The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Formal Matters
Claims 3, 5, 7-8, 10, 12, 14, 16, 18-20, 22, 24, 26, 28, 29, and 31-59 are cancelled. Claims 62-65 are new. Claims 1, 2, 4, 6, 9, 11, 13, 15, 17, 21, 23, 25, 27, 30, and 60-65 are pending and under examination.
Priority
This application is a national stage entry of PCT/US2021/021182 filed on 3/5/2021, which claims priority from US provisional applications 63/055,038 filed on 7/22/2020 and 62/985,529 filed on 3/5/2020.
Rejections Withdrawn
The rejection under USC 112(b) over claim 24 is withdrawn as this claim was cancelled rendering the rejection moot.
The rejection under USC 112(a) over claims for treating any disease or disorder and preventing a disease or disorder is withdrawn per applicant’s amendments to claims 27 and 60 to remove “preventing” and to limit the disease to alopecia areata.
The rejection under USC 102(a)(1) over Kaufman US 20180296493 is withdrawn per applicant’s amendments to indicate that the nanoparticulate cannabidiol is substantially free of lipid or polymeric nanocarriers and the amendments claim 27 and 60 to indicate alopecia areata as the disease to be treated. In applicant’s specification “substantially free of lipid or polymeric nanocarriers” is provided to be 1% or less by weight (paragraph 20 of applicant’s specification). Kaufman teaches well over 1% by weight of lipid nanocarriers in its formulations and does not provide for treating alopecia areata.
The rejection under USC 102(a)(2) over Milane is withdrawn per applicant’s amendments as stated above for the withdrawal of the 102 rejection over Kaufman. Milane’s exemplified particles have lipid nanocarrier and Milane does not provide for alopecia areata.
The rejection under USC 102(a)(1) over Bevier is withdrawn per applicant’s amendments as stated above for the withdrawal of the 102 rejection over Kaufman. Bevier’s exemplified particles have polymer nanocarrier and although Bevier provides that it may be used to treat diseases including alopecia areata does not exemplify it particularly.
As these rejections are withdrawn, applicant’s arguments toward these rejections are now moot.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Maintained Rejections – Modified as Necessitated by Amendments/New Claims
Claims 1, 2, 4, 6 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Milane WO 2020186212.
Milane teaches nano-formulations of cannabidiol (abstract and claim 1 of Milane). Milane teaches CBD and other cannabinoids and methods of treating specific skin diseases, disorders or conditions (Field of the Invention). Pages 17-18 teaches CBD. Cannabidiol is taught to be at 0.5% to 1% by weight of the nanoformulation (15 to 38 mM) (Milane, page 18), but also provides, here, that cannabidiol can be in an amount to be effective to treat a given skin condition. Milane allows for another additional active agent (top of page 19). Milane provides that the nanomaterial is about 40 nm, about 45 nm, about 50 nm, about 100 nm, between 40 and 100 nm, and other sizes (pages 20). Milane teaches in embodiments the formulation comprises a cannabidiol and a lipid (bottom of page 21 to 22). Milane defines carriers (page 8). Milane teaches nanostructured lipid carriers (definitions). Milane teaches oil-in-water nanoemulsions for the formulation, which would be the carrier (pages 24). Milane teaches various topical formulations (page 27). Milane provides for treatment of subjects with the formulations having various skin diseases/disorders (Figures 1-12). Milane teaches highly purified cannabinoids with purity greater than or equal to 98% w/w (page 10). Milane teaches particle size of between about 40 nm to 100 nm for nanoparticles and nanoparticles being micelles, nanoparticles, lipid nanocapsule and others (page 21). Milane provides for treatment of hair loss (second paragraph of claim 33). Milane teaches treating autoimmune connective tissue diseases, rheumatoid arthritis, and lupus conditions (top of page 34). Lupus and rheumatoid arthritis are an autoimmune diseases. Milane provides that nanoparticles are made to average size of 50 nm for enhanced penetration and bioavailability and that lipid based nanoparticle comprises cannabidiol that is fully encapsulated within the lipid portion of the particles (bottom of page 40). Milane provides for nanoemulsion being monophasic and being colloidal dispersions (bottom of page 11 and top of page 12). Milane provides for nanoparticles having spherical shape called nanospheres (page 12, first full paragraph). Milane allows for nanoparticles being micelles (page 21), thus, nano-micelles as one option. Milane allows for inorganic nanocarriers like metals or metal oxides as an alternative to lipids or polymers (page 21).
