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 .
Information Disclosure Statement
No Information Disclosure Statement (IDS) was filed with this application, therefore no disclosed references on behalf of the inventor were considered.
Claim Status
Claim(s) 1-20 are examined on the merits herein.
Claim Interpretation
The claims in this application are given their broadest reasonable interpretation using the plain meaning of the claim language in light of the specification as it would be understood by one of ordinary skill in the art.
Claim Rejections - 35 USC § 112
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(s) 1-16 are rejected under 35 U.S.C. 112, first paragraph, because the specification, while enabling treatment of Alzheimer's disease in a subject, does not reasonably provide enablement for preventing the occurrence of Alzheimer's disease in the subject with the use of compositions comprising CBD and melatonin. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Attention is directed to In re Wands, 8 USPQ2d 1400 (CAFC 1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation.
Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
The nature of the invention;
The breadth of the claims;
The state of the prior art;
The level of one of ordinary skill;
The level of predictability in the art;
The amount of direction provided by the inventor;
The existence of working examples; and
The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The instant specification fails to provide guidance that would allow the skilled artisan to practice the instant invention without resorting to undue experimentation, as discussed in the subsections set forth herein below.
The breadth of the claims and the nature of the invention
Applicants claim a method for treating and/or preventing Alzheimer’s disease in a subject by administering an amount of formulation comprising CBD and melatonin, to the subject. The term “preventing” is not defined in the specification. Given this fact, the breadth of the claims is extensive. The term "prevention' can be construed broadly as either prevention of the increase in clinically evident symptoms of Alzheimer’s disease altogether or preventing the onset of a preclinically evident stage of Alzheimer’s disease in individuals at risk. In other words, the Instant claims are drawn to a composition and method of preventing all preclinical stages of any and all stages of Alzheimer’s disease, which includes any undetectable stages of the disease as well.
The state of the prior art and the predictability or lack thereof in the art
The state of the prior art is such that it involves screening both in vitro and in vivo to determine which compounds exhibit the desired pharmacological activities (i.e. which compounds treat which specific disease). There is no absolute predictability even in view of the seemingly high level of skill in the art. The existence of these obstacles establishes that the contemporary knowledge in the art would prevent one of ordinary skill in the art from accepting any therapeutic or preventive regimen on its face. Alzheimer's disease is a progressive brain disorder characterized by memory loss, cognitive decline, neuromotor functional decline, and psychiatric problems, often onset by age. Accordingly, prevention of this disease requires screening to identify indeed if the person is already exhibiting symptoms consistent with the pathology, in which case their complete absence would be the only hallmark of successful prevention. An article regarding Alzheimer’s disease prevention by Khalsa et al. (Cerebrum. 2017 Mar 1;2017:cer-03-17.) teaches modern principles for the prevention of Alzheimer’s disease: diet/supplements, exercise (both physical and mental), yoga/meditation, and maintenance of psychological well-being. However, it is unclear how any one of these four prevention vectors, specifically supplementation in the case of the Instant claims, fundamentally addresses and certainly prevents the onset of the disease rather than simply and earnestly attempting at the prevention.
The amount of direction or guidance present and the presence or absence of working examples
No direction or guidance is present in the Instant specification for the prevention of Alzheimer’s disease.
The quantity of experimentation necessary
First of all, one of skill in the art would need to determine which subjects are prone to developing the neurostructural causes of the disease, requiring constant screening by MRI/biopsy throughout life. If indeed they display the set of neurostructural changes that culminate in the onset of Alzheimer’s disease, one of skill in the art has to determine when to start prophylaxis for the patient, before the symptoms start, beginning of the pseudo-symptom, etc. Additionally, one has to evaluate which symptom of the disease is the formulation preventing. Absent a reasonable a priori expectation of success for using the specific formulation to prevent Alzheimer’s disease, one skilled in the art would have to extensively test different patient populations and at various stages. Since each prospective embodiment, and indeed future embodiments as the art progresses, would have to be empirically tested, and those which initially failed tested further, an undue amount of experimentation would be required to practice the invention as it is claimed in its current scope, because the specification provides inadequate guidance to do otherwise.
