COMPOSITION AND METHOD FOR TREATING COVID-19

§102 §103

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 Status of Application/Amendment/Claims Applicant's response filed 06/10/2026 has been considered. Rejections and/or objections not reiterated from the previous office action mailed 10/27/2023 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action. With entry of the amendment filed on 06/10/2026, claims 1, 2, 6, 7, 8, 12-16, 19 and 20 are pending and currently under examination. The 103 and 112(a) Written Description rejection are withdrawn in response to claim amendments. The Petition to Accept Color Drawings filed 06/01/2026 has not been decided so the Objection is maintained for the reasons of record. Maintained Rejections and Objections Drawings Color photographs and color drawings filed on 10/27/2023 are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via EFS-Web or three sets of color drawings or color photographs, as appropriate, if not submitted via EFS-Web, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification: The patent or application file contains at least one drawing executed in color (Fig. 5B). Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee. Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2). Double Patenting The rejection of claims 1-20 provisionally rejected under the judicially created doctrine of double patenting over claims 1 and 4-17 of co-pending Application No. 18,389,272 is maintained for the reasons of record. Applicant has requested this this rejection be held in abeyance until allowable subject matter is indicated. New Claim Rejections and Objections- necessitated by claim amendments Claim Objections The amended claims are objected to because of the following informalities: The claim amendments are in light ink and would not be capable of clearly being scanned. 37 CFR § 1.52 requires all application papers, claims, and amendments to be written or printed in permanent dark ink or its equivalent. Submitting claims typed or printed in "light ink" violates formal standards because it fails to ensure long-term legibility and reliable electronic scanning. Appropriate correction is required. 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 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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, 7, 8, 13-16 and 20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ullah et al. "(Nanoparticles‐assisted delivery of antiviral‐siRNA as inhalable treatment for human respiratory viruses: a candidate approach against SARS‐COV‐2." Nano Select 1.6 (2020): 612-621 of record 892 03/26/26), Xie et al. ("A polyethylenimine‐linoleic acid conjugate for antisense oligonucleotide delivery." BioMed research international 2013.1 (2013): 710502), Miyagishi et al. (Antisense and Nucleic Acid Drug Development, 2003, 13:1-7) and Amin et al. ("Protease targeted COVID-19 drug discovery and its challenges: Insight into viral main protease (Mpro) and papain-like protease (PLpro) inhibitors." Bioorganic & medicinal chemistry 29 (2021): 115860 of record 892 03/26/26). Claim interpretations: The limitations of siUTR, siLPro and siMPro are not defined in the specification and are interpreted as the siRNA that target 5 ′-untranslated region (UTR), protease (Mpro) and papain-like protease (PLpro) in view of Amin et al cited above. The claims have been amended to recite at least one therapeutic agent selected from a PPAR gamma agonists or a siRNA targeted conserved regions of SARS CoV-2 virus or a combination of both. Regarding claims 1, 2 and 13, Ullah et al. teach a SARS-CoV-2 targeted siRNA therapy for COVID-19 is emerging as an efficient therapy (see page 614). Ullah et al. teach siRNA are negatively charged and unstable and the in vivo delivery of siRNA is still a major obstacle in therapeutic applications. Ullah et al. teach adenoviruses have been used as a siRNA carrier to ensure siRNA protection and the retention of their biological activity. But a major problem associated with viral based delivery has been immuno-response against the administered virus and, in some viral vector-like lentivirus, random insertion in chromosomes leading to gene dysfunctions. Therefore, efficient, non-toxic, biocompatible and targeted delivery methods remain an urgent goal (see page 614 section 4). Ullah et al. teach nanoencapsulation of the antiviral siRNA are becoming successful as delivery methods which address the