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 .
Priority
The present application U.S. Appln. Ser. No.: 17/923,754, Filed: November 7, 2022 is a 371 Nat. Stage Entry of WO 2021/228863 A1 Appn. (i.e., PCT/EP2021/062495, Intern.’l Filing Date: May 11, 2021, Intern.’l Pub. Date: November 18, 2021), which claims foreign priority to
EP 21168856.9, Filed: April 16, 2021 and WO 2021/228365 A1 Appln. (i.e., PCT/EP2020/063086, Intern.’l Filing Date: May 11, 2020, Intern.’l Pub. Date: November 18, 2021).
Status
This is in response to the Information Disclosure Statement Filed on November 20, 2023 in the above-identified application. Claims 1-57 are pending and under examination, claim 1 is original and claims 2-57 are newly amended in the above identified application.
Information Disclosure Statement
An Information Disclosure Statement (IDS) submitted on November 18, 2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, Information Disclosure Statements have been considered by the Examiner.
Objections to the Specification
The use of the terms “KOLLIPHOR P188” and “Lutrol F 68”, which are respective trade names or a marks used in commerce, has been noted in this application (i.e., aforementioned terms are found at [0174]-[0176], [0232]-[0234], [0284], Examples 2-5 at paras. [0293]-[0296], [0300]-[0302] in instant application identified by paragraphs from corresponding to U.S. Pat. Pub. 2023/0181485 A1). The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
[A] Claims 1, 3-18 and 20-23 are objected to under 37 CFR 1.75 as being a substantial duplicate of claim 1. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). More particularly, the difference in wording in these claims relies merely on reciting intended use limitations for an old product or structure are generally not entitled to patentable weight.
[B] Claims 10, 15 and 17, respectively, are objected to under 37 CFR 1.75 as being a substantial duplicate of claim 8. This type of objection is proper when claims are duplicates or are so similar in content that they cover the same and/or substantially overlapping subject matter, even with minor wording differences. Upon comparing claims 8, 10, 15 and 17, they were found to be identical in scope or overlapping in scope in light of the fact that each of the aforementioned claims depend from claim 1. These slight differences do not distinguish the claims as they describe the same functional limitation and corresponding structure.
[C] Claims 52 and 53, respectively, are objected to under 37 CFR 1.75 as being a substantial duplicate of each other. This type of objection is proper when claims are duplicates or are so similar in content that they cover the same and/or substantially overlapping subject matter, even with minor wording differences. Upon comparing claims 8, 10, 15 and 17, they were found to be identical in scope or overlapping in scope in light of the fact that each of the aforementioned claims depend from claim 1. These slight differences do not distinguish the claims as they describe the same functional limitation and corresponding structure.
Claims 52 and 53 are set forth as follows:
52. The cannabinoid according to claim 33, wherein the formulation, when subjected to an in vitro dissolution test in 0.1N HCl+2% CTAB following the USP paddle method, releases at least 75 wt % of the cannabinoid within 60 minutes, in preferably at least 90 wt % within 60 minutes.
53. The cannabinoid according to claim 33, wherein the formulation, when subjected to an in vitro dissolution test in 0.1N HCl+2% CTAB following the USP paddle method, releases at least 75 wt % of the cannabinoid within 45 minutes, preferably at least 85 wt % within 45 minutes.
[D] Claims 8 is objected to because of the following informalities: there is an extraneous “and” in the listing of symptoms. Appropriate correction is required.
To overcome these objections, Applicants are requested to review each of the claims, determine the significance of any additional limitations made to each subsequent claim is, consolidate and/or cancel redundant claims and/or subject matter.
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 1-57 are rejected under 35 U.S.C. 101 because the claimed invention is directed to :
non-statutory subject matter (i.e., does not fall within one of the four categories of patent eligible subject matter); and
to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. (i.e., without additional elements significantly more than the exception itself).
The instant claim(s) are directed to a natural phenomenon, which is:
the natural product cannabidiol (CBD), a product of nature; and
specifically it is unclear how a cannabidiol (CBD) natural product would come into contact or interact with SARS-CoV-2 (i.e., e.g., see claim 2).
In essence:
The claimed subject matter does not describe administration of naturally occurring cannabidiol (CBD) product, for any therapeutic purpose.
The claim fails to provide any additional elements that, either individually or as an ordered combination, amount to significantly more than the natural phenomenon itself. The claim, therefore, simply recites the natural phenomenon and does not integrate it into an inventive concept.
Merely reciting a new use for a known, naturally occurring product does not add enough to transform the claim into a patent-eligible invention; i.e., claims merely naturally occurring CBD and its inherent properties. (i.e., see MPEP § 7.05.02)
For the above reasons, the above-identified claims are rejected as being directed to patent-ineligible subject matter under 35 U.S.C. § 101.
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 1, 3-4, 9, 11-12, 16, 18-19, 22-23, 28, 30-31 and 34 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 Applicants), regards as the invention.
In general, the claims of the present invention fail to define the metes and bounds of the claimed invention due to use of indefinite, vague, ambiguous or unclear or poorly defined functional terms and/or language (i.e., such that exact scope of the claimed invention cannot be ascertained) without support from the specification within the claim itself. Claims Must Particularly Point Out and Distinctly the claimed invention. Moreover, claims identified above also lack clarity, due to unnecessary use of repetitive and/or redundant terms.
[1] Claim 1 is directed to a cannabinoid (i.e., a compound claim) which contains recitation of intended use language, which carries no patentable weight and will not be “treatment of patient suffering from an infection with SARS-CoV-2 or a subject at risk to be infected with SARS-CoV-2”
[2] Claim 7 lacks antecedent basis, clarity and is vague, ambiguous, indefinite for recitation of the phrase the treatment “is initiated during the non-severe symptomatic period”, because
Claim 1 from which claim 7 depends does not refer to any associated initiation or treatment steps, let alone “the treatment” being initiated for “the or any” non-severe symptomatic period;
While the specification states “non-severe symptomatic period” is “virus detectable” (Page 3), it remains unclear what symptoms occur during such a “non-severe symptomatic period”, other than whatever happens during that period “is not severe” and that it can encompass a broad range of symptoms. No specific criteria is set forth in the specification such that a skilled artisan would know when this period has occurred or past (i.e., what defines when the patient has moved from the non-severe symptomatic period to the severe respiratory symptomatic stage (Stage II to Stage III)?), which renders the metes and bounds of the claims indefinite.
[2] Claim 17 recites the phrase "in particular, wherein the patient suffers from adipositas", which renders the claim indefinite and ambiguous with regard to limitation scope (i.e., unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d)).
Specifically:
term 'adipositas' is not clearly defined or quantified in the specification and also that term lacks a single, universally accepted definition in the art (i.e., insufficient for defining a patient population).
phrase “in particular” implies certain things are especially important, without exclusion of other possibilities, leaving claim scope uncertain and also lacks antecedent basis (i.e., does not refer back or introduce new element(s) with definite clarity).
A person of ordinary skill in the art would not be able to determine with reasonable certainty the bounds of the claimed invention; i.e., e.g., given above definitions, with no specific metric or clinical standards associated with types of adipositas and patient population, given that it can be interpreted in various ways, such as based on different Body Mass Index (BMI) ranges, or different clinical standards of diagnosis.
To overcome this rejections, it is suggested that Applicants may amend the claims to define 'adipositas' with specific and quantifiable metrics, such as a patient population with a BMI greater than 30 kg/m² and to delete the phrase “in particular”.
