Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
This Office Action is responsive to Applicant’s Amendment and Remarks, filed July 23, 2026. The amendment, filed July 23, 2026, is entered, wherein claims 1, 3, 8 – 9, 12, 16, 23, 26, 29, 38 – 39, and 41 are amended and claims 2, 4 – 7, 24 – 25, 27 – 28, 30 – 34, and 36 are canceled.
Claims 1, 3, 8 – 23, 26, 29, 35, and 37 – 41 are pending in this application and are currently examined.
Priority
This application is a domestic application, filed February 12, 2024, and claims benefit as a continuation in part of PCT/US2022/038505, filed July 27, 2022, which claims benefits of domestic application 63/233,578 and 63/337,804, filed August 16, 2021 and May 3, 2022, respectively.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/23/2026, 04/15/2026, 07/24/2026, and 08/04/2026 were filed after the mailing date of the previous Office Action on March 24, 2026. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
The following are maintained / modified grounds of rejection necessitated by Applicant’s Amendment and Remarks, filed July 23, 2026, wherein claims 1, 3, 8 – 9, 12, 16, 23, 26, 29, 38 – 39, and 41 are amended and claims 2, 4 – 7, 24 – 25, 27 – 28, 30 – 34, and 36 are canceled. Previously cited references have been used to establish the maintained / modified grounds of rejection.
Maintained / Modified 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:
i. Determining the scope and contents of the prior art.
ii. Ascertaining the differences between the prior art and the claims at issue.
iii. Resolving the level of ordinary skill in the pertinent art.
iv. Considering objective evidence present in the application indicating obviousness or
nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3, 8 – 23, 26, 29, 35, and 37 – 41 are rejected under 35 U.S.C. 103 as being unpatentable over Newman et al. (US10729735B1, August 4, 2020, first cited in the PTO-892 in October 25, 2024) in view of Kumar et al. (Pharmacognosy Reviews, 2013, Vol. 7, Issue 14, cited in PTO-892 on March 24, 2026) and Wang et al. (PLOS ONE, 2013, Vol. 8, Issue 2, cited in PTO-892 on March 24, 2026).
Newman et al. teaches a pharmaceutical composition and method for treating and/or preventing viral infection in a mammalian subject (Col. 6, lines 48 – 50), wherein “subject” is interpreted as warm blooded animals, such as cows and pigs (Col. 18, lines 36 – 38). The pharmaceutical composition is an antiviral composition comprises oleandrin (Col. 6, line 67). Oleandrin may be extracted from Nerium plant biomass using subcritical liquid carbon dioxide. (Col. 12, lines 33 – 41). The extract may comprise at least one other pharmacologically active agent, obtained along with oleandrin (Col. 12, lines 54 – 56). In some embodiments, the extract comprises one or more cardiac glycosides and one or more cardiac glycoside precursors (Col. 12, lines 66 – 67; Col. 13, line 1). The extract may further comprises alkaloid (Col. 12, line 53). The composition can be administered systemically, such as orally (Col. 11, lines 36 and 39), to the mammal in one or more therapeutically effective doses (Col. 8, lines 63 – 64) for treating viral infection that is caused by Arterviridae (should be spelled as Arteriviridae) (Col. 7, lines 5 – 6). Thus, Newman et al. teach a method of treating or preventing viral infection in cows and pigs, which corresponds to the limitation “livestock animal”, wherein the method comprising systemically administering to the animal one or more therapeutically effective doses of the antiviral comprising oleandrin. The disclosures also read on the limitations “a)” of claim 16, “alkaloid(s)” of claims 17 and 23, “an extract” of claim 18, “supercritical fluid extraction” of claim 19, “a combination of oleandrin and one or more other compounds extracted from plant biomass” of claim 20, “Nerium species” of claim 21, “one or more cardiac glycoside precursors” of claim 22, “orally” administration of claims 29, 35, 37, and 40.
