DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Application
Receipt is acknowledged of Applicants’ amendment and remarks, filed on 12/16/2025, in which claims 1, 4, 16-18, 25, 27, 32, 33-34 are amended, claims 2-3, 7, 10, 14-15, 19-24, 26, 29-31, and 36-40 are canceled, and claim 42 is newly added.
Claims 1, 4-6, 8-9, 11-13, 16-18, 25, 27-28, 32-35, and 41-42 are pending and are examined on the merits herein.
Priority
The instant application is a 371 of PCT/US2021/059263 filed on 11/12/2021, which claims domestic benefit to 63/112,857, filed on 11/12/2020.
Information Disclosure Statement
The information disclosure statements (IDS) dated 12/16/2025 complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, the information disclosure statement has been considered by the examiner.
Objections and Rejections Withdrawn
Applicant’s amendment and remarks, filed 12/16/2025, with respect that the drawings are objected to because the table data in figure 2b and the residue labels in figure 5c contain illegible text has been fully considered and is persuasive, as replacement drawings have been submitted.
Applicant’s amendment and remarks, filed 12/16/2025, with respect that claims 1 and 32 are objected to because both claims 1 and 32 recite “a compound of Formula (I)” referring to two distinct chemical formula has been fully considered and is persuasive, as claim 1 has been amended to remove the limitation “provided that the compound of Formula (I) comprises at least one C4-15 alkenyl” such that the Formula (I) recitations are no longer referring to distinct formula.
This objection has been withdrawn.
Applicant’s amendment and remarks, filed 12/16/2025, with respect that claims 4 and 25 are rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention has been fully considered and is persuasive, as claim 4 has been amended to depend from claim 1 and claim 25 has been amended to list particular compounds.
This rejection has been withdrawn.
Applicant’s amendment and remarks, filed 12/16/2025, with respect that claims 27-28 and 32-35 are rejected under 35 U.S.C. 112(a) has been fully considered and is persuasive, as claims 27 and 32 have been amended to remove the scope of preventing.
This rejection has been withdrawn.
Applicant’s amendment and remarks, filed 12/16/2025, with respect that claim 25 is rejected under 35 U.S.C. 112(d) for failing to include all the limitations of the claim upon which it depends has been fully considered and is persuasive, as the scope of claim 25 has been amended to alter the scope of compounds.
This rejection has been withdrawn.
Applicant’s amendment and remarks, filed 12/16/2025, with respect that claims 1, 4-6, 8-9, 11-13, 16-17, and 25 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Park has been fully considered and is persuasive, as the scope of claim 1 has been amended to limit that the compound of Formula (I) is not broussonol E.
This rejection has been withdrawn.
Applicant’s amendment and remarks, filed 12/16/2025, with respect that claims 32 and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Rosa-Calatrava has been fully considered and is persuasive, as the scope of claim 1 has been amended to limit that the compound of Formula (I) is not apigenin.
This rejection has been withdrawn.
Applicant’s amendment and remarks, filed 12/16/2025, with respect that claim 41 is rejected under 35 U.S.C. 103 as being unpatentable over Guo has been fully considered and is persuasive, as the scope of claim 1 has been amended to limit that the compound of Formula (I) is not neobavaisoflavone.
This rejection has been withdrawn.
The following are modified or new grounds of rejection necessitated by Applicant’s amendment, in which claims 1 and 32 are amended to recite wherein the compound of Formula (I) is not any one of the group consisting of apigenin, amentoflavone, baicalin, bavachinin, broussonol E, corylifol A, gallocatechin gallate, genistein, glycyrrhisoflavone, herbacetin, hesperetin, kaempferol, kazinol A, kazinol B, luteolin, myricetin, naringenin, neobavaisoflavone, pectolinarin, puerarin, quercetin, quercetin-3-β-galactoside, and rhoifolin.