[3] Claim 50 is rejected for lacking clarity and for being vague, ambiguous, indefinite for recitation of the phrase “ wherein the solid dispersion is free or essentially free of triglycerides; and/or mono- and diglycerides; and/or fatty acids.” A person of ordinary skill in the art would not be able to determine with reasonable certainty the bounds of the claimed invention is because how are “free or essentially free” components recited after that phrase actually quantifiable ; i.e., e.g., given that no specific metrics, such as amounts, percentages and the like are defined in the claim.
[5] In light of preceding number [4] above, it noted that the term “and/or” is recited in multiple sections of the instant claim set and is indefinite for introducing ambiguity into the claimed invention. Applicants are requested to review all the pending claims for the “and/or” and make amendments.
Based on the foregoing with regard to [1] to [5] supra, appropriate correction and amendment is required accordingly.
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 3-18 and 20-57 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 1 upon which it depends, or for failing to include all the limitations of the claim upon which it depends; i.e. for failure to limit the 1, 3-18 and 20-23, which do not further limit the cannabinoid of claim 1 of the claimed invention.
To overcome this rejection, Applicants may cancel the claims, amend the claims to place the claims in proper dependent form, rewrite the claims in independent form, or present a sufficient showing that the dependent claims comply with the statutory requirements.
Correction is required accordingly in the above-identified application.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 19 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), 1st para., as failing to comply with the written description requirement.
The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Factors to be considered in making the determination as to whether one skilled in the art would recognize that applicant was in possession of the claimed invention as a whole at the time of filing include:
(a) Actual reduction to practice;
(b) Disclosure of drawings of structural chemical formulas;
(c) Sufficient identifying characteristics such as: (i) Complete structure, (ii) Partial structure, (iii) Physical and/or chemical properties or (iv) Functional characteristics when coupled with a known or disclosed correlation between function and structure;
(d) Method of making the claimed invention;
(e) Level of skill and knowledge in the art and
(f) Predictability in the art. While all of these factors are considered, a sufficient number for a prima facie case are discussed below:
Pending claim 19 is directed to the cannabinoid according to claim 1, wherein the cannabinoid (CBD) is applied in combination with a drug against idiopathic pulmonary fibrosis; or in combination with a drug against blood clots or a drug against cardiac arrhythmias.
The specification:
does not provide a representative class of compounds or structure that can be used as a drug against idiopathic pulmonary fibrosis, blood clots, or cardiac arrhythmias.
does not describe these compounds other than what they accomplish when administered to the patient.
The artisan would only be able to determine what compounds fall within each of those classes from a posteriori testing and analysis, and would not be able to know prior to using the compound in conjunction with CBD if the compound will perform as claimed. There is no specific core structure or class of compounds defined that will provide the basis for the breadth of the claims.
The artisan would generally understand what each compound functionally does, but without specific guidance from the specification as to what compounds or classes of compounds can be used as claimed in the invention, there would be no expectation of predictability for practicing this invention.
The Examples taught in the specification specifically disclose compositions or formulations are directed only to use of cannabindiol, i.e.,, which is 2-[(1R,6R)-3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1,3-benzenediol.
Based on the foregoing, there is no support in the specification that Applicants were in possession of the claimed invention as a whole at the time of filing.
Claims 1-57 are rejected under 35 U.S.C. 112(a), because the specification,
[A] which may be enabling for:
a method for treating inflammation and specific symptoms associated with a Covid infection comprising administration of cannabidiol, which is 2-[(1R,6R)-3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1,3-benzenediol
PNG
media_image1.png
363
256
media_image1.png
Greyscale
to a patient suffering from or at risk for being infected with SARS-CoV-2;
(i.e., or in original language set forth in claims “Cannabidiol (i.e.: (2-[(1R,6R)-3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1,3-benzenediol) for treatment of a patient suffering from an infection with SARS-CoV-2 or of a subject at risk to be infected with SARS-CoV-2”); and
[B] is enabling for:
Corresponding compositions or formulations of cannabidiol (i.e., defined in specification Examples 1-10, compositions based on different weight ratios comprised of cannabidiol granulate (solid dispersion), and other pharmaceutically or conventionally acceptable excipients (i.e., e.g., inc. but not limited to non-ionic amphiphilic polymer (i.e., such as Kolluphor® P188), solubilizer, disintegrant, glidant, lubricant, binders, absorbents, anti-oxidants, diluents, granulation liquids and the like) formed or processed into granules, pellets, tablets and the like etc. (i.e., e.g., see support for these materials found throughout the specification), which do not further limit the treatment methods of claims 1-24 of the claimed invention.
DOES NOT REASONABLY PROVIDE ENABLEMENT FOR INVENTIONS [A] AND [B] AS SET FORTH BELOW:
That does not mean that CBD treats or cures the underlying SARS-CoV-2 viral infection. The scientific findings suggest CBD may have a protective role in managing certain effects of the disease, but this is different from treating the virus itself.
Distinction between treating a virus and treating symptoms
The core difference lies in targeting the cause versus managing the effects.
Treating the virus (antiviral activity): This means directly inhibiting the virus's ability to infect cells, replicate, and spread within the body. Some laboratory research has shown that high-purity CBD may inhibit SARS-CoV-2 replication in human lung cells and mice. However, this is distinct from proving an effective human treatment.
Treating symptoms: This involves alleviating the harmful effects that the virus has on the body. The research you cited focuses on CBD's anti-inflammatory properties, particularly its potential to reduce the "cytokine storm," which is a severe immune overreaction associated with acute respiratory distress syndrome (ARDS) in COVID-19 patients.
[A] ALL TREATMENT METHODS: CLAIMS 1-24 (INCLUSIVE)
Comprised of:
ALL cannabinoids for treatment of a patient suffering from an infection with ALL VARIANTS OF SARS-CoV-2 or of a subject at risk to be infected with ALL VARIANTS OF SARS-CoV-2 (i.e., as in claim 1);
for preventing or ameliorating:
ALL symptoms associated with:
ALL diseases associated with cytokine release syndrome (CRS) and/or acute respiratory distress syndrome (ARDS);
ALL elements associated with reducing viral load (i.e., as in claims 3-4 and 6);
reduces ALL serum IL-6 level(s) (i.e., as in claim 5);
ALL treatments based on ALL and ANY symptoms rather than ACTUAL medical diagnosis (i.e., as in claims 8-12);
where patient belongs to ALL risk(s) group(s) (i.e., as in claim 18);
ALL cannabinoid(s) applied in combination with one or more or ALL antiviral agents:
selected from remdesivir (an inhibitor of the RNA polymerase of the virus) and ritonavir/lopinavir (an HIV medicament);
in combination with ALL drug(s) against idiopathic pulmonary fibrosis; and/or
in combination with ALL drug(s) against blood clots or ALL drug(s) against cardiac arrhythmias (i.e., as in claim 19).