Thus, factors such as “sufficient working examples”, “the level of skill in the art”, and “predictability”, etc. have been demonstrated to be sufficiently lacking in the instant claimed methods. In view of the breadth of the claims, the chemical nature of the invention, and the lack of working examples regarding the activity of the formulation, one having ordinary skill in the art would have to undergo an undue amount of experimentation to use the invention commensurate with the scope of the claims. Genetech Inc. V. Novo Nordisk A/S (CA FC) 42 USPQ2d 1001, states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion" and “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”. Therefore, in view of the Wands factors discussed above, to practice the claimed invention herein, a person of skill in the art would have to engage in undue experimentation to test which diseases can be treated or prevented by the compound encompasses in the instant claims, with no assurance of success.
Therefore, rejection of claims 1-16 under 35 U.S.C. §112, first paragraph, is deemed proper, and the mentioned claims are rejected herein.
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.
Claim(s) 1-3, 10, 12-14, and 17 are rejected under 35 U.S.C. 102 as being unpatentable over Mukunda et al (WO 2019190608 A1; PCT Filed: 29 March 2019; henceforth Mukunda).
Mukunda teaches compositions and methods for treating Central Nervous System (CNS) diseases, specifically Alzheimer's disease, in humans and in veterinary animals, by administering a formulation comprising melatonin and CBD. In regards to the claims above, Mukunda anticipates several of the limitations disclosed by the Instant invention.
Mukunda addresses the limitation of the invention being a method of treating Alzheimer's disease (AD) comprising administering a therapeutically effective amount of a composition to a subject in need thereof, wherein the composition comprises cannabidiol (CBD) and melatonin by teaching compositions of their invention being ones for treating Alzheimer's and related CNS diseases in humans and veterinary animals, and including, at least, the components CBD and melatonin, in amounts that are sufficient to provide efficacy while not inducing side effects commonly associated with cannabis and/or melatonin, for the purpose of administering orally in a suitable carrier [pg. 12; [0043]; line 10-16]. Mukunda further exemplifies an embodiment of such a composition, wherein the composition includes: (i) CBD in a dose amount per 70kg patient of from about 14 mg to about 200 mg; and (ii) melatonin in a dose amount per 70 kg patient of from about 1.4 mg to about 20.0 mg [pg. 11; [0036] lines 21-25], as required by Claim 1, line 01-05; also Claim 17, line 01-03. Additionally, Mukunda meets the limitation for the composition to comprise one or more emulsifiers, specifically lecithin, by teaching a nonionic emulsifier, such as lecithin, be preferably added to increase the solubility of cannabinoids and other active ingredients in the solution [pg. 19; [0078]; lines 23-25], as required by Claim 10, lines 01-02; also Claim 12, lines 01-02
Mukunda also meets the limitation for administering the composition either orally or nasally by teaching, in a single embodiment containing CBD and melatonin, oral administration [pg. 13; [0044]; lines 19-22], as required by Claim 13, lines 01-02. Furthermore, Mukunda also meets the limitation for daily administration of the composition by teaching an exemplary embodiment wherein a subject may be administered a melatonin/CBD-containing composition three-to-four times per day [pg. 19; Example 4; [0072]; line 21], as required by Claim 14, lines 01-02.
Mukunda, in such an embodiment, also addresses several of the range limitations for compositional amounts of the Instant invention. Mukunda meets the limitation for the comprisal of CBD in the composition at 0.2 mg/kg by teaching the use of CBD in the embodiment at a range from 0.2 to about 2.85 mg/kg for a 70 kg subject [pg. 11; [0036] lines 21-25], as required by Claim 2, line 01-05. Mukunda also meets the limitation for the comprisal of melatonin in the composition at 0.04 mg/kg by teaching the use of melatonin in the embodiment at a range from 0.02 to about 0.28 mg/kg in a 70 kg subject [pg. 11; [0036] lines 21-25], as required by Claim 3, line 01-05.
