DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 10/2/25 has been entered.
Maintained rejections and claim amendments
Applicants have amended the claim set to include new claims 132-134. The new claims are directed to a method of treating skin inflammation by topically administering an effective amount of Urolithin A. New claims also comprise a limitation directed to the effect of treatment that is an improvement in autophagy. The rejection of record already addresses treatment of skin inflammation by topical administration of urolithin A. Rejection of record is therefore maintained. Additional limitation directed to improvement in autophagy is addressed in the new section of the obviousness discussion.
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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claim 114 and 132-134 is/are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Gonzalez-Sarrias et al (Gonzalez) (British Journal of Nutrition 2010, 104, 503-512) in view of Friedman et al (J Cutan Med Surg 2002, 6(5):449-59).
Scope of prior art
Gonzalez teaches that urolithins are ellagic acid derived metabolites, which is present in the pomegranate extract (Abstract). While previous studies have reported anti-inflammatory properties of pomegranate extracts, Gonzalez was able to demonstrate that the anti-inflammatory properties are can be attributed to urolithins and to the ellagic acid. On page 510, column 2, 2nd full paragraph, Gonzalez teaches that Urolithin A achieves anti-inflammatory effect through decreased production of PGE2 by downregulating COX2 and mPGES-1 expression. From the teaching of Gonzalez it is clear that urolithin, especially urolithin A is an anti-inflammatory agent.
Ascertaining the difference
While Gonzalez teaches anti-inflammatory activity of Urolithins A and B, Gonzalez does not teach a method of treating skin inflammation by administering to a subject a composition comprising urolithin.
Gonzalez is silent with regards to improvement in autophagy or mitophagy (claims 132-134)
Secondary reference
Friedman teaches nonsteroidal anti-inflammatory drugs (NSAID) serve an important role in dermatology because inflammation is a common component of many skin diseases. The inti-inflammatory function is facilitated by the ability of NSAISs to disrupt the production of prostaglandins by inhibiting COX enzymes (page 449, paragraph 1). Friedman also teaches various methods of administration of NSAIDs in treatment of various skin diseases, including topical application resulting in suppressing prostaglandin production (page 450, column 2, paragraph 4).
Obviousness
A person of ordinary skill in the arts would have found it obvious to try treating skin inflammation in a subject in need thereof by administrating to the subject an effective amount of Urolithin A. Treatment of skin inflammation by topical administration of a NSAIDs is taught by Friedman. Friedman teaches that treatment of inflammation by NSAIDs takes place by inhibiting production of prostaglandins through inhibition of COX2 and also teaches on page 450 that topical administration of a NSAID resulted in inhibition of PG production. At issue is whether it would have been obvious to use Urolithin A as a NSAID in treatment of skin inflammation instead of one of the agents described by Friedman. Gonzalez teaches that Urolithin A has anti-inflammatory activity which is achieved by decrease of PGE2 expression through inhibition COX2. The mechanism of action described by Gonzalez is the same as the one described by Friedman. Since Urolithin A is not a steroid, it can effectively be classified as a NSAID. A person of ordinary skill would have found it obvious to try treating skin inflammation by administering to a subject Urolithin A because its activity is in line with other anti-inflammatory agents used for the same purpose. A POSA would have also found it obvious to try topical application to the affected area of the skin because a topical application (as opposed to systemic) provides a more targeted administration. There is a reasonable expectation of success because Gonzalez teaches Urolithin A as having the desired anti-inflammatory activity.
Claims 132-134:
Claims 132-134 comprise a limitation directed to the effect of practicing the claimed method of topically administering Urolithin A. Improvement in autophagy or mitophagy is inherent to topical administration of Urolithin A. Since cited art renders obvious the method of topically administering Urolithin A, it is inherent that upon said administration the effect of improvement in autophagy or mitophagy is realized. The effect claimed by the applicants is a property of Urolithin A. “A compound and its properties are inseparable” In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963).
Claim 125 and 127 rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Gonzalez in view of Friedman as applied to claim 114 above, and further in view of Ndiaye et al (Arch Biochem Biophys 2011, 508(2) 164-170)
Scope of prior art
Combination of Gonzalez and Friedman renders obvious treatment of skin inflammation by administration of Urolithin A for the reason stated above.
Ascertaining the difference
Neither Gonzalez or Friedman teach administration of a combination of Urolithin A and Resveratrol.