[B] CANNABINOID COMPOSITIONS OR FORMULATIONS: CLAIMS 25-57
Cannabinoid compositions or formulations comprised of:
ALL cannabinoid(s);
ALL solid dispersion(s) (i.e., claim 25, 26);
ALL solubilizer(s) and/or ALL amphiphilic block copolymer(s) (i.e., as in claim 26);
ALL block copolymer containing at least one or ALL polyoxyethylene block(s) and at least one or ALL polyoxypropylene block(s) (i.e., as in claim 26) ;
ALL solubilizer(s) is/are ALL poloxamer(s) (i.e. as in claim 28);
ALL antioxidant(s) (i.e. as in claims 30-31);
ALL solid dispersion(s) comprises in ALL admixture ALL cannabinoid(s), ALL amphiphilic block copolymer(s) as ALL solubilizer(s) and ALL water-soluble film former(s) (i.e. as in claim 33-35 and 37);
ALL component(s) are present in a weight ratio ALL cannabinoid(s):
ALL amphiphilic block copolymer(s): ALL water soluble film(s) (i.e., as in claim 40);
ALL solid dispersion(s) in addition comprises ALL antioxidant(s) (i.e., as in claim 41-42);
ALL solid dispersion(s) comprises ALL diluent(s) (i.e., claim 44);
ALL solid dispersion(s) comprises ALL moisture adsorbent (i.e., as in claims 47-48);
ALL moisture adsorbent comprises ALL silicon dioxide(s) (i.e., as in claims 47-49); and/or
ALL core(s) and ALL coating(s) on the core, where the ALL coating(s) comprises
ALL cannabinoid(s), one or more or ALL water-soluble film former(s) (i.e., as in claim 54).
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make the invention commensurate in scope with these claims.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the application coupled with information known in the art without undue experimentation. (United States v. Teletronics Inc., 8 USPQ2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is needed is not based on a single factor, but rather a conclusion reached by weighing many factors (See Ex parte Forman 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988).
These factors include the following:
Amount Of Guidance Provided By Applicant.
In the instant specification and examples contained therein teach:
a method for treating a SARS-CoV-2 infection comprising administration of cannabidiol, which is 2-[(1R,6R)-3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1,3-benzenediol
PNG
media_image1.png
363
256
media_image1.png
Greyscale
to a patient suffering from or at risk for being infected with SARS-CoV-2;
(i.e., or in original language set forth in claims “Cannabidiol (i.e.: (2-[(1R,6R)-3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1,3-benzenediol) for treatment of a patient suffering from an infection with SARS-CoV-2 or of a subject at risk to be infected with SARS-CoV-2”); and
Corresponding cannabidiol compositions or formulations (i.e., see specification Examples 1-10, compositions based on different weight ratios comprised of cannabidiol granulate (solid dispersion), and other pharmaceutically or conventionally acceptable excipients (i.e., e.g., inc. but not limited to non-ionic amphiphilic polymer (i.e., such as Kolluphor® P188), solubilizer, disintegrant, glidant, lubricant, binders, absorbents, anti-oxidants, diluents, granulation liquids and the like) formed or processed into granules, pellets, tablets and the like etc. (i.e., e.g., support for these materials found throughout the specification), which do not further limit the treatment methods of claims 1-24 of the claimed invention.
However, other than that described above-identified and in the specification, there are NO working examples directed to:
Use of all cannabinoids for the treatment of all variants of SARS-CoV-2 for a patient suffering from or at risk of being infected with SARS-CoV-2, other than invitro activity assays; and
With only anecdotal case reports in Example 12 of the specification, it is unclear whether a patient’s improved Covid-19 symptoms were the result of:
the patient first taking a pre-treatment drug course that included antiviral drug Remdesivir (i.e., known to treat coronavirus disease 2019 (COVID-19) by blocking viral replication in the body); or
taking the subsequent drug administration of cannabindiol composition of Example 7 of the claimed invention.
because there was no control study.
Regarding information above, these cannot be simply willed into existence. As was stated in Morton International Inc. v. Cardinal Chemical Co., 28 USPQ2d 1190:
“The specification purports to teach, with over fifty examples, the preparation of the claimed compounds with the required connectivity. However, there is no evidence that such compounds exist...the examples of the '881 patent do not produce the postulated compounds...there is...no evidence that such compounds even exist.”
The same circumstance appears to be true here. Hence, Applicants must show that the claims as written, other than those exemplified in the present invention and identified in examples can be made and used for the stated purpose, or limit the claims to be commensurate with that which is exemplified accordingly.
The Nature Of The Invention And Predictability In The Art.
The invention is directed toward medicine and is therefore physiological in nature. It is well established that “the scope of enablement varies inversely with the degree of unpredictability of the factors involved,” and physiological activity is generally considered to be an unpredictable factor. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
In terms of the law, MPEP 2107.03 states “evidence of pharmacological or other biological activity of a compound will be relevant to an asserted therapeutic use if there is a reasonable correlation between the activity in question and the asserted utility. Cross v. Iizuka, 753 F.2d 1040, 224 USPQ 739 (Fed. Cir. 1985); In re Jolles, 628 F.2d 1322, 206 USPQ 885 (CCPA 1980); Nelson v. Bowler, 626 F.2d 853, 206 USPQ 881 (CCPA 1980).” If correlation is lacking, it cannot be relied upon, Ex parte Powers, 220 USPQ 924; Rey-Bellet and Spiegelberg v. Engelhardt v. Schindler, 181 USPQ 453; Knapp v. Anderson, 177 USPQ 688. Indeed, the correlation must have been established “at the time the tests were performed”, Hoffman v. Klaus, 9 USPQ2d 1657.
Number Of Working Examples.
[A] Applicants have provided sufficient guidance to make and use:
compositions or formulations comprised only of cannabidiol (i.e., defined in specification Examples 1-10, compositions based on different weight ratios comprised of cannabidiol granulate (solid dispersion), and other pharmaceutically or conventionally acceptable excipients (i.e., e.g., inc. but not limited to non-ionic amphiphilic polymer (i.e., such as Kolluphor® P188), solubilizer, disintegrant, glidant, lubricant, binders, absorbents, anti-oxidants, diluents, granulation liquids and the like) formed or processed into granules, pellets, tablets and the like etc. (i.e., e.g., see support for these materials found throughout the specification), which do not further limit the treatment methods of claims 1-24 of the claimed invention.
[B] Invitro Antiviral Assay
PNG
media_image2.png
178
332
media_image2.png
Greyscale
PNG
media_image2.png
178
332
media_image2.png
Greyscale
[C] Anecdotal Evidence: Treatment of Covid-19 with Formulations
Example 12 in the instant specification only offers an Anecdotal Case Report to demonstrate that the cannabindiol composition of Example 7 may be used to treat Covid-19 (i.e., see paras [0358]-[0359]. However, it is apparent that this report has critical limitations;
i.e., e.g., where a outcome is described for one individual without an objective comparator or control or comparator group", control group that did not receive the treatment. Without a control group, it's impossible to know if the outcome was due to the treatment, the placebo effect, or other factors, based on insufficient scientific rigor, fails to establish a cause-and-effect relationship and does not provide definitive proof of the compound’s effectiveness for Covid-19 disease indicated such other factors that might have caused the reported outcome cannot be reliably ruled out (i.e., also given the fact that Example 12 also teaches that a reported patient 1 was taking other medications (i.e., trmt. with Remdesivir, a known antiviral medication used to treat COVID-19). It is administered intravenously and works by blocking the virus from replicating in the body. or following other treatments before taking Example 7 Formulation , which may be the real reason health improvement)
PNG
media_image3.png
708
809
media_image3.png
Greyscale
However, other than cannabindiol compositions or formulations set forth in the instant specification, this originally filed disclosure is not sufficient to allow extrapolation of the limited examples to enable treatment of all Sars-Cov-2 disease variants other than COVID-19
Within the specification, “specific operative embodiments or examples of the invention must be set forth. Examples and description should be of sufficient scope as to justify the scope of the claims. Markush claims must be provided with support in the disclosure for each member of the Markush group. Where the constitution and formula of a chemical compound is stated only as a probability or speculation, the disclosure is not sufficient to support claims identifying the compound by such composition or formula.” See MPEP 608.01(p).
