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 .
Claim Status
Claims 1-13, 16-17, 26-27, 29, 31-32 and 34-37 are pending.
Claims 1 and 6 are currently amended.
Claims 14-15, 18-25, 28, 30, 33 and 38-39 have been canceled.
Claims 1-13, 16-17, 26-27, 29, 31-32 and 34-37 are currently under consideration.
Claims 1-13, 16-17, 26-27, 29, 31-32 and 34-37 are rejected.
Acknowledgement of Receipt
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 07/20/2025 has been entered.
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.
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 (a) are summarized as follows:
Determining the scope and contents of the prior art.
Ascertaining the differences between the prior art and the claims at issue.
Resolving the level of ordinary skill in the pertinent art.
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. Applicants are 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 1-13, 16-17, 26-27, 29, 31-32 and 34-37 are rejected under 35 U.S.C. § 103 as being unpatentable over Wortzman et al. (WO 2009/051839 A1, cited on IDS) in view of Patel et al. (Clinical Assessment of the Combination Therapy with Liposomal Gels of Tretinoin and Benzoyl Peroxide in Acne, published 2001) and further in view of Lapidot et al. (US 2010/0255107 A1, equivalent to US 2002/0064541 A1 cited on IDS), herein after are referenced Wortzman, Patel, and Lapidot, respectively.
The claims are directed to method of providing early onset of action in the treatment of acne comprising topically applying onto an effected skin area of subject in need thereof, once a day for period time of at least about 4, 8, or 12 weeks, a topical medicament which consists of the active ingredients about 0.1% tretinoin, about 3% benzoyl peroxide, a pharmaceutically acceptable carrier or excipient; wherein the medicament is a cream;, wherein the absolute reduction in non-inflammatory lesion count after about 2 weeks is at least about twice the absolute reduction in non-inflammatory lesion count during the period starting at about week 2 and ending at about week 4 of treatment (instant claim 1) and/or to achieve a percentage decrease in the number of non-inflammatory lesions of about 25.2% (mean percentage change from baseline) after about 2 weeks, compared to a percentage decrease in the non-inflammatory lesions of about 17.8% after treatment with vehicle control for about 2 weeks (instant claim 6). The claims are further directed to the method wherein the administration is to the face (instant claim 3). The claims are further directed to the acne being mild acne, moderate acne, or severe acne (instant claims 16 and 17). The claims are further directed to at least one active agent, i.e., tretinoin, benzoyl peroxide, is encapsulated in a metal oxide shell (instant claims 36 and 37).
Wortzman teaches a composition comprising about 1.0% to about 0.01%, preferably 0.025% tretinoin, and comprising about 3% to about 9%, preferably about 5% benzoyl peroxide, a high molecular weight polymeric gelling agent, and water ([13], [20], claim 16). Acne is treated by applying peas sized amount of tretinoin/benzoyl peroxide gel to the fingertips and spread over the face ([52], Ex. 10).
Wortzman does not teach wherein the application occurs daily for at least 4 weeks.
Wortzman lacks a teaching wherein the tretinoin and benzoyl peroxide are individually encapsulated by a semi-metal oxide or metal oxide and/or the composition is a cream.
Patel teaches a treatment of acne comprising applying benzoyl peroxide to the face in the morning and then tretinoin to the face before bedtime for a treatment period of 3 months (at least 12 weeks) (pg. 2, col. 1, para. 1-2).
Lapidot teaches a topical composition comprising at least one of benzoyl peroxide and retinoid encapsulated in a microcapsules having a core-shell structure, wherein said core includes said active ingredient, and wherein said shell comprises at least one metal oxide inorganic polymer obtained by a sol-gel process ([0019], claim 1). Lapidot teaches that combinations of benzoyl peroxide and oxidation-sensitive active ingredients such as retinoids and antibiotics are highly useful in formulations for the treatment of acne, and therefore encapsulation of benzoyl peroxide can facilitate obtaining a stable formulation containing both ingredients ([0253], Ex. 7). In preferred embodiments the final form of the composition is selected from the group that includes an emulsion and a cream ([0052], [0142]).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the filing of the instant application apply the composition of Wortzman for at least 12 weeks once daily and have a reasonable expectation of success. One would have been motivated to do so since Patel teaches that this is a well-established and common treatment regimen. It would have been prima facie obvious to one of ordinary skill in the art at the time of the filing of the instant application to adjust the amount of tretinoin to 0.1% and benzoyl peroxide to 3% and have a reasonable expectation of success. In the case where 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).
