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 .
Status of the claims
Claims 3, 5, and 21 have been cancelled in a previous communication. Claim 22 has been withdrawn. New claims 24-25 have been added.
Claims 1-2, 4, 6-20, and 23-25 are currently under examination.
Examiner’s Note
Claim 23 is under examination although it depends from Claim 22 because they are two statutory distinct claims.
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.
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.
Claims 1-2, 4, 6-20, and 23-25 are rejected under 35 U.S.C. 103 as being unpatentable over Bhatt et al. (EP0688564B1, Published 08/04/1999) in view of Woolfson et al. (US20090004246A1, Published 01/01/2009) and further in view of Blanda et al. (US20170224823A1, Published 08/10/2017) further in view of Muraoka et al. (US 6077528A, Published 06/20/2000) further in view of Agarwal et al (WO2018083675A1, Published 05/11/2019).
Applicant’s invention
Applicant’s claims are drawn to a curable liquid silicone rubber composition comprising a two-part component system comprising Part A and Part B, wherein, Part A comprises (A) at least one organopolysiloxane having at least two silicon- bonded alkenyl groups per molecule, said alkenyl groups each containing from 2 to 14 carbon atoms, (D) optionally at least one filler selected from the group consisting of finely divided silica, hydrophobic silica hydrogel. surface treated silica, fumed silica and fumed silica in situ treated with hexamethyldisilazane and/or tetramethyldivinyldisilazane, and (C) at least one hydrosilylation catalyst comprising Pt, Rh, Ru, Pd, Ni, or any combinations thereof: Part B comprises (A) at least one organopolysiloxane having at least two silicon- bonded alkenyl groups per molecule, said alkenyl groups each containing from 2 to 14 carbon atoms, (D) optionally at least one filler selected from the group consisting of finely divided silica, hydrophobic silica hydrogel. surface treated silica, fumed silica and fumed silica in situ treated with hexamethyldisilazane and/or tetramethyldivinyldisilazane, (B) at least one organosilicon compound having at least two silicon-bonded hydrogen atoms per molecule, (G)at least one cure rate controller, (E) from 0.01% to 10 % by weight based on total weight of the curable liquid silicone rubber composition of a mixture comprising at least one fatty acid ester and benzotriazole, and (F) a therapeutically effective amount of at least one active pharmaceutical ingredient comprising in its chemical structure at least one terminal alkene, or at least one terminal alkyne, wherein the fatty acid ester is formed from an alcohol of 2 to 20 carbon atoms and a fatty acid.
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claims 1, 20 and 24, Bhatt teaches the method of controlling release of active agents/drugs from a silicon rubber matrix wherein the silicon rubber matrixes are produced by curing a liquid silicone rubber comprised of (a) a polyorganosiloxane containing at least two alkenyl radicals per molecule; (b) an organohydrogensiloxane containing at least two silicon-bonded hydrogen atoms per molecule; and (c) a hydrosilylation catalyst in an amount sufficient to promote curing of said composition (page 2, paragraph [0008]). Bhatt also teaches wherein the polyorganosiloxane (a) must contain at least two silicon-bonded alkenyl radicals in each molecule. Suitable alkenyl radicals contain from 1 to 10 carbon atoms and are exemplified by vinyl (page 2, paragraph [0011]). Bhatt further teaches hydrosilylation catalysts useful in the instant invention are platinum metal, platinum compounds, platinum complexes and others such as rhodium compounds, nickel compounds, palladium metals (paragraph [0022]). Bhatt further teaches finely divided forms of silica are preferred reinforcing fillers. Colloidal silicas are particularly preferred (page 4, paragraph [0032]). Bhatt continues to teach drugs that may be released from the silicone rubber matrix are exemplified by hormonal agents such as estradiol (page 6, paragraph [0045]). Bhatt also teaches wherein the organohydrogensiloxane (b) is present in an amount sufficient to provide a molar ratio of alkenyl radicals in polyorganosiloxane (a) to silicon-bonded hydrogen atoms in the organohydrogensiloxane (b) of from 0.5:1 