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 .
Current Status of 17/755,182
This Office Action is responsive to the amended claims and Applicant remarks of 04/30/2026. Claims 1-2, 12-15, 27-29, and 34 are pending and have been examined on the merits.
Priority
The instant application is a national stage entry of PCT/CN2021/124587, international filing date, 10/19/2021, which claims priority to CN 202011381947.8, filed 11/19/2020, and CN 20211074555.0, filed 01/20/2021.
Response to Arguments
Applicants have amended the title of the invention to make it clearly indicative of the invention to which the claims are directed. The previous objection to the title is withdrawn.
Regarding the rejections under 35 U.S.C. §103 in view of references Laberge, Encyclopedia Britannica, Carrara, and Torsekar. Applicants argue that Laberge does not teach or suggest any specific gel compositions and that the instant claims are not directed to a broad gel composition, but rather to a specific pharmaceutical composition. Applicants further contend that the claimed invention is not merely the substitution of a known API into a known delivery vehicle. In support, Applicants emphasize the uncertainty associated with developing compositions suitable for transdermal delivery, asserting that without specific guidance, the artisan would not have arrived at the claimed combination of excipients that allegedly produces superior results relative to systemic administration of ABT-737.
Applicants assert that claim 1 defines a specific combination of the API and DMSO that achieves complete dissolution of the drug in the gel matrix for topical application. Applicants further argue that the APIs of Carrara possess materially different solubility characteristics from ABT-737. The artisan would not have reasonably expected that 1% DMSO would be sufficient to dissolve ABT-737 and produce a stable gel. Applicants argue that although Carrara teaches a broad range of DMSO concentrations that arriving at the instantly claimed amount would require hindsight reasoning. Applicants further contend that selecting a particular amount from a broad range is not prima facie obvious, particularly where, the claimed amount allegedly produces unexpected results.
Additionally, Applicants argue that the claimed DMSO concentration is significant because it not only facilitates complete dissolution of the API, but also avoids potential skin-related issues associated with higher DMSO concentrations. Applicants contend that the combined teachings of Laberge and Carrara do not teach or suggest the claimed concentrations would produce superior efficacy and safety compared to systemic injection. Applicants contend that the prior art would have led the artisan to expect systemic administration to provide better bioavailability and efficacy relative to topical administration. Applicants assert that the claimed composition produces the opposite result and highlight the results of Examples 6 and 7 of the specification in support of their claim to non-obviousness.
Applicants contend that the claimed composition produces synergistic effect by enhancing local drug efficacy while avoiding systemic toxicity. Applicants support their contentions using Example 6, which allegedly demonstrates that the gel composition acts primarily locally and does not induce systemic immunosuppression, unlike conventional administration. Applicants therefore argue that the prior art does not teach or suggest the claimed compositions which possess high local efficacy and safety profiles. These arguments have been fully considered and are persuasive. The previous rejections are withdrawn.
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, 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.
Claims 1-2, 12-15, 27-29, and 34 are rejected under 35 U.S.C. 103 as being unpatentable over Jorgensen (US 4,933,330) in view of Laberge (US 9,993,472 B2) and Carrara (US 2009/0069364 A1).
The Examiner notes that claim 13 further recites that psoriasis is in a progressive, stationary, or regressive phase. This limitation does not meaningfully narrow the scope of the claim, as any such disease necessarily exists in one of these phases. Accordingly, claim 13 is coextensive in scope with claim 1.
Jorgensen teaches a pharmaceutical composition used in the treatment of psoriasis comprising 4-aminosalicyclic acid or 5-aminosalicyclic acid or a functional derivative thereof, said composition being in a form suitable for topical administration and selected from a compound which includes a gel (Claim 1). The reference teaches that psoriasis appears in many different forms including psoriasis vulgaris, pustular psoriasis, and psoriatic arthritis (Col 1, lines 30-41). The reference teaches that the pharmaceutical compositions may comprise any suitable pharmaceutical excipients or carriers as well as emulsifying agents, antioxidants, buffering agents, preservatives, humectants, penetration enhancers, coloring agents, chelating agents, gel forming agents, ointment bases, pH-regulators, perfumes, and skin protective agents (Col 3, lines 3-9). The reference teaches DMSO and azone as a penetration enhancers (Col 3, lines 29-32). Benzalkonium chloride is identified as a suitable preservative (Col 3, lines 44-46). Humectants include glycerin, propylene glycol, sorbitol, mannitol, urea, sodium chloride, PCA, lactic acid, and xylitol (Col 3, lines 23-25). The reference does not teach the use of ABT-737 as the active pharmaceutical ingredient in the gel compositions and does not teach the specified weight percentages of the excipients of the instantly claimed gels.
