DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Current Status of 17/921,532
This Office Action is responsive to the amended claims and Applicant remarks of 02/25/2026. Claims 1-20 are pending and have been examined on the merits.
Priority
The instant application is a national stage entry of PCT/US2021/029388, international filing date April 27, 2021, which claims priority to U.S. Provisional Patent Application No. 63/017,289, filing date April 29, 2020.
Response to Applicant Remarks and Amendments
Applicants have amended claims 1, 4-8, and 17 to correct typographical errors. These amendments render the previous objections moot. The objections are withdrawn.
Regarding the rejections of claims 15 and 17 under 35 U.S.C. §102, Applicants have amended the claims to remove the poly(ADP-ribose) polymerase (PARP) inhibitors rucaparib and quercetin from the claims. Reference Altschul does not disclose other PARP inhibitors and therefore no longer anticipates the claimed compositions. These rejections are withdrawn.
Regarding the rejections under 35 U.S.C. §103, Applicants have amended claim 1 to remove tamoxifen, raloxifene, and Glycyrrhiza glabra extracts from the claimed list of intracellular steroid hormone response modifiers. Applicants assert that Ivanevski does not teach the claimed TMPRSS2 inhibitors in combination with the intracellular steroid hormone response modifiers of the claimed subject matter. Claims 16 and 18 have been amended to remove the SKP2 inhibitor niclosamide, rucaparib, and quercetin. The references relied upon for these rejections are silent on the other SKP2 inhibitors and PARP inhibitors of the amended claims. In view of these amendments the previous 103 rejections are withdrawn.
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.
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, 2, 4-7, 9, 14, 19, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Ivanevski (Ianevski, Aleksandr et al. “Expanding the activity spectrum of antiviral agents.” Drug discovery today vol. 24,5 (2019): 1224-1228. doi:10.1016/j.drudis.2019.04.006, found in IDS submitted 26 October 2022) in view of Wambier (Wambier, Carlos Gustavo, and Andy Goren. “Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is likely to be androgen mediated.” Journal of the American Academy of Dermatology vol. 83,1 (2020): 308-309. doi:10.1016/j.jaad.2020.04.032) and Johansen (Johansen, Lisa M et al. “FDA-approved selective estrogen receptor modulators inhibit Ebola virus infection.” Science translational medicine vol. 5,190 (2013): 190ra79. doi:10.1126/scitranslmed.3005471).
Determining the scope of the prior art:
Ivanevski teaches:
The most effective and tolerable broad-spectrum antivirals (BSAs) could reinforce the arsenal of available antiviral therapeutics (Abstract).
Academic institutions and pharmaceutical companies have urged the discovery and development of such BSAs to overcome time and cost issues associated with the development of virus-specific drugs and vaccines (pg. 1224, left column, first paragraph).
Another option would be to combine BSAs to obtain even broader antiviral effects. For example, a cocktail of nitazoxanide, favipiravir, and niclosamide could be developed for the treatment of infections of viruses belonging to 11 families. Such combinations could also have synergistic or additive effects on a particular viral disease and thereby increase the effectiveness and/or reduce the dosage of antiviral therapeutics. Further clinical investigations could show an effectiveness of such combination therapies and could lead to the development of novel treatment options for emerging and re-emerging viral diseases (pg. 1227, right column, third full paragraph), reading on the antiviral agents of instant claims 9 and 14, and on the methods of instant claims 19 and 20.
Glycopeptides (teicoplanin, dalbavancin, oritavancin, and telavancin) serine protease inhibitors (camostat and nafamostat), protease inhibitors (bortezomib) and niclosamide prevent endocytosis of viruses (pg. 1227, left column, first full paragraph), reading on the TMPRSS2 inhibitors of instant claims 1, 4, 5, and the SKP2 inhibitors of instant claims 2, 7.