to 20:1 (page 9, claim 1). The examiner notes that the claimed range falls within the range of Bhatt. Bhatt further teaches platinum catalyst inhibitors such as acetylenic alcohols (i.e., “cure rate controller”) (page 4, paragraph [0027]). Bhatt continues to teach in making rubber 1, A liquid silicone rubber was prepared by combining 1 part of a mixture containing approximately 65 wt% of a dimethylvinylsiloxy-terminated dimethylsiloxane having a plasticity of 1.5 mm (60 mils) (i.e., organopolysiloxane) and 2 wt% of a trimethylsiloxy-terminated methylhydrogen dimethylsiloxane having an average silicon-bonded hydrogen atom content (i.e., organosilicon compound) (paragraph [0052]). Bhatt also teaches 10 to 60% percent by weight of silica, based on the weight of the rubber components (paragraph [0032]). Bhatt further teaches the concentration of catalyst (c) in the present compositions is equivalent to a concentration of from 0.1 to 500 parts by weight of catalyst metal (e.g., platinum metal) (paragraph [0024]). Bhatt also teaches platinum catalyst inhibitors concentrations as low as one mole of inhibitor per mole of platinum will in some instances impart satisfactory storage stability and cure rate. In other instances inhibitor concentrations of up to 500 or more moles of inhibitor per mole of platinum are required. The optimum concentration for a given inhibitor in a given composition can readily be determined by routine experimentation and does not constitute part of this invention (paragraph [0028]). The Examiner points out that the preamble recites a curable liquid silicone rubber composition as a resulting of the mixing of the two component system. The fact that Applicants are describing the composition with its constituent parts is product by process because in order to claim the final product one must combine the two component system, whereas Applicants are claiming the final curable liquid silicon rubber composition. The final product taught in Bhatt is still a curable liquid silicone rubber composition reading to the final product instantly claimed.
Regrading claims 9 and 25, Bhatt teaches curing the liquid silicone rubber composition while being molded into a shape (page 9, claim 1). The examiner points out that the instant claims recite a limitation on how the product was made (i.e., curing and molding); however, this does not limit the structural element of the claimed product. "[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). See MPEP 2113 (I).
Regarding claims 13 and 14, Bhatt teaches suitable alkenyl radicals contain from 1 to 10 carbon atoms and are exemplified by vinyl, allyl and 5-hexenyl (paragraph [0008]).
Regarding claim 15, Bhatt teaches if polyorganosiloxane (A) contains only two alkenyl radicals per molecule, organohydrogensiloxane (B) must contain an average of more than two (i.e., at least three) silicon-bonded hydrogen atoms to achieve a crosslinked structure in the final cured product (paragraph [0016]).
Regarding claim 16, Bhatt teaches hydrosilylation catalysts useful in the instant invention are platinum metal, platinum compounds, platinum complexes and others (paragraph [0022]).
Regarding claim 17, Bhatt teaches the concentration of catalyst (C) in the present compositions is equivalent to a concentration of from 0.1 to 500 parts by weight of catalyst metal (e.g., platinum metal), preferably from 1 to 50 parts by weight of catalyst metal, per million parts (ppm), based on the combined weight of components (A) and (B) (paragraph [0021]).
Regarding claim 18, Bhatt teaches when a silica filler is used, it is preferably treated in the presence of at least a portion of the other ingredients of the present compositions by blending these ingredients together until the filler is completely treated and uniformly dispersed to form a homogeneous material (paragraph [0032]).
Regarding claim 19, Bhatt teaches colloidal silicas can be a fume type (i.e., fumed silica) (paragraph [0029]). Bhatt also teaches organosilicon compounds such as hexaorganodisiloxanes and hexaorganodisilazanes that hydrolyze under the conditions used to treat the filler to form compounds with silicon-bonded hydroxyl groups (paragraph [0030]). Bhatt further teaches 31wt% of hexamethydisilazane treated silica in the example rubber 3 (paragraph [0051]).