The recited limitations "wherein the absolute reduction in non-inflammatory lesion count after about 2 weeks is at least about twice the absolute reduction in non-inflammatory lesion count during the period starting at about week 2 and ending at about week 4 of treatment and/or to achieve a percentage decrease in the number of non-inflammatory lesions of about 25.2% (mean percentage change from baseline) after about 2 weeks, compared to a percentage decrease in the non-inflammatory lesions of about 17.8% after treatment with vehicle control for about 2 weeks,” would necessarily be present in the method of Wortzman as modified by the teachings of Patel since the composition and method steps of the prior art are indistinguishable from
the instant claims.
It would have been prima facie obvious to one of ordinary skill in the art at the time of
the filing of the instant application to encapsulate the tretinoin and benzoyl peroxide of
Wortzman in the microcapsule of Lapidot and have a reasonable expectation of success. One would have been motivated to do so in order to provide a more stable composition by preventing contact between the active agents. Specifically, Lapidot provides enhanced stability of benzoyl peroxide, by its encapsulation within the microcapsules and that the benzoyl peroxide is present in the microcapsular core, preferably as an oil-in-water emulsion or as a solid-in-oil-in-water emulsion, and is encapsulated by the microcapsular shell. The microcapsular shell protects the benzoyl peroxide from contacting the is environment and thus reduces its reactivity and/or sensitivity ([0204]). The microcapsular shell further protects the benzoyl peroxide from reacting with other active ingredients in the composition ([0204]).
It would have been prima facie obvious to one of ordinary skill in the art at the time of
the filing of the instant application to formulate the composition of Wortzman into a
cream and have a reasonable expectation of success. One would have been motivated to do so
since Lapidot teaches that the composition can be formed into a variety of preferred forms ([0052], [0142]). Further, Lapidot underscores the benefits of microcapsule cream formulations in which the release/delivery of the active ingredient is produced by disintegration of the micro-capsules upon topical application thereof via for example sheer forces applied by a spreading action commonly used to spread creams, gels or ointments ([0152], claim 20).
For the foregoing reasons, the instant claims are rendered obvious by the teachings of
the prior art.
Claims 1-13, 16-17, 26-27, 29, 31-32 and 34-37 are rejected under 35 U.S.C. § 103 as being unpatentable over Mallard et al. (US 2009/0318550 A1, 12/24/2009) in view of Patel et al. (Clinical Assessment of the Combination Therapy with Liposomal Gels of Tretinoin and Benzoyl Peroxide in Acne, published 2001) and further in view of Toledano et al. (US 2012/0202695 A1, pub. 08/09/2012, equivalent to US 10,512,796 B2 cited on IDS) evidenced by Rosso et al. (Absence of Degradation of Tretinoin When Benzoyl Peroxide is Combined with an Optimized Formulation of Tretinoin Gel (0.05%), J Clin Aesthet Dermatol, 2010; 3(10):26-28) and Casanova and Santos (Encapsulation of cosmetic active ingredients for topical application – a review, J Microencapsulation, 2016; 33(1):1-17), herein after referenced Mallard, Toledano, Rosso; Casanova and Santos, respectively.
The applied reference has a common joint inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. § 102(a)(2).
Mallard discloses stable dermatological/cosmetic emulsions useful for the treatment of acne vulgaris formulated into a physiologically acceptable medium, a homogeneous dispersion of at least one dispersed retinoid, dispersed benzoyl peroxide, at least one fatty phase, at least one hydrophilic phase and at least one emulsifier (abstract, [0040], claim 1) wherein the emulsion comprises from 0.0001% to 20% of at least one retinoid and from 0.0001% to 20% of benzoyl peroxide ([0062], claims 2-3), wherein an exemplary retinoid may be retinoic acid, tretinoin and/or tazarotene ([0077], claim 11). The benzoyl peroxide is preferably included at concentrations ranging from 2.5% to 5% by weight, and the retinoid for its part is included in this type of composition at concentrations generally ranging from 0.01 % to 1 % by weight ([0114]). Mallard discloses a regimen or regimen for the prevention or treatment of acne vulgaris, comprising topically applying onto the skin of an individual in need of such treatment, a thus effective amount of the stable dermatological emulsion as disclosed (claim 27).
Mallard does not teach wherein the application occurs daily for at least 4 weeks.
Mallard lacks a teaching wherein the tretinoin and benzoyl peroxide are individually encapsulated by a semi-metal oxide or metal oxide.
