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
Preliminary amendment filed on 06/22/2023 is acknowledged. Claims 4-6, 8-9, 12, 14-16, 18, and 22 were amended. Claims 1-22 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.
Information Disclosure Statement
The information disclosure statement (IDS) dated 06/22/2023 complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, the IDS document has been placed in the application file and the information therein has been considered as to the merits.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 4, 5, 11, 14, and 15 are rejected 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.
Regarding claims 4, 5, 11, 14, and 15, the phrase "optionally" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 19, 20, and 22 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon without significantly more than the judicial exception.
The claims are evaluated below using the “Subject Matter Eligibility Test for Products and Processes” flow chart as shown in MPEP § 2106 III.
Step 1: Is the claim to a process, machine, manufacture or composition of matter?
Yes. The claims are drawn to a composition of matter which is one of the four statutory categories.
Step 2A, Prong One: Does the claim recite an abstract idea, law of nature, or natural phenomenon?
Yes, the claims are directed to a natural phenomenon. The claim(s) recite(s) “a pharmaceutical composition for use in treating coronavirus 19 (COVID-19) or another viral respiratory disease, wherein the pharmaceutical composition comprises a therapeutically effective amount of an agent that neutralizes a hyaluronan receptor and a pharmaceutically acceptable carrier” and “wherein the composition further comprises one or more additional agent selected from the group consisting of an agent that neutralizes a hyaluronan synthase (HAS), hyaluronidase, an agent that neutralizes interleukin- 13 (IL-13), an agent that neutralizes interleukin-6 (IL-6) and an agent that neutralizes Janus kinase (JAK).. As evidenced by Wang (Br J Pharmacol, published 02/01/2020, see IDS dated 06/22/2023) verbascoside binds to CD44 and suppressed its dimerization (abstract). Therefore, verbascoside neutralizes a hyaluronan receptor. Wang further teaches that verbascoside is an active compound of traditional herbal medicine that is mainly found in species in all the families of the Lamiales order (page 3010). There is no indication in the record that isolation of verbascoside results in a marked difference in structure, function or other. As such this is a product of nature exception. Ilyinshii et al. (US 20190142974 A1, published 05/16/2019, see PTO-892) teaches a pharmaceutical composition comprising a PKC inhibitor and an immunosuppressant (claim 1 and claim 2). The PKC inhibitor may be verbascoside (paragraph 0079) and the immunosuppressant may be resveratrol (paragraph 0101). As evidenced by Ma et al. (Acta Biochim Biophys Sin, published 02/03/2015, see PTO-982) resveratrol is a natural product (page 211) that inhibits IL-6 (page 210). There is no indication in the record that isolation of resveratrol results in a marked difference in structure, function or other. As such this is a product of nature exception.
Step 2A, Prong Two: Do the claims recite additional elements that integrate the judicial exception into a practical application?
No. There are no additional steps recited in the claim that integrate the judicial exceptions into a practical application. The judicial exception is not integrated into a practical application because beyond the “the pharmaceutical composition comprises a therapeutically effective amount of an agent that neutralizes a hyaluronan receptor and a pharmaceutically acceptable carrier "; the claim adds pharmaceutically acceptable carrier which the instant specification defines as a means a chemical composition with which an appropriate compound or derivative can be combined and which, following the combination, can be used to administer the appropriate compound to a subject (instant specification page 22). Regarding instant claim 20, the additional elements of a “the agent that neutralizes a hyaluronan receptor is an agent that neutralizes CD44”.
Step 2B: Does the claim recite additional elements that amount to significantly more than the judicial exception?
Regarding instant claims 19, 20 and 22, the instant claims do not recite additional elements that amount to significantly more than the judicial exception.
While instant claims 19 and 20 recites a pharmaceutical composition comprising the pharmaceutical composition comprises a therapeutically effective amount of an agent that neutralizes a hyaluronan receptor and a pharmaceutically acceptable carrier, which is met by the agent verbascoside, which is a nature-based product. The specification does not teach a combination of the natural products resulting in a markedly different characteristic. Therefore, the claims do not include additional elements that are sufficient to amount to significantly more than the product of nature exception as those additional elements were well understood, routine and conventional in the field as taught above.