Regarding claim 23, the examiner points out that the limitations of claim 22 which claim 23 depends from are method claims making claim 23 product by process limitations, therefore it is not given patentable weight.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Bhatt does not teach from 0.01 to 10% by weight based on total weight of the curable liquid silicone rubber composition of a mixture comprising at least one fatty acid ester and benzotriazole (instant claim 1); a therapeutically effective amount of at least one active pharmaceutical ingredient comprising in its chemical structure at least one terminal alkene, or at least one terminal alkyne (instant claim 1); wherein said fatty acid ester G is formed from an alcohol of 2 to 20 carbon atoms (instant claim 1); wherein the mixture contains from 0.1 to 10% by weight of benzotriazole and from 99.9 to 90% by weight of fatty acid ester (instant claim 2); wherein said fatty acid is selected from the group consisting of caproic acid, lauric acid, myristic acid, oleic acid, linoleic acid, adipic acid and lanolin acid (instant claim 4); wherein said alcohol is an alkanol of 2 to 4 carbon atoms (instant claim 6); wherein said fatty acid ester is isopropyl myristate (instant claim 7); wherein said active pharmaceutical ingredient is chosen from the group consisting of levonorgestrel, ethynyl estradiol, norethisterone, ethynodiol diacetate, desogestrel, lynestrenol, and mixtures thereof (instant claim 8); a drug delivery device comprising a molded silicone rubber (instant claim 10); a drug delivery device prepared via an injection molding apparatus or a compression molding apparatus (instant claim 11); and wherein the drug delivery device is an intravaginal drug delivery device (instant claim 12). However, these deficiencies are cured by Woolfson et al., Blanda et al., Muraoka et al., and Agarwal et al.
In the analogous art of controlled release of drugs, Woolfson teaches an intravaginal drug delivery device wherein at least one drug-containing insert comprises at least one water-soluble release enhancer in an amount ranging from about 1% to about 70% (page 4, paragraph [0044]), wherein the release enhancer includes fatty acid esters, preferably containing 2 to 20 carbon atoms of which myristate esters are preferred (page 4, paragraph [0045]). Woolfson also teaches contraceptives suitable for intravaginal release from the device body levonorgestrel, norethisterone, desogestrel, estradiol, and ethinyl estradiol (page 7, paragraph [0067]). Woolfson further teaches the insert carrier material may be a silicone elastomer (page 6, paragraph [0063]) wherein the insert is prepared by a suitable method such as injection molding (page 6, page [0056]). Woolfson also teaches the drug delivery device is an intravaginal device (page 6, paragraph 0057]). Woolfson further teaches at least one drug suitable for inclusion in the device body can be antifungals (page 7, paragraph [0066]). Woolfson also teaches At least one drug suitable for intravaginal release from the device body can be employed for use in the present invention. Drugs suitable for inclusion in the device body are those typically suitable for conventional formulation, wherein typically, the amount of device body drug used in the device body ranges from about 0.005% to about 65% w/w (paragraph [0066]).
In the analogous art of controlled release of drugs, Blanda teaches intravaginal rings (i.e., drug delivery device) of the invention comprise polysiloxanes (page 9, paragraph [0087]); wherein the intravaginal drug delivery devices further comprises an antimicrobial compound (page 2, paragraph [0016]); wherein antimicrobial compound embraces antifungal agents (page 6, paragraph [0063]) such as fluconazole, terconazole and itraconazole (i.e., triazole compounds) (page 13, paragraph [0132]). Blanda further teaches wherein the antimicrobial agent is present in the ring in a range of 10mg to 1600mg (page 13, paragraph [0143]).
In the analogous art of biomedicine, Muraoka teaches specific examples of fatty acid esters include myristates such as isopropyl (i.e., alkanol of 3 carbons) myristate (column 5, lines 12-16).
Agarwal et al. teaches the present invention relates to the use of synergistic antimicrobial composition comprising quaternary ammonium compound and antimicrobial active in pharmaceuticals (page 12, lines 13-14). Agarwal further teaches the antimicrobial active of the present invention is selected from the group comprising fluconazole, terconazole, itraconazole, and benzotriazole (page 8, lines 24-29). Agarwal also teaches In one embodiment the present invention provides synergistic antimicrobial compositions comprising antimicrobial active is present in an amount of 0.0025-25% w/w (page 4, lines 5-6).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious to one of ordinary skill in the arts at the time of filing to have a fatty acid ester in Bhatt’s method of controlling release of a drug from curable silicone liquid silicone rubber composition. Bhatt teaches release additives as an additional component which effects the release of the drug or active from the silicone rubber matrix may be added such as polyethylene glycols (page , paragraph [0040]). One would have understood in view of Woolfson that water-soluble release enhancers are selected from polyethylene glycols, fatty acid esters etc., wherein the fatty acid esters preferably containing 2 to 20 carbon atoms, of which myristate esters are preferred (page 4, paragraph [0045]); wherein the “release enhancer” is capable of increasing cumulative release of the drug for a given time period (page 3, paragraph [0034]). It would have been obvious to use fatty acid ester in Bhatt’s method of controlling release of a drug from curable silicone liquid silicone rubber composition because Bhatt teaches release additions such as polyethylene glycols and Woolfson teaches release enhancers such as fatty acid esters preferably myristate esters and polyethylene glycols. Therefore, fatty acid esters preferably myristate esters would have been suitable for the purpose of a release additive in Bhatt’s composition. See MPEP 2144.07.
