 6, and 7 under 35 U.S.C. 103 as being unpatentable over Einav et al. (US 8,895,598 B2, published November 25, 2014, see PTO-892 dated 06/27/2025) has been fully considered and is persuasive. Applicant has canceled claim 1 and amended claims 6 and 7 to be dependent from claim 2 rendering the rejection moot. The rejection is hereby withdrawn.
Applicant’s amendment, filed on 09/29/2025, with respect to the rejection of claim 18 under 35 U.S.C. 103 as being unpatentable over Einav et al. (US 8,895,598 B2, published November 25, 2014, see PTO-892 dated 06/27/2025) and Wang et al. (Cel Research, published February 4, 2020, see PTO-892 dated 06/27/2025) as applied to claim 8 above, and further in view of Dyall et al. (Drugs, published November 15, 2017, see PTO-892 dated 06/27/2025) has been fully considered and is persuasive. Applicant has canceled claim 18 rendering the rejection moot. The rejection is hereby withdrawn.
Rejections Necessitated by Amendment
The following are maintained and new ground(s) necessitated by Applicants' amendment, filed on 09/29/2025, wherein instant independent claims 1 was canceled and instant independent claims 2 and 8 were amended to alter the breadth and scope of the claim, and wherein the remaining pending claims 2-7 and 9-17 depend from said independent claims.
Objections
Nucleotide and/or Amino Acid Sequence Disclosures
The incorporation by reference paragraph in the specification amendment of 03/03/2023 recites the size of the ASCII file in KB, rather than the bytes as required by 37 CFR 1.821. See 1.a.iii and 1.b.iii below.
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821I requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a “Sequence Listing,” as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 – 1.825. This “Sequence Listing” part of the disclosure may be submitted:
In accordance with 37 CFR 1.821I(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter “Legal Framework”) as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
New or Maintained Grounds of Rejection
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 11 is 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 terms “mild” and “severe” in claim 11 are relative terms which renders the claim indefinite. The terms “mild” and “severe” 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 examiner will interpret claim 11 as “the method is used to alleviate at least one symptom”.
Response to Arguments
Applicant's arguments filed 09/29/2025 have been fully considered but they are not persuasive.
Regarding instant claim 11, applicant argues that the terms “mild” and "severe" are not vague or ambiguous in this context, because they correspond to well-established, standardized definitions set forth in clinical practice guidelines published by globally recognized authorities such as the World Health Organization (WHO). The argument is not persuasive. The applicant provided WHO definitions for “mild pneumonia” and “severe pneumonia” further rely on additional subjective “severe” qualifications such as “severe respiratory distress” or “very severe chest indrawing” and the definition for “mild pneumonia” is relative to the disease being “not severe pneumonia”. Further, instant claim 11 is not restricted to just pneumonia as the illness, but can encompass any illness associated with a coronavirus infection, therefore, the WHO definition for “mild” and “severe” pneumonia are insufficient to define the terms “mild” and “severe” in the absence of a definition in the instant disclosure.
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 2-10, and 12-14 are rejected under 35 U.S.C. 103 as being unpatentable over Einav et al. (US 8,895,598 B2, published November 25, 2014, see PTO-892 dated 06/27/2025) and Wang et al. (Cell Research, published February 4, 2020, see PTO-892 dated 06/27/2025).
Einav is drawn to compositions, pharmaceutical compositions, and methods of treating a host infected with a virus from the Flaviviridae family of viruses (abstract). Einav teaches the combination therapy of nitazoxanide, ribavirin, and pegylated interferon (column 88, lines 12-14). The pharmaceutical composition may have the compounds present in the form of its pharmaceutically acceptable salts (paragraph 2, lines 22-23). Einav further teaches a triple combination therapy during the treatment interval, including treatment with clemizole plus nitazoxanide, treatment with clemizole followed by nitazoxanide, and treatment with clemizole followed by nitazoxanide plus ribavirin. One of ordinary skill in the art would understand that in a combination therapy, the compounds would necessarily be administered either simultaneously or sequentially. Einav further teaches that the pharmaceutical compositions can be administered to patients in a number of different routes including oral, inhalation, parenteral, intramuscular, and subcutaneous (column 7, lines 41-44). Routes of administration may be combined or adjusted depending upon the agent and/or the desired effect (column 108, lines 50-52).
Einav does not teach the method of treating a coronavirus infection or a disease or a condition caused by a coronavirus infection.
Wang is drawn to the study of antiviral agents for SARS-CoV-2. Wang teaches that several drugs such as ribavirin have been used in patients with SARS or MERS. Wang evaluated the antiviral efficiency of ribavirin and nitazoxanide against a clinical isolate of SARS-CoV-2. Wang teaches that SARS-CoV-2 can cause pneumonia and is closely related to severe acute respiratory syndrome CoV (SARS-CoV) (column 1, page 269).
It would have been prima facie obvious to combine the teachings of Einav and Wang before the effective filing date of the claimed invention by modifying the method of treating a virus from the Flaviviridae family of viruses with the composition containing both ribavirin and nitazoxanide administered either orally or by inhalation, or a combination of orally and inhalation to meet the limitations of instant claim 14, as taught by Einav to treat SARS-CoV-2 as taught by Wang to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to apply the method of administering the composition of Einav containing ribavirin and nitazoxanide to treat Flaviviridae viruses with the routes of administration as taught by Einav to administer it to a subject with SARS-CoV-2 because Wang teaches that both ribavirin and nitazoxanide have antiviral efficiency against SARS-CoV-2. One of ordinary skill in the art would have a reasonable expectation of success because Einav teaches the combination therapy of ribavirin and nitazoxanide for viral treatment, oral and inhalation administration, and that the of routes of administration can be combined and Wang teaches that both compounds have antiviral efficiency against SARS-CoV-2.
