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 .
Status of Application
Receipt of the Preliminary Amendment filed on May 29, 2024 is acknowledged.
Claims 1-23 are pending in this application.
Claims 3, 5-16, and 19-22 have been amended. Claims 17-18 and 23 have been cancelled.
All pending claims are under examination.
Information Disclosure Statement
Receipt of the Information Disclosure Statements filed on May 29, 2024 and April 21, 2025 is acknowledged. A signed copy is attached to this office action.
Claim Objections
Claim 11 is objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim cannot depend from any other multiple dependent claim. See MPEP § 608.01(n). Accordingly, the claim has not been further treated on the merits.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 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.
Claims 1-16 and 19-22 are rejected under 35 U.S.C. § 112, first paragraph, 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(s), at the time the application was filed, had possession of the claimed invention.
M.P.E.P. § 2163 states, “An applicant shows possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention...one must define a compound by 'whatever characteristics sufficiently distinguish it'. A lack of adequate written description issue also arises if the knowledge and level of skill in the art would not permit one skilled in the art to immediately envisage the product claimed from the disclosed process.''
The specification does not describe any species of the instantly claimed clofazimine polymorph, derivative, or analogues. Thus, it does not describe a sufficient number of species as to convey possession of the entire genus encompassed.
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 2, 5, 8, 9, 11, 12, 19, and 22 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding 2, an optional embodiment is recited to be “band”. However, this is not an art recognized formulation type and its unclear what this component would include/exclude.
Regarding claim 5, the claim recites “further comprising an emulsifying agent, wherein the content of the emulsifying agent is less than 50% w/w, and greater than 20% w/w water”. It is unclear if the emulsifying agent is greater than 20% water or the composition is 20% water. Clarification is requested.
Regarding claim 8, the claim recites “further comprising, wherein the content…” however, no additional component is recited. Clarification is requested.
Regarding claim 9, the claim recites “emulsion or suspensions with an average diameter of most about 1 mm”. It is unclear how an emulsion or suspension can have a particle size and if said diameters are about 1 mm or if the diameters are at most 1 mm. Clarification is requested.
Regarding claim 11, it is unclear how the composition is in the form of a suspension and gel (claim 7), foam, aerosol, or spray (claim 8), emulsion (claim 9) at the same time. Clarification is requested.
Regarding claim 12, the claim “recites wherein the composition is a suspension of clofazimine, hypersonic saline 3-7%, sodium bicarbonate, bismuth, gallium, or amino acids”. The type of composition is listed in the alternative, therefore, it is unclear if the composition can be merely a suspension of sodium bicarbonate, for example. Clarification is requested.
Regarding claim 19, the claim recites use for a composition but no active method steps are recited. Therefore, it is not clear what the metes and bounds of the claim are.
Regarding claim 22, A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 22 recites the broad recitation “percentage of 50-98%” and “geometric standard deviation <2.2”, and the claim also recites “preferably 60-90%” and “preferably <1.8” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
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.
Claim 19 is rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because the claim is directed to a use of the composition and not a process, machine, manufacture, or composition of matter.
The claim will not be examined on the merits.
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 1-7, 11-12, and 14-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wang et al. (WO 2021209025).
Wang discloses a pharmaceutical composition comprising clofazimine, at least one solubilizers and optionally at least one stratum corneum penetration enhancer, where the composition is formulated for topical administration (Abstract).
The recitation of “for treatment of dermal infections with Mycobacterium ulcerans” is regarded as future intended use of the topical pharmaceutical composition.
Regarding claim 2, embodiments of topical formulations including solutions, lotions, pastes, ointments, creams, gels, aerosols, sprays, powders, and patches (occlusive dressings) (paragraph 00131). A suspension is also disclosed in the examples.
Regarding claim 3, Example 1 discloses the preparation of a clofazimine suspension.
Regarding claim 4, dosage levels on the order of from 1 mg to about 100 mg/kg of body weight per administration are useful in the treatment of a disease (paragraph 00146).