Newman et al. teaches a method of treating a subject at risk of contracting a viral infection, wherein the method comprising chronically administering to the subject one or more doses of an antiviral composition on a recurring basis over an extended treatment period prior to the subject contracting the viral infection, thereby preventing the subject from contracting the viral infection (Col. 6, lines 60 – 66), which reads on the limitation “a)” of claims 38 and 41. The subject at risk of viral infection may be a subject living with other subject having viral infection (Col. 18, lines 42 – 43). The chronic administration of the antiviral composition provides relief of symptoms associated with the viral infection or amelioration of the viral infection. Thus, Newman et al. teach the method, wherein the animal has been living with other subject having viral infection, which corresponds to the limitation “sharing shelter with” the virally infected livestock animal recited in claim 8
Administration of the composition to the subject can begin immediately after infection or any time within one day to 5 days after infection or at the earliest time after definite diagnosis of infection with virus (Col. 8, lines 53 – 59). The anticipated oleandrin plasma concentration based on human clinical data will be in the range of 0.005 to about 10 ng/mL (Col. 39, lines 14 – 26). The dose of oleandrin can be about 0.2 to about 1 microg/kg body weight/day, about 0.5 to about 1.0 microg/kg body weight/day, about 0.75 to about 1.5 microg/kg body weight/day, about 1.5 to about 2.52 microg/kg body weight/day, about 2.5 to about 3.0 microg/kg body weight/day, about 3.0 to 4.0 microg/kg body weight/day or about 3.5 to 4.5 microg oleandrin/kg body weight/day (Col. 39, lines 29 – 35). Thus, Newman et al. teach the dose of the antiviral composition recited in claim 10.
In some embodiments, the cardiac glycoside is administered in at least two dosing phases: a loading phase and a maintenance phase (Col. 11, lines 23 – 25). In some embodiments, one or more doses of oleandrin are administered per day for plural days until the viral infection is cured. In other embodiments, one or more doses of cardiac glycoside are administered per day for plural days and plural weeks until the viral infection is cured. One or more doses can be administered in a day. One, two, three, four five, six, or more doses can be administered per day (Col. 10, lines 14 – 21). The treatment period can be one or more weeks, one or more months, one or more quarters, and/or one or more years (Col. 10, lines 53 – 55). Thus, Newman et al. teach that 1 – 6 or more doses of the antiviral composition may be administered per day for a treatment period of one or more weeks, one or more months, one or more quarters, and/or one or more years or until the viral infection is cured, which reads on the limitations “a)”, “b)”, and “c)” of claim 13 and the limitations of claims 14 – 15. Furthermore, Newman et al. teaches that oleandrin can be used in combination with digoxin (Col. 9, line 33).
However, Newman et al. does not explicitly teach that said viral infection is porcine reproductive and respiratory syndrome virus (PRRSV) and Newman et al. do not explicitly teach the maximum plasma concentration of oleandrin is less than about 10 ng/mL in livestock animal.
Kumar et al. teach that oleandrin, a toxic cardiac glycoside of N. oleander L., inhibits the activity of nuclear factor kappa-light-chain-enhancer of activated B chain (NF-κB) in various cultured cell lines (Abstract).
Wang et al. teach that PRRSV is an Arterivirus that has been devastating the swine industry worldwide since the late 1980s. Wang et al. disclose that activation of NF-κB is required for PRRSV replication(Abstract). By negatively regulating the NF-κB pathway, miR-125b reduces PRRSV replication (Title).
It would have been prima facie obvious for a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the method for treating viral infection comprising administering oleandrin as taught by Newman et al. into administering oleandrin to treat PRRSV infection specifically in view of Kumar et al. and Wang et al. because Newman et al. teach the use of oleandrin for treating viral infections, including infections caused by viruses of the Arteriviridae family, in mammalian subjects including pigs, Kumar et al. teach that oleandrin inhibits NF-κB activity, and Wang et al. specifically identify PRRSV as an Arterivirus and teach that activation of NF-κB is required for PRRSV replication and that suppression of NF-κB activation inhibits PRRSV replication. Thus, one of ordinary skill in the art would have been motivated to select PRRSV as the viral infection to be treated using oleandrin-containing antiviral composition of Newman et al. because PRRSV is an Arterivirus encompassed by the viral infections taught by Newman et al. and the known NF-κB inhibitory activity of oleandrin provides a mechanism directed to a pathway identified by Wang et al. as required for PRRSV replication. Accordingly, one of ordinary skill in the art would have had a reasonable expectation of success to modify the method for treating viral infection comprising administering oleandrin as taught by Newman et al. into administering oleandrin to treat PRRSV infection specifically in view of Kumar et al. and Wang et al. because the administration of oleandrin as taught by Newman eta l. would inhibit NF-κB activation and thereby suppress PRRSV replication.