Claim Rejections - 35 USC § 112(a)
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, 4-6, 8-9, 11-13, 16-18, 27-28, 32, 35, and 41 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Claims 1 and 32 have been amended to recite wherein the compound of Formula (I) is not any one of the group consisting of apigenin, amentoflavone, baicalin, bavachinin, broussonol E, corylifol A, gallocatechin gallate, genistein, glycyrrhisoflavone, herbacetin, hesperetin, kaempferol, kazinol A, kazinol B, luteolin, myricetin, naringenin, neobavaisoflavone, pectolinarin, puerarin, quercetin, quercetin-3-β-galactoside, and rhoifolin. Thus the scope of claims 1, 4-6, 8-9, 11-13, 16-18, 27-28, 32, 35, and 41 now excludes the sub-genus of compounds of Formula I which are apigenin, amentoflavone, baicalin, bavachinin, broussonol E, corylifol A, gallocatechin gallate, genistein, glycyrrhisoflavone, herbacetin, hesperetin, kaempferol, kazinol A, kazinol B, luteolin, myricetin, naringenin, neobavaisoflavone, pectolinarin, puerarin, quercetin, quercetin-3-β-galactoside, and rhoifolin. However, this sub-genus has not been previously disclosed and thus there is no support for a claim excluding the recited sub-genus. MPEP 2163(I)(B) states that newly added claims or claim limitations must be supported in the specification through express, implicit, or inherent disclosure. MPEP 2173.05(I) states that any negative limitations or exclusionary proviso must have basis in the original disclosure and that the mere absence of a positive recitation is not basis for an exclusion.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 33 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 33 is dependent from claim 32, and recites that the compound of Formula (I) is not, among others, luteolin, quercetin-3-β-galactoside, or rhoifolin. However, claim 33 recites where in the compound is selected from, among others, luteolin, quercetin-3-β-galactoside, or rhoifolin. Thus claim 33 fails to include all the limitations of the claim upon which it depends.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
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.
Claims 27 and 28 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yang et al. (Pharmacological Research, 2020, vol. 157, article 104820; PTO-892).
Yang discloses a detailed analysis of the chemical composition and the pharmacological mechanism of Qingfei Paidu Decoction (QFPD), a clinically used Chinese medicine for treating COVID-19 patients in China (abstract) Yang teaches that QFPD comprises numerous compounds, including Baicalein (Figure 4).
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Thus Yang discloses that the known treatment of a COVID-19 infection comprising administration of Qingfei Paidu Decoction is the administration of a composition comprising Baicalein, which a compound of instant Formula (I), thereby anticipating the instant claims.
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 nonobviousness.
Claims 1, 4-6, 8-9, 11-13, 16, 18, and 27-28 are rejected under 35 U.S.C. 103 as being unpatentable over ul Qamar et al. (Journal of Pharmaceutical Analysis, 2020; PTO-892 09/16/2025) in view of Altay et al. (iScience, 2020, vol. 23, article number 101303).
Ul Qamar discloses an in silico study to gain structural insights into the SARS-CoV-2 3CLpro and to discover potent anti-COVID-19 natural compounds (paragraph bridging pages 313-314). Ul Qamar teaches that SARS-CoV-2 protease 3-chymotrypsin-like cysteine protease (3CLpro) plays a critical role in the replication of virus particles (abstract and paragraph bridging pages 313-314). Ul Qamar discloses a summary of the top ranked phytochemicals screened against SARS-CoV-2 3CLpro receptor binding site and includes the compound PubChem 11610052, shown below (Table 2).
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Ul Qamar teaches that these top phytochemicals are expected to inhibit SARS-CoV-2 3CLpro activity and hence virus replication. Ul Qamar teaches that the next step is further in-vitro and in-vivo analyses to transform these potential inhibitors into clinical drugs (paragraph bridging pages 319-320).
The teachings of ul Qamar differ from that of the instantly claimed invention in that ul Qamar provides an in silico analysis which does not exemplify modulating SARS-CoV-2 main protease or treating a COVID-19 infection in a subject.
