Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Pursuant to the amendment dated 05/05/2026, claims 1, 9, 13-16 and 19 were amended, claims 7 and 20-32 were canceled, and claim 34 was newly added. Claims 1-6, 8-19, and 33-34 are pending in the instant application and are examined on the merits herein.
Priority
This application is a National Stage Application of PCT/US2021/064983, filed on 12/22/2021 and claims benefit of 63/129,145 filed on 12/22/2020.
Withdrawn Rejections
Applicant’s amendment, filed on 05/05/2026, with respect to the rejection of claims 4, 5, 11, 14, and 15 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention, has been fully considered and is persuasive. Applicant has amended independent claims 4, 5, 11, 14, and 15 to remove the phrase “optionally”. The rejection is hereby withdrawn.
Applicant’s amendment, filed on 05/05/2026, with respect to the rejection of claims 19, 20, and 22 under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more than the judicial exception, has been fully considered and is persuasive. Applicant has canceled claims 19, 20, and 22 rendering the rejection moot. The rejection is hereby withdrawn.
Applicant’s amendment, filed on 05/05/2026, with respect to the rejection of claim 10-12 under 35 U.S.C. 102(a)(1) as being anticipated by Song et al. (Food Funct, published 06/06/2016, IDS dated 06/22/2023) as evidenced by Wang (Br J Pharmacol, published 02/01/2020, IDS dated 06/22/2023) and as evidenced by PubChem (https://pubchem.ncbi.nlm.nih.gov/compound/Acteoside, accessed 12/09/2025, published 02/25/2020, PTO-892 dated 12/16/2025), has been fully considered and is persuasive. Applicant has amended independent claim 10 to add the limitation that the that composition further comprises a hyaluronidase which is not exemplified by Song. The rejection is hereby withdrawn.
Applicant’s amendment, filed on 05/05/2026, with respect to the rejection of claims 19, 20, and 22 under 35 U.S.C. 102(a)(1) as being anticipated Chen et al. (US 2019/0107538 A1, published 03/11/2019, IDS dated 06/22/2023) and as evidenced by Nagy et al. (Front. Immunol., published 03/22/2015, PTO-892 12/16/2025), has been fully considered and is persuasive. Applicant has canceled claims 19, 20, and 22 rendering the rejection moot. The rejection is hereby withdrawn.
Applicant’s amendment, filed on 05/05/2026, with respect to the rejection of claims 2 and 12 under 35 U.S.C. 103 as being unpatentable over Chen et al. (US 2019/0107538 A1, published 03/11/2019, IDS dated 06/22/2023) and Li et al. (bioRxiv preprint, https://scholars.hkbu.edu.hk/ws/files/55629304/RO_hkbu_staff publication-6257_JA0291 91 .pdf, published 11/05/2020, IDS dated 06/22/2023), has been fully considered and is persuasive. Applicant has canceled claims 2 and 12 rendering the rejection moot. The rejection is hereby withdrawn.
Rejections Necessitated by Amendment
The following are new ground(s) necessitated by Applicants' amendment, filed on 05/05/2026, wherein instant independent claims 1 and 10 were amended to alter the breadth and scope of the claims, claims 23-28 are newly added, and wherein the remaining pending claims 3-9, 11, and 13-18 depend from said independent claims 1 and 10.
New and Modified Grounds of Rejection
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1, 3-5, 8-11, 13-14, 18, 23, 26 and 27 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (US 2019/0107538 A1, published 03/11/2019, IDS dated 06/22/2023) and Li et al. (bioRxiv preprint, https://scholars.hkbu.edu.hk/ws/files/55629304/RO_hkbu_staff publication-6257_JA0291 91 .pdf, published 11/05/2020, IDS dated 06/22/2023) and as evidenced by Nagy et al. (Front. Immunol., published 03/22/2015, PTO-892 dated 12/16/2025) and as evidenced by Garvin et al. (eLife, published 07/07/2020, PTO-892).
Chen is drawn to the evaluation of the severity of patients with flavivirus infection by blood hyaluronan levels and therapeutic agents to block the hyaluronan (title).
Chen teaches a method for treating a subject suffering from a Flavivirus infection including administering to the subject a pharmaceutical composition including one selected from the group consisting of a first pharmaceutically effective amount of a 4-methyl umbelliferone sodium salt (4-MU), a second pharmaceutically effective amount of a CD44 small interfering RNA (siRNA), a third pharmaceutically effective amount of an anti-CD44 antibody, a fourth pharmaceutically effective amount of a hyaluronidase and a combination thereof (paragraph 0021). As evidenced by Nagy, 4-MU binds to glucuronic acid instead of UDP so that HAS cannot build HA. As evidenced by Garvin, 4-MU is a potent inhibitor of HAS1, HAS2, and HAS3 (page 9). 4-MU Therefore, 4-MU meets the limitation of an agent that neutralizes HAS1. Chen discloses that CD44 small interfering RNA (siRNA) was used to inhibit the CD44 expression of the vascular endothelial cells of the dengue fever patients, and block the combination between hyaluronan and CD44. Therefore, the CD44 siRNA can be used to prepare a pharmaceutical composition (paragraph 52).