Scope Of The Claims.
The scope of the claims relates to:
PNG
media_image4.png
66
710
media_image4.png
Greyscale
Thus, the scope of claims is very broad.
Nature Of The Invention.
The nature of this invention relates to methods for treating a SARS-CoV-2 infection comprising administration of cannabinoid (i.e., more specifically, cannabindiol which is 2-[(1R,6R)-3-methyl-6-(1-methylethenyl)-2-cyclohexen-1-yl]-5-pentyl-1,3-benzenediol) to a patient suffering from or at risk for being infected with SARS-CoV-2; and/or
corresponding cannabidiol compositions or formulations thereof.
Level Of Skill In The Art.
An ordinary artisan in the area of organic, biological, biopharma, biotech and /or related drug development would have experience making, using and/or screening such chemical compounds and/or amorphous amyloids (i.e., such as amorphous amyloid B1-42)to prepare aggregate cluster compositions for particular activities. Screening of new drug candidates, while complex, is routine in the art. The process of finding new drugs that have in vitro activity against a particular biological target, (i.e., receptor, enzyme, etc.) is well known. Additionally, while high throughput screening assays can often be employed, developing a therapeutic method, as claimed, is generally not well-known or routine, given the complexity of certain biological systems.
MPEP §2164.01 (a) states, "A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)."
That conclusion is clearly justified here as Applicants are not enabled for making or using all these compounds (i.e., as described in general terms, inc., but not limited to starting materials, intermediates, etc.) or pharmaceutical compositions thereof (i.e., e.g., by using not specifically reagents and/or, reactions conditions, etc. ) or treating the diseases taught in the specification.
Appropriate action is required accordingly in the instant application.
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.
Claims 1-26 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wang (Preprints, doi:10.20944/preprints202004.0315.v1, Posted: 19 April 2020).
Wang (See IDS, 20 November 2023) provides an analysis of the relationship between cannabidiol use and modulation of expression of the receptor angiotensin-converting enzyme II (ACE2), which the SARS-CoV2 virus uses to gain entry into cells. Wang discloses a cannabinoid (cannabidiol) that can be used for the treatment of a patient suffering from an infection with SARS-CoV-2.
As the claims are written with intended use language, the limitations which follow “the cannabinoid” in each claim does not result in a structural difference from what is taught by Wang.
The prior art structure is capable of performing the intended use, meeting the limitations of the claim (See MPEP § 2112.02 (II)).
Therefore, Wang anticipates the claimed invention.
Claims 1-24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Byrareddy (Brain Behav. Immun, 2020 April 28; 87:120-121).
Byrareddy (See IDS, 20 November 2023) provides a review of the use of cannabinoids to treat SAR-CoV2 induced respiratory distress. Byrareddy discloses a cannabinoid (cannabidiol) that can be used for the treatment of a patient suffering from an infection with SARS-CoV-2. As the claims are written with intended use language, the limitations which follow “the cannabinoid” in each claim does not result in a structural difference from what is taught by Byrareddy. The prior art structure is capable of performing the intended use, meeting the limitations of the claim (See MPEP § 2112.02 (II)).
Therefore, Byrareddy anticipates the claimed invention.
Claims 1-25 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mamber (Preprints, 27 April 2020).
Mamber (See IDS, 20 November 2023) describes four unconventional but commercially accessible immunomodulatory agents that could be employed in clinical trials to evaluate their effectiveness at alleviating disease symptoms and severity: low dose oral interferon-α, microdose DNA, low-dose thimerosal, and phytocannabinoids (Abstract). Phytocannabinoids such as cannabidiol (CBD) have been shown to inhibit inflammatory and Th1 cytokines, and promote an anti-inflammatory and Th2 immune response both in vitro and in vivo. Mamber discloses a cannabinoid (cannabidiol) that can be used for the treatment of a patient suffering from an infection with SARS-CoV-2. As the claims are written with intended use language, the limitations which follow “the cannabinoid” in each claim does not result in a structural difference from what is taught by Mamber.
The prior art structure is capable of performing the intended use, meeting the limitations of the claim (See MPEP § 2112.02 (II)).
Therefore, Mamber anticipates the claimed invention.
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.
The factual inquiries 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
[1] Claims 1-28, 30, and 52 are rejected under 35 U.S.C. 103 as being unpatentable over Byrareddy (Brain Behav. Immun, 2020 April 28; 87:120-121), alone, in view of or in combination with Faraci (WO 2018/152334; Publication Date: 23 August 2018).
Byrareddy, as described previously, teaches that the cannabinoid CBD has promise as a treatment of COVID-19 due to its immunomodulatory capabilities and states that its use in conjunction with remdesivir should be explored and considered.
Byrareddy does not disclose formulations of cannabidiol.
However, Faraci discloses cannabinoid formulations, including self-emulsifying formulations and micellar dispersions as well as methods of making and using the same. The formulations comprise a cannabinoid and surfactant. The invention provides for formulations comprising at least one active ingredient, including self-emulsifying formulations and micellar dispersions, as well as methods of making and using the same. The formulations comprise at least one active ingredient and surfactant (Abstract).
The present invention relates to compositions comprising at least one active ingredient, e.g., a cannabinoid, cannabinoid extract, terpene, terpene extract, or other active ingredient and surfactant. The compositions include self-emulsifying formulations and formulations that form micelle solution/dispersions (Page 1, Lines 8-10). In one embodiment, the at least one active ingredient is selected from a cannabinoid, cannabinoid extract, terpene, or terpene extract. In another embodiment, the composition is a non-aqueous formulation. In another embodiment, the composition is a pharmaceutical composition, preferably an oral dosage form, more preferably a solid or semi-solid oral dosage form (Page 3, Lines 5-9). A composition of the present invention may further comprise an additional surfactant, antioxidant, viscosity modifying agent, cytochrome P450 metabolic inhibitor, P-GP efflux inhibitor, or semi-solid inducer. Viscosity modifying agents include… hydroxymethylpropyl cellulose…(Page 44, Lines 4-15). In one embodiment, the composition comprises a cannabinoid or cannabinoid extract and a surfactant. The compositions of the present invention form emulsions, preferably nanoemulsions, microemulsions, or micelle dispersions in an aqueous solution (Page 11, Lines 23-27). In some embodiments, the surfactant is selected from… polyethylene-polypropylene glycol (poloxamer 188)… hydroxypropyl methylcellulose (HPMC)… or a combination thereof (Page 14, Lines 12-25). In compositions of the present invention are preferably for oral administration (Page 33, Line 15). In one embodiment, the composition of the present invention is self-emulsifying in an aqueous solution. In a further embodiment, the composition forms a micellar dispersion in an aqueous solution (Page 34, Lines 23-25). In an embodiment of the invention, the cannabinoid is THC or CBD (Page 42, Line 8).
Byrareddy and Farci are considered analogous to the claimed invention as all are involved in the therapeutic application of cannabinoids, in particular, cannabidiol.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to apply the formulations of cannabidiol disclosed by Farci for the treatment of COVID-19, as taught by Byrareddy, arriving at the claimed invention.