Patel teaches a treatment of acne comprising applying benzoyl peroxide to the face in the morning and then tretinoin to the face before bedtime for a treatment period of 3 months (at least 12 weeks) (pg. 2, col. 1, para. 1-2).
It would have been prima facie obvious to one of ordinary skill in the art at the time of the filing of the instant application apply the composition of Mallard for at least 12 weeks once daily and have a reasonable expectation of success. One would have been motivated to do so since Patel teaches that this is a well-established and common treatment regimen. It would have been prima facie obvious to one of ordinary skill in the art at the time of the filing of the instant application to adjust the amount of tretinoin to 0.1% and benzoyl peroxide to 3% and have a reasonable expectation of success. In the case where 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).
The recited limitations "wherein the absolute reduction in non-inflammatory lesion count after about 2 weeks is at least about twice the absolute reduction in non-inflammatory lesion count during the period starting at about week 2 and ending at about week 4 of treatment and/or to achieve a percentage decrease in the number of non-inflammatory lesions of about 25.2% (mean percentage change from baseline) after about 2 weeks, compared to a percentage decrease in the non-inflammatory lesions of about 17.8% after treatment with vehicle control for about 2 weeks,” would necessarily be present in the method of Mallard as modified by the teachings of Patel since the composition and method steps of the prior art are indistinguishable from
the instant claims.
Regarding wherein the medicament is a cream, Mallard provides cream type formulations where adapalene (i.e., retinoid) is at 0.1% and the benzoyl peroxide is at 2.5% ([0244]). It would have been prima facie obvious to a person of ordinary skill in the art, ahead of the effective filing date of the claimed invention, to substitute one known retinoid of Mallard with the tretinoin taught by Mallard for a similar purpose of providing a regimen in the treatment of acne. Simple substitution of one retinoid for another is within the purview of the skilled artisan and would yield predictable results.
It is noted that Mallard cites a study published in late 1990’s that compares adapalene and tretinoin that impresses upon Mallard that the decomposition of benzoyl peroxide is not desirable insofar as it is harmful to the effectiveness of the composition in which they are present ([0028]). However, over a decade later, Rosso provides evidence that there is no benzoyl peroxide-induced degradation of tretinoin when the formulation is optimized and suggests that this particular combination may be utilized concurrently without concerns about tretinoin oxidation and degradation (abstract). Nevertheless, Toledano evidenced by Casanova and Santo address Mallard’s concerns of the effectiveness of such compositions.
Toledano provides core-stabilized microcapsules wherein said core comprises at least one active agent encapsulated within a metal oxide shell, processes for their preparations, comparisons comprising them and uses thereof (abstract, [0031], claim 50). Toledano teaches that obtaining a microcapsule having a metal-oxide shell wherein the incorporation of phase changing material into the core of said microcapsule provides unexpected stability to the encapsulated active agents in the core of said microcapsule ([0029]). Toledano teaches that the term “core” refers to the inside part of the microcapsules comprising at least one active agent and at least one phase changing material that are both surrounded by a metal oxide shell of a microcapsule ([0034]).
Toledano teaches that said core comprises a dermatological agent selected from anti-acne agents selected from benzoyl peroxide, retinoid, and mixtures thereof, wherein the retinoid may be for example tretinoin (all trans retinoic acid, ATRA), tazarotene, iso-tretinoin, adapalene or mixtures thereof ([0055-0058], claims 53, 64). Toledano discloses a composition comprising the discloses microcapsules, wherein the core comprises a dermatological agent, for the treatment of a disease or disorder selected from acne, infection, inflammation ([0110-0112], claims 52, 63). Toledano provides formulations of encapsulated ATRA and encapsulated BPO (E-ATRA 0.1%/E-BPO 6%) ([0210], Ex. 16).
While Toledo discloses a microcapsule capable of being stable (i.e., maintain at least about 0 to 5% of said encapsulated at least one active agent) for a period of between about 2 weeks to about 2 years at room temperature ([0053], [0093], claim 65), Toledo does not specifically address Mallard’s concerns surrounding effectiveness. As evidenced by Casanova and Santos, encapsulation and stabilization of oxidatively sensitive dermatological agents (i.e., Vitamin C) can be achieved with metal oxide further providing improved controlled release behavior, biological activity and transdermal delivery efficiency (pg. 5, para. 3).