Estrogen receptor modulators (tamoxifen and raloxifene) affect both viral binding to cells and post-binding events, including endocytosis (pg. 1227, left column, third full paragraph), reading on the intracellular steroid hormone response modifiers of instant claim 1
BSAs to overcome time and cost issues associated with the development of virus-specific drugs and vaccines (pg. 1224, left column, first paragraph); Glycyrrhizin, a sweet-tasting constituent of Glycyrrhiza glabra root, and niclosamide, an orally available immunosuppressant, i.e. drugs, vaccines and oral administration all inherently contain pharmaceutically acceptable carriers (pg. 1224, right column, first paragraph).
Figure 1 discloses lopinavir, remdesivir, chloroquine, and hydroxychloroquine as BSA agents.
Wambier teaches that TMPRSS2 expression is regulated by androgen receptor signaling and that suppression of androgen signaling (via finasteride or dustasteride) may reduce SARS-CoV-2 infectivity by decreasing TMPRSS2 expression (pg. 308, second paragraph).
Johansen teaches that clomiphene (sometimes referred to as clomifene) and tormifene are effective antiviral agents useful in the treatment of viral disease (Abstract; Discussion pg. 7, first para, left col.; pg. 7, second para, right col.; pg. 8, first para, right col.). The reference also teaches that current efforts are focused on the development of these drugs alone or in combination with other antiviral drugs for the treatment of viral disease (pg. 8, first para, right col.).
Ascertaining the differences between the prior art and the claims at issue:
Ivanevski does not explicitly teach the specific combinations of the TMPRSS2 inhibitors camostat and nafamostat with the intracellular steroid hormone response modifiers.
Wambier does not teach camostat or nafamostat explicitly, nor does it teach combination compositions.
Johansen does not teach camostat or nafamostat.
Resolving the level of ordinary skill in the pertinent art:
The artisan would have experience in antiviral drug development and host-virus biology, including a familiarity with viral entry and replication mechanisms and the pharmacological activity of small-molecule therapeutics. The artisan would be capable of selecting and combing known antiviral agents and host-targeting modulators based on their mechanisms of action and would be familiar with the use of combination therapies to achieve additive or synergistic antiviral effects. The artisan would be able to interpret mechanistic and pharmacological data to identify combinations affecting viral infection pathways, such as TMPRSS2-mediated viral entry.
Considering objective evidence present in the application indicating obviousness or nonobviousness:
In view of the teachings of the references discussed above, the artisan would have been motivated to combine a TMPRSS2 inhibitor as taught by Ivanevski with an intracellular steroid hormone response modifier such as tormifene or clomiphene, as taught by Johansen, to achieve enhanced antiviral efficacy through complementary mechanism, such as direct inhibition of TMPRSS2 activity and modulation of host pathways involved in viral entry. Such a combination would have been expected to provide additive or synergistic antiviral effects, consistent with Ivanevski’s express teaching regarding combination antiviral therapies.
Claims 1, 3, and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Ivanevski, Wambier, and Johansen in view of Guo (Guo, Tingting et al. “ADP-ribosyltransferase PARP11 modulates the interferon antiviral response by mono-ADP-ribosylating the ubiquitin E3 ligase β-TrCP.” Nature microbiology vol. 4,11 (2019): 1872-1884. doi:10.1038/s41564-019-0428-3).
Determining the scope of the prior art:
The teachings of Ivanevski, Wambier, and Johansen are found above and incorporated by reference into this rejection. The combined teachings of the references teach the limitations of claim 1.
Guo teaches:
The poly(ADP-ribose) polymerase (PARP) inhibitor rucaparib can target PARP11 to stabilize IFNAR1 and therefore exhibits efficient enhancement of IFN-I signaling and the host antiviral response (Abstract).
Rucaparib renders mice more resistant to viral infection (Abstract).
Our study clearly showed that rucaparib can target PARP11 to regulate IFNAR1 protein stability and consequently significantly enhance IFN-I antiviral efficacy (pg. 1882, left column, second full paragraph).
Ascertaining the differences between the prior art and the claims at issue:
Ivanevski, Wambier, and Johansen do not teach the use of poly(ADP-ribose) polymerase inhibitors.