One of ordinary skill in the art before the time of filing would have used the teachings of Milane to provide monodisperse formulations of a nanoparticulate cannabidiol in forms such as micelles (nano-micelles) that is substantially free of lipid or polymeric nanocarriers and at least 95% by wt of cannabidiol since Milane provides that its cannabidiol can be of single size ranges (e.g. about 40, about 45, about 50, etc.), are monophasic (one phase) in embodiments, and the cannabinoid (e.g. cannabidiol) can be fully encapsulated and greater than 98% w/w pure which means that the lipid or polymer would not be mixed with the cannabinoid itself when fully encapsulated. Milane also provides that nanoparticles can be micelles, which would be construed as nano-sized micelles. Thus, there was a reasonable expectation of success that by the teachings of Milane in respect to its nanoparticulate cannabidiol formulations (including nano-micelles) with fully encapsulated, 98% w/w pure cannabidiol/cannabinoid, one of ordinary skill in the art would arrive at a formulation as applicant has claimed. Milane also allows formulations to treat hair loss as well as to treat various autoimmune disorders that it provides as treatable with its formulations such as lupus and rheumatoid arthritis.
Claims 1, 2, 11, 13, 15, 25, 27, 30, 60, and 62-65 are rejected under 35 U.S.C. 103 as being unpatentable over Bevier US 20140302121.
Bevier teaches cannabinoid receptor binding agents contained in a particle for treatment of skin conditions (abstract). Bevier teaches the particle may be a nanoparticle (abstract). Bevier also teaches a vesicle can carry the cannabinoid binding agent and nanoparticle (claims 1 and 2 of Bevier). Bevier teaches “Cannabidiol loaded PLGA nano-spheres in the range of about 150-300 nm are obtained.” (paragraph 119). Bevier teaches “if desired, other hair growth modulators, such as minoxidil, may be included” (paragraph 160). Bevier teaches sizes of nanoparticle transdermal delivery vehicles with sizes of about 100 nm to about 200 nm among others (paragraphs 46-48). Bevier teaches a composition with cannabidiol, ethanol or propylene glycol and water (table 2), and thus, recognizes these ingredients for carriers of cannabidiol. Bevier teaches gel delivery vehicle with propylene glycol and water (paragraph 112). Bevier teaches pigmentation and hair growth treatments (paragraph 154). Bevier teaches transdermal delivery through a viable epidermis (paragraph 73). Tables 2 and 3 in Bevier are provided as antifungal treatment (paragraphs 147-150). Bevier teaches hair growth and treating alopecia areata (AA is an autoimmune disease) and other alopecia conditions (paragraphs 159-160). Bevier teaches “A nanoparticle may be in the form of a nanosphere (a matrix in which an active ingredient is dispersed throughout) and a nanocapsule (that is, the active ingredient is confined in a cavity surrounded by a polymeric membrane).” (paragraph 57). Paragraph 206 provides for purified cannabidiol. Bevier allows for nanoparticle with metal and provides for metallic layers like nanoshells, or Bevier provides for magnetic particles (paragraphs 53-55). This is an alternative to other forms of nanoparticles in Bevier.
One of ordinary skill in the art before the time of filing would have been capable of combining minoxidil with cannabidiol nanoparticles and an acceptable carrier and used the formulations for a variety of skin conditions including alopecia areata and to help grow hair/reduce hair loss by the teachings of Bevier as all these elements are taught for options of drug combination and treatments in Bevier. Bevier also provides for an overlapping range of CBD nanoparticle size with applicant’s claim 2 (see MPEP 2144.05). Thus, there was a reasonable expectation of success in producing formulations and treatments as in applicant’s claims with teachings of Bevier.
Claims 9 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Bevier US 20140302121 and Biro WO 2017055846A1.
Bevier teaches claims as discussed previously.
Bevier does not teach concentrations of CBD of the claims.
Biro teaches cannabinoids in the treatment of an inflammatory skin disease including cannabidiol (abstract). Biro teaches using amounts of cannabinoids of 0.3 uM and 3 uM (paragraph 99) exhibiting anti-inflammatory action on IL-6 release (also see paragraph 105 and table 1 for CBD specifically). Biro teaches alopecia areata as an inflammatory skin disease (paragraph 4 and paragraph 73). Biro provides for using a dose of less than 2000 mg cannabinoid (paragraph 42). Biro teaches an oral or topical composition (paragraph 47). Biro also teaches using 20 uM (6.3 ug/ml) of CBD in treating HaCaT cells (paragraph 136). Biro teaches creams and sunscreens for such formulations (paragraph 51).