Altay reviews the state of the art in the treatment of COVID-19n including drug repurposing and in silico studies of drug development efforts against SARS-CoV-2 (abstract). Altay teaches that earlier studies with other viruses of the Coronaviridae family have identified, among others, coronavirus main protease (Mpro, also called 3CLpro) as candidate drug targets. An appealing biological target for coronaviruses is the main protease by virtue of its crucial role in viral gene expression and replication. Virtual screening of main protease offers emergence of a powerful strategy for the rapid identification of candidate compounds from existing drugs targeting SARS-CoV. Altay describes how in silico screening followed by cell-based validation indicated that ebselen, a drug with anti-inflammatory, antioxidant, and cytoprotective activities, may be repurposed to treat COVID-19. Altay concludes that these studies audibly support the view that an antiviral compound targeting Mpro could provide a strong defense against coronavirus-associated diseases (paragraph bridging page 8-9).
One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to modulate the activity of SARS-CoV-2 main protease using the compounds of ul Qamar as well as to administer the compounds of ul Qamar to treat a SARS-CoV-2 infection, thereby arriving at the instantly claimed invention, because ul Qamar teaches that these compounds are expected to inhibit the protease of SARS-CoV-2 and directs one of ordinary skill in the art to test these compounds in the development of clinical drugs for the treatment of SARS-CoV-2 infection. One of ordinary skill in the art would have had a reasonable expectation of success in administering the compounds of ul Qamar to treat a SARS-CoV-2 infection because Altay teaches in silico studies of compounds inhibiting SARS-CoV-2 main protease as providing drugs to treat COVID-19 and ul Qamar teaches phytochemicals that are expected to inhibit SARS-CoV-2 3CLpro activity based on in silico screening.
Claims 1, 4-6, 8-9, 11-13, 16, 18, 25, 27-28, and 42 are rejected under 35 U.S.C. 103 as being unpatentable over Rasool et al. (Structural Chemistry, 2020; PTO-892) in view of Altay et al. (iScience, 2020, vol. 23, article number 101303).
Rasool discloses a study to identify effective inhibitor candidates against the main protease (Mpro) of 2019-nCoV using computational studies (abstract). Rasool teaches that Mpro is considered a potent target for developing viral inhibitor drugs toward coronavirus (paragraph bridging pages 1777-1778) and teaches that the compounds of this study can be analyzed through the experiment in the future clinical trials of drugs against 2019-nCoV (page 1782, paragraph 1). Phytochemicals were collected from various literature sites, articles, and online databases, screened through ADMET analysis, and molecular docking and DFT analysis against Mpro of 2019-nCoV was accomplished for 108 selected compounds (page 1708, paragraph 1 to paragraph bridging pages 1708-1709). Rasool teaches that all the compounds exhibited great binding properties with Mpro, and provides a list of 60 compounds which were selected after applying cut-off value of ≥ − 6.5 kcal/mol. Rasool teaches that the compounds reported in this study exhibit great potential as future drugs against Mpro of 2019-nCoV (paragraph bridging pages 1708-1709). Table 1 of Rasool discloses these 60 compounds, which include among others Osajin, Sigmoidin A, Wighteone, and Abyssinone V.
The teachings of Rasool differ from that of the instantly claimed invention in that Rasool provides an in silico analysis which does not exemplify modulating 2019-nCoV main protease or treating a COVID-19 infection in a subject.
Altay reviews the state of the art in the treatment of COVID-19n including drug repurposing and in silico studies of drug development efforts against SARS-CoV-2 (abstract). Altay teaches that earlier studies with other viruses of the Coronaviridae family have identified, among others, coronavirus main protease (Mpro, also called 3CLpro) as candidate drug targets. An appealing biological target for coronaviruses is the main protease by virtue of its crucial role in viral gene expression and replication. Virtual screening of main protease offers emergence of a powerful strategy for the rapid identification of candidate compounds from existing drugs targeting SARS-CoV. Altay describes how in silico screening followed by cell-based validation indicated that ebselen, a drug with anti-inflammatory, antioxidant, and cytoprotective activities, may be repurposed to treat COVID-19. Altay concludes that these studies audibly support the view that an antiviral compound targeting Mpro could provide a strong defense against coronavirus-associated diseases (paragraph bridging page 8-9).