Secondary reference
Ndiaye teaches that they have shown that topical application of resveratrol results in inhibition of inflammation (page 4, last paragraph).
Obviousness
A person of ordinary skill in the arts would have found it obvious to co-administer urolithin A and resveratrol to a subject in need of treatment of skin inflammation. Both agents are described in the arts as having anti-inflammatory properties and are therefore equivalents with regards to reduction of inflammation. Since it is obvious to use either agent in treatment of skin infmamation, there is expectation that the combination of the two can also be successfully used for treatment of skin inflammation.
MPEP 2144.06 Art Recognized Equivalence for the Same Purpose [R-08.2012]
I. COMBINING EQUIVALENTS KNOWN FOR THE SAME PURPOSE
“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.” In reKerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In reCrockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parteQuadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious)
Claim 126 rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Gonzalez in view of Friedman as applied to claim 114 above, and further in view of Nolan et al (Journal of Drugs in Dermatology, 2012, 11(2), 220-224)
Scope of prior art
Combination of Gonzalez and Friedman renders obvious treatment of skin inflammation by administration of Urolithin A for the reason stated above.
Ascertaining the difference
Neither Gonzalez or Friedman teach administration of a combination of Urolithin A and vitamin C.
Secondary reference
Nolan teaches Vitamin C has been shown to have anti-inflammatory function on the skin (page 221, section “ascorbic acid”)
Obviousness
A person of ordinary skill in the arts would have found it obvious to co-administer urolithin A and vitamin C to a subject in need of treatment of skin inflammation. Both agents are described in the arts as having anti-inflammatory properties and are therefore equivalents with regards to reduction of inflammation. Since it is obvious to use either agent in treatment of skin inflammation, there is expectation that the combination of the two can also be successfully used for treatment of skin inflammation.
MPEP 2144.06 Art Recognized Equivalence for the Same Purpose [R-08.2012]
I. COMBINING EQUIVALENTS KNOWN FOR THE SAME PURPOSE
“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.” In reKerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In reCrockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parteQuadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious)
Reply to applicant’s’ remarks
Applicants have traversed the rejection over Gonzalez in view of Friedman in the reply filed on 10/02/25. The arguments presented in the reply have been fully considered and found to be unconvincing.
On page 1 of the reply applicants argue that mere fact that COX inhibiting drugs are known, does not support the proposition that any COX inhibiting drug would be effective in treating skin inflammation. This argument is not an accurate summary of the Examiner’s position. Friedman provides a teaching directed to the mechanism of inflammation reduction through COX inhibition and suggests using compounds that exhibit COX inhibitory activity in treatment of skin inflammation. COX2 inhibition is a very well-known mechanism for reducing inflammation. This is very well documented in the literature. Examiner selected Friedman because Friedman specifically addresses inflammation of the skin and topical administration of the anti-inflammatory agent.
Applicants also argue that Gonzalez-Sarrias (GS) does not propose treatment of any disorder and only discloses an in vitro inflammation model. Applicants are correct, G-S does not teach treatment of skin inflammation. If this teaching was present in G-S, there would no need to rely on secondary reference.
Applicants also attack G-S for stating that further research is needed to elucidate the mechanism implicated in the anti-inflammatory effects. Because of this statement applicants allege that expectation of success is lacking. Examiner disagrees. The statement does not say that Urolithin A lacks anti-inflammatory activity or that there is any uncertainty with regards its’ anti-inflammatory activity. While there is no teaching directed to the detailed mechanism of how Urolithin A inhibits cyclooxygenase expression, the fact that Urolithin A is a COX inhibitor is not in question.
Lastly, applicants argue that it could not have been predicted that UA treated the effects of sunburn in subjects by reducing inflammation by 14.3%. It’s true, the exact % by which inflammation is reduced in sunburned subjects could not have been predicted. However, 1) the subject population is not limited to sunburned subjects and 2) In order to argue unexpected results, one first need to establish what constitutes an expected outcome. No statements or evidence directed what one would expect from topical administration of COX inhibitor have been presented.
Conclusion
Claims 114, 116-123, 125-127 and 132-134 are pending
Claims 114, 125-127 and 132-134 are rejected
Claims 116-123 are withdrawn
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/YEVGENY VALENROD/Primary Examiner, Art Unit 1628