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
The Preliminary Amendment filed on 04/01/24 is acknowledged.
Claims 1-28 were cancelled.
New claims 29-32 were added and are included in the prosecution.
Priority
This Application is a 371 of PCT/IB2022/059329 filed on 09/30/22. This Application also claims foreign priority to ZA 2021/07408 filed on 10/01/21. Receipt is acknowledged of certified copies of papers submitted under 35 U.S.C. 119 (a)-(d), which papers have been placed of record in the file.
Information Disclosure Statement
The information disclosure statement (IDS) filed on 04/01/24 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97 and 1.98. Accordingly, the examiner is considering the information disclosure statement. Please see the attached copy of PTO-1449.
Specification
The disclosure is objected to because of the following informalities:
Although the description of Figures 1-4 is provided in the Specification (starting on Page 5, line 8), this description is not preceded by the section heading "BRIEF DESCRIPTION OF THE DRAWINGS." Based on MPEP § 608.01 (a) and (f), as well as 37 C.F.R. § 1.77(b), the Specification should be amended to recite the section heading "Brief Description of Drawings" on Page 5, after line 6.
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 of this title, 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.
Claims 29-32 are rejected under 35 U.S.C. 103 as being unpatentable over Rubinstenn et al. (US 2002/0028186 A1 – “Rubinstenn”) in view of Patyal et al. (International Journal of Pharmacy & Life Sciences, 2019, 10(5), 6236–6251 – “Patyal”), Li et al. (US 2020/0069806 A1 – “Li”), Essien et al. (World Journal of Pharmaceutical Research, 2015, Volume 4, Issue 6, 274-285 – “Essien”), Barot et al. (Research & Reviews: Journal of Dairy Science and Technology, 2015, Volume 4, Issue 1, 15-27 – “Barot”), and Wassel et al. (US 2015/0164846 A1 – “Wassel”).
Instant claim 29 is drawn to a formulation for transdermal delivery of diosgenin to a patient to treat type II diabetes mellitus in the patient, the formulation comprising diosgenin encapsulated in a nanoemulsion matrix, wherein the nanoemulsion matrix is an oil-in-water nanoemulsion comprising diosgenin dissolved in an oil phase of the nanoemulsion matrix; the oil phase comprises a 1:1 combination of sesame oil and bottle gourd seed oil; and the ratio of oil to water is 4:1.
Rubinstenn teaches a composition in any pharmaceutical form normally used for topical application to the skin in the form of an oil-in-water nanoemulsion ([0042], [0088], [0090], [0092], [0094], [0096], [0098], [0100]). The composition comprises at least one sapogenin and a solubilizing system which makes it possible to dissolve a sufficient amount of sapogenin, without crystallization, for a period of time which is acceptable for cosmetic or dermatological use (Abstract). Sapogenins are included in the composition (Abstract) in an amount of from 0.001% to 10% of the total weight of the composition ([0024]). The sapogenins include diosgenin ([0004], [0023], Examples 1-11, claims 1 and 13-14). The emulsion contains a fatty phase which ranges from 5% to 80% by weight ([0045]). The composition contains a plant oil to solubilize the sapogenin (Abstract, [0011], [0020], [0031], claims 1 and 17). The plant oil is included in a proportion of from 0.1% to 80% by weight relative to the total weight of the composition ([0032]). The composition contains emulsifiers and co-emulsifiers in a proportion ranging from 0.3% to 30% by weight and include oxyethylenated sorbitan stearates available under the trade names Tween®20 or Tween®60 ([0047]).
Rubinstenn does not expressly teach the treatment of diabetes mellitus or the oil phase comprising a 1:1 combination of sesame oil and bottle gourd seed oil.