The application formulation of CBD, and subsequent application for the treatment of COVID-19 is prima facie obvious combination of prior art elements according to known methods to yield predictable results (See MPEP § 2143 I (A)); Byrareddy discloses a cannabinoid (CBD), while Farci discloses formulations of CBD which meet the limitations of those claimed; the artisan would recognize this, and would be motivated to combine these teachings as the formulations of Farci provided improved pharmacokinetic properties; CBD is highly lipophilic and poorly water soluble. The formulations disclosed by Farci lead to improved solubility, allowing for more consistent dosing and improved therapeutic outcomes for the patient in need of treatment.
Regarding Claims 1-28, 30 and 52, the claims are written with intended use language; the limitations which follow “the cannabinoid” in each claim does not result in a structural difference from what is taught by Byrareddy. The prior art structure is capable of performing the intended use, meeting the limitations of the claim (See MPEP § 2112.02 (II)).
Regarding Claim 52, Farci does not explicitly demonstrate that their particles will perform as described in the claim. However, the examples provided (Tables 3, 4, 5, 6 and 7) demonstrate that the alteration of the concentrations and ratios of the various components of the formulation alter the solubility and other performance characteristics of said formulation. It flows from the art that these parameters could be adjusted within routine experimentation and optimization that is normally done during formulation work to arrive at a formulation that performs as claimed in Claim 29 (See MPEP § 2144.05 II (A)); the artisan would be motivated to perform this optimization in order to develop a formulation with an improved dissolution profile, allowing for more rapid delivery of the therapeutic.
[2] Claims 1-28, 30, 52 and 54-57 are rejected under 35 U.S.C. 103 as being unpatentable over Byrareddy (Brain Behav. Immun, 2020 April 28; 87:120-121), alone, in view of or in combination with Nowak (WO 2020/016653; Publication Date: 23 January 2020).
Byrareddy, as described previously, teaches that the cannabinoid CBD has promise as a treatment of COVID-19 due to its immunomodulatory capabilities and states that its use in conjunction with remdesivir should be explored and considered.
Byrareddy does not disclose formulations of cannabidiol.
Nowak discloses compositions for the extended release of one or more cannabinoids, in which the compositions comprise a population of particles. Each particle may comprise the one or more cannabinoids, one or more drug-releasing agents, and a core. The APIs may be a cannabinoid, such as CBD or THC. The core may comprise an inert material. The one or more cannabinoids may comprise THC, cannabidiol, or a combination thereof (Abstract). The invention provides multi-particulate solid oral dosage forms comprising one or more cannabinoids. These dosage forms can be administered as capsules, tablets (regular tablets, orally-disintegrating tablets, self-disintegrated tablets, chewable tablets), sachets, sprinkles, or stick pack. The system may comprise particles having a size that may range from about 30µm to about 1500 µm (Paragraph 0017). In some embodiments, the core may comprise an inert material selected from the group consisting of microcrystalline cellulose, celluloses, starches, saccharides, and mixtures thereof. In some embodiments, the core may comprise a coating that comprises one or more cannabinoids and the one or more drug-releasing agents. In certain embodiments, the core may comprise a coating that comprises the one or more cannabinoids, the one or more drug releasing agents, the one or more solubilizers, and the one or more surfactants (Paragraph 0021). In some embodiments, the one or more surfactants in the compositions of the invention may comprise… poloxamers…(Paragraph 0047). The compositions of the present invention may further comprise one or more stabilizing agents, including tocopherols, ascorbic acid, butylated hydroanisole, and other antioxidants (Paragraph 0048). Examples of binders include but are not limited to hydroxypropylmethyl cellulose (Paragraph 0051). According to embodiments of the present invention, compositions comprising one or more cannabinoids according to the present invention may be prepared by dispersing the one or more cannabinoids in one or more solubilizers (such as an ethanol and water mixture) along with one or more drug-releasing agents (such as one or more release-controlling polymers and/or one or more release-accelerating polymers) (and optionally one or more stabilizing agents), and the drug dispersion may then be applied onto cores (such as microcrystalline cellets or sugar spheres). According to these embodiments, the one or more cannabinoids may be mixed in the one or more solubilizers to form a homogenous dispersion. The one or more drug-releasing agents (e.g., one or more release-controlling polymers and/or one or more release-accelerating polymers) (and optionally one or more stabilizing agents) may be then mixed with the dispersion using, for example, a vortex mixer, until a homogenous mixture is formed. The mixture may be then loaded onto the cores. In some embodiments, the mixture may be sprayed onto the cores using, for instance, a fluid bed processor. The particle size and size distribution of the cores can be narrowed/adjusted to achieve uniform drug distribution and targeted delivery profile (Paragraph 0060).
Byrareddy and Nowak are considered analogous to the claimed invention as all are involved in the therapeutic application of cannabinoids, in particular, cannabidiol. Therefore, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to apply the formulations of cannabidiol disclosed by Nowak for the treatment of COVID-19, as taught by Byrareddy, arriving at the claimed invention. The application formulation of CBD, and subsequent application for the treatment of COVID-19 is prima facie obvious combination of prior art elements according to known methods to yield predictable results (See MPEP § 2143 I (A)); Byrareddy teaches the use of CBD for the treatment of COVID-19, while Nowak discloses formulations of CBD which meet the limitations of those claimed; the artisan would recognize this, and would be motivated to combine these teachings as the formulations of Nowak provided improved pharmacokinetic properties; CBD is highly lipophilic and poorly water soluble. The formulations disclosed by Nowak lead to improved solubility, allowing for more consistent dosing and improved therapeutic outcomes for the patient in need of treatment.
Regarding Claims 1-28, 30, 52 and 54-57, the claims are written with intended use language; the limitations which follow “the cannabinoid” in each claim does not result in a structural difference from what is taught by Byrareddy. The prior art structure is capable of performing the intended use, meeting the limitations of the claim (See MPEP § 2112.02 (II)).
Regarding Claims 52 and 57, Nowak does not explicitly disclose formulations which have the dissolution parameters as claimed. However, Figures 3A, 3B, 4A, 4B, 5A, and 5B demonstrate that the release profile of the formulations of the invention, demonstrating that by altering the ratios of various components, the release rate of the cannabinoid can be altered. It flows from the art that these parameters could be adjusted within routine experimentation and optimization that is normally done during formulation work to arrive at a formulation that performs as claimed in Claim 29 (See MPEP § 2144.05 II (A)); the artisan would be motivated to perform this optimization in order to develop a formulation with an improved dissolution profile, allowing for more rapid delivery of the therapeutic.
Regarding Claims 54 and 56, the optimization of the amounts and ratios of excipients such as the film former can be determined through routine experimentation that is done during formulation work, as is standard during the development of an extended release formulation. Determining the exact ratio of the excipients in the formulation is prima facie routine optimization through routine experimentation (See MPEP § 2144.05 II (A)); the artisan would be motivated to perform this optimization in order to develop a formulation with an improved dissolution profile, allowing for more rapid delivery of the therapeutic.
[3] Claims 1-28, 30, 52 and 54-57 are rejected under 35 U.S.C. 103 as being unpatentable over Byrareddy (Brain Behav. Immun, 2020 April 28; 87:120-121) alone, in view of or in combination with Temtsin-Krayz (WO 2017/072774; Publication Date: 4 May 2017)
Byrareddy, as described previously, teaches that the cannabinoid CBD has promise as a treatment of COVID-19 due to its immunomodulatory capabilities and states that its use in conjunction with remdesivir should be explored and considered.