Laberge teaches a method of treating psoriasis comprising administering to a subject in need thereof a BCL-2 inhibitor, specifically ABT-737 as part of a topical (external) preparation (Col 1, lines 54-55, Col 1 line 66-Col 2 line 3, Col 2 lines 13-16, Col 2, lines 36-44, Col 4 lines 45-47, Col 5, lines 3-5, Col 97 lines 50-54, Col 99 line 53-Col 100 line 4). The reference teaches gels as one such topically administered composition (Col 99 line 53-Col 100 line 4). Laberge also teaches preservatives as excipients for the senolytic agent formulations, suitable preservatives include ethyl paraben, sodium benzoate, and chlorobutanol (Col 99 line 64-Col 100 line 4). The reference teaches that the treatment can reduce the likelihood of cellular senescence-related diseases; delay onset or progression of cellular senescence-related diseases; or inhibit, delay, slow or retard the progression or severity of cellular senescence-related diseases (Col 14 lines 24-52). The reference further discloses embodiments comprising multiple senolytic agents for use in the treatment regimen, which amounts to the use of additional active ingredients or drugs in treating psoriasis (Col 36 lines 15-37).
Carrara (US 2009/0069364 A1) discloses one such transdermal gel for the delivery of 5-alpha-reductase inhibitors (Abstract, claim 1). The gels are comprised of their active ingredient (5-alpha-reductase inhibitor), gelling agents; permeation enhancers, preservatives, anti-oxidants, buffers, humectants, sequestering agents, moisturizers, surfactants, emollients, film-forming agents, solubilizers, flavors, fragrances, stabilizers, and solubilizers (Claims 1, 12, and 13). [0097] of Carrara teaches gelling agents of the formulations and expressly lists cellulose derivatives such as hydroxypropyl methylcellulose, carboxymethyl cellulose, carbomer, chitosan, polyvinyl alcohols, and alginates. The reference teaches that the gelling agent or thickener is present from about 0.2-30%w/w depending on the type of polymer, as known by one of skill in the art [0097].
[0098] of Carrara teaches penetration enhancers of the formulations and specifically identifies DMSO, DMA, DMF, polyethylene glycol, and oleic acid as exemplary penetration enhancers. The reference teaches that the penetration enhancer is present from about 0.1-30% w/w depending on the compound.
[0100] of Carrara teaches buffering agents as part of the formulations. Exemplary buffers include carbonate buffers, acetate buffers, borate buffers, and citrate buffers. The reference teaches that the amount of buffer present is determinable by one of ordinary skill in the art. The reference also discloses that the composition typically comprises a primary vehicle comprising a mixture of water, at least one short-chain alcohol, a monoalkylether of diethylene glycol, and a glycol [0094].
[0101] of Carrara teaches that the formulations may further include preservatives such as benzalkonium chloride and derivatives, benzoic acid, benzyl alcohol and derivatives, bronopol, parabens, centrimide, chlorhexidine, cresol and derivatives, imidurea, phenol, phenoxyethanol, phenylethyl alcohol, phenylmercuric salts, thimerosal, sorbic acid and derivatives. The reference additionally teaches that the preservative is present from about 0.01-about 10% w/w depending on the compound, as known by one skilled in the art.
[0102], [0107-0108], and claims 12 and 13 disclose that the formulations may also include humectants.
The artisan would have a background in pharmaceutical sciences, organic chemistry, chemical engineering, or a related field and would have experience in the formulation and development of topical and transdermal drug delivery systems. The artisan would be familiar with gel-based formulations for dermatological applications including the selection and optimization of excipients, penetration enhancers, preservatives, and solvent systems. The artisan would understand the challenges of transdermal delivery of small molecule APIs and would be knowledgeable about topical treatment approaches for psoriasis.
The instant invention amounts to formulating a known psoriasis active ingredient in a known topical gel dosage form using conventional gel excipients in conventional amounts. Jorgensen establishes gels as suitable topical pharmaceutical compositions for treating psoriasis and expressly demonstrates gels as suitable topical dosage forms. Jorgensen further teaches that such these topical gel formulations may include conventional excipients. Laberge teaches that ABT-737 is a known BCL-2 inhibitor useful for treating psoriasis and psoriasis-associated diseases. Carrara teaches the claimed excipients in topical gels such as carbomer, DMSO, and water are conventional excipients, and that the claimed amounts fall within ordinary ranges typical in such gel compositions. Thus, the artisan would have been motivated to use ABT-737 for treating psoriasis as part of a gel composition. It would have been obvious to substitute one API known for treating psoriasis for another into a gel because the art establishes gels as a suitable dosage form. The artisan would adjust the amounts of the excipients of the gels through routine optimization to improve efficacy of the composition. Absent persuasive evidence that the particular claimed percentages of the composition produce critical or unexpected results, the claimed ranges appear to represent routine optimization of conventional gel formulations.
Conclusion
Claims 1-2, 12-15, 27-29, and 34 are rejected.
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/C.K.E./Examiner, Art Unit 1625 /Andrew D Kosar/Supervisory Patent Examiner, Art Unit 1625
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