Guo does not teach the BSA compositions or their treatment methods.
Resolving the level of ordinary skill in the pertinent art:
The artisan would have experience in antiviral drug development and host-virus biology, including a familiarity with viral entry and replication mechanisms and the pharmacological activity of small-molecule therapeutics. The artisan would be capable of selecting and combing known antiviral agents and host-targeting modulators based on their mechanisms of action and would be familiar with the use of combination therapies to achieve additive or synergistic antiviral effects. The artisan would be able to interpret mechanistic and pharmacological data to identify combinations affecting viral infection pathways, such as TMPRSS2-mediated viral entry.
Considering objective evidence present in the application indicating obviousness or nonobviousness:
The artisan would have been motivated to incorporate the PARP inhibitor rucaparib into a BSA composition as taught by Ivanevski in order to enhance antiviral efficacy through modulation of host immune response pathways. Such a combination would have been expected to provide improved antiviral activity consistent with Ivanevski’s teaching that combinations of antiviral agents yield additive or synergistic therapeutic effects. The combination of a known agent (rucaparib) with other agents known to treat viral infections represents a predictable variation, well within the skill of the artisan, and would have required no more than routine experimentation and optimization to arrive at a composition with enhanced antiviral properties.
Claims 1 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over Ivanevski, Wambier, and Johansen in view of Kelly (US 5,208,031) Zeligs (US 8,236,848 B2), Ho (Ho, Jin-Yuan, et al. "Characterization of the anti-influenza activity of the Chinese herbal plant Paeonia lactiflora." Viruses 6.4 (2014): 1861-1875.), and Stamets (US 9,931,316 B2).
Determining the scope of the prior art:
The teachings of Ivanevski, Wambier, and Johansen are found above and incorporated by reference into this rejection. The combined teachings of the references teach the limitations of claim 1.
Kelly teaches the use of zinc salts as anti-viral agents (Abstract).
Zeligs teaches compositions comprising Dindolymethane alone or in combination with immune potentiating steroids for the treatment of viral diseases (verrucae and HPV, see Abstract).
Ho teaches that Paeonia lactiflora is commonly used to treat viral infection (Abstract).
Stamets teaches compounds having antiviral properties and that Ganoderma lucidum anti-flu activity (Abstract, Col 4, lines 44-54).
Ascertaining the differences between the prior art and the claims at issue:
Ivanevski, Wambier, and Johansen do not teach the use of the steroid hormone response modifiers of instant claim 10.
Guo does not teach the BSA compositions or their treatment methods.
Resolving the level of ordinary skill in the pertinent art:
The artisan would have experience in antiviral drug development and host-virus biology, including a familiarity with viral entry and replication mechanisms and the pharmacological activity of small-molecule therapeutics. The artisan would be capable of selecting and combing known antiviral agents and host-targeting modulators based on their mechanisms of action and would be familiar with the use of combination therapies to achieve additive or synergistic antiviral effects. The artisan would be able to interpret mechanistic and pharmacological data to identify combinations affecting viral infection pathways, such as TMPRSS2-mediated viral entry.
Considering objective evidence present in the application indicating obviousness or nonobviousness:
The artisan would have been motivated to incorporate the steroid hormone response modifiers taught by Kelly, Zeligs, Ho, and Stamets into the BSA compositions of Ivanevski because each modifier was known in the art to possess antiviral activity. In view of Ivanevski’s teaching that BSAs and BSA containing compositions are useful for broadening antiviral coverage and improving antiviral treatment options, the artisan would have had reason to combine these antiviral modifiers with BSA compositions with a reasonable expectation that the resulting compositions would exhibit enhanced or broadened antiviral efficacy.
Claims 1, 2, and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Ivanevski, Wambier, and Johansen in view of Li (Li, Shiming, et al. "Chemistry and bioactivity of nobiletin and its metabolites." Journal of Functional Foods 6 (2014): 2-10.).