One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to modulate the activity of 2019-nCoV main protease using the compounds of Rasool as well as to administer the compounds of Rasool to treat a 2019-nCoV infection, thereby arriving at the instantly claimed invention, because Rasool teaches that these compounds are expected to inhibit the main protease of 2019-nCoV and directs one of ordinary skill in the art to test these compounds in future clinical trials against 2019-nCoV infection. One of ordinary skill in the art would have a reasonable expectation of success because Rasool teaches that Mpro is considered a potent target for developing viral inhibitor drugs toward coronavirus. In addition, one of ordinary skill in the art would have had a reasonable expectation of success in administering the compounds of Rasool to treat a 2019-nCoV infection because Altay teaches in silico studies of compounds inhibiting SARS-CoV-2 main protease as providing drugs to treat COVID-19 and Rasool teaches compounds that are expected to inhibit the main protease of 2019-nCoV based on in silico screening.
Claims 1, 4-6, 8-9, 11-13, 17-18, and 27-28 are rejected under 35 U.S.C. 103 as being unpatentable over Vijayakumar et al. (Research Square, 2020; PTO-892 09/16/2025) in view of Altay et al. (iScience, 2020, vol. 23, article number 101303).
Vijayakumar discloses an in silico pharmacokinetic and molecular docking study of natural flavonoids and synthetic indole chalcones against essential proteins of SARS-CoV-2, including main protease (Mpro). Vijayakumar teaches that compounds were shown to be capable of Mpro deactivation as well as potentially lowering the efficiency of Mpro function (abstract). Forty compounds at protease regulatory sites and 30 at critical junctures are responsible for activation/shaping of the catalytic site, with 22 compounds common to both categories (page 6, paragraph 5). These compounds are shown in Figure 4, which indicates as Eriodictyol as having interactions at the regulatory sites of Mpro. Vijayakumar shows the structure of Eriodictyol in Figure 1.
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Vijayakumar teaches that the discloses flavonoids and indole chalcones can be plausible agents against SARS-CoV-2 inhibition and that in vitro studies should be implemented to understand their anti-SARS-CoV-2 properties (paragraph bridging page 8-9). Vijayakumar teaches that Eriodictyol, among others, interacts on the SARS-CoV-2 spike proteins’ key RBD and may inhibit spread to receptors limiting viral spread (page 9, paragraph 1).
The teachings of Vijayakumar differ from that of the instantly claimed invention in that Vijayakumar provides an in silico analysis which does not exemplify administration Eriodictyol to a subject or the modulation of SARS-CoV-2 main protease.
Altay reviews the state of the art in the treatment of COVID-19n including drug repurposing and in silico studies of drug development efforts against SARS-CoV-2 (abstract). Altay teaches that earlier studies with other viruses of the Coronaviridae family have identified, among others, coronavirus main protease (Mpro, also called 3CLpro) as candidate drug targets. An appealing biological target for coronaviruses is the main protease by virtue of its crucial role in viral gene expression and replication. Virtual screening of main protease offers emergence of a powerful strategy for the rapid identification of candidate compounds from existing drugs targeting SARS-CoV. Altay describes how in silico screening followed by cell-based validation indicated that ebselen, a drug with anti-inflammatory, antioxidant, and cytoprotective activities, may be repurposed to treat COVID-19. Altay concludes that these studies audibly support the view that an antiviral compound targeting Mpro could provide a strong defense against coronavirus-associated diseases (paragraph bridging page 8-9).
One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to modulate the activity of SARS-CoV-2 main protease using the Eriodictyol of Vijayakumar as well as to administer the Eriodictyol of Vijayakumar to treat a SARS-CoV-2 infection, thereby arriving at the instantly claimed invention, because Vijayakumar teaches that Eriodictyol is expected to inhibit the main protease of SARS-CoV and suggests that the disclosed compounds can be plausible agents against SARS-CoV-2, thereby suggesting the treatment of SARS-CoV-2 infection. One of ordinary skill in the art would have had a reasonable expectation of success in administering the compounds of Vijayakumar to treat a SARS-CoV-2 infection because Altay teaches in silico studies of compounds inhibiting SARS-CoV-2 main protease as providing drugs to treat COVID-19 and Vijayakumar teaches compounds that are expected to inhibit SARS-CoV-2 Mpro activity based on in silico screening.