Regarding the maximum plasma concentration of oleandrin of less than about 10 ng/mL recited in claims 1, 3, 9, 12, and 39, it would have been prima facie obvious for a person of ordinary skill in the art to administer the oleandrin-containing antiviral composition of Newman et al. to a livestock animal in an amount that provides a maximum plasma concentration of less than about 10 ng/mL because Newman et al. explicitly teach an anticipated oleandrin plasma concentration ranging from 0.005 to about 10 ng/mL and further teach oleandrin dosing on a body-weight basis. Although the disclosed anticipate plasma concentration is based on human clinical data, Newman et al. explicitly contemplate administration of antiviral composition to mammalian subjects, including cows and pigs. A person of ordinary skill in the art administering oleandrin to such livestock animals would have recognized that an appropriate dose would depend on the particular subject and would have routinely adjusted the administered dose to provide a therapeutically effective exposure while avoiding excessive exposure to oleandrin. In view of the teaching of an oleandrin plasma concentration ranging from 0.005 to about 10 ng/mL as an anticipated exposure associated with its antiviral treatment, one of ordinary skill in the art would have had reason to use that disclosed concentration range as a starting target and to optimize the weight-based dose for the particular livestock animal to obtain an appropriate plasma concentration within that range. Such routine optimization would have resulted in a maximum plasma concentration of oleandrin of less than about 10 ng/mL.
Responses to Applicant’s Remarks:
Applicant’s Remarks, filed July 23, 2026, have been fully considered and are found to be not persuasive.
Applicant argues that the combination of Newman et al., Kumar et al., and Wang et al. fails to teach that oleandrin’s inhibition of NF-κB would result in inhibition of PRRSV replication. Applicant relies on the previously submitted Declaration and Exhibit A and B to assert that oleandrin is ineffective against Dengue virus and Nipah virus even though these viruses also activate NF-κB. Applicant further relies on Exhibit C as indicating uncertainty regarding the relationship between oleandrin and NF-κB-dependent viral replication. Applicant therefore contends that NF-κB activation alone does not predict susceptibility to oleandrin and that oleandrin’s modulation of NF-κB would not have provided a person of ordinary skill in the art with a motivation to administer oleandrin for treating PRRSV based on Wang et al. However, the argument is not persuasive. The rejection does not rely on a general proposition that any virus associated with NF-κB activation would necessarily be susceptible to oleandrin. Instead, Newman et al. specifically teach the use of an antiviral composition comprising oleandrin for treating viral infections, including infections caused by viruses of the Arteriviridae family, in mammalian subjects including pigs, Wang et al. identify PRRSV as an Arterivirus and teach that miR-125b reduces PRRSV replication through negative regulation of the NF-κB pathway, and Kumar et al. teach that oleandrin inhibits NF-κB activity. Thus, the motivation to treat PRRSV with oleandrin is based on the combined and specific teachings of Newman et al., Kumar et al., and Wang et al. rather than merely on the fact that NF-κB may be activated during viral infection generally. Accordingly Applicant’s evidence that oleandrin is not active again Dengue virus or Nipah virus does not negate the articulate reason for administering oleandrin for treating PRRSV. Furthermore, Applicant’s evidence that oleandrin is subsequently determined to be inactive against Dengue virus and Nipah virus does not establish that a person of ordinary skill in the art, based on the prior art available before the effective filing date of the claimed invention, would have expected oleandrin to be ineffective against viruses associated with NF-κB activation. The relevant inquiry is what the prior art would have suggested to a person of ordinary skill in the art, rather than whether subsequent experimentation ultimately demonstrated that oleandrin is ineffective against particular viruses. Exhibit C relied upon by Applicant does not teach that oleandrin would be ineffective against NF-κB-dependent viral replication, but instead states that oleandrin “may” abolish viral replication of certain viruses whose replication is dependent on NF-κB. Thus, Exhibit C suggests that potential antiviral effect of oleandrin against NF-κB-dependent viral replication rather than discouraging such use. Accordingly, Applicant’s evidence that oleandrin is ultimately found to be inactive against Dengue virus and Nipah virus does not negate the motivation provided by the prior art to administer oleandrin for treating PRRSV or otherwise rebut the prima facie case of obviousness.
