DETAILED ACTION
This Office action details a non-final action on the merits for the above referenced application No. Claims 1-20 are pending in this application.
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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 15 Sep. 2025 has been entered.
Response to Amendment
The amendments filed on 15 Sep. 2025 have been entered.
Response to Arguments
The rejection of claims 1-10 and 12-20 under 35 USC 103 as being unpatentable over Abou-Chacra et al. (WO 2008/006888 A1; published 17 Jan. 2008), in view of Schafran et al. (WO 97/328845 A1; published 12 Sep. 1997) and Orsoni et al. (AU 2002364427 B2; published 2002) is withdrawn.
The rejection of claims 1-20 under 35 USC 103 as being unpatentable over Abou-Chacra et al. (WO 2008/006888 A1; published 17 Jan. 2008), in view of Schafran et al. (WO 97/328845 A1; published 12 Sep. 1997) and Orsoni et al. (AU 2002364427 B2; published 2002), in further view of FDA ANDA 61-112 (published 2004) is withdrawn.
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 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.
Claim(s) 1-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ramirez et al. (US 2009/0076170 A1; published 19 Mar. 2008), in view of Abou-Chacra et al. (WO 2008/006888 A1; published 17 Jan. 2008) and Orsoni et al. (AU 2002364437 B2; published 2002) for the reasons cited in the Office action filed on 14 Mar. 2025.
Applicants Arguments
Applicants assert that although Ramirez teaches a kit, the kit comprises BPO composition containing an antioxidant (not in substantially pure form). A person of ordinary skill in the art would not be motivated to modify the kit of Ramirez to include BPO in substantially pure form, because Ramirez already solved the problem that the claimed invention addresses. Neither Abou-Chacra nor Orsoni disclose or suggest the use of substantially pure BPO in a kit for compounding a BPO product.
Applicant's arguments filed 15 Sep. 2025 have been fully considered but they are not persuasive. Ramirez provides for a kit which may include an outer package such as for example a cardboard box containing therein at least two separate containers each filled with different compositions. One of the containers contains the BPO composition according to the disclosure. The other contains a topical at least partially neutralized salicylic acid composition. Instructions for accomplishing the regiment may be printed on the outer container or provided as a separate sheet insert. At [0015] Ramirez teaches the following BPO composition according to the disclosure: commercially available pure BPO (98% active crystals). That form of BPO can be used to form compositions of the disclosure. At [0030], Ramirez teaches that the organic peroxide corrective composition may be in solid form. At [0017] Ramirez acknowledges that BPO molecules in solution will react more readily than in solid crystal form. Accordingly, Ramirez provides some teaching and suggestion that solid BPO is more stable. Ramirez does contemplate mixing BPO with antioxidant; however, Ramirez teaches that the amount of BPO with the antioxidant will vary according to a number of factors: BPO mixed with a small amount (≤1%) antioxidant would still read on BPO in substantially pure form when ≥90% of a solid mixture is BPO and <10% of the mixture is antioxidant. At [0012], Ramirez teaches an antioxidant amount of 0.1% by weight of the total composition.
See In re Williams, 36 F.2d 436, 438, 4 USPQ 237 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). In this case, a person of ordinary skill in the art would have had reason and motivation to optimize the container of the kit taught by Ramirez that contains the BPO so the BPO is in solid crystalline substantially pure form optionally admixed with a small amount of antioxidant since Ramirez teaches that the BPO is conveniently commercially available and less reactive in solid crystalline substantially pure form and since Ramirez teaches that BPO composition according to the invention can be solid form. Accordingly, the amount of antioxidant admixed with BPO in solid crystal form is a result effective variable that a person of ordinary skill in the art would have been motivated to optimize at the time of invention. A person of ordinary skill would have arrived at BPO that is in substantially pure form starting from commercially available pure BPO (98% active crystals) order to arrive an optimal amount of antioxidant if any that prevents the decomposition of BPO to carcinogenic benzene.
New Grounds of Rejection
Claim Rejections - 35 USC § 112
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 1-9, and 11-20 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. In this case, substantially pure form recited in claim 1 is substantially is a relative term and the scope of the term is not understood when view together with the specification. The specification at [0095] asserts that benzoyl peroxide may be in substantially pure form (e.g. such as greater than 90% purity, greater than 95% purity, greater than 97% purity, greater than 98% purity, greater than 99% purity, greater than 99.9% purity or more); however, the recitation of for example “greater than 90% purity” is recited not as a requirement but as a non-limiting example. “Substantial portion” was held to be indefinite because the specification lacked some standard for measuring the degrees intended. See Ex parte Oetiker, 23 USPQ2d 1641 (Bd. Pat. App. & Inter. 1992. The degree of purity required to qualify as substantially pure form is not clear from the specification. Claims 2-9, and 11-20 depend to claim 1 and fall therewith.