Chen does not teach the method of treating COVID-19. Chen does not teach the method of treating a viral respiratory disease.
Li is drawn to the study of the underlying mechanism of how SARS-CoV-2 interacts with its host (abstract). Li teaches that hyaluronan level in plasma of COVID-19 patients is tightly correlated with severity and high risk for acute respiratory distress syndrome (ARDS) and may act as a predictor for the progression of COVID-19. HIS antagomirs, which downregulate hyaluronan level effectively, and 4-Methylumbelliferone (4-MU), an inhibitor of hyaluronan synthesis, are potential drugs to relieve the ARDS related ground-glass pattern in lung for COVID-19 treatment. Li teaches that
unprecedented HIS elements of SARS-CoV-2 contribute to the cytokine storm and ARDS in COVID-19 patients. Thus, blocking HIS-involved activating processes or hyaluronan synthesis directly by 4-MU may be effective strategies to alleviate COVID-19 progression (page 2). Li teaches that the accumulation of hyaluronan in the lung has been recognized in ARDS for more than three decades (page 6). Higher level of hyaluronan in severe patients’ plasma suggests hyaluronan may act as a
predictor of COVID-19 progression (page 8). Li teaches that 4-MU downregulated hyaluronan and may block the progression of COVID-19 (page 8).
It would have been prima facie obvious to combine the teachings of Chen and Li before the effective filing date of the claimed invention by applying the pharmaceutical composition including one selected from the group consisting of a first pharmaceutically effective amount of a 4-MU, a second pharmaceutically effective amount of a CD44 small interfering RNA (siRNA), a third pharmaceutically effective amount of an anti-CD44 antibody, a fourth pharmaceutically effective amount of a hyaluronidase as taught by Chen to treat covid-19 as taught by Li to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to apply the pharmaceutical composition comprising 4-MU as taught by Chen to treat a virus by administering an agent to block hyaluronan to treat covid-19 because Li teaches the use of 4-MU as a treatment for covid-19. One of ordinary skill in the art would have a reasonable expectation of success because Li teaches that 4-MU is an inhibitor of hyaluronan synthesis and can be used to treat covid-19.
Claims 6, 7, 16, and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (US 2019/0107538 A1, published 03/11/2019, see IDS dated 06/22/2023) and Li et al. (bioRxiv preprint, https://scholars.hkbu.edu.hk/ws/files/55629304/RO_hkbu_staff publication-6257_JA0291 91 .pdf, published 11/05/2020, IDS dated 06/22/2023) and as evidenced by Nagy et al. (Front. Immunol., published 03/22/2015, PTO-892 dated 12/16/2025) and as evidenced by Garvin et al. (eLife, published 07/07/2020, PTO-892) as applied to claims 1 and 10 above, and further in view of Thangaraju et al. (SN Comprehensive Clinical Medicine, published 09/10/2020, PTO-892 dated 12/16/2025).
Claims 1 and 10 are rejected above.
The combined teachings of Chen and Li are discussed above.
The combined teachings of Chen and Li do not teach the composition further comprises at least one agent that neutralizes interleukin -13 (IL-13), interleukin-6 (IL-6), or Janus kinase (JAK).
Thangaraju is drawn to the study of dupilumab in approved indications of covid-19 patients (title). Thangaraju teaches that a significant anti-viral role of cells, namely, CD4+ T (production of essential specific antibodies) and CD8+ T (cytotoxic toward virus infected cells), plays a very important in balancing against the infection of SARS-CoV-2 and associated inflammation. In addition, there is major trigger for differentiation of T cells into T-helper 1 (Th1) and Th17 in series to the massive release of pro-inflammatory cytokines, namely, tumor necrosis factor (tnf β), interleukin (IL) (1, 6, 8, and 21), and monocytes chemoattractant protein-1 (MCP1) by the viral infection. So these lead to the cytokine storm that will prevent the activation of CD8+ T cells. The corona virus also seems to stimulate the secretion of IL-4 and IL- 10 (Th-2 cytokines). This in turn suppresses the inflammation mediated by T helper cell (1/17). Dupilumab inhibits the function of IL-4 and IL-13 and has been associated with a reduced infection rate in atopic dermatitis (AD) patients (page 2126). Duplimab has been cited as a safe choice of medication, which has largely been attributed to its targeted mode of action rather than widespread immunosuppression. Thangaraju teaches that with studies showing that heightened immune response and rise in levels of IL4 could potentially worsen the hyperinflammatory response, the immune-modulation by dupilumab in COVID19 might prove to be beneficial (page 2129).