Patyal teaches oil-in-water microemulsions for the delivery of Trigonella foenum graecum wherein the oil phase contains Tween 80 and Span 20 as surfactant and cosurfactant respectively (Abstract). Patyal teaches that Trigonella foenum graecum belongs to Fabaceae family, is also known as methi, contains diosgenin, and is used for the treatment of diabetes mellitus (Abstract) since administration of defatted seeds caused reduction in fasting and postprandial blood levels of glucose, glucagon, somatostatin, insulin, triglycerides, and HDL-cholesterol levels in diabetic dogs, and has an anti-hyperglycemic effect (Page 6237, ¶ bridging Col. 1 and Col. 2).
Li teaches a pharmaceutical carrier containing sesame oil wherein the pharmaceutical carrier is used in the preparation of an anti-diabetic pharmaceutical composition (Abstract, claims 1-4, 6-11, 13-14, and 16). The sesame oil is present in an amount of 40-85% by weight, relative to the weight of the pharmaceutical composition (Abstract). The pharmaceutical composition is in the form an emulsion ([0042]).
Essien teaches the polyphenols content and antioxidant activity of Lagenaria siceraria seed oils of four bottle gourd cultivars and conclude that seeds of these bottle gourds provide health benefits (Abstract, Tables 1 and 2, Page 282 - Conclusion). Ethno-medicinal usage reveals that L. siceraria seed is used in the treatment of diabetes mellitus (Page 275, penultimate ¶).
Barot teaches that in Ayurveda, bottle gourd is advocated for treatment of diabetes mellitus (Abstract and Page 15 – Introduction section, Page 16, Col. 1, penultimate ¶). Seeds of bottle gourd contain enormous phyto-chemicals, vitamins, minerals, amino acids and omega fatty acids, and the oil extracted from bottle gourd seeds has pale yellow color (Page 18, Col. 1). The wild bottle gourd Lagenaria sphaerica seed is rich in protein and minerals and contained high lipid levels similar to those found in other oilseeds (Page 18, Col. 2).
Wassel teaches a microemulsion topical delivery platform (Title) comprising an oil-in-water microemulsion comprising an oil and a pair of surfactants including a polysorbate and glycerol (claim 19). Polysorbates are sold under the name Tween ® ([0057]).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to prepare a composition for application to the skin in the form of an oil-in-water nanoemulsion which contains diosgenin, a fatty phase which contains a plant oil, and emulsifiers and co-emulsifiers, as taught by Rubinstenn, in view of the use of diosgenin in the treatment of diabetes mellitus, as taught by Patyal, the use of sesame oil in an emulsion form of an anti-diabetic pharmaceutical composition, as taught by Li, the use of bottle gourd seed oil in the treatment of diabetes mellitus, as taught by Essien and Barot, and the use of polysorbate and glycerol as surfactants in an emulsion formulation for topical delivery, as taught by Wassel, and produce the instant invention.
One of ordinary skill in the art would have been motivated to include the sesame oil taught by Li in the nanoemulsion of Rubinstenn because both references teach emulsion formulations and it is obvious to combine prior art elements according to known methods to yield predictable results. Please see MPEP 2141(III)(A).
One of ordinary skill in the art would have been motivated to include the sesame oil taught by Li, and the bottle gourd seed oil taught by Essien and Barot in the nanoemulsion taught by Rubinstenn, since Rubinstenn teaches that a plant oil is used to solubilize the sapogenin (Abstract, [0011], [0020], [0031], claims 1 and 17) and the simple substitution of one known element (sesame oil and bottle gourd seed oil taught by Li, Essien and Barot) for another (plant oil – taught by Rubinstenn) to obtain predictable results (prepare a nanoemulsion) is obvious. Please see MPEP 2141(III)(B).
Moreover, the sesame oil (taught by Li) and bottle gourd seed oil (taught by Essien and Barot) are used in the treatment of diabetes mellitus and since the active ingredient used in the composition of Rubinstenn, i.e., diosgenin, is used in the treatment of diabetes mellitus, as taught by Patyal (Abstract), it would have been obvious to combine the oils and use them in the composition of Rubinstenn. MPEP 2144.06 states: "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose .... [T]he idea of combining them flows logically from their having been individually taught in the prior art." Thus, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made or before the effective filing date of the claimed invention to combine the sesame oil of Li and the bottle gourd seed oil of Essien and Barot with the diosgenin of Rubinstenn with a reasonable expectation of success because each component is taught to be useful for the same purpose, i.e., use in an anti-diabetic composition, and it is prima facie obvious to combine said actives to form a third composition to be used for the very same purpose.
