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 . Claims 1-15 filed March 17, 2025 are currently pending.
Election/Restrictions
Applicant’s election without traverse of Group (I) in the reply filed on 04/15/2026 is acknowledged. Claims 14-15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 04/15/2026.
Priority
Acknowledgement is made of the national stage entry of PCT/CA22/50722 filed 05/09/2022 which claims priority to U.S. Provisional Application 63185994 filed 05/07/2021.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 02/28/2025, 06/04/2025 and 04/15/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claims 1, 4-5, 8, 11-12 are objected to because of the following informalities: Claim 1 recites the phrase “administering or applying a small molecule compound” and also recites “wherein the compound is selected from the group consisting of”. Appropriate correction of the phrase “the compound” to “the small molecule compound” for proper antecedent basis is required. This situation is duplicated in claims 4-5, 8, 11-12.
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 (i.e., changing from AIA to pre-AIA ) 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.
Claim(s) 1-2, 6-9 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Thorel (WO2017/068424 published 04/27/2017; machine translation provided) and Ghahary (WO2014/194407 published 12/11/2014).
Thorel (WO2017/068424 published 04/27/2017; machine translation provided) teaches that in atrophic acne scars, hyperactivity of lyric mixed metalloproteinases (MMPs) following acne cause a degradation of collagen fibers during regeneration and remodeling of extracellular matrix. Thorel teaches that this regeneration and remodeling of extracellular matrix leads to visible depressions and scars in the naked eye. (Google translate). Thorel teaches compounds that inhibit collagenase activity and thereby inhibit the expression of type-1 collagen are efficacious at treating atrophic scars of acne (Figure 3, claims 1-7).
The difference between the present claims and that of Thorel is that Thorel does not specifically teach wherein atrophic acne scarring is treated with kynurenine.
Ghahary (WO2014/194407 published 12/11/2014) teaches that kynurenine is efficacious by reducing the expression of type-1 a1 collagen in applied dermal wounds (pages 12-13, page 27, Figures 10, 12-13). Ghahary additionally teaches the treatment of keloid and hypertrophic scarring in a subject in need comprising administering a therapeutically effective amount of kynurenine in a mammalian subject (abstract, claims 21-23). Topical administration of kynurenine of 500 mg/ mL formulated in a gel effectively reduced scarring in wounds compared to control patients (page 22, page 27-28; Figures 12-13). Ghahary teaches that the amount of kynurenine in the topically administered gel as well as the frequency of administration of the topical gel to the scar are dependent on the age, weight of the administered patient as well as the severity of the condition (pages 17-18). Ghahary further teaches that kynurenic acid (FS-2) is also effective at inhibiting Type 1 a1-collagen expression in dermal fibroblasts, similar to kynurenine (FS-1)(page 29; Figure 15).
Therefore, one of ordinary skill in the art prior to the time of the invention knowing that compounds that inhibit collagenase activity, thereby inhibiting the expression of type-1 collagen are efficacious at treating atrophic acne scars in a subject in need as taught by Thorel, said skilled artisan would have found it prima facie obvious to administer kynurenine or kynurenic acid to the patient with atrophic acne scars in view of Ghahary, arriving at the presently claimed methodology.
MPEP 2143 provides rationale for a conclusion of obviousness including (A): Combining prior art elements according to known methods to obtain predictable results;
In the present case, it was known in the prior art of Thorel that compounds that inhibit collagenase activity and thereby inhibit the expression of type-1 collagen are efficacious at treating atrophic scars of acne. Considering Ghahary teaches that kynurenine and kynurenic acid are each efficacious at reducing the expression of type-1 a1 collagen in applied dermal wounds and that topical administration effectively treats hypertrophic scarring in a subject, said artisan would have applied the type-1 collagen inhibiting kynurenine or kynurenic acid to a subject with atrophic acne scarring with a reasonable expectation that the topically applied kynurenine or kynurenic acid would have inhibited type-1 collagen production, thereby treating the atrophic acne scars.
Regarding the limitation wherein the composition is applied once or twice per day, the optimum dosing cycle and frequency of administration of the collagen inhibiting kynurenine or kynurenic acid to the atrophic acne scarred patient would have been a matter well within the insight of one of ordinary skill in the art. Such a determination would have been made in accordance with a variety of factors, such as the route of administration, pharmacological considerations, such as activity, efficacy, pharmacokinetics and toxicology profiles of the combined regimen, as well as the age, weight, sex, diet and severity of the medical condition of the patient, as indicated by Ghahary (pages 17-18). Thus, the dosing cycle and frequency of administration regimen that would have been employed would have varied widely and, in the absence of evidence to the contrary, the current claimed specific administration regimen is not seen to be inconsistent with one that would have been determined by the skilled artisan. Furthermore, absent and evidence demonstrating a patentable difference between the kynurenine or kynurenic acid compositions administered and the criticality of the claimed frequency and dosing cycles, the determination of the optimum or workable frequency of administration given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. Please see MPEP 2144.05 [R-2](II)(A) and In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)(”[W]here the general conditions of the claim are disclosed in the prior art, it is not inventive to discover the workable ranges by routine experimentation.”)