Regarding claim 5, Table 25 discloses excipients suitable to be used to prepare emulsions include labrasol (surfactant/emulsifier) and propylene glycol (surfactant/emulsifier).
Regarding claim 6, Example 1 discloses a suspension of clofazimine in an aqueous media.
Regarding claim 7, Example 6 discloses a gel preparation comprising water.
Regarding claim 11, Table 7 discloses clofazimine suspension formulation with tween 80 (polysorbate 80).
Regarding claim 12, as noted above, the examples disclose a suspension of clofazimine.
Regarding claim 14, Example 8 discloses a clofazimine gel with a pH of 7.0.
Regarding claim 15, example 30 discloses the use of a buffer salt solution.
Wang, therefore, anticipates the rejected claims.
Claims 1-3 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Walter et al. (US 11,572,588).
Walter discloses topical administration of a composition comprising clofazimine (Claim 2). The pharmaceutically acceptable composition comprises pharmaceutically acceptable carriers (column 10, lines 35-55).
Regarding claims 2-3, the composition can be in the form of a solid, gel, or liquid formulation such as a solution, suspension, or dispersion (column 16, lines 15-28).
Walter, therefore, anticipates the rejected claims.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-4 and 10-11 are rejected under 35 U.S.C. 103 as being unpatentable over Barry et al. (US 5,610,198).
Barry discloses compounds, pharmaceutical compositions, and methods for the treatment of mycobacterial diseases (abstract).
The compounds include clofazimine (column 6, line 8). The pharmaceutical composition comprises the compound in a pharmaceutically acceptable carrier (column 5, lines 39-41).
The compound can be administered encapsulated in liposomes, pharmaceutical delivery vehicles wherein the active ingredient is contained either dispersed or variously present in capsules consisting of aqueous concentric layers adhere rent to lipidic layers (column 7, line 65 through column 8, line 3). The compositions can be in the form of a liposomal suspension having diameters of the liposomes in the range of 15 nm to about 5 microns (column 8, lines 10-12).
Regarding claims 2-3, as noted above, the composition can be in the form of a suspension. Topical formulations can additionally include gels, oil in water or water in oil emulsions, typically including emollients, emulsifiers, wax, fat, alcohol, and oils (column 10, lines 8-29).
Regarding claim 4, the dosage of the therapeutic compound ranges from about 10 micrograms to about 100 mm per kg per day (column 11, line 31-34).
Regarding claim 10, the composition can be a sterile aerosol solution (column 9, line 35-45). The recitation of a solution indicates there are no solid particles.
Regarding claim 11, the suspension can comprise tween 80 (column 9, lines 45-51).
While Barry does not exemplify a topical pharmaceutical formulation, it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the invention to have prepared said formulation utilizing the compounds disclosed by Barry since it is disclosed as discussed within the prior arts teachings.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (WO 2021209025) as applied to claims 1-7, 11-12, and 14-15 above, and further in view of Danaei et al. (Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier System, Pharmaceutics, Published May 18, 2018).
The teachings of Wang are discussed above. Wang does not disclose the average diameter of at most about 1 mm and/or a polydispersity index of at most about 1 D.S.
Danaei discloses lipid based drug delivery systems. The behavior of which is determined by average particle size/diameter and the polydispersity index, which is an indication of their quality with respect to size distribution (abstract). Table 1 discloses transdermal (topical) administration ranges in particle size of 100-600 nm.
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the invention to have prepared the emulsions of Wang since Danaei discloses controlling and validating average particle diameter and polydispersity are of key importance of the effective clinical applications of nanocarrier formulations.
Claims 1-7, 11-13, and 14-15 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (WO 2021209025).
The teachings of Wang are discussed above.
Wang does not explicitly disclose the composition has an antibiotic concentration of 1 mg/mL.