current challenges of stability and fragile nature of siRNA (see page 616). Ullah et al. teach siRNA as nanoparticles can be used to develop inhalable treatments for SARs (see abstract). Ullah et all do not specifically teach using a targeted nanoparticle comprising a linoleic acid. Regarding the limitation of claim 1 reciting the targeting moiety is a linoleic acid, Xie et al. teach a nanoparticle conjugated with a linoleic acid was an efficient carrier of inhibitory oligonucleotides, such as an antisense oligonucleotide (see abstract). Xie et al. teach this nanoparticle delivered the antisense oligonucleotide that was capable of downregulation of protein expression (Figures 6 and 7). Xie et al. teach this nanoparticle conjugated with a linoleic acid is a promising agent for delivery of antisense oligonucleotides. It would have been obvious to use the nanoparticle conjugated with a linoleic acid with the siRNA taught by Ullah et al. to increase the efficiency of delivery of siRNA given Ullah et al. teach nanoencapsulation of the antiviral siRNA are becoming successful as delivery methods which address the current challenges of stability and fragile nature of siRNA (see page 616). The prior art teach ASO and siRNA are functionally equivalent. Miyagishi et al. teach that ASO and siRNAs can be designed to be targeted to the same target sites with a reasonable expectation to observe reduced target expression levels with both molecules. (See siRNAs and antisense ASOs targeted to target sites 3, 4, 5, and 6 in Figure 1, wherein the ASO comprise all first 19 nucleotides of the antisense strand sequence of the siRNAs). Thus one of skill in the art would have expected to be capable of using the nanoparticle conjugated with a linoleic acid with a siRNA. In view of KSR (Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007)), one of ordinary skill in the art would have been capable of applying this known and efficient nanoparticle to siRNA that was ready for improvement, given the problems with delivery, and the results would have been predictable. Regarding the limitation of the siRNA targeting UTR, (Mpro) and papain-like protease (PLpro) of claim 1, Amin et al. teach recent studies revealed that SARS-CoV 2 has a comparable genomic pattern to other corona viruses wherein they comprise a 5 ′-untranslated region (UTR), a replicase complex for encoding non-structural proteins (nsps), spike protein (S) gene, envelope protein (E), membrane protein (M) gene, nucleocapsid protein (N) gene, 3 ′-UTR, and numerous unknown non-structural parts which provide them support against the environmental factors. 22–24 Usually, these viruses harvest several polypeptides which promote proteolytic breakdown to produce 20 additional proteins during their lifecycle. Among them two crucial proteases such as main protease (Mpro) and papain-like protease (PLpro) are vital for virus replication. Amin further teach that a tremendous effort has been spent on studying these proteases in order to discover specific inhibitors against this noxious COVID-19 (see page 115860-115861). It would have been obvious to one of ordinary skill in the art to use the siRNA of Ullah et al. and encapsulate in the nanoparticle taught by Xie et al. to target SARS-CoV 2 to treat a COVID 19 infection to ensure efficient delivery and silencing. It would have further been obvious to target the UTR, (Mpro) and papain-like protease (PLpro) because they have been found to be vital for virus replication. Regarding claims 7, 8, 14, 15 and 16, It would have been obvious to one of ordinary skill in the art to use this antiviral nanoparticle system to treat and prevent SARS CoV2 given Amin et al. (introduction) teach this virus is more contagious and more catastrophic compared to other flu-viruses with severe symptoms and given there was no specific targeted therapy against this novel virus one of skill would have wanted to try to prevent the virus from spreading. Thus in the absence of evidence to the contrary, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed. Claim(s) 6, 12 and 19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ullah et al. "(Nanoparticles‐assisted delivery of antiviral‐siRNA as inhalable treatment for human respiratory viruses: a candidate approach against SARS‐COV‐2." Nano Select 1.6 (2020): 612-621), Xie et al. ("A polyethylenimine‐linoleic acid conjugate for antisense oligonucleotide delivery." BioMed research international 