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 .
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.
This office action is a response to applicant’s communication submitted February 16, 2024. This application is a 371 of PCT/US22/75216 filed 08/19/2022 and claims benefit to US provisional application 63/234,902 filed 08/19/2021.
Claims 9-14, 16-21, 33-34, 36, 38-39, 41-43 are pending in this application.
Claim Interpretation
Claim 9 as recited does not require the agents to be in separate compositions. Wherein a prior art reference teaches administration of a composition comprising both agents, the reference anticipates the claim. Accordingly, claim 19 which specifies additional dose of the anti-PHR agent, would be anticipated by a reference that teaches daily administration of the composition comprising both agents.
With respect to instant claim 33, which is directed to a kit and recites the phrase “for treatment of COVID-19 infection”. The Examiner notes that it is well settled that “intended use” of a composition or product, e.g., “for treatment”, will not further limit claims drawn to a composition, so long as the prior art discloses the same composition comprising the same ingredients in an effective amount, as the instantly claimed (See MPEP 2111.02 (II)).
Specification
The disclosure is objected to because of the following informalities:
In the specification “Extract (HCT)” should read “(HCT) extract” (pg. 5, para. 0028, pgs. 15-16, para. 0075-0076, pg. 32, para. 0131).
Appropriate correction is required.
Claim Objections
Claims 33, 38, 43 are objected to because of the following informalities:
In claims 33 and 38 the acronym PHR should be defined.
In claim 43 “Extract (HCT)” should read “(HCT) extract”. Appropriate correction is required.
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 11, 16, 36, 41, and 43 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 claim 11: Claim 11 recites “wherein the coronavirus infection is selected from the group consisting of include…”. The phrase “include” renders the claim indefinite because usage of the phrase “consisting of” is a closed group of alternatives, and the word “include” implies a contradiction suggesting that other unrecited elements are to be considered. The transitional term "comprising", which is synonymous with "including," "containing," or "characterized by," is inclusive or open-ended and does not exclude additional, unrecited elements or method steps (See MPEP 2111.3 (I)). The transitional phrase "consisting of" excludes any element, step, or ingredient not specified in the claim (See MPEP 2111.03 (II)). Thus using both types of transitional phrases leads to a lack in clarity in scope, rendering the claim indefinite.
Regarding claims 16 and 36: Claims 16 and 36 depend from cancelled claims, thus the metes and bounds of the invention cannot be determined. For Examination purposes, the claim will be interpreted to be dependent from claim 9 since both claims 16 and 36 are method claims. The Examiner notes that claim 16 and 36, if they were amended to be dependent from claim 9, would be substantial duplicates of one another.
Regarding claims 41: Claim 41 depends from a cancelled claim, thus the metes and bounds of the invention cannot be determined. For Examination purposes, the claim will be interpreted to be dependent from claim 38 since claim 41 is directed to a pharmaceutical composition.
Regarding claim 43: Claim 43, which depends from claim 38, recites inter alia “The pharmaceutical composition of claim 38 further defined as comprising at least four of….”. It is unclear whether the subsequent list of compounds are in addition to the at least one antiviral agent and at least one anti-PHR agent as recited by instant claim 38 (i.e. at least 2 compounds, plus 4 selected from the list), or whether the subsequent list of compounds are specific antiviral agents/ anti-PHR agents to be selected from (i.e. minimum 4 compounds whereby at least one is antiviral and at least one is anti-PHR). According to the instant specification, the compounds recited by claim 38 are anti-PHR compounds (pg. 32, para. 0131). However, some of them are also anti-viral agents, for example quercetin (pg. 13, para. 0065). It is unclear if infringement would occur with a composition comprising four of the recited compounds, or with at least one antiviral agent and one anti-PHR agent and then additionally at least four of the recited compounds. The lack of clarity renders claim 43 indefinite. The claim will be interpreted such that the list encompasses anti-viral agents/ anti-PHR compounds and four must be selected from wherein at least one is antiviral and at least one is anti-PHR.