Byrareddy does not disclose formulations of cannabidiol.
Temtsin-Krayz discloses a pharmaceutical composition for transmucosal administration of an active lipophilic compound through the oral mucosa comprising a lipophilic active compound, a polymeric matrix formed by two or more water soluble polymers, and a rapid dissolution agent. At least one of the water-soluble polymers is an amphiphilic polymer and at least one is either a hydrophilic polymer or an amphiphilic polymer (Abstract). In a specific embodiment, the lipophilic active compound is a cannabinoid selected from THC and CBD (Paragraph 0013). The pharmaceutical composition of an embodiment of the present application contains the amphiphilic polymer selected from the group consisting of… poloxamers… (Paragraph 0015). In a further embodiment, the transmucosal pharmaceutical composition contains the hydrophilic polymer selected from the group consisting of sodium carboxymethyl cellulose, hydroxyethylcellulose, polyvinyl alcohol, sodium alginate, chitosan, and carrageenan (Paragraph 0016). In a further embodiment, the amphiphilic polymer may be poloxamers…Hypromellose (also known as hydroxypropyl methyl cellulose)… (Paragraph 0033). The pharmaceutical composition of an embodiment may further comprise one or more pharmaceutically acceptable carriers or excipients. The composition may be prepared in a form of a powder, powder microsphere, coated powder microspheres, liposomal dispersions, and combinations thereof. It may be formulated into a dosage form for oral administration selected from capsules, tablets, beads, grains, pills, granulates, granules, powder, pellets, sachets, troches, disks, films, oral suspensions, and aerosol (Paragraph 0019). Exemplary embodiments have the following combinations of polymers, such as three polymers to form the polymeric matrix, two of the polymers being amphiphilic polymers, preferably poloxamer 407 and PVP, and the other polymer being a hydrophilic polymer preferably NaCMC (Paragraph 0035). An exemplary pharmaceutical composition of the application includes cannabidiol, poloxamer 407 NaCMC, and mannitol (Paragraph 0036). It would be within the parameters of what is disclosed to include hypromellose (hydroxypropyl methyl cellulose) within the formulation, and the artisan could arrive at the use of poloxamer 188 through routine experimentation in order to optimize solubilization and dissolution of the pharmaceutical formulation of cannabidiol.
Byrareddy and Temtsin-Krayz are considered analogous to the claimed invention as all are involved in the therapeutic application of cannabinoids, in particular, cannabidiol. Therefore, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to apply the formulations of cannabidiol disclosed by Temtsin-Krayz for the treatment of COVID-19, as taught by Byrareddy, arriving at the claimed invention. The application formulation of CBD, and subsequent application for the treatment of COVID-19 is prima facie obvious combination of prior art elements according to known methods to yield predictable results (See MPEP § 2143 I (A)); Byrareddy teaches the use of CBD for the treatment of COVID-19, while Temtsin-Krayz discloses formulations of CBD which meet the limitations of those claimed; the artisan would recognize this, and would be motivated to combine these teachings as the formulations of Temtsin-Krayz provided improved pharmacokinetic properties; CBD is highly lipophilic and poorly water soluble. The formulations disclosed by Temtsin-Krayz lead to improved solubility and enhanced permeability across the oral mucosa, allowing for more consistent dosing and improved therapeutic outcomes for the patient in need of treatment.
Regarding Claims 1-28, 30, 52 and 54-57 , the claims are written with intended use language; the limitations which follow “the cannabinoid” in each claim does not result in a structural difference from what is taught by Byrareddy. The prior art structure is capable of performing the intended use, meeting the limitations of the claim (See MPEP § 2112.02 (II)).
Regarding Claims 52 and 57, Temtsin-Krayz does not explicitly disclose formulations which have the dissolution parameters as claimed. However, Table 7 and Figure 5 demonstrate that the release profile of a formulation of cannabidiol compared to unformulated cannabidiol in fasted state simulated intestinal fluid, demonstrating that by altering the ratios of various components, the release rate of the cannabinoid can be altered. It flows from the art that these parameters could be adjusted within routine experimentation and optimization that is normally done during formulation work to arrive at a formulation that performs as claimed in Claim 29 (See MPEP § 2144.05 II (A)); the artisan would be motivated to perform this optimization in order to develop a formulation with an improved dissolution profile, allowing for more rapid delivery of the therapeutic.
Regarding Claims 54 and 56, the optimization of the amounts and ratios of excipients such as the film former can be determined through routine experimentation that is done during formulation work, as is standard during the development of an extended-release formulation. Determining the exact ratio of the excipients in the formulation is prima facie routine optimization through routine experimentation (See MPEP § 2144.05 II (A)); the artisan would be motivated to perform this optimization in order to develop a formulation with an improved dissolution profile, allowing for more rapid delivery of the therapeutic.
Based on the foregoing, the claimed invention is rendered obvious by each of the cited rejections [1] to [3] under 35 USC 103.
[4] Claims 1-15 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over
UK Pat. Appln. No. GB2542797A (i.e., Filing Date: September 29, 2015, Pub. Date: April 5, 2017; “GB ‘797 Appln.”),
Moore et al., “Cytokine Release Syndrome In Severe COVID-19”, Science, (May 1, 2020), Vol. 368, Iss.: 6490, pp. 473-474.
Atalay et al., “Antioxidative and Anti-Inflammatory Properties of Cannabidiol”, Antioxidants (Basel), 2019 Dec 25, 9(1):21. doi: 10.3390/antiox9010021, respectively, alone, in view of or in combination with each other
The present invention relates to a cannabinoid or more particular, cannabidiol (“CBD”) and/or corresponding compositions/formulations thereof; i.e., e.g.,
while intended use language carries no patentable weight, cannabinoids, such as CBD, may be used for treatment of patients suffering from COVID-19, a disease caused by infection with coronavirus or SARS-Cov-2; cytokine release syndrome and/or reducing viral load (see claim 3) acute respiratory syndrome (ARS) (see claim 6), miscellaneous disease symptoms (see claim 8, 10 ); i.e., e.g.,
where patients are diagnosed with at least one symptom of disease selected from:
fever, dry cough, shortness of breath, and evidence of rales/crackles on physical examination, myalgia, fatigue, dyspnea, anorexia, loss of sense of smell and taste, and nephritis.
the mechanism of action associated with CBD regulation/suppression of specific receptors and inflammatory cytokines the immune system (i.e., see specification excerpts below):
Excerpts on Associated Mechanisms of Action From Instant Specification
[AltContent: rect]
PNG
media_image5.png
120
451
media_image5.png
Greyscale
PNG
media_image6.png
219
443
media_image6.png
Greyscale
[AltContent: rect]
PNG
media_image7.png
303
448
media_image7.png
Greyscale
; and
Atalay provides background and specific details on mechanism of action and background on
PNG
media_image8.png
348
1067
media_image8.png
Greyscale
GB ‘797 Appln. relates to the use of one or more cannabinoids (i.e., inc. cannabidiol (CBD)) in the treatment of an inflammatory skin disease (i.e., inc. microbial infection-induced dermatitis, a solar dermatitis or an atopic dermatitis); i.e., where CBD is form of a highly purified extract of cannabis such that it is present at greater than 95% of the total extract (w/w), or it may be synthetically produced, used at a dose of between and 10 and 1000mg and may be administered concomitantly with one or more medicaments . . ..
