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 .
Election/Restrictions
Claims 8-10 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on September 27, 2025.
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.
Claims 1-7 are rejected under 35 U.S.C. 103 as being unpatentable over
Margolin (US 20210386779 A1, priority to April 30, 2020) and Lipp (US 20210346416 A1, priority to May 5, 2020) in view of Thallapureddy (US 20210308071 A1, published October 7, 2012), Pan (CN 1493571 A, published on May 5, 2004), Yuen et al. (US 20050215494 A1, September, 29, 2005) (“Yuen” hereunder), Theoharides (US 20070141187 A1, published June 21, 2007) and Majeed (US 5744161, April 28, 1998).
Claim 1 is directed to a composition for management of COVID-19 and associated disorders, said composition comprising:
(i) active constituents comprising:
Hesperidin in an amount ranging from 10% to 25% by weight of the active constituents;
Curcumin in an amount ranging from 15% to 35% by weight of the active constituents;
Epigallocatechin in an amount ranging from 15% to 30% by weight of the active constituents;
Rutin in an amount ranging from 10% to 25% by weight of the active constituents;
Quercetin in an amount ranging from 0.5% to 8% by weight of the active constituents;
Luteolin in an amount ranging from 1% to 10% by weight of the active constituents;
Baicalin in an amount ranging from 1% to 15% by weight of the active constituents; and
Piperine in an amount ranging from 0.03% to 3% by weight of the active constituents; and
(ii) one or more excipients.
Margolin teaches a composition for dietary enhancement of immune system function, the composition comprising zinc and zinc ionophores, which comprise quercetin, vitamins C, D and E. Zinc ionophores are said to enhance transport of zinc into human cells and also include curcumin and epigallocatechin gallate. See [0033]. The reference further teaches that quercetin has been known to have an independent antiviral activity against the COVID-19-causing coronavirus and block viruses from entering cells. See [0039]. The reference teaches that quercetin can be present in the composition in a mass ranging from 50-1500 mg. The composition can be formulated into powders, drops, suspension, capsules and tablets and administered via oral route. See [0058]. Margolin further teaches and suggests to combine additional/ancillary components, including extracts of natural products such as piper nigrum, etc. See [0045-0050].
Margolin fails to teach hesperidin, rutin, luteolin and baicalin; although the reference teaches piper nigrum, piperine, which is an extract compound from the plant, is not mentioned.
Lipp discloses a nasal spray composition comprising at least one antiviral agent and a pharmaceutically acceptable carrier for application to the respiratory tract. The composition is useful in treating virus infections including COVID-19. See abstract. The reference teaches that flavonoids such as hesperidin, epigallocatechin gallate, rutin, etc and derivatives thereof have high affinity to the spike of a virus and inhibit the activation of virus protein. See [0022-0025]. Example 1 discloses a nebulizer comprising a suspension comprising 250 mg of hesperidin in 5 ml of a 2% polysorbate 80 solution in water. The reference further teaches that the flavonoid can be used alone or in combination with other virus activation inhibitors. See reference claim 3. The reference teaches that the formulations can be solutions, emulsions, suspensions and powders and applied to the respiratory tract (e.g., nasal and/or pulmonary delivery) to target areas of high viral load in the host. See [0034-0035].
Thallapureddy discloses a gargle liquid formulation for treating upper respiratory viral associated with COVID-19, the composition comprising curcumin from curcuma longa root powder and additional immune boosting actives including piper nigrum, zinc, and others. The reference teaches that curcumin’s potent antiviral activities against COVID-19 infection including inflammation, apoptosis and RNA replication have been well documented. See [0039—0049]. The reference teaches that curcumin can be administered as high as 8-12 gm/day. See [0040]. The reference further teaches that piper nigrum improves the absorption of curcumin and teaches to include piper nigrum from 5 mg to 20 mg in the formulation. See [0050]. Thallapureddy further teaches using Coleus Amboinicus, which include “important flavonoids” such as luteolin and rutin and have antiviral/anti-inflammatory properties, and acts as a natural expectorant and relieves coughs and headaches. See [0063].
Pan teaches a synthesized luteolin metal salt and rutin useful for preventing and treating the pulmonary fibrosis. The reference teaches that luteolin is well known for treating cough and phlegm; the reference that synthetic luteolin is used due to scarcity of the natural product extraction rate. Pan further teaches that a combination of rutin and synthesized luteolin and a metal salt of luteolin is shown to have antiviral activities to inhibit transmissible gastroenteritis coronavirus and prevents or cure liver fibrosis.
Yuen teaches that baicalin is extracted and purified from the Chinese medicinal plant Scutellaria baicalensis Georgi and exhibits potent antiviral activity a. See abstract. Baicalin compounds are known for the treatment, amelioration, management or prevention of diseases associated Coronavirus in human. The reference teaches that suitable dosage ranges depend on the route of administration and the seriousness of the disease or the disorder; the reference also discloses procedures for determining efficacy of dose of therapeutic agents. See [0102]. The reference teaches an oral dose of 1.5 gm of baicalin and intravenous administration of 360 mg of baicalin. See [0070]. For intravenous administration, generally about 1-15 mg the active compound per kg body weight is recommended. See [0117].