Claim Rejections - 35 USC § 112 (d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 16, 36, 41 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 16 depends from claim 15 which is cancelled. Claim 36 depends from claim 35 which is cancelled. Claim 41 depends from claim 40 which is cancelled. Thus, claims 16, 36, 41 are rejected as being incomplete (See MPEP 608.01(n) (V)).
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 33-34, 38-39 and 43 are rejected under 35 U.S.C. 101 because the claims are directed to a natural product without significantly more.
Claim 33 is directed to a kit for treatment of COVID-19 infection, comprising:
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Claim 34 further specifies the anti-viral agent, including rutin and quercetin, which are natural products and specifies the anti-PHR agent can be rutin quercetin, or hesperidin, which are natural products Claim 38 is directed to a pharmaceutical composition comprising
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Claim 39 specifies the anti-viral agent, including rutin and quercetin, which are natural products and specifies the anti-PHR agent can be rutin quercetin, or hesperidin, which are natural products. Claim 43 further defines the composition of claim 38 to comprise four compounds including quercetin, hesperidin, tannic acid, betulinic acid, which are natural products. Claim 1 is drawn to the compound itself.
Pereira (Microorganisms, 2023, cited on PTO-892) discloses Psidium guajava extract contains tannic acid, rutin, hesperidin, and quercetin (pg. 5, figure 1).
Goc (PLOS ONE, 2021, cited on PTO-892) discloses various phenols and plant extracts can inhibit the binding of SARS-COV-2 spike protein to the hACE2 receptor, including quercetin, rutin, hesperidin, tannic acid, curcumin, licorice extract (pg. 8, para. 2, pg. 9, table 1, pg. 10, table 2).
Mohajeri (Iran J Pharm Res. 2025, cited on PTO-892) discloses curcumin is a natural compound (abstract).
The claims are directed to kits/compositions comprising nature-based products (i.e., rutin, licorice extract, androphis extract, rutin, curcumin, quercetin, hesperidin, baicalin, green tea extract, rose extract, betulinic acid, tannic acid and more), which is not markedly different from its closest naturally-occurring counterpart because there is no indication that their combination or preparation has caused the nature-based product to have any characteristics that are markedly different from the closest naturally-occurring product and the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception. The rationale for this determination is explained below:
Step 1: Determine if the claims are directed to one of the four statutory categories of patentable subject matter identified by 35 U.S.C. 101: a process, machine, manufacture or composition of matter. YES, the claims are directed to a composition of matter, which is a statutory category within at least one of the four categories of patent eligible subject matter.
Step 2A: PRONG ONE: Evaluate whether the claim recites a Judicial Exception
(e.g., law of nature, natural phenomenon, or an abstract idea). YES, the claims are product claims reciting a nature-based product (i.e., i.e., rutin, licorice extract, androphis extract, rutin, curcumin, quercetin, hesperidin, baicalin, green tea extract, rose extract, betulinic acid, tannic acid and more) which is not markedly different from the closest naturally-occurring counterpart (i.e., the individual nature-based products or plant extracts comprising the ingredients).
Note: with respect to extracts of natural products such as plants, the closest naturally-occurring counterpart is always the same compounds found in the extract, present in the non-isolated form in the source plant material. Extracts that are made simply by separating the extracted components from the non-extracted components, is a partitioning process that absent any specific chemical modification, merely separates the compounds leaving their activities unchanged.
Ingredients recited in the claims are natural products that would occur naturally; thus, the claims involve the use of judicial exceptions. There is no indication in the record of any markedly different characteristics (either structural or functional) of the composition as broadly claimed. For example, there is no evidence of record of a structural difference between the extract(s) in the claimed composition and that of their nature-based counterparts. Consequently, the claimed compositions are structurally the same as their closest naturally- occurring counterparts.