It would have been prima facie obvious to a person of ordinary skill in the art, ahead of the effective filing date of the claimed invention, to combine the metal-oxide shell taught by Toledano evidenced by Casanova and Santos with the teachings of Mallard in view of Patel with expected results. One would be motivated to do so with a reasonable expectation of success because Toledano further notes that the microcapsules obtained demonstrate a higher stability, as measured in the amount of leakage measured upon long storage of said microcapsules ([0052]) would contribute to the art, absent a clear showing of evidence to the contrary. In addition, Toledano complements Mallard’s disclosure of cream formulations by teaching that emulsions in which the core of said microcapsule may comprise said at least one active agent and at least one phase forming material ([0032-0034]); material to be crucially important in cream formulations.
For the foregoing reasons, the instant claims are rendered obvious by the teachings of
the prior art.
Response to Arguments
Applicants’ arguments filed 07/20/2025 have been fully considered but they are not persuasive
35 U.S.C. § 103 - Wortzman, Patel, and Lapidot
Applicants argue that Wortzman teaches away from cream formulations because as one form is solubilized tretinoin and the other being suspended crystalline (i.e., Ziana® gel), where it is believed that oxidation is avoided with benzoyl peroxide separating from the solubilized tretinoin in the aqueous gel (Remarks, pg. 7, para. 4).
In response, the Examiner respectfully submits that disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or non-preferred embodiments. Lapidot teaches active ingredients useful for topical application i.e., tretinoin, and provides stability specifically to anti-acne combinations of benzoyl peroxide and oxidation-sensitive active ingredients such as retinoids ([0010], [0169], [0253] Ex. 7).
Applicants assert that the experimental data showing the specific combination of 3% BPO and 0.1% tretinoin in a cream in paragraph [00261] of the instant disclosure provides enhanced efficacy and reduced side effects (Remarks, pg. 7, para. 5).
Applicant's data as presented does not demonstrate that the 3% BPO and 0.1% tretinoin enhances the efficacy of the composition for the treatment of acne. Specifically, paragraph [00261] of the instant specification cited by Applicants includes Table 23 in paragraph [00262], shows differences from the baseline over time of the said composition “compared to the change from baseline after treatment with vehicle alone.” The Examiner submits that the composition and method of Wortzman inherently possess the instantly claimed effect. "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art's functioning, does not render the old composition patentably new to the discoverer." There is no requirement that the skilled artisan would have recognized the inherent disclosure at the relevant time; only that the subject matter is in fact inherent in the prior art reference.
Applicant argues that Patel does not suggest that a significantly lower amount of tretinoin would be effective and does not teach a once-daily administration (Remarks, pg. 9, para. 1).
Applicants’ claimed regimen employs a greater ratio of actives (see Patel, Materials and Methods). As such, one would expect a higher reduction. Even as Patel uses less TRE and BPO, reduction was observed after two weeks, to suggest enhanced efficacy. Moreover, the combination of references when taken together, suggest applying single composition of 0.1% tretinoin and 3% benzoyl peroxide in the form of cream to treat acne by applying such a composition to the face of a patient suffering from acne once a day for at least 4 weeks. Given that the composition is suggested and the method steps are suggested by the prior art, an early onset of action and reduction in non-inflammatory lesion count would be inherent to the method suggested by the cite prior art.
Applicants argue that Lapidot does not offeree any guidance or motivation to select a cream over a gel and there is not teaching in Lapidot that would motivate a skilled artisan to combine its broad disclosure with Wortman and Patel to arrive at the claimed invention (Remarks, pg. 9, para. 3-4).
Lapidot teaches that the described preferred embodiments the acceptable carrier and the final form of the composition is selected from the group that includes an emulsion, and a cream ([0048], [0052], [0142]). Lapidot underscores how cream formulations would benefit from micro-capsules of microcapsule cream formulations by teaching that the release/delivery of the active ingredient is achieved by disintegration of the micro-capsules upon topical application thereof via for example sheer forces applied by a spreading action commonly used to spread creams, gels or ointments ([0152], claim 20).
For these reasons, Applicants’ arguments are found unpersuasive.
Conclusion
Claims 1-13, 16-17, 26-27, 29, 31-32 and 34-37 are rejected; no claims are currently allowable.
The Examiner asks Applicant to provide support for the amendments in the application disclosure by referencing page numbers, paragraphs, figures, etc. for the sake of compact prosecution.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Karen Ketcham whose telephone number is (571)270-5896. The examiner can normally be reached 900-500 ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ali Soroush can be reached at 571-272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Karen Ketcham/Examiner, Art Unit 1614
/ALI SOROUSH/Supervisory Patent Examiner, Art Unit 1614