Claims 1, 4-6, 8-9, 11-13, 17-18, and 27-28 are rejected under 35 U.S.C. 103 as being unpatentable over Nallusamy et al. (Research Square, 2020; PTO-892 09/16/2025) in view of Altay et al. (iScience, 2020, vol. 23, article number 101303).
Nallusamy discloses the investigation of phytochemicals in inhibiting major protein targets of SARS-CoV-2 (page 2, paragraph 1). Nallusamy teaches that this study has shortlisted potential phytochemicals having inhibitory activity against SARS-CoV-2 to be taken for further testing and drug formulation studies (page 9, paragraph 4). In an in silico study, small molecules 3,8’-biapigenin had significant binding activity against RNA-dependent RNA polymerase (RdRp), which is responsible for replication of COVID19 genome inside the host (page 6, paragraph 2). 3,8’-biapigenin also was ranked among the top 10 molecules for highest binding affinity against the NSP-NSP16 protein complex (page 7, paragraph 4). Nallusamy indicates that 3,8'-biapigenin was found to possess significant interactions with at least two protein targets of SARS-CoV-2 (page 8, paragraph 2). Nallusamy also teaches that, in an in silico study, 3,8'-biapigenin was shortlisted as a natural compound for inhibition of the MERS main protease (Table 4 on page 15).
The teachings of Nallusamy differ from that of the instantly claimed invention in that Nallusamy provides an in silico analysis which does not exemplify administration of 3,8'-biapigenin to a subject or the modulation of MERS-CoV main protease.
Altay reviews the state of the art in the treatment of COVID-19n including drug repurposing and in silico studies of drug development efforts against SARS-CoV-2 (abstract). Altay teaches that earlier studies with other viruses of the Coronaviridae family have identified, among others, RdRp and coronavirus main protease (Mpro, also called 3CLpro) as candidate drug targets. Altay describes how in silico screening followed by cell-based validation indicated that ebselen, a drug with anti-inflammatory, antioxidant, and cytoprotective activities, may be repurposed to treat COVID-19 (paragraph bridging page 8-9).
One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to modulate the activity of MERS-CoV main protease using the 3,8'-biapigenin of Nallusamy as well as to administer the 3,8'-biapigenin of Nallusamy to treat a SARS-CoV-2 infection, thereby arriving at the instantly claimed invention, because Nallusamy teaches that 3,8'-biapigenin is expected to inhibit the main protease of MERS-CoV as well as directing one of ordinary skill in the art to test 3,8'-biapigenin – a shortlisted potential phytochemicals having inhibitory activity against SARS-CoV-2 – for drug formulation studies in the development of clinical drugs for the treatment of SARS-CoV-2 infection. One of ordinary skill in the art would have had a reasonable expectation of success in administering the compounds of Nallusamy to treat a SARS-CoV-2 infection because Altay teaches in silico studies of compounds inhibiting SARS-CoV-2 RdRp as providing drugs to treat COVID-19 and Nallusamy teaches phytochemicals that are expected to inhibit SARS-CoV-2 RdRp activity based on in silico screening.
Claims 32 and 34-35 are rejected under 35 U.S.C. 103 as being unpatentable over Nallusamy et al. (Research Square, 2020; PTO-892 09/16/2025) in view of in view of Altay et al. (iScience, 2020, vol. 23, article number 101303) and Berg et al. (WO 2008/106979 A2; PTO-892 09/16/2025).
Nallusamy discloses the investigation of phytochemicals in inhibiting major protein targets of SARS-CoV-2 (page 2, paragraph 1). Nallusamy teaches that this study has shortlisted potential phytochemicals having inhibitory activity against SARS-CoV-2 to be taken for further testing and drug formulation studies (page 9, paragraph 4). In an in silico study, small molecules 3,8’-biapigenin had significant binding activity against RNA-dependent RNA polymerase (RdRp), which is responsible for replication of COVID19 genome inside the host (page 6, paragraph 2). 3,8’-biapigenin also was ranked among the top 10 molecules for highest binding affinity against the NSP-NSP16 protein complex (page 7, paragraph 4). Nallusamy indicates that 3,8'-biapigenin was found to possess significant interactions with at least two protein targets of SARS-CoV-2 (page 8, paragraph 2). Nallusamy also teaches that, in an in silico study, 3,8'-biapigenin was shortlisted as a natural compound for inhibition of the MERS main protease (Table 4 on page 15).