Nor is there any difference in functional characteristics. To show a marked difference, the characteristic(s) must be changed as compared it closest natural-occurring counterpart. For example, and assertion of changed functionality must be accompanied with evidence of a comparison of the claimed composition with its closest naturally-occurring counterpart and should apply to the full scope of the claim. Furthermore, inherent or innate characteristics of the naturally occurring counterpart cannot show a marked difference. Likewise, differences in the characteristics that came about or were produced independently of any effort or influence by Applicant cannot show a marked difference. The phrase “anti-viral agent” or “anti-PHR agent” are interpreted as reciting the functional properties necessarily possessed by the compound itself and therefore encompass the compound itself
Thus, there is no evidence of record to indicate that the claimed product is markedly different, structurally, chemically, functionally, than its closest naturally occurring counterpart.
PRONG TWO: Evaluate whether the judicial exception is integrated into a practical application. The claims are directed to a composition, not its practical use such as a particular treatment or prophylaxis for a disease or medical condition.
Thus the cited claims are directed to a judicial exception to patentable subject matter.
Step 2b: Determine whether the claim directed to a judicial exception provides an inventive concept. For example, the claims may recite additional elements that amount to significantly more than the judicial exception. In the instant case, NO, the claims are directed to a composition without any other components that could add significantly more to the exception. This judicial exception is not integrated into a practical application because claims 33-34, 38-39 and 43 compounds formulated as a kit or pharmaceutical composition and at least one carrier in a generic level of detail which is no more than generally linking the use of the natural product to a field of use. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because claim 33-34 implies unspecified other material in the kit, and claims 38-39 and 43 recite the agents or compounds formulated as a pharmaceutical composition with a carrier, in a generic level of detail that would have been well-understood, routine, or conventional activity in the pertinent field of art concerning compounds or agents having a biological activity. No other specific limitations other than what is well-understood, routine and conventional in the field at a high level of generality have been added to the claimed nature-based product (e.g., addition of well-known ingredients).
Thus, the claimed product is not eligible subject matter under current 35 USC 101 standards.
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 9-14, 18-19, 21, 33-34, 38-39, and 43 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Rath (WO 2022/173456, cited on PTO-892, filed February 15, 2021) as evidenced by Walpole (BMC Public Health 2012, cited on PTO-892).
Regarding claims 9-14, 18-19, 33-34, 38-39, and 43: Rath teaches a pharmaceutical micronutrient composition mixture D comprising ascorbate, N-acetylcysteine, theaflavins, resveratrol, cruciferous plant extracts, curcumin, quercetin, naringenin, and baicalin which mitigates, inhibits, prevents and stops diseases caused by viral infections (abstract). The middle east respiratory syndrome -related coronavirus and severe acute respiratory syndrome-related coronavirus as well as their variants and mutants affecting mammals and causing infection are successfully treated using mixture D (abstract). The pharmaceutical micronutrient composition, in one embodiment, is used to treat the human and other species with severe acute respiratory syndrome-related coronaviruses (SARSCoV-1, SARS-CoV2 and their variants) (pg. 4, para. 019). Drug formulations suitable for these administration routes can be produced by adding one or more pharmacologically acceptable carrier to the agent and then treating the micronutrient composition through a routine process known to those skilled in the art (pg. 20, para. 091). Rath teaches the mixture D was administered at 5 and 10 mcg/mL doses individually and in combinations with vitamin D (pg. 18, para. 083). Rath teaches a pharmaceutical micronutrient composition, comprising: an ascorbate in the range of 10 mg to 200,000 mg, N-acetylcysteine in the range of 2 mg to 30,000 mg, theaflavin in the range 5 mg to 3,000 mg, resveratrol in the range of 10 mg to 5,000 mg, cruciferous plant extracts in the range of 5 mg to 5,000 mg, curcumin in the range of 5 mg to 10,000 mg, quercetin in the range of 5 mg to 2,000 mg, naringenin in the range of 5 mg to 3,000 mg, polyphenol extract from green tea in the range of 1 mg to 10,000 mg, brazilin in the range of 1 mg to 5,000 mg and baicalin in the range of 5 mg to 3,000 mg (pg. 27, claim 1). Rath teaches the subject compositions may be administered once, or may be divided into a number of smaller doses to be administered at varying intervals of time, depending in part on the release rate of the compositions and the desired dosage (i.e. additional dose, pg. 25, para. 0113). Although Rath does not explicitly demonstrate continued administration, a person of ordinary skill in the art upon reading the reference would at once envisage continuing administration (i.e. additional dose) to treat the disease (See MPEP 2131.02 (III)).