One of ordinary skill in the art would have found it obvious to include the polysorbate and glycerol as taught by Wassel as the emulsifiers and co-emulsifiers in the nanoemulsion taught by Rubinstenn since the simple substitution of one known element for another to yield predictable results is obvious. Please see MPEP 2141(III)(B). Also, based on MPEP 2144.06, one of ordinary skill in the art would have found it obvious to combine the emulsifiers and co-emulsifiers taught by Wassel in the nanoemulsion formulation of Rubinstenn and have a reasonable expectation of success in producing a functional nanoemulsion formulation.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Regarding instant claims 29 and 32, the limitations of the formulation comprising diosgenin encapsulated in a nanoemulsion matrix wherein the nanoemulsion matrix is an oil-in-water nanoemulsion comprising diosgenin dissolved in an oil phase of the nanoemulsion matrix (instant claim 29) and a method of producing a formulation (instant claim 32) would have been obvious over the preparation of the composition used for topical application to the skin in the form of an oil-in-water nanoemulsion ([0042], [0088], [0090], [0092], [0094], [0096], [0098], [0100]), wherein the composition comprises at least one sapogenin and a solubilizing system which makes it possible to dissolve a sufficient amount of sapogenin, without crystallization, for a period of time which is acceptable for cosmetic or dermatological use (Abstract), and wherein the sapogenin includes diosgenin ([0004], [0023], Examples 1-11, claims 1 and 13-14), as taught by Rubinstenn.
Regarding instant claims 29 and 32, the limitations of the oil phase comprising a 1:1 combination of sesame oil and bottle gourd seed oil would have been obvious over the sesame oil (Abstract, claims 1-4, 6-11, 13-14, and 16) present in an amount of 40-85% by weight, relative to the weight of the pharmaceutical composition (Abstract), as taught by Li, and the bottle gourd seed oil taught by Essien (Abstract, Tables 1 and 2, Page 275, penultimate ¶, and Page 282 – Conclusion) and Barot (Abstract, Page 15 – Introduction, Page 16, Col. 1, penultimate ¶, Page 18, Col. 1 and Col. 2). One of ordinary skill in the art would have found it obvious to include the sesame oil and the bottle gourd seed oil in equal amounts, i.e., in a ratio of 1:1, in the nanoemulsion formulation.
Regarding instant claim 29, the limitation of the ratio of oil to water of 4:1 would have been obvious over the emulsion which contains a fatty phase which ranges from 5% to 80% by weight ([0045]), as taught by Rubinstenn. Based on this teaching of Rubinstenn, one of ordinary skill in the art would have found it obvious to calculate the remaining aqueous or water phase in the emulsion as 20% to 95% water. Based on the upper limit of 80% of fatty phase (or oil) taught by Rubinstenn and the calculated remaining 20% of water, the ratio of oil to water is 4:1.
Regarding instant claim 29, the limitation of transdermal delivery of diosgenin to a patient to treat type II diabetes mellitus in the patient is a future intended use of the claimed formulation. A recitation of the intended use of the claimed invention must result in a structural difference between the claimed invention and the prior art in order to patentably distinguish the claimed invention from the prior art. If the prior art structure is capable of performing the intended use, then it meets the claim. In the instant case, the prior art nanoemulsion containing diosgenin and a plant oil, as taught by Rubinstenn, in view of the use of diosgenin in the treatment of diabetes mellitus, as taught by Patyal, the use of sesame oil in an emulsion form of an anti-diabetic pharmaceutical composition, as taught by Li, and the use of bottle gourd seed oil for the treatment of diabetes, as taught by Essien and Barot, would be capable of performing the intended use. Moreover, the primary reference, Rubinstenn, also teaches the application of the composition to the skin ([0042]), and one of ordinary skill in the art would have expected transdermal delivery of the diosgenin included in the composition.