2013.1 (2013): 710502), Miyagishi et al. (Antisense and Nucleic Acid Drug Development, 2003, 13:1-7), Amin et al. ("Protease targeted COVID-19 drug discovery and its challenges: Insight into viral main protease (Mpro) and papain-like protease (PLpro) inhibitors." Bioorganic & medicinal chemistry 29 (2021): 115860 of record 892 03/26/26), Ciavarella et al. ("Pharmacological (or synthetic) and nutritional agonists of PPAR-γ as candidates for cytokine storm modulation in COVID-19 disease." Molecules 25.9 (2020): 2076 of record 892 03/26/26) and Rodríguez-Pascau, Laura, et al. ("PPAR gamma agonist leriglitazone improves frataxin-loss impairments in cellular and animal models of Friedreich Ataxia." Neurobiology of Disease 148 (2021): 105162 of record 892 03/26/26). Ullah et al., Xie et al. Miyagishi et al. and Amin et al. are relied upon as above but do not teach using a PPAR-γ agonist. Ciavarella et al. teach the cytokine storm is an abnormal production of inflammatory cytokines, due to the over-activation of the innate immune response. This mechanism has been recognized as a critical mediator of influenza-induced lung disease, and it could be pivotal for COVID-19 infections. Thus, an immunomodulatory approach targeting the over-production of cytokines could be proposed for viral aggressive pulmonary disease treatment. In this regard, the peroxisome proliferator-activated receptor (PPAR)-γ, a member of the PPAR transcription factor family, could represent a potential target. Beside the well-known regulatory role on lipid and glucose metabolism, PPAR-γ also represses the inflammatory process. Similarly, the PPAR-γ agonist thiazolidinediones (TZDs), like pioglitazone, are anti-inflammatory drugs with ameliorating effects on severe viral pneumonia (see abstract). Ciavarella et al. teach PPAR-γ could be a valid option to strengthen the immune system via natural methods in order to prevent cytokine storm occurrence in the case of infections due to coronavirus (see conclusion). Pascau et al. teach Leriglitazone (5-[[4-[2-[5-(1-hydroxyethyl)pyridin-2-yl]ethoxy] phenyl]methyl]-1,3-thiazolidine-2,4-dione hydrochloride) is the hydrochloride salt of the active metabolite M4 (M-IV) of pioglitazone (Actos®, Takeda). Leriglitazone is a novel and orally bioavailable PPARγ agonist that engages the target receptor at the levels required for efficacy within the CNS (see page 105162). It would have been obvious to use a PPAR-γ agonist thiazolidinediones (TZDs) alone or in combination with a siRNA in methods of treating SARS given it was known to be pivotal for treatment of inflammatory cytokine storms in COVID infections. Given Leriglitazone is a novel and orally bioavailable PPARγ agonist and a hydrocholoride salt of pioglitazone, it would have been obvious to try this as an anti-inflammatory drug in COVID infections. Thus in the absence of evidence to the contrary, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed. Conclusion 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). 706.07(a) Final Rejection, When Proper on Second Action [R-07.2015] PNG media_image1.png 18 19 media_image1.png Greyscale Second or any subsequent actions on the merits shall be final, except where the examiner introduces a new ground of rejection that is neither necessitated by applicant’s amendment of the claims, nor based on information submitted in an information disclosure statement filed during the period set forth in 37 CFR 1.97(c) with the fee set forth in 37 CFR 1.17(p). Where information is submitted in an information disclosure statement during the period set forth in 37 CFR 1.97(c) with a fee, the examiner may use the information submitted, e.g., a printed publication or evidence of public use, and make the next Office action final whether or not the claims have been amended, provided that no other new ground of rejection which was not necessitated by amendment to the claims is introduced by the examiner. See MPEP § 609.04(b). 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. Any inquiry concerning this communication or earlier communications from the examiner should be directed to KIMBERLY CHONG at 571-272-3111. The examiner can normally be reached Monday thru Friday 9-5 pm. If attempts to reach the examiner by telephone are unsuccessful please contact the SPE for 1636 Neil Hammell at 571-272-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. 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