It would have been prima facie obvious to one of ordinary skill in the art at the time of filing to have benzotriazole in Bhatt’s method of controlling release of a drug from curable silicone liquid silicone rubber composition. Woolfson teaches that the intravaginal drug delivery device can further comprise antifungals as an additional drug in the device (page 2, paragraph [0018]). One would have understood in view of Blanda wherein the intravaginal drug delivery devices further comprises an antimicrobial compound (page 2, paragraph [0016]); wherein antimicrobial compound embraces antifungal agents (page 6, paragraph [0063]) such as fluconazole, terconazole and itraconazole (i.e., triazole compounds) (page 13, paragraph [0132]). One would have further understood in view of Agarwal that antimicrobial actives of the present invention is selected from the group comprising fluconazole, terconazole, itraconazole, and benzotriazole (page 8, lines 24-29). It would have been obvious to one of ordinary skill in the art to have a benzotriazole in Bhatt’s method of controlling release of a drug from curable silicone liquid silicone rubber composition because Woolfson teaches an intravaginal drug delivery device comprising a curable liquid silicone that further comprises antifungals as a drug in the device and Blanda teaches antifungal agents used in a intravaginal drug delivery device can be bifonazole, butoconazole, eberconazole, ketoconazole, tioconazole etc. (i.e., triazole compounds)(page 13, paragraph [0132]) which are capable of inhibiting or destroying the growth of a microbial organism (page 12, paragraph [0126]) and Agarwal teaches that antimicrobial actives can be selected from fluconazole, terconazole, itraconazole, and benzotriazole. Therefore, benzotriazole was known to serve the same purpose of an antimicrobial agent in the form of a triazole compound. See MPEP 2144.06 (II).
With regards to wherein the mixture contains from 0.1 % to 10% by weight of benzotriazole and fatty acid ester, it would have been obvious to one of ordinary skill in the art to vary the amounts of the fatty acid ester and the triazole compound depending on the desired result. Woolfson teaches an intravaginal drug delivery device wherein at least one drug-containing insert comprises at least one water-soluble release enhancer in an amount ranging from about 1% to about 70% (page 4, paragraph [0044]), and Blanda teaches wherein the antimicrobial agent is present in the ring in a range of 10mg to 1600mg (page 13, paragraph [0143]), therefore it would have been obvious to one of ordinary skill in the art to optimize the amounts of the triazole compound and the fatty acid ester. Determining optimal concentrations is routine experimentation and is practiced by one of ordinary skill. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. In re Aller, 220 F. 2d 454, 105 USPQ 233 (CCPA 1955). In addition, according to the MPEP, “It is to be presumed also that skilled workers would as a matter of course, if they do not immediately obtain desired results, make certain experiments and adaptations, within the skill of the competent worker.” (MPEP 716.07).
With regards to the limitations wherein at least one active pharmaceutical ingredient comprises in its chemical structure at least one terminal alkene, or at least one terminal alkyne, wherein said active pharmaceutical ingredient is chosen from the group consisting of levonorgestrel, ethynyl estradiol, norethisterone, ethynodiol diacetate, desogestrel, lynestrenol, and mixtures thereof, it would have been prima facie obvious to one of ordinary skill at the time of filing to have at least one active pharmaceutical ingredient comprising in its chemical structure at least one terminal alkene, or at least one terminal alkyne in Bhatt’s method of controlling release of a drug from curable silicone liquid silicone rubber composition. Bhatt teaches drugs that may be released from the silicone rubber matrix are exemplified by hormonal agents such as estradiol (page 6, paragraph [0045]). One would have understood in view of Woolfson that contraceptives suitable for intravaginal release from the device body levonorgestrel, norethisterone, desogestrel, estradiol, and ethinyl estradiol (page 7, paragraph [0067]). It would have been obvious to one of ordinary skill in the art to have least one active pharmaceutical ingredient comprising in its chemical structure at least one terminal alkene, or at least one terminal alkyne in Bhatt’s method of controlling release of a drug from curable silicone liquid silicone rubber composition because Bhatt teaches drugs that may be released from the silicone rubber matrix are exemplified by hormonal agents such as estradiol (page 6, paragraph [0045]) and Woolfson that contraceptives suitable for intravaginal release from the device body such as estradiol, and ethinyl estradiol (page 7, paragraph [0067]), therefore ethinyl estradiol is obvious as an active pharmaceutical ingredient because Bhatt teaches the genus of estradiol and Woolfson teaches the species of estradiol as contraceptives which is ethinyl estradiol which has an terminal alkene. See MPEP 2144.08.