In particular,
“Inflammatory skin diseases such as psoriasis and atopic dermatitis can be caused by the overproduction of cytokines. For example the cytokines IL-1, IL-6 and IL-8 have all been found to be over-expressed in psoriatic plaques, (Sauder, 1990). In atopic dermatitis, also known as atopic eczema, during the chronic phase, there is activation of TNF-alpha and IL-8 and IL-12 cytokines, (Nedoszytko et al., 2014) (i.e., see [0015] therein). Currently the most effective and commonly used prescription drugs for treating inflammation are the corticosteroids, particularly the glucocorticoid related steroids. They are very effective for many forms of eczema, including atopic dermatitis, and are fairly effective in ameliorating the symptoms of psoriasis (i.e., see para. [0016])”.
While GB ‘797 Appln. teaches activation specific receptors and inflammatory cytokines the immune system as in the claimed invention, it does not teach that CBD may be used to treat SARS-Cov-2, Covid 19 and the like.
However, the Moore reference explicitly teaches and indicates that:
there is a nexus or link between CBD, its activation of the same specific receptors and inflammatory cytokines the immune system, inflammatory skin diseases and Sars-Cov-2/Covid; i.e., e.g.,
cytokine release syndrome (CRS) to SARS-CoV and MERS-CoV infections as a major cause of SARS-CoV infected immune cells that contributes to immunopathology;
the mechanism of action has a link established between cytokine release syndrome (CRS) (i.e., occurs when immune system releases large amounts of cytokines into bloodstream) and different diseases which causes inflammation, bacterial and viral infections or autoimmune diseases;
where:
the original SARS-CoV, identifying a "cytokine storm" as a major factor in the pathology and poor outcomes of severe cases.
the same receptor sites are activated in related signaling pathways by CBD via the same mechanism of action directed to regulation/ suppression of the same receptors and inflammatory cytokines of the same immune system with a variety of diseases (i.e., inc. inflammatory skin disorders and/or COVID-10/Sars-Cov-2)
“suppression of inflammation by IL-6 antagonists might delay viral clearance. However, IL-6 blockade also results in rapid reduction of serum IL-10, an immunosuppressive cytokine secreted by macrophages, which may mitigate concerns about prolonging viral clearance (11) (i.e., see Moore, col. 2, lines 11-18 at page 474).”
See Moore, col. 2, paras.2-3:
PNG
media_image9.png
325
408
media_image9.png
Greyscale
PNG
media_image10.png
518
404
media_image10.png
Greyscale
PNG
media_image11.png
424
406
media_image11.png
Greyscale
Common mechanism of Action
PNG
media_image12.png
542
369
media_image12.png
Greyscale
sample or subject ( [0017]) (i.e., which reads on claim 13 of the instant invention).
Based on the foregoing and the teachings of the art, the ordinary artisan would meet with a reasonable expectation of success in applying the use of CBD in the treatment of Sars-Cov2/Covid-19, because:
[1] of the nexus or link between CBD, its activation of the same specific receptors and inflammatory cytokines the immune system, inflammatory skin diseases and Sars-Cov-2/Covid and the underlying MOA of cytokine release syndrome (CRS)/cytokine storm (i.e., occurs when immune system releases the cytokine storm, which causes inflammation, bacterial and viral infections or autoimmune diseases); i.e., e.g.,
where:
the same receptor sites are activated in related signaling pathways by CBD via the same mechanism of action directed to regulation/ suppression of the same receptors and inflammatory cytokines of the same immune system with a variety of diseases (i.e., inc. inflammatory skin disorders and/or COVID-10/Sars-Cov-2); and
“suppression of inflammation by IL-6 antagonists might delay viral clearance. However, IL-6 blockade also results in rapid reduction of serum IL-10, an immunosuppressive cytokine secreted by macrophages, which may mitigate concerns about prolonging viral clearance (11) (i.e., see Moore, col. 2, lines 11-18 at page 474) as taught by Moore.
One of ordinary skill in the art would have been motivated in in administering CBD for treatment of Sars-Cov-2/Covid-19 and other related inflammatory diseases and disorders associated with the cytokine immune suppression pathway as discussed supra method would meet with a reasonable expectation of success, because there remains an urgent need in the art for additional therapeutic agents for the treatment of these diseases associated with this pathway.
Based on the foregoing, claimed invention is rendered obvious over WO ‘880 Appln alone, in view of or in combination with the references cited above.
NON-STATUTORY DOUBLE PATENTING
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
[1] Claims 4, 21 and 52 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3, 20 and 29 of co-pending U.S. Appln. No. 17/923,731, Filed: November 7, 2022 is a 371 Nat.’ l Stage Entry of WO 2021/228365A1 (i.e., PCT/EP2020/063086, Intern.’ l Filing Date: May 11, 2020)
17923754
17923731
PNG
media_image13.png
119
778
media_image13.png
Greyscale
PNG
media_image13.png
119
778
media_image13.png
Greyscale
PNG
media_image14.png
65
634
media_image14.png
Greyscale
PNG
media_image15.png
72
771
media_image15.png
Greyscale
PNG
media_image16.png
114
791
media_image16.png
Greyscale
PNG
media_image17.png
179
791
media_image17.png
Greyscale
PNG
media_image18.png
136
733
media_image18.png
Greyscale
With regard to the above corresponding claims between the 2 identified patent applications, respective claimed subject matter are obvious variants of the other, i.e., e.g., when corresponding claims are compared against each other, they represent broader or narrower variation specific subsets or obvious variants of the other and vice versa, nothing inherently new of unobvious
[2] Claims 1-27, 52 and 54-57 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 6, 13-16, and 18-31 of copending Application No. 17/923,749 (‘749) (Amended Claims of 7 November 2022).
Claim 1 of ‘749 claims a cannabinoid for treatment of a patient suffering from an inflammatory condition characterized by elevated IL-6 levels. Claim 2 claims the cannabinoid of claim 1 wherein the cannabinoid is cannabidiol. Claim 5 claims that the patient suffers from an inflammatory condition in connection with an infection. Claim 6 claims the cannabinoid according to claim 5 wherein the treatment is for preventing or ameliorating cytokine release syndrome. Claim 13 claims the cannabinoid according to Claim 1 wherein the treatment reduces serum IL-6 levels. Claims 14, 15, and 16 have diagnostic criteria for treatment which are identical to those of Claims 13 and 15 of the examined application. Claim 18 claims the cannabinoid according to claim 1 wherein the cannabinoid is administered orally. Claims 19-22 claim the dosages of the cannabinoid, which overlaps with those claimed in the examined application. Claim 23 claims that the cannabinoid is formulated as a solid dispersion. Claim 24 claims the cannabinoid of Claim 23 wherein the solid dispersion comprises the cannabinoid and a solubilizer which is an amphiphilic block copolymer capable of forming a micellar solution if combined with an aqueous medium. Claim 25 claims the cannabinoid of claim 23 wherein the solubilizer is a block copolymer containing at least one polyoxyethylene block and at least one polyoxypropylene block. Claim 26 claims the cannabinoid according to claim 25 wherein the solubilizer is a poloxamer, and claim 27 claims the cannabinoid according to claim 26 herein the formulation comprises cannabidiol as the active substance, poloxamer 188 as the solubilizer, and optionally an antioxidant. Claim 28 claims the cannabinoid according to claim 23 wherein the formulation, when subjected to an in vitro dissolution test in 0.1N HCl following the USP paddle method, releases at least 60 wt% of the cannabinoid within 60 minutes. Claim 29 claims the cannabinoid according to claim 1 wherein the cannabinoid is incorporated in a formulation comprising a core and a coating on the core, wherein the coating comprises the cannabinoid, one or more water-soluble film formers, and not more than 20 wt% based on the weight of all components, other excipients. Claim 30 claims the cannabinoid according to claim 29 wherein HPMC is used as the water-soluble film former. Claim 31 claims the cannabinoid according to claim 29 wherein the film former/formers, based on the total amount of cannabinoid, are comprised in a total proportion of 0.3-10 wt%. Claim 32 claims the cannabinoid according to claim 29 wherein more than 30 wt% and less than 8- wt% of the cannabinoid is released within two hours; and/or wherein more than 40 wt% and less than 90 wt% of the cannabinoid is released within three hours; and/or wherein more than 50 wt% and less than 95 wt% of the cannabinoid contained is released within four hours.