Claim Rejections - 35 USC § 103
Claim(s) 1-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ramirez et al. (US 2009/0076170 A1; published 19 Mar. 2008), in view of Abou-Chacra et al. (WO 2008/006888 A1; published 17 Jan. 2008) and Orsoni et al. (AU 2002364437 B2; published 2002), in further view of Vishnupad et al. (CA 2174031 C; issued 17 Dec. 2002).
Ramirez et al. teach as discussed above. Ramirez et al. teach stable organic peroxide compositions (see title). BPO compositions are stabilized against decomposition by the use of antioxidants, resulting in increased shelf-life of products made using the compositions (see abstract). Ramirez et al. teach methods for treating acne vulgaris (see [0010]). Suitable antioxidants include BHT, BHA, vitamin E. The antioxidant is present in an amount of about 0.1 percent to 10 percent by eight of the total composition (see [0012]). Benzyl peroxide is normally commercially available as either pure (98% active) crystals or in a wet crystalline state containing 70 to 80% active BPO in 20-30% water ([0015]). BPO free radicals can attack the cell walls of the bacteria thus destroying the bacteria. The decomposition of BPO will result in forming benzoic acid, benzene, phenyl benzoate and biphenyls, all such compounds can be toxic to cell. Molecules in solution will react more than in solid crystal form ([0017]). Ramirez et al. teach decomposition mechanisms for the decomposition of organic peroxides ([0020]). Ramirez et al. teach compositions that when in a closed container remain within tolerances and limits set forth in US pharmacopoeia and/ the US FDA guidelines (see [0046]). Ramirez et al. claim a kit comprising at least two separated components (a) and (b) intended to be applied sequentially to an area of a users skin of afflicted with truncal acne wherein component (a) is a composition containing BPO, and component (b) is a topical salicylic acid composition (see claim 2). The kit may include an outer package (such as for example a cardboard box). (A cardboard box prevents exposure to light.) Instructions for the kit may be printed on the outer container or provided as a separate sheet (see [0066]). Ramirez et al. teach retinol (see [0030]). Ramirez et al. teach gels and lotions (see [0008]).
Ramirez et al. does not expressly teach the claim kit wherein the BPO in the first container is in substantially pure form such as greater than 90% or optionally as a crystalline powder or the when the first container/compounded drug product is heat to 70oC for 7 d or more a concentration of benzene is less than 2 ppm. Ramirez et al. does not disclose a kit wherein the other active ingredient is a retinoid. Ramirez et al. does not expressly teach that the BPO drug product is for use in an individual with a period of time such as 36 months or less. Ramirez et al. do not expressly teach a method of producing a producing a BPO drug product using the kit of claim 1.
Abou-Chacra et al. teach a combination of adapalene (retinoid) and benzoyl peroxide for treating acne lesions (see title). Abou-Chacra et al. teach that preferably composition A and composition B are presented in the form of a kit, preferably comprising two isolated compartments each containing one of the two pharmaceutical compositions A or B and allowing simultaneous administration of the two compositions, or alternatively in the form of a kit combining in the same presentation at least the two products in two separate packages (see pg. 4). The compositions are intended to be applied to the skin simultaneously or one after the other in a sequential order withing a time period of less than 1 h, more preferably less than 5 min or even less than 1 min (see pg. 4). (Combining an amount of BPO with an amount of adapalene for form a compounded BPO drug product such that the BPO is present in the compounded BPO drug product in an amount to treat a disease such as acme). Abou-Chacra et al. teach a kit form comprising at least two components: (i) a first component comprising adapalene; and (ii) a second component comprising benzoyl peroxide. Components A and B are intended topical application (see pg. 5). Adapalene and BPO are present in synergistic amounts (see pg. 6). The emulsions are in the form of creams, pads, gels, sprays, lotions or suspensions (see pg. 6). The emulsions may comprise antioxidant additives such as α-tocopherol, or BHT (see pg. 7). Useful pharmaceutical compositions are described in WO 03/005472 (see pg. 8). Abou-Chacra et al. teach a formulation of 2.5% BPO in an acrylamide gel (BPO in a formulation effective reduce or prevent degradation of the BPO to benzene; see pg. 8). Preferred gels are at pH 5 (see pg. 8). Preferably the container comprises two compartments, each of these compartments comprises either composition A or composition B (pg. 10). (A kit comprising: (a) a first container containing BPO wherein the BPO is for use by an individual within a period of generating the compounded BPO drug product such as less than 1 h; and (b) a second container comprising containing therein at least one adapalene ingredient.) Abou-Chacra et al. teach clinical study results for human patients (animal) (connotes room temperature, ~25oC; see example 1). The combining adapalene+BPO was numerically superior in terms of efficacy in comparison with individual active substances (see pg. 14). Abou-Chacra et al. teach the evaluation of anti-inflammatory in ear oedema on Balb/c mice (see example 2). Page 27 teaches the chemical stability of adapalene and tretinoin when combined with BPO in the presence and in the absence of visible light and ultraviolet light.