The examiner also points out that it would have been obvious to one of ordinary skill in the art to optimize the effect of hormonal agents in Bhatt’s method of controlling release of a drug from curable silicone liquid silicone rubber composition because Bhatt teaches drugs that may be released from the silicone rubber matrix are exemplified by hormonal agents (page 6, paragraph [0045]), and Woolfson teaches that contraceptives suitable for intravaginal release from the device body levonorgestrel, norethisterone, desogestrel, estradiol, and ethinyl estradiol (page 7, paragraph [0067]). One of ordinary skill in the art would have the understanding of optimizing how to apply the examples of hormonal agents taught by Woolfson to achieve desired results for example contraception.
It would have been prima facie obvious to one of ordinary skill in the art at the time of filing to have a fatty acid ester formed from an alcohol of 2 to 20 atoms, wherein said alcohol is an alkanol of 2 to 4 carbon atoms, wherein said fatty acid ester is isopropyl myristate in Bhatt’s method of controlling release of a drug from curable silicone liquid silicone rubber composition. Bhatt teaches release additives as an additional component which effects the release of the drug or active from the silicone rubber matrix may be added such as polyethylene glycols (page 5, paragraph [0040]). Woolfson teaches release enhancers such as fatty acid esters preferably myristate esters and polyethylene glycols; wherein the fatty acid esters preferably containing 2 to 20 carbon atoms, of which myristate esters are preferred (page 4, paragraph [0045]). One would have understood in view Muraoka that isopropyl myristate is a type of myristate ester (i.e., fatty acid ester) (column 5, lines 12-16). It would have been obvious to one of ordinary skill in art to have isopropyl myristate in Bhatt’s method of controlling release of a drug from curable silicone liquid silicone rubber composition because Bhatt teaches release additives and Woolfson teaches release enhancers such as fatty acid esters preferably myristate esters and Muraoka teaches that isopropyl myristate is a type of myristate ester. Therefore, isopropyl myristate is suitable in biomedicine as a myristate ester.
With regards to claim 24 wherein Part-A and Part-B are mixed in a 1:1 weight ratio, it would have been obvious to optimize the amounts of each component in Part-A and Part-B to formulate a 1:1 weight ratio of the mixture. Bhatt teaches in making rubber 1, A liquid silicone rubber was prepared by combining 1 part of a mixture containing approximately 65 wt% of a dimethylvinylsiloxy-terminated dimethylsiloxane having a plasticity of 1.5 mm (60 mils) (i.e., organopolysiloxane) and 2 wt% of a trimethylsiloxy-terminated methylhydrogen dimethylsiloxane having an average silicon-bonded hydrogen atom content (i.e., organosilicon compound) (paragraph [0052]). Bhatt also teaches 10 to 60% percent by weight of silica, based on the weight of the rubber components (paragraph [0032]). Bhatt further teaches the concentration of catalyst (c) in the present compositions is equivalent to a concentration of from 0.1 to 500 parts by weight of catalyst metal (e.g., platinum metal) (paragraph [0024]). Bhatt also teaches platinum catalyst inhibitors concentrations as low as one mole of inhibitor per mole of platinum will in some instances impart satisfactory storage stability and cure rate. In other instances inhibitor concentrations of up to 500 or more moles of inhibitor per mole of platinum are required. The optimum concentration for a given inhibitor in a given composition can readily be determined by routine experimentation and does not constitute part of this invention (paragraph [0028]). Woolfson teaches an intravaginal drug delivery device wherein at least one drug-containing insert comprises at least one water-soluble release enhancer in an amount ranging from about 1% to about 70% (page 4, paragraph [0044]), wherein the release enhancer includes fatty acid esters, preferably containing 2 to 20 carbon atoms of which myristate esters are preferred (page 4, paragraph [0045]). Woolfson also teaches at least one drug suitable for intravaginal release from the device body can be employed for use in the present invention. Drugs suitable for inclusion in the device body are those typically suitable for conventional formulation, wherein typically, the amount of device body drug used in the device body ranges from about 0.005% to about 65% w/w (paragraph [0066]). Agarwal also teaches in one embodiment the present invention provides synergistic antimicrobial compositions comprising antimicrobial active is present in an amount of 0.0025-25% w/w (page 4, lines 5-6). It would have been obvious to optimize the amounts of each component in Part-A and Part-B to formulate a 1:1 weight ratio of the mixture because Bhatt, Woolfson, and Agarwal teach amounts of each component present in in Part-A and Part-B, therefore it would be obvious for one of ordinary skill in the art to optimize the concentrations of the components such that the ingredients in Part-A and Part-B are in a 1:1 weight ratio through routine experimentation to achieve desired results.