Thus, Claim(s) 1-3, 10, 12-14, and 17 are rejected herein under 35 U.S.C. 102.
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.
Claim(s) 4-9, 11, 15-16, and 18-20 are rejected under 35 U.S.C. 103 as being unpatentable over Mukunda et al (WO 2019190608 A1; PCT Filed: 29 March 2019; henceforth Mukunda), as applied to Claim(s) 1-3, 10, 12-14, and 17 above, in view of Cao et al (US 20220280613 A1; Filed: 10 July 2020; henceforth Cao).
Mukunda teaches compositions and methods for treating Central Nervous System (CNS) diseases, specifically Alzheimer's disease, in humans and in veterinary animals, by administering a formulation comprising melatonin and CBD.
Mukunda addresses the limitations of Claims 1-3, 10, 12-14, and 17 as recited above. Mukunda also meets the limitations of the relative reduction of amyloid beta 42 peptide and/or amyloid beta 40 peptide of the subject by teaching their compositions and methos are effective in human and veterinary animals to reduce amyloid beta expression [pg. 10; [0036]; line 26-30], wherein the amyloid beta is referenced to perhaps be amyloid beta 40 and amyloid beta 42 [pg. 2; [0007]; line 12], as required by Claim 15, lines 01-03. It would be an obvious stance to reason, however, that “amyloid beta”, herein, would be amyloid beta 40 or amyloid beta 42 as there is agreement in the field that they are the constituents that are characteristic of Alzheimer’s disease. Furthermore, Mukunda also meets the limitation of the relative reduction of p-tau in a subject by teaching their compositions and methods effectively decrease the phosphorylation of tau protein in humans and veterinary animals [pg. 10; [0036]; line 32], as required by Claim 16, line 01-02.
Mukunda, furthermore, meets the limitations of the concentration ranges for CBD (about 300 – about 1500 mg/mL) and melatonin (about 10 – about 1000 mg/mL) in a single composition by teaching a preferred 1 ml oral suspension for a 70-kg human to comprise up to 1.5 mg of melatonin and up to 200 mg CBD [pg. 13; [0049]; lines 14-17], as required by Claim 19, line 01-05. While the efficacious concentrations of CBD and melatonin were taught by Mukunda to encompass a smaller range than those of the referenced claim (Cl.19), it would be obvious to optimize the amounts of CBD and melatonin for effective delivery of the compounds. Therefore, it is noted that “[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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Mukunda, while still disclosing the use of an emulsifier, does not outline their inventive composition to be explicitly an aqueous/oil emulsion, especially a nanoemulsion, or to comprise medium chain triglyceride (MCT) oil, or insulin.
Cao teaches the use of insulin in nanoemulsified compositions of cannabinoids and melatonin used to treat Alzheimer’s disease. In regards to Claim(s) 1, 4-18, and 20, Cao meets several of the limitations of the Instant invention.
Primarily, Cao addresses the limitations set for in the independent claims by teaching compositions comprising a cannabinoid and melatonin and their uses for treating Alzheimer's disease [pg. 1; [0005]; lines 01-06], as required by Claim 1, lines 01-05; also Claim 17, lines 01-03.