Claims 11 and 15-17 are rejected under 35 U.S.C. 103 as being unpatentable over Einav et al. (US 8,895,598 B2, published November 25, 2014, see PTO-892 dated 06/27/2025) and Wang et al. (Cel Research, published February 4, 2020, see PTO-892 dated 06/27/2025) as applied to claim 8 above, and further in view of Dell’Orco et al. (Cel Research, published February 4, 2020, see PTO-892 dated 06/27/2025).
The combined teachings of Einav and Wang are discussed above.
Einav further teaches that nitazoxanide could be taken up to 500 mg po BID which equals 1000 mg per day (column 88, line 43).
The combined teachings of Einav and Wang are silent about the ribavirin dosage.
Dell’Orco is drawn to the inhalable antiviral pharmaceutical compositions of ribavirin and the use of such compositions in the treatment of virally associated respiratory infections, and associated diseases and conditions (abstract). Dell’Orco teaches a method of ameliorating respiratory infection-induced exacerbations of a respiratory disorder in a subject compromising administering to the subject a therapeutically effect amount of the ribavirin composition (claim 85 page 93). Dell’Orco teaches that the respiratory disorder could be asthma (claim 93, page 94). Dell’Orco teaches that the clinical dosing regimen is 1-100 mg once per day or 1-50 mg twice per day (page 46, lines 6-8).
It would have been prima facie obvious to combine the combined teachings of Einav and Wang with the teachings of Dell’Orco before the effective filing date of the claimed invention by applying the method of administering the combination of ribavirin and nitazoxanide for coronavirus treatment as taught by the combined teachings of Einav and Wang to administer the composition for asthma treatment caused by a viral infection as taught by Dell’Orco to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to apply the method of treatment from the combined teachings of Einav and Wang to treat asthma caused by a viral infection as taught by Dell’Orco because Dell’Orco teaches that ribavirin can be used for treatment of asthma caused by a viral infection. One of ordinary skill in the art would have a reasonable expectation of success because Dell’Orco teaches that ribavirin can be used to treat asthma caused by a viral infection.
It would have been prima facie obvious to combine the combined teachings of Einav and Wang with the teachings of Dell’Orco before the effective filing date of the claimed invention by applying the method of administering the ribavirin in a total daily dose of about 20 mg to about 1200mg, a single dose of about 100 mg to 600 mg, or a single dose of about 20 mg to about 400 mg to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in to modify the ribavirin dosage because Dell‘Orco teaches that a clinical dosing regimen is 1-100 mg once per day or 1-50 mg twice per day. One of ordinary skill in the art would have a reasonable expectation of success because Dell’Orco teaches the ribavirin dosing range. In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). (MPEP § 2144.05(I)) Moreover, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). (MPEP § 2144.05(II)) “The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.” In re Peterson, 315 F.3d 1325, 1330, 65 USPQ2d 1379, 1382-83 (Fed. Cir. 2003).
Response to Arguments
Applicant's arguments filed 09/29/2025 have been fully considered but they are not persuasive.
Applicant argues that Einav requires the combination therapy to include the administration of the drug clemizole in the combination regimens. The argument is not persuasive. The instantly claimed method of treating a coronavirus infection or a disease or condition caused by a coronavirus infection does not exclude the administration of additional actives based on the use of the “comprising” in the claim. Therefore, the administration of clemizole in addition to nitazoxanide and ribavirin meets the limitations of the instantly claimed method.
Applicant argues that Wang teaches away from ribavirin for treating coronavirus. The argument is not persuasive. MPEP 2123 (II) states “Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). ‘A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use.' In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994)… Furthermore, ‘[t]he prior art' s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….' In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).” Einav teaches that ribavirin can be used in combination with nitazoxanide for the treatment of a viral infection and Wang teaches that ribavirin and nitazoxanide could be used to treat coronavirus, therefore there would have been a reasonable expectation of success in treating coronavirus infection with the combination of ribavirin and nitazoxanide.
Applicant argues that there are unexpected results when combining nitazoxanide and ribavirin. The argument is not persuasive. Table 1 shows minimal difference in CC50 or EC50 between nitazoxanide alone compared to the combined nitazoxanide and ribavirin (instant specification paragraph 0089). While the applicant shows an improved selectivity index can be used, the independent claims do not require any specific dosages. Further, the dosages claimed in dependent claims are within the ranges taught by Einav for nitazoxanide and by Dell’Orco for ribavirin. Additionally, the results are not commensurate in scope with entire claim scope as there are no results suggesting unexpected results when combining ribavirin with tizoxanide.
Applicant argues that while Dell-Orco does teach the dosage and inhalation form of ribavirin, one of ordinary skill in the art would not reasonably expect to choose ribavirin as part of a treatment towards a coronavirus infection based on the results shown by Wang. The argument is not persuasive. Wang teaches that ribavirin has been tested on SARS and MERs and that it has an EC 109.50 µM towards SARS-CoV-2. Einav teaches combining ribavirin with nitazoxanide and that ribavirin can be administered by inhalation. Dell-Orco teaches that the ribavirin can be administered by inhalation and the dosages it may be administered for treatment of asthma associated with a viral infection. Based on the combined references, one would have a reasonable expectation of success of treating a coronavirus infection with a combination treatment of nitazoxanide and ribavirin. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Conclusion
No claims are 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.
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/SAMANTHA LYNN SCHACHERMEYER/Examiner, Art Unit 1693
/JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647