Orsoni et al. teach a gel comprising a retinoid and BPO (see title). In order to maintain the optimum efficacy of BPO, it is important to prevent its decomposition before use, i.e. during storage (see pg. 4). It is known that BPO is more stable in water and propylene glycol since it is not degraded after storage for 90 d in these solvents. Retinoids are sensitive to natural oxidation, to visible light and to UV light (see pg. 6). Orsoni et al. teach acme (see pg. 8). No degradation of active agents over time and at a temperature between 4 and 40oC is observed (see pg. 8). Orsoni et al. teach compositions comprising BPO dispersed with a pH independent gelling agent including a polyacrylamide (see pg. 8). Orsoni et al. teach antioxidants (see pg. 14). The compositions are suitable for dermalogical complaints, etc (see pg. 19-22). Orsoni et al. teach a examples of preparation processes (see example 6). Orsoni et al. teach a stability study at RT and T40oC over 3 months with 2.5% BPO (pgs. 31-33). Orsoni et al. teach the stability of BPO over time and as a function of storage temperature by measuring BPO in the compositions starting with 100% pure BPO (see example 7).
Vishnupad et al. teach benzoyl peroxide compositions. Vishnupad et al. teach non-irritating compositions containing BPO and non-irritating benzoic acid ester useful in preparing products suitable for use in contact with the skin (see abstract). BPO is completely stable in the ester. Due to the increased stability, the present compositions provide excellent vehicles for use in cosmetic lotions, gels and creams and in drug preparations (pg. 3). BPO is commercially available as pure (98% active) crystals or in a wet crystalline state containing 70 to 80% active BPO in 20-30% water. Any of these forms of BPO can be mixed with benzoic acid ester for form compositions in accordance with the disclosure. Generally, the BPO will constitute from 1 to 99% weight percent of the BPO/benzoate ester mixture (pg. 5). Vishnupad et al. teach lotions, creams, and gels (pg. 5). Vishnupad et al. teach 100% pure BPO (pg. 6).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify the kit of Ramirez et al. (kit for forming a compounded drug product of human use effective for treating a skin condition, the kit comprising at least two separated components (a) and (b) intended to be applied sequentially to an area of a skin of afflicted with truncal acne wherein component (a) is a composition containing BPO, and component (b) is a topical salicylic acid composition and wherein the kit comprises instructions) so that a first container contains up to 99% BPO in substantially pure form, optionally using commercially available crystalline BPO excluding other ingredients, and a second container that contains salicylic acid/retinoid as taught by Ramirez et al. Abou-Chacra et al. and Vishnupad et al. because a first container that contains substantially pure optionally crystalline BPO would have been expected to enable a kit having one container comprising pharmaceutical grade BPO optionally dispersed in a stabilizing benzoate ester and optionally including a small amount of antioxidant (≤1%) wherein the amount of BPO may be up to 99% substantially pure BPO by total weight advantageously stabilized in solid form (less likely to react) and amenable for dilution with the second component for form a safe and efficacious drug product.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify the kit of Ramirez et al. so that compound drug is subjected to stability testing according to FDA guidelines and so that when the first container/compounded drug product is heated to 70oC for 7 d or more, a concentration of benzene in the formulation is less than about 2 ppm (a well-known FDA exposure limit for benzene) and so that the compounded BPO drug product comprises 2.5%-10% w/w BPO (gel) and is for use by an individual within 1 h or less after generation as taught by Ramirez et al., Abou-Chacra et al., and Orsoni et al. because the it would have been expected to advantageously enable a kit comprising pure BPO stabilized in solid form having an optimal shelf-life (remains unchained in the presence of heat, moisture and air) such that the kit compositions remains within US pharmacopeia and FDA tolerance limits, the compounded drug product formed from the kit providing safety and efficacy to the public throughout the shelf life.
Instructions, such as instruction for combining BPO with the at least one ingredient to generate a compounded BPO drug product or instruction to store a container at a temperature of 25oC or lower amount to non-limiting, non-functional functional printed matter. See In re Ngai, 367 F.3d 1336, 1339, 70 USPQ2d 1862, 1864 (Fed. Cir. 2004).
It would have been obvious to a person of ordinary skill in the art before the effective filing date to further modify Ramirez et al. so that the packaging prevents or reduces degradation of BPO optionally by light as taught by Ramirez et al. and Orsoni et al. because it would have been expected to advantageously enable reduced degradation of BPO/retinoid or other ingredients to products toxic to a cell.
It would have been obvious to a person of ordinary skill in the art before the effective filing date to modify Ramirez et al. so that forming the compounded drug product comprises combining an obvious amount of the substantially pure BPO from the first container with an amount of adapalene/salicylic from a second container to form a compounded BPO drug product effective to treat acme or skin condition as taught by Ramirez et al. and Abou-Chacra et al. because it would have been expected to advantageously enable formation compounded BPO drug product that minimizes exposure of skin to toxic degradation products.
Conclusion
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/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618
/SEAN R. DONOHUE/
Examiner, Art Unit 1618