Cao also meets the limitation of their cannabinoid-containing composition further comprising insulin by teaching their composition to comprise a cannabinoid (THC) and insulin [pg. 9; Claim 1; line 01-04], as required by Claim 4, line 01-02. Furthermore, Cao addresses several range limitations for the amount of insulin in the composition set forth in the Instant invention, by teaching the use of insulin in the administered composition as 0.24 mg/kg in their mouse studies (Figure 1C) [pg. 7; [0083]; Example 1; Table], as required by Claim 5, line 01-05. Cao also meets the limitation of the insulin being present in the instant composition at range of 1 U/mL to 100 U/mL, especially at 20 U/mL by teaching the use of insulin in their composition at a range of 1 IU to about 50 IU [pg. 10; Claim 31; line 01-02], wherein 1 IU is 1 insulin unit [pg. 2; [0019]; line 01-02], wherein 448.7 insulin units are used in a 15 mL nanoemulsion composition, or 29.9 units per mL [pg. 7; [0083]; Example 1; Table], as required by Claim 20, line 01-04. With respect to ranges, it is noted that “[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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Cao also meets the limitations of the composition being an emulsion by teaching their cannabinoid/melatonin/insulin composition being an emulsion [pg. 9; Claim 4, lines 01-02], as required by Claim 6, line 01. Cao also meets the limitation of the emulsified composition being a nanoemulsion by teaching their emulsified cannabinoid/melatonin/insulin composition being a nanoemulsion [pg. 9; Claim 5, lines 01-02], as required by Claim 7, line 01. Coa also meets the limitation of the nanoemulsion comprising an oil phase and an aqueous phase by teaching their definition of "nanoemulsion" to be a heterogenous mixture including an organic phase dispersed in an aqueous phase, or an aqueous phase dispersed in an organic phase. [pg. 2; [0024]; lines 01-03], as required by Claim 8, line 01-02. Furthermore Cao meets the limitation of the nanoemulsion particle size ranging between 1 nm and 900 nm by teaching each phase of the nanoemulsion is in the form of discrete droplets each having a diameter of from about 5 to about 200 nm [pg. 2; [0024]; lines 04-06], as required by Claim 9, lines 01-05; also Claim 18, lines 01-06. In regards to particle size ranges, it is noted that “[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.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955).
Cao also addresses the requirements of the invention to comprise oil and emulsifiers. Specifically, Cao meets the limitation of the composition comprising at least one type of oil, aqueous phase, and/or emulsifier by teaching their nanoemulsions may include one or more oils and/or organic solvents that form an organic phase in which the cannabinoid, melatonin, and insulin are dissolved or suspended, an aqueous phase, and one or more emulsifiers or surfactants [pg. 3; [0038]; lines 01-06], as required by Claim 10, lines 01-02. Cao also meets the limitations wherein the oil phase comprises medium chain triglyceride oil (MCT) and the emulsifier comprises lecithin by teaching that oils and/or organic solvents of their compositions may include, but are not limited to, lecithin and MCT oil [pg. 3; [0038]; lines 10-12], as required by Claim 11, line 01-02; also Claim 12, lines 01-02.
Cao also addresses the requirement of the invention to reduce the abundance of peptide species. Specifically, Cao meets the limitation wherein amyloid beta 42/40 is reduced or eliminated in the brain of the subject by teaching reduction of amyloid beta (some embodiments -40, other embodiments -42) aggregation by about 25% to about 100% [pg. 5; [0066]; lines 01-07], as required by Claim 15, line 01-03.
A prima facie case of obviousness can be made for one of ordinary skill in the art, to combine the emulsifier-assisted formulations of Mukunda, already containing therapeutically effective amounts of CBD and melatonin, with the aqueous / oil cannabinoid nanoemulsion methodologies taught by Cao, effectively incorporating insulin for the similar treatment of Alzheimer’s disease, to produce therapeutic CBD/melatonin compositions that can be administered orally and/or nasally. One of ordinary skill in the art would have a reasonable expectation of success, given the efficacious implementation of the non-emulsified composition by Mukunda with enhanced efficacy of the nanoemulsified cannabinoid compositions of Cao, containing melatonin and insulin for the treatment of Alzheimer’s disease.
Therefore, Claim(s) 4-9, 11, 15-16, and 18-20 are rejected herein under 35 USC § 103.
Conclusion
No claims are allowed in this action.
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/STANLEY BRAM/Examiner, Art Unit 1691
/RENEE CLAYTOR/Supervisory Patent Examiner, Art Unit 1691
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