The claims are not patentably distinct because COVID-19 is an inflammatory condition that is characterized by, among other manifestations, elevated IL-6 levels. As the claims are written with intended use language, the limitations which follow “the cannabinoid” in each claim does not result in a structural difference from what is claimed in ‘749. The prior art structure is capable of performing the intended use, meeting the limitations of the claim (See MPEP § 2112.02 (II)).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
[3] Claims 1-27, 52 and 54-57 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 5, 6, 13-26, 31, 33, 34, and 52-55 of copending Application No. 17/923,786 (‘786) (Amended Claims of 7 November 2022).
Claim 1 of ‘786 claims a cannabinoid for treatment of a patient suffering from an inflammatory condition characterized by elevated IL-6 levels or being at risk of suffering from such conditions. Claim 2 claims the cannabinoid according to claim 1 wherein the cannabinoid is CBD. Claim 5 claims the cannabinoid according to claim 1 wherein the patient suffers from an inflammatory condition in connection with an infection. Claim 6 claims the cannabinoid according to claim 5 wherein the treatment is for preventing or ameliorating cytokine release syndrome. Claim 13 claims the cannabinoid according to claim 1 wherein the treatment reduces the serum IL-6 level. Claims 14-17 claims the cannabinoid according to claim 1 wherein the treatment occurs if diagnostic criteria are met which are identical to those claimed in the examined application. Claim 18 claims the cannabinoid according to claim 1 wherein the cannabinoid is administered orally. Claims 19-22 claims the cannabinoid according to claim 1 wherein there are dosing patterns identical to those claimed in the examined application. Claim 23 claims the cannabinoid according to claim 1 wherein the cannabinoid is formulated as a solid dispersion. Claim 24 claims the cannabinoid according to claim 23 wherein the solid dispersion comprises the cannabinoid and a solubilizer which is an amphiphilic block copolymer capable of forming a micellar solution if combined with an aqueous medium. Claim 25 claims the cannabinoid according to claim 23 wherein the solubilizer is a block copolymer containing at least one polyoxyethylene block and at least one polyoxypropylene block. Claim 26 claims the cannabinoid according to claim 25 wherein the solubilizer is a poloxamer, in particular poloxamer 188. Claim 31 claims the cannabinoid according to claim 23 wherein the solid dispersion comprises a cannabinoid, an amphiphilic block copolymer and a water soluble film former. Claim 33 claims the cannabinoid according to claim 31 wherein the amphiphilic block copolymer is a block copolymer containing at least one polyoxymethylene block and at least one polyoxypropylene block, and Claim 34 specifies that it is polyoxamer 188. Claim 52 claims the cannabinoid according to claim 1 wherein the cannabinoid is incorporated in a formulation comprising a core and a coating on the core, wherein the coating comprises the cannabinoid, one or more water-soluble film formers and not more than 20 wt% based on the weight of all components, of other excipients. Claim 53 claims the cannabinoid according to claim 52 wherein HPMC is used as the water soluble film former. Claim 54 claims the cannabinoid according to claim 52 wherein the film former/formers based on the total amount of cannabinoid, is/are comprised in a total proportion of 0.3-10 wt%. Claim 55 claims the cannabinoid according to claim 52 wherein more than 30 wt% and less than 8- wt% of the cannabinoid is released within two hours; and/or wherein more than 40 wt% and less than 90 wt% of the cannabinoid is released within three hours; and/or wherein more than 50 wt% and less than 95 wt% of the cannabinoid contained is released within four hours.
The claims are not patentably distinct because COVID-19 is an inflammatory condition that is characterized by, among other manifestations, elevated IL-6 levels. As the claims are written with intended use language, the limitations which follow “the cannabinoid” in each claim does not result in a structural difference from what is claimed in ‘749. The prior art structure is capable of performing the intended use, meeting the limitations of the claim (See MPEP § 2112.02 (II)).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
[4] Claims 1-27 and 52 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3 of copending Application No. 18/287,096 (‘096) (Amended Claims of 12 August 2024) in view of Byrareddy (Brain Behav. Immun, 2020 April 28; 87:120-121) (is an obvious modification of the compound claim in your issued patent. ).
Claim 1 of ‘096 is directed to a pharmaceutical formulation in the form of a solid dispersion wherein the solid dispersion comprises in admixture a cannabinoid, an amphiphilic block copolymer as a solubilizer, and a water-soluble film former, wherein the components are present in a weight ratio cannabinoid: amphiphilic block copolymer: water soluble film former ratio of 1: 0.11-0.41:0.03-0.33. Claim 3 is directed to the formulation of claim 1 wherein the amphiphilic block copolymer is a block copolymer containing at least one polyoxyethylene block and at least one polyoxypropylene block, wherein the amphiphilic block copolymer preferably is a poloxamer, in particular poloxamer 188.,
‘096 does not claim that the cannabinoid is CBD.
Byrareddy, as described previously, teaches that the cannabinoid CBD has promise as a treatment of COVID-19 due to its immunomodulatory capabilities and states that its use in conjunction with remdesivir should be explored and considered.
Byrareddy and ‘096 are considered analogous to the claimed invention as all are involved in the pharmaceutical application of cannabinoids.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art the time of the effective filing date of the instant application to utilize cannabidiol in the formulations of ‘096 as Byrareddy teaches that CBD has potential utility as a treatment for COVID-19, and further utilize these formulations in the methods claimed in the examined application. Byrareddy discloses a cannabinoid (cannabidiol) that can be used for the treatment of a patient suffering from an infection with SARS-CoV-2. As the claims are written with intended use language, the limitations which follow “the cannabinoid” in each claim does not result in a structural difference from what is taught by Byrareddy. The prior art structure is capable of performing the intended use, meeting the limitations of the claim (See MPEP § 2112.02 (II)).
This is a provisional nonstatutory double patenting rejection.
Based on the foregoing, appropriate action is required for [1] to [4] accordingly in the above-identified application.
Conclusion
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to GRACE C HSU whose telephone number is (571) 270-1689. The Examiner can normally be reached Monday-Friday 7:30 am - 6 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, Applicants is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Jeffrey H. Murray can be reached on 571-272-9023.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/G.C.H./
Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624
Prosecution Insights