Wang does disclose dosage levels of the formulation can range from 0.001 mg/kg to about 1,000 mg/kg (page 0146). It is additionally disclosed that the clofazimine can be present in the formulation is the range of 0.001% to about 10% of the total weight of the composition (paragraph 0063).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the invention to have prepared a formulation having an antibiotic concentration of 1 mg/mL depending on the type of formulation (i.e. solution, dispersion, emulsion) since Wang discloses the formulation can be prepared in wide range of dosages and concentrations. Applicant is directed to MPEP 2141.03 which discloses "A person of ordinary skill in the art is also a person of ordinary creativity, not an automaton." KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 421, 82 USPQ2d 1385, 1397 (2007).
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (WO 2021209025) as applied to claims 1-7, 11-12, and 14-15 above, and further in view of Hofmann et al. (WO 2021/222740).
The teachings of Wang are discussed above.
Wang does not explicitly disclose the osmolality and ion concentration of the composition.
Hofmann discloses clofazimine composition in the form of a solution, suspension, or a dry powder. The composition can have an acceptable carrier and/or excipient (paragraph 0011).
The clofazimine is present in the amount of 1mg to 30 mg per dose (paragraph 0014).
Regarding claim 16, the osmolality of the formulation can be adjusted based on the type of formulation, for example, a hypertonic or hypotonic solution or suspension (paragraph 0040).
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the invention to have prepared a formulation having different osmolality’s based on their intended function and type of formulation. Applicant is reminded that where the general conditions of the claims are met, burden is shifted to applicant to provide a patentable distinction. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See In re Aller, 220 F.2d 454 105 USPQ 233,235 (CCPA 1955).
Claims 20 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (WO 202109025) as applied to claims 1-7, 11-12, and 14-15 above, and further in view of Burger et al. (Formulation of Natural Oil Nano-Emulsion for the Topical Delivery of Clofazimine, Artemisome, and Decoquinate, Pharm Res (2018) 35:186).
The teachings of Wang are discussed above.
Wang does not disclose the preparation of an emulsion according to the instant claims.
Burger discloses the preparation of nano emulsions for topical delivery (abstract).
Regarding claim 20, Table 1 discloses multiple formulations in which the clofazimine is dissolved in the oil phase and tween 80 (nonionic surfactant) is in the aqueous phase.
Regarding claim 22, Table 3 discloses the droplet sizes 83-126 nm, which is <5 pm.
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the invention to have prepared a formulation having different droplet/ particle size of the nanoemulsions based on their intended function and type of formulation to improve permeation and absorbption of the composition. Applicant is reminded that where the general conditions of the claims are met, burden is shifted to applicant to provide a patentable distinction. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See In re Aller, 220 F.2d 454 105 USPQ 233,235 (CCPA 1955).
Claims 21 is rejected under 35 U.S.C. 103 as being unpatentable over Wang et al. (WO 202109025) Burger et al. (Formulation of Natural Oil Nano-Emulsion for the Topical Delivery of Clofazimine, Artemisome, and Decoquinate, Pharm Res (2018) 35:186) as applied to claims 1-7, 11-12, 14-15, 20 and 22 above, and further in view of Rensburg (Formulation and Topical Delivery of liposomes and proliposomes containing clofaziminie, November 2016).
The teachings of Wang are discussed above.
Wang does not disclose the preparation of the emulsion and liposomes recited in claims 20 and 21.
Rensburg discloses clofazimine encapsulated in liposomes for topical delivery. (page 4).
Rensburg discloses a drug molecule will not be able to cross the stratum corneum if its highly hydrophilic (section 2.8.7). It is disclosed liposomes are essentiona in regards to poorly water soluble drugs. They act by encapsulating the poorly soluble drugs, like clofazimine into the micelle structure.
It would have been obvious to one of ordinary skill in the art prior to the effective filing date of the invention to have prepared a formulation having different droplet/ particle size of the nanoemulsions based on their intended function and type of formulation to improve permeation and absorbption of the composition. Applicant is reminded that where the general conditions of the claims are met, burden is shifted to applicant to provide a patentable distinction. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. See In re Aller, 220 F.2d 454 105 USPQ 233,235 (CCPA 1955).
Conclusion
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/MELISSA S MERCIER/Primary Examiner, Art Unit 1615