The teachings of Nallusamy differ from that of the instantly claimed invention in that Nallusamy does teach the intranasal route of administration.
Altay reviews the state of the art in the treatment of COVID-19n including drug repurposing and in silico studies of drug development efforts against SARS-CoV-2 (abstract). Altay teaches that earlier studies with other viruses of the Coronaviridae family have identified, among others, RdRp and coronavirus main protease (Mpro, also called 3CLpro) as candidate drug targets. Altay describes how in silico screening followed by cell-based validation indicated that ebselen, a drug with anti-inflammatory, antioxidant, and cytoprotective activities, may be repurposed to treat COVID-19 (paragraph bridging page 8-9).
Berg teaches compositions for the treatment of viral infections (abstract), including coronavirus infections (page 31, lines 3-4). The compositions comprise purified flavonoids and one or more sugar alcohols (claim 1). Berg teaches that the compositions may be formulated for aerosol administration, particularly to the respiratory tract and including intranasal administration (page 63, lines 14-16).
One of ordinary skill in the art before the effective filing date of the claimed invention would have been motivated to administer the 3,8'-biapigenin of Nallusamy to treat a SARS-CoV-2 infection, thereby arriving at the instantly claimed invention, because Nallusamy teaches that 3,8'-biapigenin is expected to inhibit the protease of SARS-CoV-2 and directs one of ordinary skill in the art to test 3,8'-biapigenin in the development of clinical drugs for the treatment of SARS-CoV-2 infection. One of ordinary skill in the art would have had a reasonable expectation of success in administering the compounds of Nallusamy to treat a SARS-CoV-2 infection because Altay teaches in silico studies of compounds inhibiting SARS-CoV-2 RdRp as providing drugs to treat COVID-19 and Nallusamy teaches phytochemicals that are expected to inhibit SARS-CoV-2 RdRp activity based on in silico screening. Furthermore, it would have been prima facie obvious before the effective filing date of the claimed invention for one of ordinary skill in the art to intranasally administer the 3,8'-biapigenin of Nallusamy in the method of treating a SARS-CoV-2 infection suggested by Nallusamy because Berg teaches that the intranasal route is suitable for treating coronavirus infections. One of ordinary skill in the art would have had a reasonable expectation of success because Berg teaches the administration of compositions comprising flavonoids in methods of treating coronavirus infections and Nallusamy suggests the administration of 3,8'-biapigenin for the treatment of SARS-CoV-2 infection.
Claims 32-33 and 35 are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al. (Pharmacological Research, 2020, vol. 157, article 104820; PTO-892) in view of Berg et al. (WO 2008/106979 A2; PTO-892 09/16/2025).
Yang discloses a detailed analysis of the chemical composition and the pharmacological mechanism of Qingfei Paidu Decoction (QFPD), a clinically used Chinese medicine for treating COVID-19 patients in China (abstract) Yang teaches that QFPD comprises numerous compounds, including Isoschaftoside (Table S1, entry 43 on page 3 of supporting information). Thus Yang discloses that the known treatment of a COVID-19 infection comprising administration of Qingfei Paidu Decoction is the administration of a composition comprising Isoschaftoside, which a compound of instant Formula (I).
The teachings of Yang differ from that of the instantly claimed invention in that Yang does not teach the intranasal route of administration.
Berg teaches compositions for the treatment of viral infections (abstract), including coronavirus infections (page 31, lines 3-4). The compositions comprise purified flavonoids and one or more sugar alcohols (claim 1). Berg teaches that the compositions may be formulated for aerosol administration, particularly to the respiratory tract and including intranasal administration (page 63, lines 14-16).