Regarding claim 21: Although Rath does not teach doses in ranges of mg/kg, according to Walpole the average human body mass is 62 kg (pg. 3, col. 2, para. 2). Thus looking at the ranges provided for quercetin (antiviral) 5mg/62kg to 5000mg/62kg = approx. 0.08 mg to 81 mg/kg and baicalin (antiPHR) 5mg/62 kg to 3000 mg/62kg = approx. 0.08 mg/kg to 48 mg/kg. Thus the ranges of ingredients anticipate the claimed doses.
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 16, 36, and 41 are rejected under 35 U.S.C. 103 as being unpatentable over Rath (WO 2022/173456, cited on PTO-892, filed February 15, 2021) and Walpole (BMC Public Health 2012, cited on PTO-892) as applied to claims 9-14, 18-19, 21, 33-34, 38-39, and 43 above in view of Franco (Polymers, 2021, cited on PTO-892).
Regarding claims 16, 36 and 41: As discussed above Rath teaches treatment of SARS-COV-2 with a composition comprising the claimed agents as recited by claims 9-14, 18-19, 33-34, 38-39, and 43 above. Rath further teaches the composition can comprise rutin (pg. 3, para. 013). Rath demonstrates Rutin prevents RBD of SARS-COV-2 binding and ACE2 receptor binding (pg. 15, para. 073). Thus it would have been obvious to include in the composition given this activity.
Rath does not teach where rutin is a cyclodextrin-modified form with Beta-cyclodextrin.
However, Franco teaches the preparation of rutin (RUT)–beta-cyclodextrin (beta-CD) inclusion complexes (abstract). Franco teaches rutin (RUT) is poorly water soluble, resulting in low bioavailability (pg. 1, paras. 1-2). Franco teaches efforts have been conducted to increase rutin dissolution rate, and consequently its bioavailability (pg. 1, para. 3). Franco teaches the complexes have significant increases in dissolution rate of rutin compared to pure rutin alone (pg. 13, para. 1).
Taken together it would have been prima facie obvious to a person of ordinary skill in the art to modify the composition of Rath such that rutin is replaced with the beta-cyclodextrin modified form of rutin taught by Franco. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success as the art recognizes this as a known improvement over rutin alone, in order to increase dissolution rate, and consequently bioavailability of rutin in order to more effectively treat the infection.
Claims 17, 19-21, and 42 are rejected under 35 U.S.C. 103 as being unpatentable over Rath (WO 2022/173456, cited on PTO-892, filed February 15, 2021) and Walpole (BMC Public Health 2012, cited on PTO-892) as applied to claims 9-14, 18-19, 21, 33-34, 38-39, and 43 above in view of Borody (US 2021/0244705, IDS filed February 12, 2024)
Regarding claims 17 and 42: As discussed above Rath teaches treatment of SARS-COV-2 with a composition comprising the claimed agents as recited by claims 9-14, 18-19, 33-34, 38-39, and 43 above. Rath further teaches the composition can comprise rutin (pg. 3, para. 013). Rath demonstrates Rutin prevents RBD of SARS-COV-2 binding and ACE2 receptor binding (pg. 15, para. 073). Thus it would have been obvious to include in the composition given this activity.
Rath does not teach where the at least one anti-viral agent comprises ivermectin.
