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 .
Withdrawn Rejections:
Applicant's amendments and arguments filed on 12/04/2025 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Any rejection and/or objection not specifically addressed below is herein withdrawn.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set of rejections and/or objections presently being applied to the instant application.
The application is examined in view of Olanzapine as specific active pharmaceutical ingredient and transdermal therapeutical system as specific dosage form. Claims 1, 3-14 and 16-17 reads on the elected species and are under examination.
Claims 1, 3-17 are pending, claims 1, 3-14 and 16-17 are under examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/25/2025 is being considered by the examiner.
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 of this title, 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 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 1,3-8, 10-11, 13-14 and 16-17 are rejected under 35 U.S.C. 103 as being unpatentable over Tagliaferri et al. (US20110190688) in view of Perricone (US20160136169) and Lee et al. (US20200338012).
Determination of the scope and content of the prior art
(MPEP 2141.01)
Tagliaferri et al. teaches patch, system, and method for delivery of a permeant composition into a subject via at least one formed pathway through a biological membrane of the subject (abstract). In a first aspect, the present invention is a patch which contains a matrix, at least one hydrophilic permeant and at least one permeability enhancer disposed within the matrix. In one embodiment of the present invention, the hydrophilic permeant is a bioactive agent ([0007-0008]). As used herein, the term “patch”, in non-limiting examples, may include traditional drug reservoir or drug matrix patches or any other type of patch suitable for use in transdermal drug delivery techniques. In one embodiment of a drug reservoir design, the reservoir may be sandwiched between a backing and a rate controlling membrane. The drug releases only through the rate-controlling membrane, which can be microporous or nonporous. In the drug reservoir compartment, the drug can be in a form such as, but not limited to, a solution, suspension, or gel or dispersed in a solid framework or polymer matrix. On the outer surface of the membrane a thin layer of drug-compatible, hypoallergenic adhesive polymer may be optionally applied. In one embodiment of the drug matrix design, both commonly known types, the drug-in-adhesive system and the matrix dispersion system are to be included. In one embodiment of the drug-in-adhesive system, the drug reservoir may be formed by dispersing the drug in an adhesive polymer and then spreading the medicated polymer adhesive by solvent casting or by melting the adhesive (in the case of hot-melt adhesives) onto an impervious backing layer. On top of the reservoir, layers of unmedicated adhesive polymer may be applied. In one embodiment of the matrix dispersion system, the drug is dispersed homogeneously in a hydrophilic or lipophilic polymer matrix and fixed onto a drug-impermeable backing layer. In another embodiment, instead of applying the adhesive on the face of the drug reservoir, it is applied to form a peripheral adhesive. All forms of patches that can be placed on the skin, including the above traditional drug reservoir and drug matrix style patches, are to be included as embodiments of the present invention ([0003-0004, 0060]). The matrix includes ethylene vinyl acetate (EVA) co-polymer, ethyl cellulose (EC), polyethylene, polyethyl acrylate, and copolymers of ethylene and ethyl acrylate and any combination thereof ([0081]). As used herein, a “bioactive agent” includes any drug, chemical, or biological material that induces a desired biological or pharmacological effect ([0083]). The bioactive agent portion of the permeant composition can account for about 1 to about 30 weight % ([0090]). According to one aspect, the present invention is a patch which contains exenatide and at least one permeation enhancer ([0091]). Furthermore, it is to be understood that pH control agents are only one type of permeability enhancer, but that all permeability enhancers are to be considered part of this invention ([0092]). The pH control agent can be present about 1 to about 30 weight % ([0095]). The active agent includes sedative ([0083]), Olanzapine, felodipine ([0088]). Salting-out agents as described in the embodiment control the dissolution rate of the bioactive agent inside the matrix. Agents such as buffers and plasticizers could enhance or retard aqueous solubility of an active agent. It has been discovered that some agents, when used in water insoluble polymer matrices, can control the dissolution rate of the bioactive agent due to its solubility effect. Agents which retard the aqueous solubility of an active agent will slow down the dissolution rate of the active agent into the dissolution media ([0101]).