Claim(s) 3-5 and 10-12 are rejected under 35 U.S.C. 103 as being unpatentable over the combination of Thorel (WO2017/068424 published 04/27/2017; machine translation provided) and Ghahary (WO2014/194407 published 12/11/2014) as applied to claims 1-2, 6-9 and 13 above, in view of Uchikuga (EP1038516 published 09/27/2000).
As disclosed above, the combination of Thorel and Ghahary render obvious the topical administration of kynurenic acid to treat atrophic acne scarring in a subject in need as it was known in the prior art of Thorel that compounds that inhibit collagenase activity and thereby inhibit the expression of type-1 collagen are efficacious at treating atrophic scars of acne coupled with the knowledge that Ghahary teaches that kynurenine and kynurenic acid are each efficacious at reducing the expression of type-1 a1 collagen in applied dermal wounds and that topical administration of kynurenine is efficacious at treating hypertrophic scarring in a subject.
The difference between the presently claimed methodology and that of the combination of Thorel and Ghahary is that the combination of Thorel and Ghahary do not specifically teach wherein kynurenine is administered as a cream, nor kynurenine nor kynurenic acid is administered in a dose of either 0.05% wt. kynurenine or 0.5%wt. kynurenic acid in the topical composition.
Uchikuga (EP1038516 published 09/27/2000) teaches that it is known in the art to prepare creams comprising kynurenine and kynurenic acid ([0043]-[0045]). Regarding the limitation directed to the topically administered composition comprises 0.5% wt. kynurenic acid or 0.05% wt. kynurenine, Uchikuga teaches doses of 0.05% wt. to 8% wt. kynurenine or derivatives thereof in topically applied creams are safe and effective for topical administration ([0038]). Said 0.05% wt. to 8% wt. kynurenine in the topically applied composition of Uchikuga overlaps with the 0.05% wt. kynurenine embodied within the claims. Applicant is reminded of MPEP 2144.05 wherein the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990).
Therefore, one of ordinary skill in the art prior to the time of the invention would have found it prima facie obvious to formulate the collagen inhibiting and atrophic acne scar treating kynurenine or kynurenic acid of Thorel and Ghahary, as a cream composition in view of Uchikuga, arriving at the presently claimed methodology.
MPEP 2143 provides rationale for a conclusion of obviousness including (A): Combining prior art elements according to known methods to obtain predictable results;
In the present case, it was known in the prior art of Uchikuga to prepare topical cream compositions comprising kynurenine or kynurenic acid and that doses of 0.05% wt. to 8% wt. kynurenine in topically applied creams are safe and effective cosmetic compositions. Consistent with this reasoning, it would have been obvious to have selected the kynurenine cream topical formulation from within the prior art of Uchikuga above and apply it to the collagen inhibiting and atrophic acne scar treating kynurenine of Thorel and Ghahary, arriving at the claimed methodology “yielding no more than one would expect from such an arrangement”.
Regarding the limitation of wherein kynurenic acid is administered as a cream, or is formulated in a composition comprising 0.5% wt. kynurenic acid, it is considered well within the capabilities of one of ordinary skill in the art to optimize the amount of kynurenic acid in the topical composition to provide optimal efficacy of topical composition. The amount of kynurenic acid in the topical composition is a result effective parameter that will affect the physical properties of the final composition and is clearly a results effective parameter that a person of ordinary skill would routinely optimize, as disclosed in pages 17-18 of Ghahary. Optimization of parameters is a routine practice that would have been obvious for a person of ordinary skill in the art to employ and reasonably would expect success. Moreover, the safe and effective concentrations of kynurenine in topical compositions taught by Uchikuga provide a range of workable conditions and it would have been customary for an artisan of ordinary skill to determine the optimal amount of kynurenic acid in the topical composition to best achieve the desired result. Furthermore, absent any evidence demonstrating a patentable difference between the topical kynurenic acid composition and the criticality of the claimed amounts, the determination of the optimum workable range(s) given the guidance of the prior art would have been generally prima facie obvious to the skilled artisan. Please see MPEP 2144.05 [R-2](II) (A) and In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) “[W]here the general conditions of the claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.").
Conclusion
In view of the rejections set forth above, no claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GEORGE W KOSTURKO whose telephone number is (571)270-5903. The examiner can normally be reached M-F 9:00-5:30.
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/GEORGE W KOSTURKO/Primary Examiner, Art Unit 1621
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