Determining the scope of the prior art:
The teachings of Ivanevski, Wambier, and Johansen are found above and incorporated by reference into this rejection. The combined teachings of the references teach the limitations of claims 1 and 2.
Li teaches:
Polymethoxyflavones (PMFs) exhibit various biological activities, such as anti-carcinogenic, anti-inflammatory, anti-viral, anti-atherogenic, and anti-diabetic properties (pg. 3, left column, first paragraph).
Nobiletin is the most prevalent flavone exclusively existing in citrus genus and particularly copious in citrus peels (pg. 3, beginning on left column, final paragraph).
Ascertaining the differences between the prior art and the claims at issue:
Ivanevski, Wambier, and Johansen does not explicitly disclose the SKP2 inhibitors of instant claim 11.
Li does not explicitly disclose the BSA compositions or treatment methods.
Resolving the level of ordinary skill in the pertinent art:
The artisan would have experience in antiviral drug development and host-virus biology, including a familiarity with viral entry and replication mechanisms and the pharmacological activity of small-molecule therapeutics. The artisan would be capable of selecting and combing known antiviral agents and host-targeting modulators based on their mechanisms of action and would be familiar with the use of combination therapies to achieve additive or synergistic antiviral effects. The artisan would be able to interpret mechanistic and pharmacological data to identify combinations affecting viral infection pathways, such as TMPRSS2-mediated viral entry.
Considering objective evidence present in the application indicating obviousness or nonobviousness:
The artisan would have been motivated to incorporate nobiletin into a BSA composition because PMF, such as nobiletin, are well known in the art to exhibit antiviral properties. Given its established antiviral efficacy, the artisan would have reasonably expected that inclusion of nobiletin in a BSA composition could enhance the overall antiviral profile and improve therapeutic outcomes. The combination of a known antiviral agent such as nobiletin with other agents known for treating viral infections represents a predictable variation, well within the skill of the artisan, and would have required no more than routine experimentation and optimization to arrive at a composition with enhanced antiviral properties
Claims 1, 3, and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Ivanevski, Wambier, Johansen, and Guo in view of Wu (Wu, W.; Li, R.; Li, X.; He, J.; Jiang, S.; Liu, S.; Yang, J. Quercetin as an Antiviral Agent Inhibits Influenza A Virus (IAV) Entry. Viruses 2016, 8, 6. https://doi.org/10.3390/v8010006).
Determining the scope of the prior art:
The teachings of Ivanevski, Wambier, Johansen, and Guo are discussed above and are incorporated by reference into this rejection. The references teach the elements of instant claims 1 and 3.
Wu teaches:
quercetin inhibited influenza infection with a wide spectrum of strains, including A/Puerto Rico/8/34 (H1N1), A/FM-1/47/1 (H1N1), and A/Aichi/2/68 (H3N2) (Abstract).
Combination applications of multiple therapeutic methods provide several advantages over the single-agent treatment, such as enhanced antiviral potency, reduced drug dosage, delayed emergence of drug resistance, and fewer side effect . Since the antiviral mechanism of quercetin was different from the commonly prescribed anti-influenza drug, it may prove to be effective when used in combination with other anti-retroviral agents (pg. 11, final full paragraph).
Ascertaining the differences between the prior art and the claims at issue:
Ivanevski, Wambier, Johansen, and Guo do not explicitly teach the PARP inhibitors of instant claim 12.
Wu does not teach the BSA compositions.
Resolving the level of ordinary skill in the pertinent art:
The artisan would have experience in antiviral drug development and host-virus biology, including a familiarity with viral entry and replication mechanisms and the pharmacological activity of small-molecule therapeutics. The artisan would be capable of selecting and combing known antiviral agents and host-targeting modulators based on their mechanisms of action and would be familiar with the use of combination therapies to achieve additive or synergistic antiviral effects. The artisan would be able to interpret mechanistic and pharmacological data to identify combinations affecting viral infection pathways, such as TMPRSS2-mediated viral entry.