Thus, one of ordinary skill in the art before the time of filing would work with the range of 0.3 and 3 uM of Biro using cannabidiol to treat an inflammatory skin disease like alopecia areata as also presented in Bevier and reasonably expect successful treatment due to its anti-inflammatory effect at values of 0.3 (0.094 ug/ml) and 3 uM (0.94 ug/ml) cannabidiol. One would also consider adjusting the dose based on the type of administration and desired effect since Biro also recognizes topical forms and a wider range of dose amounts in mg (less than 2000 mg or between 10mg and 1000 mg claims 10 and 11 of Biro). If one would desire more anti-inflammatory effectiveness of CBD they would raise the value of cannabidiol used in the formulation.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over Bevier US 20140302121 and Pena US 7442369.
Bevier teaches the claims as discussed previously.
Bevier does not teach an amount of the minoxidil for the formulation.
Pena teaches concentrations of minoxidil of about 5% to about 6% and about 5% (claims 2 and 3 of Pena). Pena teaches “wherein said pharmaceutically acceptable solvent is selected from the group consisting of ethanol, propanol, butanol, propylene glycol, dipropylene glycol, hexylene glycol, 1,3-butylene glycol, PEG-200, PEG-400, glycerol and mixtures thereof” (claim 4 of Pena). Pena teaches hair growth and hair loss treatment (abstract).
One of ordinary skill in the art before the time of filing would utilize amounts of minoxidil of about 5% to about 6% of teachings of Pena in formulations to treat hair loss in Bevier as these are seen as acceptable amounts to promote hair growth and/or to reduce hair loss. There would be a reasonable expectation of success in utilizing such amounts of minoxidil and having a formulation that treats hair loss in a subject.
Claims 23 are rejected under 35 U.S.C. 103 as being unpatentable over Bevier US 20140302121, Biro WO 2017055846A1 and Pena US 7442369.
The teachings of Bevier, Biro and Pena are all found above.
Bevier does not teach the amounts of cannabidiol or minoxidil of claim 23 or a ratio of cannabidiol and minoxidil of claim 24.
Biro teaches an array of dosage ranges for cannabinoids including CBD which is a tested cannabinoid for its anti-inflammatory effects. The dose amounts can range into mg and there are exemplary uses in the ug/ml range (see Biro teachings above). Biro teaches alopecia areata as a condition with inflammation on the skin.
Pena teaches about 5% (50 mg/ml) to about 6% (60 mg/ml) of minoxidil for hair growth and reducing hair loss (see Pena teaches above).
One of ordinary skill in the art before the time of filing would have routinely adjusted the formulations to provide useful amounts of cannabidiol and minoxidil in the formulation for their effects on treating inflammation and hair loss in subjects with alopecia and optimized such values as motivated by the prior art to arrive at other useful dose concentrations of the two drugs. In doing so, applicant would be capable of arriving at dosages to provide effective treatments for certain forms of hair loss in subjects.
New Rejection – As Necessitated by Amendment to Claim 60, which changed the scope of Claim 61
(Claim 61 was formerly taught by Milane)
Claim 61 is rejected under 35 U.S.C. 103 as being unpatentable over Bevier US 20140302121 and Milane WO 2020186212.
Bevier teaches the claims as discussed above. Bevier’s teachings provide for alopecia areata as a condition to be treated with its formulations (see teachings above).
Bevier does not teach the form of micelle as in claim 61.
Milane allows for nanoparticles being micelles (page 21), thus, nano-micelles as one option. Milane teaches nano-formulations of cannabidiol (abstract and claim 1 of Milane). Milane teaches CBD and other cannabinoids and methods of treating specific skin diseases, disorders or conditions (Field of the Invention). Milane teaches various topical formulations (page 27).
One of ordinary skill in the art before the time of filing would have seen micelles as an acceptable form for a pharmaceutically acceptable carrier for nanoparticulate cannabidiol formulations by the combined teachings of Bevier and Milane which are both to treating disease with nanoparticulate forms of cannabidiol that is administered topically to the user. Therefore, there was a reasonable expectation of success in being able to also use micelles as pharmaceutical carriers for nanoparticulate cannabidiols of the prior art to treat conditions including alopecia areata by the combined teachings of the references.