It would have been prima facie obvious before the effective filing date of the claimed invention for one of ordinary skill in the art to intranasally administer the composition comprising Isoschaftoside in the method of treating a COVID-19 infection taught by Yang because Berg teaches that the intranasal route is suitable for treating coronavirus infections. One of ordinary skill in the art would have had a reasonable expectation of success because Berg teaches the administration of compositions comprising flavonoids in methods of treating coronavirus infections and Yang teaches the administration of the flavonoid comprising Qingfei Paidu Decoction for the treatment of COVID-19 infection.
Claim 41 is rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (Molecules, 2020; PTO-892).
Wang provides a structure activity relationship study of natural flavonoids against thrombin in a search for thrombin inhibitors to treat blood coagulation cascade and thrombotic diseases (abstract). Wang describes molecular docking of flavonoids into the active site of a thrombin model, and 42 target flavonoids where selected for further research (section 2.2). In a following in vitro study, at 4 mg/mL substrate concentration, 22 flavones inhibited thrombin with IC50 values less than 500 µM, and these flavonoids where classified as strong inhibitors. These inhibitors include, among others, scutellarein (section 2.3). The strong inhibitor scutellarein is indicated as having an IC50 of 70.8 (Table 2, entry 2), and its structure is provided in Figure S1, which is reproduced below for convenience.
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The teachings of Wang differ from that of the instantly claimed invention in that Wang does not exemplify administration of scutellarein to treat thrombosis.
However, it would have been prima facie obvious to administer scutellarein to treat a patient with thrombosis before the effective filing date of the claimed invention to arrive at the instantly claimed invention because Wang teaches that scutellarein has antithrombotic activity and that naturally occurring flavonoids with antithrombotic activities hold considerable promise as therapeutic agents against thrombosis.
Response to Arguments
Applicant's arguments filed 12/16/2025 have been fully considered but they are not persuasive.
Insofar as Applicant’s arguments are applicable to the current rejections, Applicant argues that ul Qamar only teaches that select phytochemicals are expected to inhibit SARS-CoV-2 3Clpro activity but does not teach or suggest modulating SARS-CoV-2 main protease or treating COVID-19 in a subject using the claimed compounds (page 88, paragraph 4). This is not persuasive.
As defined in the instant specification, 3-chymotrypsin-like (3CL) protease is also known as the SARS-CoV-2 main protease (page 16 line 32-page 17 line 3). Thus ul Qamar teaches compounds inhibiting SARS-CoV-2 main protease. Furthermore, as described in the above grounds of rejection ul Qamar directs one of ordinary skill in the art to test these compounds in the development of clinical drugs for the treatment of SARS-CoV-2 infection, thereby teaching and suggesting the treatment of a SARS-CoV-2 infection.
Applicant further argues that neither Nallusamy nor Berg teach or suggest the specifically claimed genus of compounds taught and exemplified by Applicant, and are insufficient to guide a person of ordinary skill in the art towards the specific functional groups which are efficacious in a method of treating a viral infection caused by a coronavirus selected from SARS-CoV, SARS-CoV-2, and MERS-CoV in a subject as required by claim 32 (page 89, paragraph 2). This is not persuasive.
The rejection of the instant claims over Nallusamy in view of Berg has been modified as necessitated by Applicant’s amendment, in which claims 1 and 32 are amended to recite wherein the compound of Formula (I) is not any one of the group consisting of apigenin, amentoflavone, baicalin, bavachinin, broussonol E, corylifol A, gallocatechin gallate, genistein, glycyrrhisoflavone, herbacetin, hesperetin, kaempferol, kazinol A, kazinol B, luteolin, myricetin, naringenin, neobavaisoflavone, pectolinarin, puerarin, quercetin, quercetin-3-β-galactoside, and rhoifolin. The instant rejection recites 3,8'-biapigenin, which is recited in the instant specification as a compound of formula I in instant claim 34, and claim 41 on page 81. Thus the instant rejection renders obvious the claimed genus of compounds.
Because Applicant’s arguments are not persuasive, the instant claims are rejected for the reasons of record with modifications made to account for the claim amendments filed 12/16/2025.
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 extension fee 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 date of this final action.
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/S.G.H./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693
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