Considering objective evidence present in the application indicating obviousness or nonobviousness:
The artisan would have been motivated to incorporate quercetin into a BSA composition because quercetin is well known in the art to possess antiviral properties against a wide range of viruses, including influenza. Given its established antiviral efficacy, the artisan would have reasonably expected that the inclusion of quercetin in a BSA composition could enhance the overall antiviral profile and improve therapeutic outcomes. The combination of a known antiviral agent (quercetin) with other agents already recognized for treating viral infections represents a predictable variation, well within the skill of the artisan, and would have required no more than routine experimentation and optimization to arrive at a composition with enhanced antiviral properties.
Claims 1 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Ivanevski, Wambier and Johansen in view of Prochaska (Prochaska, H J et al. “Oltipraz, a novel inhibitor of human immunodeficiency virus type 1 (HIV-1) replication.” Journal of cellular biochemistry. Supplement vol. 22 (1995): 117-25. doi:10.1002/jcb.240590815).
Determining the scope of the prior art:
The teachings of Ivanevski, Wambier, and Johansen are found above and incorporated by reference into this rejection. Ivanevski, Wambier, and Johansen teach claim 1.
Prochaska teaches the oltipraz and other antiviral 1,2-dithiole-3-thiones appear to inhibit acute HIV-1 replication by inactivating reverse transcriptase (RT). Oltipraz was able to inhibit HIV-1 replication in a chronic infection model and appears to have an additional antiviral mechanism distal to viral integration (Abstract).
Ascertaining the differences between the prior art and the claims at issue:
Ivanevski, Wambier, and Johansen do not explicitly disclose angiotensin 2 response modifiers including oltipraz.
Prochaska does not disclose the BSA compositions.
Resolving the level of ordinary skill in the pertinent art:
The artisan would have experience in antiviral drug development and host-virus biology, including a familiarity with viral entry and replication mechanisms and the pharmacological activity of small-molecule therapeutics. The artisan would be capable of selecting and combing known antiviral agents and host-targeting modulators based on their mechanisms of action and would be familiar with the use of combination therapies to achieve additive or synergistic antiviral effects. The artisan would be able to interpret mechanistic and pharmacological data to identify combinations affecting viral infection pathways, such as TMPRSS2-mediated viral entry.
Considering objective evidence present in the application indicating obviousness or nonobviousness:
The artisan would have been motivated to incorporate the angiotensin 2 response modifier oltipraz into a BSA composition because oltipraz is well known to possess antiviral properties. Given its established antiviral efficacy, the artisan would have reasonably expected that inclusion of oltipraz in a BSA composition could enhance the overall antiviral profile and improve therapeutic outcomes. The combination of a known antiviral agent such as oltipraz with other agents already recognized for treating viral infections represents a predictable variation, well within the skill of the artisan, and would have required no more than routine experimentation and optimization to arrive at a composition with enhanced antiviral properties.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Ivanevski, Wambier, Johansen, Wu, and Li.
Determining the scope of the prior art:
Ivanevski, Wambier, Johansen, Wu, and Li are discussed above and are incorporated by reference into this rejection.
Ascertaining the differences between the prior art and the claims at issue:
Ivanevski and Guo do not explicitly teach the PARP inhibitors of instant claim 12.
Wu does not teach the BSA compositions.
Resolving the level of ordinary skill in the pertinent art:
The artisan would have experience in antiviral drug development and host-virus biology, including a familiarity with viral entry and replication mechanisms and the pharmacological activity of small-molecule therapeutics. The artisan would be capable of selecting and combing known antiviral agents and host-targeting modulators based on their mechanisms of action and would be familiar with the use of combination therapies to achieve additive or synergistic antiviral effects. The artisan would be able to interpret mechanistic and pharmacological data to identify combinations affecting viral infection pathways, such as TMPRSS2-mediated viral entry.