Perricone teaches an article for transdermal delivery (claim 1) in the form of patch ([0088]). In another set of embodiments, the composition may also include one or more transdermal penetration enhancers. Examples of transdermal penetration enhancers include, but are not limited to, 1,3-dimethyl-2-imidazolidinone or 1,2-propanediol. Other examples include cationic, anionic, or nonionic surfactants (e.g., sodium dodecyl sulfate, polyoxamers, etc.); fatty acids and alcohols (e.g., ethanol, oleic acid, lauric acid, liposomes, etc.); anticholinergic agents (e.g., benzilonium bromide, oxyphenonium bromide); alkanones (e.g., n-heptane); amides (e.g., urea, N,N-dimethyl-m-toluamide); organic acids (e.g., citric acid); sulfoxides (e.g., dimethylsulfoxide); terpenes (e.g., cyclohexene); ureas; sugars; carbohydrates or other agents. The transdermal penetration enhancers can be present in any suitable amount within the composition. For example, at least about 10 wt %, at least about 20 wt %, at least about 30 wt %, at least about 40 wt %, or at least about 50 wt % of the composition may comprise one or more transdermal penetration enhancers. In some cases, no more than about 60 wt %, no more than about 50 wt %, no more than about 40 wt %, no more than about 30 wt %, no more than about 20 wt %, no more than about 10 wt %, no more than about 9 wt %, or no more than about 5 wt % of the composition comprises transdermal penetration enhancers. Combinations of any of these are also possible. For example, the composition may have between about 0 wt % and about 5 wt % of one or more transdermal penetration enhancers ([0060]). 1,3-dimethyl-2-imidazolidinone is dimethylethylene urea according to applicant’s specification (page 4, 2nd paragraph).
Lee et al. teaches an apixaban transdermal patch for treatment of thrombosis and related disorders (abstract). In one embodiment, the transdermal delivery system comprises a permeation enhancer ([0030]). In one embodiment, the permeation enhancer is in an amount ranging from about 5% to about 30% by weight (wt %) relative to total weight of the drug-containing layer, or the reservoir layer ([0043]). Preferred permeation enhancers that provide good solubility include organic solvents such as dichloromethane (DCM), as well as 1,3-Dimethyl-2-imidazolidinone (DMI) ([0163])
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02)
The difference between the instant application and Tagliaferri et al. is that Tagliaferri et al. do not expressly teach dimethyleneurea and amount. This deficiency in Tagliaferri et al. is cured by the teachings of Perricone and Lee et al.
Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Tagliaferri et al., as suggested by Perricone and Lee et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to include 1,3-dimethyl-2-imidazolinone in the patch of Tagliaferri et al. because 3-dimethyl-2-imidazolinone is a suitable ingredient in the patch. MPEP 2144.07. Under guidance from Tagliaferri et al. teaching patch teaches patch comprising permeability enhancer (penetration enhancer), Perricone and Lee et al. teaching 1,3-dimethyl-2-imidazolinone as known penetration enhancer in the patch, it is obvious to include 1,3-dimethyl-2-imidazolinone in the patch of Tagliaferri et al. and produce instant claimed invention with reasonable expectation of success.
Regarding claims 1, 3-5 and 14, prior art teaches a patch comprising backing (layer), a reservoir comprising an active agent such as sedative, Olanzapine and felodipine; and an enhancer (penetration enhancer) 1,3-dimethyl-2-imidazolinone (dimethylethylene urea according to applicant’s specification). Olanzapine has a logP more than 3, in arguendo that the aqueous solubility not less than 0.01 mg/ml, claim 3 would not read on the elected Olanzapine species and would be withdrawn from the examination.
Regarding the ratio of penetration enhancer to the active agent in claim 1, and claims 6, 11 and 16-17, Tagliaferri et al. teaches active agent at about 1-30%; Perricone teaches penetration enhancer 1,3-dimethyl-2-imidazolinone (dimethylethylene urea) at 10% to 30%; Lee et al teaches penetration enhancer 1,3-dimethyl-2-imidazolinone at about 5% to about 30% by weight. When active agent is 10% and penetration enhancer 1,3-dimethyl-2-imidazolinone is 15%, the ratio of penetration enhancer to the active agent is1.5:1, more than 1:1.
Regarding claim 7, Tagliaferri et al. teaches the matrix includes ethylene vinyl acetate (EVA) co-polymer or polyethylacrylate.
Regarding claim 8, Tagliaferri et al. teaches the reservoir may be sandwiched between a backing and a rate controlling membrane. The drug releases only through the rate-controlling membrane, which can be microporous.
Regarding claim 10, Tagliaferri et al. teaches plasticizers.
Regarding claim 13, Tagliaferri et al. teaches single permeability enhancer (not required as mixture), and prior art teaches 1,3-dimethyl-2-imidazolinone (dimethylethylene urea as permeability enhancer, thus, prior art teaches 1,3 -dimethyl-2-imidazolinone exclusive as permeability enhancer (penetration accelerator).
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Claims 9 and 12 are rejected under 35 U.S.C. 103 as being unpatentable over Tagliaferri et al. (US20110190688) in view of Perricone (US20160136169) and Lee et al. (US20200338012), as applied for the above 103 rejection for claims 1,3-8, 10-11, 13-14 and 16-17, further in view of Berthold et al. (WO0107017) and Breitenbach et al. (US20060014832).