Determining optimal concentrations is routine experimentation and is practiced by one of ordinary skill. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. In re Aller, 220 F. 2d 454, 105 USPQ 233 (CCPA 1955). In addition, according to the MPEP, “It is to be presumed also that skilled workers would as a matter of course, if they do not immediately obtain desired results, make certain experiments and adaptations, within the skill of the competent worker.” (MPEP 716.07).
Response to Arguments
Applicants arguments filed 06/23/2026 have been fully considered but they are not persuasive.
On page 9 of Applicants remarks, Applicants argue that the two-part Part-A/Part B architecture recited in claim 1 is structurally meaningful. The Part A comprises the hydrosilylation catalyst (C), while part B comprises the organosilicon compound having silicon-bonded hydrogen atoms (B), the mixture comprising fatty acid ester and bezotriazole €, and the active pharmaceutical ingredient (F). This segregation of the platinum catalyst from the Si-H crosslinker is what makes the composition a “curable liquid” silicone rubber than an already-curing composition. If the Pt catalyst and Si-H crosslinker were commingled the hydrosilylation reaction would commence and the composition would no longer be shelf-stable or “curable”. This partition therefore imposes a real structural constraint on which components coexist in which sub-composition, and is not mere process recitation.
This argument is not persuasive. The Examiner points out that the claim recites a curable liquid silicone rubber composition in the preamble, nothing in the claims recites that Part A and Part B are kept segregated. Applicants are claiming a single composition that comprise two parts but once it is a single composition, the two parts are combined to make one composition. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., the segregation of the platinum catalyst from the Si-H crosslinker) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). The Examiner further points out that Bhatt teaches to maximize storage stability, our curable compositions are preferably kept in closed containers until used. If greater storage stability is desired, the compositions can be packaged in two or more containers with the organohydrogensiloxane (b) and the hydrosilylation catalyst (c) in a separate container (paragraph [0041]). Therefore the structural constraint on the components is taught by Bhatt.
On pages 10-11 of Applicants remarks, Applicants argue that the office has acknowledged that Bhatt does not teach certain limitations, therefore these are product features not process features. The claimed composition structurally differs from Bhatt’s composition by virtue of these components. Applicants further argue that there is no teaching or motivation in any of the cited references to select benzotriazole specifically among the universe of antimicrobials and combine it with a fatty acid ester in a curable silicone rubber composition carrying an alkene/alkyne-bearing API. Applicants also argue that Woolson’s fatty acid esters serve as release enhancers to increase cumulative release of water-soluble drugs not to prevent drug-platinum complexation or drug binding into the elastomeric network. Moreover, Woolfson does not teach or suggest combining a fatty acid ester with benzotriazole. Applicants continue to argue that the mere fact that isopropyl myristate is known as a fatty acid ester in transdermal patches does not provide motivation to combine with benzotriazole in a curable silicone rubber composition to achieve the function recited in the present claims.