Regarding instant claim 30, the limitation of a non-ionic surfactant and a co-surfactant would have been obvious over the emulsifiers and co-emulsifiers in a proportion ranging from 0.3% to 30% by weight which include oxyethylenated sorbitan stearates available under the trade names Tween®20 or Tween®60 ([0047]), as taught by Rubinstenn, in view of the pair of surfactants including a polysorbate (Tween ®) and glycerol (claim 19, [0057]), as taught by Wassel.
Regarding instant claim 31, the limitation of a cosmetic gel would have been obvious over the composition which is acceptable for cosmetic or dermatological use (Abstract), and the gel ([0042]-[0043]), as taught by Rubinstenn.
Regarding instant claim 32, the limitation of adding 15% emulsifiers in the form of a mixture of 1:1 non-ionic surfactant and a co-surfactant to 60% of the oil phase would have been obvious over the emulsifiers and co-emulsifiers in a proportion ranging from 0.3% to 30% by weight which include oxyethylenated sorbitan stearates available under the trade names Tween®20 or Tween®60 ([0047]), as taught by Rubinstenn, in view of the pair of surfactants including a polysorbate (Tween ®) and glycerol (claim 19, [0057]), as taught by Wassel. One of ordinary skill in the art would have found it obvious to include the polysorbate and glycerol taught by Wassel in equal amounts or in a ratio of 1:1. The claimed amount of 15% emulsifiers would have been obvious over the overlapping range of 0.3% to 30% by weight ([0047]), as taught by Rubinstenn. The limitation of 60% of the oil phase would have been obvious over the fatty phase in an overlapping range of from 5% to 80% by weight ([0045]), as taught by Rubinstenn. According to MPEP 2144.05, “In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists.” One of ordinary skill in the art would have found it obvious to modify the amount of emulsifiers in the oil phase or fatty phase based on the desired level of emulsification and solubilization of the diosgenin. The recited amounts would have been obvious variants based on the teachings of Rubinstenn absent evidence of criticality or unexpected results.
Regarding instant claim 32, the limitation of dissolving 40 mg/kg (calculated to be 0.004% by weight) diosgenin in the oil phase would have been obvious over the overlapping range of sapogenins an amount of from 0.001% to 10% of the total weight of the composition ([0024]), wherein the sapogenins include diosgenin ([0004], [0023], Examples 1-11, claims 1 and 13-14), as taught by Rubinstenn. Please see MPEP 2144.05. The limitation of ambient temperature and a magnetic stirrer would have been obvious over the preparation of phase C at room temperature and the mixing with magnetic stirring ([0087]), as taught by Rubinstenn. One of ordinary skill in the art would have found it obvious to modify the method of Rubinstenn and use room temperature and magnetic stirring to dissolve the diosgenin in the oil phase absent evidence of criticality or unexpected results.
Regarding instant claim 32, the limitation of adding distilled water dropwise to the mixture would have been obvious over the demineralized water (Examples 5-11), as taught by Rubinstenn. The limitation of adding the distilled water dropwise while stirring by the magnetic stirrer would have been obvious over the magnetic stirring ([0087]), as taught by Rubinstenn. One of ordinary skill in the art would have found it obvious to use various methods of adding the demineralized water to obtain the oil-in-water nanoemulsion of Rubinstenn. The limitation of the ratio of oil to water of 4:1 would have been obvious over the emulsion which contains a fatty phase which ranges from 5% to 80% by weight ([0045]), as taught by Rubinstenn. Based on this teaching of Rubinstenn, one of ordinary skill in the art would have found it obvious to calculate the remaining aqueous or water phase in the emulsion as 20% to 95% water. Based on the upper limit of 80% of fatty phase (or oil) taught by Rubinstenn and the calculated remainder or 20% of water, the ratio of oil to water is 4:1.
Conclusion
No claims are allowed.
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/ARADHANA SASAN/Primary Examiner, Art Unit 1615