Determination of the scope and content of the prior art
(MPEP 2141.01)
Tagliaferri et al., Perricone and Lee et al. teaching have already been discussed in the above 103 rejection and are incorporated herein by reference.
Berthold et al. teaches transdermal system (abstract). Berthold et al. a transdermal therapeutic system (hereinafter TTS) for administering calcium antagonists of the dihydropyridine type which comprises (a) a backing layer, which defines the upper surface of the device (b) a drug reservoir containing a solution comprising a calcium antagonist of the dihydropyridine type and at least one skin permeation enhancer, (c) a membrane to control the release of the active ingredient, (d) a pressure sensitive adhesive layer for attaching the system to the skin and, if necessary, a release liner on the outer face of the adhesive layer wherein the said backing layer and said membrane are connected together to form the drug reservoir (page 2, line 8-20). The membrane (3) to control the release of the calcium antagonist of the dihydropyridine type is a thin, flexible uniformly microporous, flat sheet membrane which provides a constant rate of drug release independent of time or of the amount of the active ingredient that remains in the reservoir A preferred membrane is a flat sheet membrane made from food grade polypropylene and polyethylene resins known under the Trade Mark Celgard™ 2400 or Celgard™ 2500, available from Hoechst Celanese. Celgard™ 2400 is the preferred membrane. Other suitable membranes include a microporus polyethylene membrane Solupor™ or an EVA membrane e.g. Co Tran™ (page 4, line 30 to page 5, line 5).
Breitenbach et al. teaches composition in the form of transdermal patch ([0084]). A loading of active ingredient (mg/cm2 matrix base) of 0.1-12, preferably 0.25-7.5, especially preferably from 0.3 to 4 and notably especially preferably of 0.6 to 2.5 results ([0260]).
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02)
The difference between the instant application and Tagliaferri et al. is that Tagliaferri et al. do not expressly teach polyethylene film and drug loading. This deficiency in Tagliaferri et al. is cured by the teachings of Berthold et al. and Breitenbach et al.
Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the invention of Tagliaferri et al., as suggested by Berthold et al. and Breitenbach et al., and produce the instant invention.
One of ordinary skill in the art would have been motivated to use polyethylene film as membrane in patch because use polyethylene film is a suitable membrane in patch as suggested by Berthold et al. MPEP 2144.07. Thus, it is obvious to use polyethylene film as membrane in patch and produce instant claimed invention with reasonable expectation of success.
One of ordinary skill in the art would have been motived to have drug loading at least 6 mg/cm2 because this is optimization under prior art condition or through routing experimentation. MPEP 2144.05. Under guidance from Breitenbach et al. teaching transdermal patch having a loading of active ingredient (mg/cm2 matrix base) of 0.1-12, it is obvious to have drug loading at least 6 mg/cm2, and produce instant claimed invention with reasonable expectation of success.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Argument:
Applicants argued about advantage of penetration enhancer also as solvent.
In response to this argument: this is not persuasive. It is already known in the art that 1,3-Dimethyl-2-imidazolidinone is both solvent and penetration in the art as suggested by Lee et al. Thus, the 103 rejection is still proper.
Applicants argue that there is no teaching of penetration to active agent more than 1:1, and Yu teaches away.
In response to this argument: this is not persuasive. As discussed in the above 103 rejection, Tagliaferri et al. teaches active agent at about 1-30%; Perricone teaches penetration enhancer 1,3-dimethyl-2-imidazolinone (dimethylethylene urea) at 10% to 30%; Lee et al teaches penetration enhancer 1,3-dimethyl-2-imidazolinone at about 5% to about 30% by weight. When active agent is 10% and penetration enhancer 1,3-dimethyl-2-imidazolinone is 15%, the ratio of penetration enhancer to the active agent is1.5:1, more than 1:1. Although Yu teaches the ratio of active agent to penetration enhancer is 1: (0.1-0.8), Yu does not criticize, discredit, or otherwise discourage the claimed ratio , thus, can not be considered as teaching away. "[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004). Therefore, the 103 rejection is still proper.
MPEP 2141 III states: “The proper analysis is whether the claimed invention would have been obvious to one of ordinary skill in the art after consideration of all the facts.” Respectfully, after weighing all the evidence, the Examiner has reached a determination that the instant claims are not patentable in view of the preponderance of evidence and consideration of all the facts which is more convincing than the evidence which has been offered in opposition to it.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JIANFENG SONG. Ph.D. whose telephone number is (571)270-1978. The examiner can normally be reached M-F 8-5.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian-Yong Kwon can be reached at (571)272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JIANFENG SONG/Primary Examiner, Art Unit 1613