Applicant further agrees that the mechanism by which oleandrin inhibits NF-κB is distinct from the mechanism disclosed by Wang et al. Applicant relies on Exhibits C – E to contend that oleandrin inhibits ceramide-induced NF-κB activation through reduced processing of p105 to p50, whereas Applicant relies on Exhibit F and Wang et al. to contend that Wang’s miR-125b reduced PRRSV replication through κB-Ras-mediated inhibition of IκBβ degradation and consequent reduction of NF-κB activation. Applicant contends that, because these pathways are mechanistically distinct, a person of ordinary skill in the art would have had no reason to expect that oleandrin would achieve the same PRRSV-inhibiting result as the miR-125b of Wang et al. and therefore would not have applied oleandrin for reducing PRRSV replication based on the disclosure of Wang et al. However, the argument is not persuasive because the rejection does not require oleandrin to inhibit NF-κB through the same upstream molecular mechanism disclosed for miR-125b in Wang et al. Although Applicant asserts that oleandrin affects NF-κB through the p1-5/p50 pathway whereas miR-125b of Wang et al. acts through κB-Ras and regulation of IκB degradation, both teachings concern negative regulation of NF-κB activity. Wang et al. teach that miR-125b mediated negative regulation of the NF-κB pathway, which is associated with reduced PRRSV replication, and Kumar et al. teach that oleandrin is capable of inhibiting NF-κB activity. Therefore, the fact that NF-κB activity may be modulated through different upstream mechanisms does not eliminate the reason a person of ordinary skill in the art would have had to use an agent known to inhibit NF-κB, such as oleandrin, in the PRRSV treatment contemplated by the combined teachings of the cited references. Nor is obviousness dependent upon the prior art establishing that the proposed treatment would operate through precisely the same molecular mechanism as miR-125b of Wang et al.
Applicant additionally argues that the combination of Newman et al., Kumar et al., and Wang et al. falls to disclose, teach, or suggest the recited maximum plasma concentration of oleandrin of less than about 10 ng/mL. Applicant contends that, although Newman et al. disclose a plasma concentration ranging from 0.005 to about 10 ng/mL, the disclosed concentration is calculated based on human clinical data using an average human blood volume of five liters. Because the claims recite a maximum plasma concentration in livestock animals rather than humans, and livestock animals have different average blood volumes, Applicant argues that the human clinical data of Newman et al. cannot properly be applied to the claimed livestock animals. Applicant further contends that Kumar et al. and Wang et al. do not cure this alleged deficiency of Newman et al. However, the argument is not persuasive. Newman et al. explicitly teach administration of oleandrin to mammalian subjects, including cows and pigs, and further teach therapeutically effective doses of oleandrin, including doses expressed on body-weight basis. Newman et al. also disclose that administration of oleandrin provides plasma concentrations within a range extending below about 10 ng/mL. Although Newman et al. discuss human clinical data in connection with the disclosed plasma concentration, a person of ordinary skill in the art would have understood that administration to a livestock animal would require selection of an appropriate dose for the particular animal rather than direct application of a dose calculated for a human having a five-liter blood volume. Because Newman et al. contemplate administration to cows and pigs and provide oleandrin doses on a body-weight basis, it would have been within the ordinary skill in the art to select an appropriate dose for the livestock animal to provide a therapeutically effective plasma concentration within the disclosed range. Accordingly, the difference in average blood volume between humans and livestock animals does not establish that the recited maximum plasma concentration would have been unobvious.
Conclusion
No claim is found to be allowable.
Applicant's amendment necessitated the maintained / modified 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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/H.Y.L./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693
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