Considering objective evidence present in the application indicating obviousness or nonobviousness:
The artisan would have been motivated to incorporate quercetin and nobiletin into a BSA composition because quercetin and nobiletin are well known in the art to possess antiviral properties against a wide range of viruses, including influenza. Given their established antiviral efficacy, the artisan would have reasonably expected that the inclusion of quercetin and nobiletin in a BSA composition could enhance the overall antiviral profile and improve therapeutic outcomes. The combination of a known antiviral agent (quercetin) with other agents already recognized for treating viral infections represents a predictable variation, well within the skill of the artisan, and would have required no more than routine experimentation and optimization to arrive at a composition with enhanced antiviral properties.
Claim 15 is rejected under 35 U.S.C. 103 as being unpatentable over Ivanevski in view of Fehr (Fehr, Anthony R., et al. "The impact of PARPs and ADP-ribosylation on inflammation and host–pathogen interactions." Genes & development 34.5-6 (2020): 341-359.), Lani (Lani, Rafidah, et al. "Antiviral activity of selected flavonoids against Chikungunya virus." Antiviral research 133 (2016): 50-61.), Vazquez-Calvo (Vázquez-Calvo, Ángela, et al. "Antiviral properties of the natural polyphenols delphinidin and epigallocatechin gallate against the flaviviruses West Nile virus, Zika virus, and dengue virus." Frontiers in microbiology 8 (2017): 1314.), Hsu (Hsu, Wen-Chan, et al. "Limonium sinense and gallic acid suppress hepatitis C virus infection by blocking early viral entry." Antiviral research 118 (2015): 139-147.), de Wit (De Wit, Emmie, et al. "Prophylactic and therapeutic remdesivir (GS-5734) treatment in the rhesus macaque model of MERS-CoV infection." Proceedings of the National Academy of Sciences 117.12 (2020): 6771-6776.), and Smither (Smither, Sophie J., et al. "Post-exposure efficacy of oral T-705 (Favipiravir) against inhalational Ebola virus infection in a mouse model." Antiviral research 104 (2014): 153-155.).
Determining the scope of the prior art:
Ivanevski is discussed above and are incorporated by reference into this rejection.
Fehr teaches that PARPs and ADP-ribosylation are involved in host-pathogen interactions and viral infections (Abstract). The reference also teaches that PARPs are involved in host antiviral responses to coronaviruses, as PARP inhibitors partially rescue the replication defect of ARH-deficient murine hepatitis virus in primary macrophages (pg. 347-348, Section: Some virus families encode for a macrodomain that reverses cellular ADP-ribosylation). Thus, the art recognized that modulation of PARP activity could affect coronavirus replication and antiviral host response.
Lani teaches that fisetin exhibits potent inhibition against Chikungunya virus (Abstract).
Vazquez-Calvo teaches that delphinin has antiviral properties against West Nile virus, Zika virus, and Dengue virus (Abstract).
Hsu teaches that gallic acid possesses antiviral activity and suppressed HCV infection and entry and was proposed as a prospective anti-HCV antiviral (Abstract).
de Wit teaches that remdesivir effectively inhibited MERS-CoV replication in respiratory tissues, and prevented the formation of lung lesions in nonhumane primate models (Abstract). The reference also teaches that it could be considered for a wider range of coronaviruses, including novel coronavirus 2019-nCoV (Abstract).
Smither teaches that favipiravir has broad antiviral activity (Abstract).
Ascertaining the differences between the prior art and the claims at issue:
Ivanevski does not explicitly teach the PARP inhibitors or viral replication inhibitors of claim 15.
Fehr, Lani, Vazquez-Calvo, Hsu, de Wit, and Smither do not teach the BSA compositions of the instant claim.
Resolving the level of ordinary skill in the pertinent art:
The artisan would have experience in antiviral drug development and host-virus biology, including a familiarity with viral entry and replication mechanisms and the pharmacological activity of small-molecule therapeutics. The artisan would be capable of selecting and combing known antiviral agents and host-targeting modulators based on their mechanisms of action and would be familiar with the use of combination therapies to achieve additive or synergistic antiviral effects. The artisan would be able to interpret mechanistic and pharmacological data to identify combinations affecting viral infection pathways, such as TMPRSS2-mediated viral entry.