Response to Applicant’s Arguments over the Rejections under USC 103
Applicant argues that nanoparticulate cannabidiol refers to substantially pure cannabidiol. Applicant provides examples in the specification (e.g. about 90%, 95%,…..or 100% pure by weight) (paragraph 17 of applicant’s specification). These examples may allow to down to 81% based on applicant’s use of “about 90%”. If applicant feels a certain percentage of purity of cannabidiol is important to the claimed invention, then applicant may apply this percentage in the claim, however, it should be noted that Milane previously taught claim 6 (“Milane teaches highly purified cannabinoids with purity greater than or equal to 98% w/w (page 10)”). Thus, this degree of purity was recognized by the prior art for the cannabinoids that are encompassed in Milane’s teachings, which includes cannabidiol.
Applicant argues that the nanoparticles are prepared through a process that yields cannabidiol nanoparticles without requiring encapsulation or loading into exogenous particles. If applicant desires to fully overcome the prior art that allows for various carrier substances (lipids, polymers, metals or metal oxides) to be included in the nanoparticles in addition to their high purity, Applicant might consider terminology such as wherein the carrier-free nanoparticulate cannabidiol consists of greater than 98% by weight of cannabidiol (note this is supported in paragraphs 21 and 67 of the specification, also note this is one example of a suggestion). This type of language would capture that it is significantly the substantially pure nanoparticulate cannabidiol without an associated carrier that is responsible for the functions after topical application. Note that both Milane and Bevier allow for alternative forms that are not polymeric or lipids (e.g. metals or metal oxides or inorganic nanocarrier, paragraph 53 in Bevier and third paragraph on page 21 in Milane) and these alternatives of the prior art are considered as all of the teachings of the prior art must be considered. That is, there are non-polymer and non-lipid nanocarriers that may be utilized in the prior art. Thus, the nanoparticulate cannabidiol in Bevier or Milane does not have to have lipid or polymer nanocarriers at all. Until a nanoparticulate cannabidiol properly excludes containing a carrier, the claim still would allow for it to be added and until the substantial purity is provided by percentage range in the claim, other reasonably interpreted purities or relatively high cannabidiol percentages can be deemed substantially pure in the prior art.
Applicant argues Milane’s use of lipids and Bevier providing for PLGA (a polymer) for nanoparticles. As stated above, applicant must consider the full teachings of the references including the non-preferred and alternative embodiments that they allow (MPEP 2123 I and II). The lipids or PLGA were items that were exemplified in the references, but were not the only ways recognized to carry out the invention in terms of the nanoparticulate cannabidiol as the references stated alternatives. Additionally, the claim does not exclude or limit these other alternative forms.
Applicant argues that Milane defines high purity cannabinoids, but does not provide the use of pure cannabidiol. As stated above, the claims do not yet capture a pure cannabidiol nanoparticle that would be carrier-free (nanoparticle does not include a carrier). Applicant should consider further amendments that limit the nanoparticulate cannabidiol to these desired features in a manner that overcomes the prior art.
Applicant argues that neither Biro or Pena cure the deficiencies. As argued above, Milane or Bevier are still prior art for their teachings. Biro and Pena are used to teach limitations of dependent claims.
Applicant argues results established in applicant’s specification. It is noted they rely on the particular nanoparticle cannabidiol of applicant’s work. As suggested above, this form may be limited in a manner that captures the purity of the cannabidiol and lack of carrier/nanocarrier in the nanoparticulate. Bevier recognizes the use of minoxidil, however, if applicant more particularly captures the form of nanoparticulate cannabidiol that was invented for the formulation, then the claims will be commensurate in scope with applicant’s results.
For these reasons, the rejections are maintained above. As applicant amended claim 60 to more specifically treating alopecia areata, the examiner had to recombine the prior art to teach method claim 61 with a limitation provided by formerly cited Milane. No new prior art was needed and this was based on an already cited teaching of Milane.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARK V STEVENS whose telephone number is (571)270-7080. The examiner can normally be reached on M-F 9:00 am to 6:00 pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian-Yong Kwon can be reached on (571)272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MARK V STEVENS/Primary Examiner, Art Unit 1613