These arguments are not persuasive. The fact that Applicants are describing the composition with its constituent parts is product by process because in order to claim the final product one must combine the two component system, whereas Applicants are claiming the final curable liquid silicon rubber composition. The final product taught in Bhatt in view of Blanda, Woolfson, and Agarwal is still a curable liquid silicone rubber composition reading to the final product instantly claimed.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). With regards to Applicants argument one skill in the art would find no motivation in Bhatt to arrive at the composition of the instant claims, the Examiner reiterates that Bhatt was relied on for the teaching of controlling release of active agents/drugs from a silicon rubber matrix wherein the silicon rubber matrixes are produced by curing a liquid silicone rubber comprised of (a) a polyorganosiloxane containing at least two alkenyl radicals per molecule; (b) an organohydrogensiloxane containing at least two silicon-bonded hydrogen atoms per molecule; and (c) a hydrosilylation catalyst in an amount sufficient to promote curing of said composition (page 2, paragraph [0008]). Bhatt also teaches wherein the polyorganosiloxane (a) must contain at least two silicon-bonded alkenyl radicals in each molecule. Suitable alkenyl radicals contain from 1 to 10 carbon atoms and are exemplified by vinyl (page 2, paragraph [0011]). Bhatt further teaches hydrosilylation catalysts useful in the instant invention are platinum metal, platinum compounds, platinum complexes and others such as rhodium compounds, nickel compounds, palladium metals (paragraph [0022]). Bhatt further teaches finely divided forms of silica are preferred reinforcing fillers. Colloidal silicas are particularly preferred (page 4, paragraph [0032]). Bhatt continues to teach drugs that may be released from the silicone rubber matrix are exemplified by hormonal agents such as estradiol (page 6, paragraph [0045]). Bhatt also teaches wherein the organohydrogensiloxane (b) is present in an amount sufficient to provide a molar ratio of alkenyl radicals in polyorganosiloxane (a) to silicon-bonded hydrogen atoms in the organohydrogensiloxane (b) of from 0.5:1 to 20:1 (page 9, claim 1). The examiner notes that the claimed range falls within the range of Bhatt. Bhatt further teaches platinum catalyst inhibitors such as acetylenic alcohols (i.e., “cure rate controller”) (page 4, paragraph [0027]). The examiner relied on Woolfson for the teaching of the specific API having a terminal alkene or alkyne functionalities and the use of fatty acid esters. The examiner relied on Blanda for the teaching of antifungal agents used in a intravaginal drug delivery device can be bifonazole, butoconazole, eberconazole, ketoconazole, tioconazole etc. (i.e., triazole compounds)(page 13, paragraph [0132]) which are capable of inhibiting or destroying the growth of a microbial organism (page 12, paragraph [0126]) and Agarwal teaches that antimicrobial actives can be selected from fluconazole, terconazole, itraconazole, and benzotriazole. It would have been obvious to use fatty acid ester in Bhatt’s method of controlling release of a drug from curable silicone liquid silicone rubber composition because Bhatt teaches release additions such as polyethylene glycols and Woolfson teaches release enhancers such as fatty acid esters preferably myristate esters and polyethylene glycols. Therefore, fatty acid esters preferably myristate esters would have been suitable for the purpose of a release additive in Bhatt’s composition. See MPEP 2144.07. Also Bhatt teaches drugs that may be released from the silicone rubber matrix are exemplified by hormonal agents such as estradiol (page 6, paragraph [0045]) and Woolfson that contraceptives suitable for intravaginal release from the device body such as estradiol, and ethinyl estradiol (page 7, paragraph [0067]), therefore ethinyl estradiol is obvious as an active pharmaceutical ingredient because Bhatt teaches the genus of estradiol and Woolfson teaches the species of estradiol as contraceptives which is ethinyl estradiol which has an terminal alkene. See MPEP 2144.08. It would have been obvious to one of ordinary skill in the art to have a benzotriazole in Bhatt’s method of controlling release of a drug from curable silicone liquid silicone rubber composition because Woolfson teaches an intravaginal drug delivery device comprising a curable liquid silicone that further comprises antifungals as a drug in the device and Blanda teaches antifungal agents used in a intravaginal drug delivery device can be bifonazole, butoconazole, eberconazole, ketoconazole, tioconazole etc. (i.e., triazole compounds)(page 13, paragraph [0132]) which are capable of inhibiting or destroying the growth of a microbial organism (page 12, paragraph [0126]) and Agarwal teaches that antimicrobial actives can be selected from fluconazole, terconazole, itraconazole, and benzotriazole. Therefore, benzotriazole was known to serve the same purpose of an antimicrobial agent in the form of a triazole compound. See MPEP 2144.06 (II). The motivation to combine a fatty acid ester with benzotriazole in a curable silicone rubber composition would be for the purpose of a release additive as well as an antimicrobial agent in Bhatt’s composition.