It would have been prima facie obvious to combine the combined teachings of Chen and Li with the teachings of Thangaraju before the effective filing date of the claimed invention by combining dupilumab as taught by Thangaraju with the composition taught by Chen and Li for the treatment of covid-19 to arrive at the claimed invention because each composition was taught for the same purpose of treating Covid-19. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (see MPEP 2144.06. I.). One of ordinary skill in the art would have a reasonable expectation of success because Thangaraju teaches that the immune-modulation by dupilumab in COVID-19 might prove to be beneficial, Chen teaches a method of administering therapeutic agents, such as 4-MU, to block the hyaluronan to treat a viral infection, and Li teaches that 4-MU is an inhibitor of hyaluronan synthesis that may relieve the ARDS related ground-glass pattern in lung for COVID-19 treatment.
Claims 15, 24, 25, and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al. (US 2019/0107538 A1, published 03/11/2019, IDS dated 06/22/2023) and Li et al. (bioRxiv preprint, https://scholars.hkbu.edu.hk/ws/files/55629304/RO_hkbu_staff publication-6257_JA0291 91 .pdf, published 11/05/2020, IDS dated 06/22/2023) and as evidenced by Nagy et al. (Front. Immunol., published 03/22/2015, PTO-892 dated 12/16/2025) and as evidenced by Garvin et al. (eLife, published 07/07/2020, PTO-892) as applied to claims 1, 5 and 10 above, and further in view of Hellman et al. (J. Biol. Chem. , published 09/08/2020, PTO-892).
Claims 1, 5 and 10 are rejected above.
The combined teachings of Chen and Li are discussed above.
The combined teachings of Chen and Li do not teach the hyaluronidase is an ovine hyaluronidase, a bovine hyaluronidase, or a recombinant human hyaluronidase, or that the hyaluronidase is administered intranasally.
Hellman is drawn to the study of hyaluronan in lung alveoli in severe covid-19 (title). Hellman teaches that the lungs of fatal Covid-19 contain hyaluronan and that hyaluronan is involved in ARDS caused by SARS-CoV-2. Hellman teaches that reducing the presence and production of hyaluronan in the lungs is a treatment option in severe Covid-19 (abstract). Hellman teaches that intranasal administration of exogenous hyaluronidase can reduce lung HA content and restore lung function following influenza infection (page 15420). Additionally, Hellman exemplified that bovine hyaluronidase could bind to hyaluronic acid found in autopsied lung tissue from three covid-19 cases (page 15418).
It would have been prima facie obvious to combine the combined teachings of Chen and Li with the teachings of Hellman before the effective filing date of the claimed invention by selecting a bovine hyaluronidase for intranasal administration as taught by Hellman in the method of treating a coronavirus comprising administering a hyaluronidase as taught by the combined teachings of Chen and Li to arrive at the claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to select a bovine hyaluronidase for intranasal administration because Hellman teaches that reducing hyaluronan in the lungs is a treatment option in Covid-19 and that intranasal administration of exogenous hyaluronidase can reduce lung HA content and restore lung function and because the combined teachings of Chen and Li teach the administration of hyaluronidase for the treatment of a coronavirus. One of ordinary skill in the art would have a reasonable expectation of success because Hellman teaches that reducing hyaluronan in the lungs is a treatment option in Covid-19 and that intranasal administration of exogenous hyaluronidase can reduce lung HA content and restore lung function.
Response to Arguments
Applicant's arguments filed 05/05/2026 have been fully considered in so much as they apply to the amended claims but they are not persuasive.
Applicant argues that there was no motivation to combine Chen and Li as Chen is related to attempts to treat flavivirus infection while Li teaches about hyaluronan levels being correlated with covid-19 severity without showing that inhibition of CD44 is beneficial for treatment of covid-19. Applicant argues that the alleged teachings of the cited combination of references at best amount to recognition of unsolved problems and do not support the instant rejections. In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, Chen teaches a method of treating a virus that’s severity may be characterized by the levels of hyaluronan by administering a composition that can block the combination between hyaluronan and CD44, while Li teaches that higher level of hyaluronan in severe patients’ plasma suggests hyaluronan may act as a predictor of COVID-19 progression. While Chen focuses on flaviviruses and Li focuses on covid-19, for both viruses it is taught that reducing hyaluronan in the lungs is a viable treatment option. Therefore, one of ordinary skill in the art would have a reasonable expectation of success of applying the method taught by Chen that reduces hyaluronan in the lungs to the treatment of covid-19. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
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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/S.L.S./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693
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