However, Borody teaches pharmaceutical compositions comprising combination of drugs for treating a corona virus or a covid-19 infection (abstract). Borody teaches the composition can comprise ivermectin in a dose between 3 to 240 mg per day (pg. 1, para. 0004). Borody teaches specific formulations comprising ivermectin (pg.24, para. 0341)
Taken together it would have been prima facie obvious to modify the composition of Rath by including an effective amount of ivermectin as taught by Borody. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success as Borody teaches ivermectin is also an effective drug against SARS-COV-2, and combination therapies for treating this condition is a known technique in the art in order to more effectively treat the infection. "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." (See MPEP 2144.06 (I)).
Regarding claims 19-21: Even if assuming for the sake argument that Rath does not explicitly teach administering an additional dose of the composition or the dosage ranges as recited by instant claims 19 and 21 respectively, claims 19 and 21 as well as claim 20 would have been rendered obvious over Borody. As discussed above, Rath and Borody teach the method teach treatment of SARS-COV-2 with a composition comprising the claimed agents as recited by claims 9-14, 17-19, 33-34, 38-39, and 42-43 above.
They do not explicitly teach wherein the additional dose of anti-PHR agent is repeated on a daily basis for a period in a range of from about 1 day to about 60 days. They do not explicitly teach wherein the dosage range of the antiviral agent is about 1ug/kg to about 100 mg/kg and the dosage range of the anti-PHR agent is about 1ug/kg to about 500 mg/kg.
However, Rath teaches a pharmaceutical micronutrient composition, comprising: an ascorbate in the range of 10 mg to 200,000 mg, N-acetylcysteine in the range of 2 mg to 30,000 mg, theaflavin in the range 5 mg to 3,000 mg, resveratrol in the range of 10 mg to 5,000 mg, cruciferous plant extracts in the range of 5 mg to 5,000 mg, curcumin in the range of 5 mg to 10,000 mg, quercetin in the range of 5 mg to 2,000 mg, naringenin in the range of 5 mg to 3,000 mg, polyphenol extract from green tea in the range of 1 mg to 10,000 mg, brazilin in the range of 1 mg to 5,000 mg and baicalin in the range of 5 mg to 3,000 mg (pg. 27, claim 1). According to Walpole the average human body mass is 62 kg (pg. 3, col. 2, para. 2). Thus looking at the ranges provided for quercetin 5mg/62kg to 5000mg/62kg = approx. 0.08 mg to 81 mg/kg and baicalin 5mg/62 kg to 3000 mg/62kg = approx. 0.08 mg/kg to 48 mg/kg. Additionally, Borody teaches specific formulations comprising ivermectin (pg.24, para. 0341). Borody teaches ivermectin can be administered for up to 20 or more days (pg. 4, para. 0050). Borody teaches the composition can comprise ivermectin in a dose between 3 to 240 mg per day ( 3mg/62kg to 240 mg/62kg = 0.048 mg/kg to 3.9 mg/kg, pg. 1, para. 0004).
Taken together, it would have been prima facie obvious to a person of ordinary skill in the art to continue administration of the composition for several days and optimize to arrive at the claimed doses/day range. A person of ordinary skill in the art would have had the motivation to do so with a reasonable expectation of success as daily administration and dose modification are routine practices in the art of treating viral infections in order to effectively treat the infection. Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature 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 MPEP 2144.05 (II)).
Conclusion
No claims are allowed in this action.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Xu (CN-111544442-A, 2020, cited on PTO-892, along with English translation) teaches rutin as a broad spectrum inhibitor for coronavirus (English translation, abstract).
Jicsinszky (Journal of Drug Delivery Science and Technology, 2021, cited on PTO-892) teaches antiviral drug cyclodextrins against SARS-COV2 (abstract).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SAMUEL L GALSTER whose telephone number is (571)270-0933. The examiner can normally be reached Monday - Friday 8:00 AM - 5:00 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Scarlett Y Goon can be reached at 571-270-5241. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SAMUEL L GALSTER/Examiner, Art Unit 1693
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