With regards to Applicants argument that that Woolson’s fatty acid esters serve as release enhancers to increase cumulative release of water-soluble drugs not to prevent drug-platinum complexation or drug binding into the elastomeric network, The reason or motivation to modify the reference may often suggest what the inventor has done, but for a different purpose or to solve a different problem. It is not necessary that the prior art suggest the combination to achieve the same advantage or result discovered by applicant. See, e.g., In re Kahn, 441 F.3d 977, 987, 78 USPQ2d 1329, 1336 (Fed. Cir. 2006) (motivation question arises in the context of the general problem confronting the inventor rather than the specific problem solved by the invention); Cross Med. Prods., Inc. v. Medtronic Sofamor Danek, Inc., 424 F.3d 1293, 1323, 76 USPQ2d 1662, 1685 (Fed. Cir. 2005) ("One of ordinary skill in the art need not see the identical problem addressed in a prior art reference to be motivated to apply its teachings."); In re Lintner, 458 F.2d 1013, 173 USPQ 560 (CCPA 1972) (discussed below); In re Dillon, 919 F.2d 688, 16 USPQ2d 1897 (Fed. Cir. 1990), cert. denied, 500 U.S. 904 (1991). See MPEP 2144 (IV).
On page 11 of Applicants remarks, Applicant argues the mixture comprising fatty acid ester and benzotriazole (E) serves an entirely different purpose. The function of preventing Pt-drug complexation and irreversible drug binding is wholly absent from the cited art.
This argument is not persuasive. In response to applicant's argument that the mixture comprising fatty acid ester and benzotriazole (E) serves an entirely different purpose, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
It would have been obvious to use fatty acid ester in Bhatt’s method of controlling release of a drug from curable silicone liquid silicone rubber composition because Bhatt teaches release additions such as polyethylene glycols and Woolfson teaches release enhancers such as fatty acid esters preferably myristate esters and polyethylene glycols. Therefore, fatty acid esters preferably myristate esters would have been suitable for the purpose of a release additive in Bhatt’s composition. See MPEP 2144.07. It would have been obvious to one of ordinary skill in the art to have a benzotriazole in Bhatt’s method of controlling release of a drug from curable silicone liquid silicone rubber composition because Woolfson teaches an intravaginal drug delivery device comprising a curable liquid silicone that further comprises antifungals as a drug in the device and Blanda teaches antifungal agents used in a intravaginal drug delivery device can be bifonazole, butoconazole, eberconazole, ketoconazole, tioconazole etc. (i.e., triazole compounds)(page 13, paragraph [0132]) which are capable of inhibiting or destroying the growth of a microbial organism (page 12, paragraph [0126]) and Agarwal teaches that antimicrobial actives can be selected from fluconazole, terconazole, itraconazole, and benzotriazole. Therefore, benzotriazole was known to serve the same purpose of an antimicrobial agent in the form of a triazole compound. See MPEP 2144.06 (II).
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., the function of preventing Pt-drug complexation and irreversible drug binding) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
On pages 11-12 of Applicants remarks, Applicants argue that the specification establishes that the results achieved by the claimed composition were “entirely surprisingly and unexpectedly” obtained. The claimed mixture of fatty acid ester and benzotriazole solves this problem by enabling increased API recovery- a result that the cited art neither teaches nor suggest.
This argument is not persuasive. The Examiner points out that Applicants assertion of
unexpected and non-obvious results need to be supported by evidence. Insomuch as this may be
an assertion of unexpected results, please refer to MPEP 716.02(b) which details the burden on
Applicant to establish that results in a side-by-side comparison to the closest prior art are unexpected and significant. Specifically, Applicant must establish that differences in results are
in fact unexpected and unobvious and are of both practical and statistical significance. Additionally, evidence of unexpected properties must be commensurate in scope with the claims.
In response to applicant's argument that the claimed mixture of fatty acid ester and benzotriazole solves this problem by enabling increased API recovery, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
Conclusion
No claims are 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.
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AFUA BAMFOAA BOATENGExaminer, Art Unit 1617
/ALI SOROUSH/Supervisory Patent Examiner, Art Unit 1614
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