Given the suggestions of Margolin to incorporate additional/ancillary health benefit components to the composition and the teachings of Lipp that certain flavonoids have high affinity to the spike of COVID-19 virus and inhibit the activation of the virus protein, one of ordinary skill in the art before the effective filing date of the present application would have been obviously motivated to look to other flavonoids similarly useful for same purposes to modify the teachings of Margolin. As discussed above, Lipp establishes that the flavonoids hesperidin, epigallocatechin and rutin have antiviral activities against COVID-1; Thallapureddy teaches that curcumin’s potent antiviral activities against COVID-19 infection including inflammation, apoptosis and RNA replication have been well known; Yuen teaches that baicalin compounds are known for the treatment, amelioration, management or prevention of diseases associated coronavirus and particular SARS viruses in human; Pan teaches that a combination of rutin and synthesized luteolin and a metal salt of luteolin is shown to have antiviral activities to inhibit transmissible gastroenteritis coronavirus. Thus, it would have been obvious to the person of ordinary skill in the art before the effective filing date of the present application to modify the teachings of Margolin and combine quercetin with curcumin, hesperidin, epigallocatechin, rutin, baicalin and luteolin as motivated by the above references to make a more potent antiviral composition. Since Margolin suggests that its formulation can be combined with various plant extracts for additional health benefits, and as the above compounds have been known in oral formulations, the skilled artisan would have had a reasonable expectation of successfully producing a stable oral composition with fortified antiviral activities against COVID-19 infection. See Majeed, Example 7, disclosing a beverage comprising curcumin, piperine, quercetin, rutin and hesperidin in a single formulation, which suggests compatibility of the flavonoids; US 20070141187, Example 18, disclosing table/capsule comprising rutin and luteolin.
Furthermore, since Thallapureddy teaches that piper nigrum enhances the absorption of curcumin and Majeed teaches that piperine is the active compound of the extract of piper nigrum which enhances bioavailability of nutritional compounds, the skilled artisan would have been further motivated to incorporate piperine to the above combination of the antiviral flavonoids with a reasonable expectation of success.
Regarding the concentration ranges of the ingredients, generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). In this case, the Margolin composition can comprise 50-1500 mg of quercetin; and Lipp/Thallapureddy/Pan/Yuen teach the expected health benefits of using hesperidin, curcumin, epigallocatechin, rutin, luteolin and baicalin as antiviral flavonoids. Yuen further teaches that procedures to determine the efficacy of dose of therapeutic agents is well known. Thus, finding the optimal concentrates of these flavonoids using routine experimentations would have been well within the ordinary skill in the art.
Regarding claims 2 and 3, although Margolin fails to specifically disclose the ratio of the active ingredients and the excipient, Majeed teaches capsule formulations comprising 15 mg of an active ingredient (10% beadlets, 150 mg), 5 mg of piperine (Bioperine), 250 mg of microcrystalline cellulose, a bulking agent. Such formulation would contain about 5 % of the active ingredient including piperine; in the present case, formulating an oral capsule comprising the active ingredients of the present claims within such amount in a carrier would have been prima facie obvious.
Regarding claims 4-6, Margolin further suggests tablet and oral liquid formulations including suspensions; the reference further teaches that powder formulations are mixed in liquids such as water or juice as a solvent, which suggests making a suspension. See [0058].
Claim 7 is rejected under 35 U.S.C. 103 over Margolin, Lipp, Thallapureddy, Pan, Yuen, Theoharides and Majeed as applied to claims 1-6 as above, and further in view of Kiel et al. (US 20040192618 A1, published on September 30, 2004) (“Kiel” hereunder).
Regarding claim 7, Margolin does not specifically disclose the amount of the active ingredients in an oral suspension.
Kiel suggests that oral suspensions are formulated so that ideally each 5 ml (approximately 1 teaspoon) of suspension would contain a standardized amount of an active ingredient. See [0035]. The reference teaches that approximately 0.1 – 3600 mg of gabapentin salt is formulated in 5 ml of elixirs, syrups or a preferred carrier.
Given the teachings and suggestions of Margolin to make a suspension comprising quercetin and other immunity boosting components, one of ordinary skill in the art before the effective filing date of the present application would have been obviously motivated to look to prior art such as Kiel for more specific teachings on formulating a pharmaceutical oral suspension. Since Margolin discloses that the flavonoid quercetin can be delivered in an amount of 50-1500 mg per dosage form as an antiviral agent, one of ordinary skill in the art would have used such amount as the starting point to design a suitable amount of the combined flavonoids in a composition. As Kiel teaches that an oral suspension is conventionally formulated to deliver dose in 5 ml, one of ordinary skill in the art would have been obviously motivated to incorporate the targeted dose of the combined flavonoids in 5 ml, which would result in 1-30 % w/v and approximately 1-30 % w/w, which overlaps with the presently claimed range.
Conclusion
No claims are allowed.
Zhong et al. (US 20080038382 A1, published on February 14, 2008) teach oral suspensions comprising having antiviral activity against Coronavirus, the composition comprising a total standardized extract of a Scutellariae spp, which contains baicalin as an active ingredient.
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/GINA C JUSTICE/ Primary Examiner, Art Unit 1617