Considering objective evidence present in the application indicating obviousness or nonobviousness:
Ivanevski teaches combining antiviral agents to broaden antiviral activity, Fehr teaches that PARP pathways are relevant to viral replication; and the additional cited references teach that the claimed PARP inhibitors and viral replication inhibitors are known antiviral agents. Therefore, the artisan would have been motivated to combine these known agents into a pharmaceutical composition to broaden antiviral coverage with a reasonable expectation of success.
Claim 17 is rejected under 35 U.S.C. 103 as being unpatentable over Ivanevski, Fehr, Lani, Vazquez-Calvo, Hsu, Stamets, Ho, Zeligs, and Kelly.
Determining the scope of the prior art:
The teachings of Ivanevski, Fehr, Lani, Vazquez-Calvo, Hsu, Stamets, Ho, Zeligs, and Kelly are discussed above and are incorporated by reference into this rejection.
Ascertaining the differences between the prior art and the claims at issue:
Ivanevski does not explicitly teach the PARP inhibitors or intracellular steroid hormone response modifiers of claim 17.
Fehr, Lani, Vazquez-Calvo, Hsu, Stamets, Ho, Zeligs, and Kelly do not teach the BSA compositions of the instant claim.
Resolving the level of ordinary skill in the pertinent art:
The artisan would have experience in antiviral drug development and host-virus biology, including a familiarity with viral entry and replication mechanisms and the pharmacological activity of small-molecule therapeutics. The artisan would be capable of selecting and combing known antiviral agents and host-targeting modulators based on their mechanisms of action and would be familiar with the use of combination therapies to achieve additive or synergistic antiviral effects. The artisan would be able to interpret mechanistic and pharmacological data to identify combinations affecting viral infection pathways, such as TMPRSS2-mediated viral entry.
Considering objective evidence present in the application indicating obviousness or nonobviousness:
Ivanevski teaches combining antiviral agents to broaden antiviral activity, Fehr teaches that PARP pathways are relevant to viral replication; and the additional cited references teach that the claimed PARP inhibitors and intracellular steroid response modifiers are known antiviral agents. Therefore, the artisan would have been motivated to combine these known agents into a pharmaceutical composition to broaden antiviral coverage with a reasonable expectation of success.
Claim 18 is rejected under 35 U.S.C. 103 as being unpatentable over Ivanevski, Fehr, Li, Lani, Vazquez-Calvo, and Hsu.
Determining the scope of the prior art:
The teachings of Ivanevski, Fehr, Li, Lani, Vazquez-Calvo, and Hsu are discussed above and are incorporated by reference into this rejection.
Ascertaining the differences between the prior art and the claims at issue:
Ivanevski does not explicitly teach the PARP inhibitors SKP2 inhibitors of claim 18.
Ivanevski, Fehr, Li, Lani, Vazquez-Calvo, and Hsu do not teach the BSA compositions of the instant claim.
Resolving the level of ordinary skill in the pertinent art:
The artisan would have experience in antiviral drug development and host-virus biology, including a familiarity with viral entry and replication mechanisms and the pharmacological activity of small-molecule therapeutics. The artisan would be capable of selecting and combing known antiviral agents and host-targeting modulators based on their mechanisms of action and would be familiar with the use of combination therapies to achieve additive or synergistic antiviral effects. The artisan would be able to interpret mechanistic and pharmacological data to identify combinations affecting viral infection pathways, such as TMPRSS2-mediated viral entry.
Considering objective evidence present in the application indicating obviousness or nonobviousness:
Ivanevski teaches combining antiviral agents to broaden antiviral activity, Fehr teaches that PARP pathways are relevant to viral replication; and the additional cited references teach that the claimed PARP inhibitors and SKP2 inhibitors are known antiviral agents. Therefore, the artisan would have been motivated to combine these known agents into a pharmaceutical composition to broaden antiviral coverage with a reasonable expectation of success.
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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/C.K.E./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
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