While instant claim 22 recites the composition of instant claim 19 and further comprising one ore more additional agent selected from the group consisting of an agent that neutralizes a hyaluronan synthase (HAS), hyaluronidase, an agent that neutralizes interleukin-13 (IL-13), an agent that neutralizes interleuikin-6 (IL-6), and an agent that neutralizes Janus kinase (JAK), the additional agent that neutralizes IL-6 is met by resveratrol , which is a nature-based product. The specification does not teach a combination of the natural products resulting in a markedly different characteristic. Therefore, the claims do not include additional elements that are sufficient to amount to significantly more than the product of nature exception as those additional elements were well understood, routine and conventional in the field as taught above.
As the instant claims 19, 20 and 22 recites judicial exceptions that are not integrated into a practical application and recite no elements that amount to significantly more than the judicial exceptions, the claim was found to not be drawn to eligible subject matter under 35 USC 101.
Thus, the instant claims 19, 20 and 22 do not qualify as eligible subject matter.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 10-12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Song et al. (Food Funct, published 06/06/2016, see IDS dated 06/22/2023) as evidenced by Wang (Br J Pharmacol, published 02/01/2020, see 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, see PTO-892).
Song is drawn the antiviral effects of acteoside (title). Song exemplifies the administration of acteoside to H1N1-infected mice and showed that acteoside treatment decreased the lung weight/body weight ratio and reduced alveolar exudation of the H1N1-infected mice (Figure 8).
As evidenced by Wang, verbascoside binds to CD44 and suppressed its dimerization (abstract). Therefore, verbascoside neutralizes a hyaluronan receptor.
As evidenced by PubChem, verbascoside is a synonym to acteoside.
Accordingly, the instant claims are anticipated by teachings of the prior art.
Claims 19-22 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chen et al. (US 2019/0107538 A1, published 03/11/2019, see IDS dated 06/22/2023) and as evidenced by Nagy et al. (Front. Immunol., published 03/22/2015, see 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 pharmaceutical composition comprising a pharmaceutically effective amount of a 4-methyl umbelliferone sodium salt (claim 11). Chen teaches a pharmaceutical composition comprising one selected from the group consisting of a first pharmaceutically effective amount of a 4-methyl umbelliferone sodium salt, 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 (claim 15). The pharmaceutical composition further comprises one selected form the group consisting of a pharmaceutically acceptable carrier, an excipient, a diluent, an adjuvant and a combination thereof (claim 13). As evidenced by Nagy, 4-methyl umbelliferone binds to glucuronic acid instead of UDP so that HAS cannot build HA.
Regarding claim 20, 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).
Regarding claim 21, Chen discloses the pharmaceutical composition that comprises 4-methyl umbelliferone sodium salt (claim 15) and further comprises CD44 siRNA (claim 18).
Regarding claim 19, it is noted that the prior art does not teach that the composition can be used in the manner instantly claimed, for treating coronavirus 19 or another viral respiratory disease. However, the cited recitations are considered an “intended use” of the claimed composition. The “intended use” of the claimed composition does not patentably distinguish the composition, per se, since such disclosed use is inherent in the reference composition. In order to be limiting, the intended use must create a structural difference between the claimed composition and the prior art composition. In the instant case, the intended use does not create a structural difference, thus the intended use is not limiting.
Accordingly, the instant claim is anticipated by the teachings of the prior art.
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 1-5, 8-15 and 18 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, see IDS dated 06/22/2023).
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, 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).
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-methyl umbelliferone (4-MU) sodium salt, 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, see IDS dated 06/22/2023) as applied to claims 1 and 10 above, and further in view of Thangaraju et al. (SN Comprehensive Clinical Medicine, published 09/10/2020, see PTO-892).
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.
Conclusion
No claims allowed.
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/SAMANTHA LYNN SCHACHERMEYER/Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693