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 .
Priority
This application is a national stage entry of PCT/US2020/051193 filed on 09/17/2020 which claims priority to U.S. Provisional Application No. 62/902,543 filed on 09/19/2019.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-6) drawn to a composition comprising at least 40% w/w lidocaine; an aliphatic solvent; about 0.1% w/w to about 10% w/w of a washability enhancer; and about 0.1% w/w to about 10% w/w one or more film forming excipients in the reply filed on September 16, 2025 is acknowledged. Applicant’s election without traverse of ethanol as a species of an aliphatic solvent; PEG 400 as a species of a washability enhancer; and poly(butylmethacrylate-co-(2-dimethylaminoethyl)methacrylate-co-methyl methacrylate 1:2:1 as a species of one or more film forming excipients, diethylene glycol monoethyl ether as a species of one or more penetration enhancers; and hydroxypropyl cellulose as a species of one or more viscosity increasing agents in the reply filed on September 16, 2025 is also acknowledged.
Claims 7, 9-11, 15-17, 26-29, 31, 42 and 54 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group, there being no allowable generic or linking claim.
Claims 1-6 are currently presented for examination and being examined as they read on the elected species.
Specification Objection
The disclosure is objected to because of the following informalities:
The use of the terms Transcutol® P and Eudragit® E100, in Table 4 on page 29 of the specification, which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Appropriate correction is required.
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.
Claims 1 and 3-6 are rejected under 35 U.S.C. 103 as being unpatentable over Hull et al. U.S. Publication No. 2016/0279245 A1.
Claims 1 and 3-6 of the instant application claim a composition comprising at least 40% w/w lidocaine; an aliphatic solvent; about 0.1% w/w to about 10% w/w of a washability enhancer; and about 0.1% w/w to about 10% w/w one or more film forming excipients, wherein said film forming excipient (i) has a solubility in water, at a pH between 1 and 10, that requires 30 parts or less of water to dissolve one part of said film forming excipient, (ii) has a solubility in ethanol that requires 30 parts or less of ethanol to dissolve one part of said film forming excipient; and (iii) can prevent crystallization of said lidocaine and maintain said lidocaine in an amorphous state during solvent evaporation when said composition is applied to skin; wherein said composition is a sprayable liquid solution; and wherein said composition contains less than 10% w/w water.
According to page 15 paragraph [0055] of the instant specification, examples of film forming excipients that have the desired characteristics as claimed in (i), (ii) and (iii) of claim 1, include Hydroxypropyl Cellulose (HPC or Hypromellose), Ethyl Cellulose, Hydroxypropyl Methyl Cellulose (HPMC), Eudragit® E100 (Amino Methacrylate Copolymer), Eudragit® L100 (Methacrylic Acid and Methyl Methacrylate Copolymer 1:1) (which dissolves above pH 6.0), Eudragit®S100 (Methacrylic Acid and Methyl Methacrylate Copolymer 1:2) (which dissolves above pH 7.0), Eudragit®E100 (Poly(butylmethacrylate-co-(2- dimethylaminoethyl)methacrylate-co-methyl methacrylate 1:2:1) (which dissolves below pH 5.0), Methyl Vinyl Ether-Maleic Anhydride Copolymers such as Gantrez® ES-435, a Butyl Ester of Methyl Vinyl Ether/Maleic Anhydride Copolymer; and Polyvinyl Acetate-Povidone Polymer. Thus the claims read on a liquid composition comprising at least 40% w/w lidocaine; an aliphatic solvent; about 0.1% w/w to about 10% w/w of a washability enhancer; and about 0.1% w/w to about 10% w/w one or more film forming excipients selected from the components listed above; wherein said composition contains less than 10% w/w water and further comprising one or more viscosity increasing agents.
Please note that “In determining whether the invention as a whole would have been obvious under 35 U.S.C. 103, we must first delineate the invention as a whole. In delineating the invention as a whole, we look not only to the subject matter which is literally recited in the claim in question... but also to those properties of the subject matter which are inherent in the subject matter and are disclosed in the specification. . . Just as we look to a chemical and its properties when we examine the obviousness of a composition of matter claim, it is this invention as a whole, and not some part of it, which must be obvious under 35 U.S.C. 103.” In re Antonie, 559 F.2d 618, 620, 195 USPQ 6,8 (CCPA 1977). See also Ex parte Novitski, 26 USPQ2d 1389 (Bd. Pat. App. & Inter. 1993) (The Board rejected a claim directed to a method for protecting a plant from plant pathogenic nematodes by inoculating the plant with a nematode inhibiting strain of P. cepacia. A U.S. patent to Dart disclosed inoculation using P. cepacia type Wisconsin 526 bacteria for protecting the plant from fungal disease. Dart was silent as to nematode inhibition but the Board concluded that nematode inhibition was an inherent property of the bacteria. The Board noted that applicant had stated in the specification that Wisconsin 526 possesses an 18% nematode inhibition rating.).
Hull et al. teaches topical formulations comprising a drug such as a local anesthetic, an NSAID, or a corticosteriod; and sodium lauryl sulfoacetate wherein the topical formulations can have enhanced physical and/or chemical stability as compared to similar formulations without sodium lauryl sulfoacetate (abstract).
Hull et al. teaches that generally, any local anesthetic known in the art can be incorporated into topical formulations wherein non-limiting examples of such local anesthetics include lidocaine, tetracaine, benzocaine, prilocaine, bupivacaine, dimethocaine, mepivacaine, procaine, ropivacaine, trimecaine, articaine, and combinations thereof [0056]. Hull et al. teaches that in one embodiment, the local anesthetic can include lidocaine, tetracaine, or combinations thereof [0056].
Hull et al. teaches that the drug such as a local anesthetic can typically comprise from 10 wt. % to about 50 wt. % of the topical formulations disclosed herein [0057]. Hull et al. teaches that the local anesthetic can comprise about 20 wt. % to about 45 wt. % of the topical formulation, or 30 wt. % to about 45 wt. % topical formulation [0057]. In a further embodiment, the local anesthetic can comprise about 40 wt. % of the topical formulation [0057].
Hull et al. teaches that the topical formulations can also include other components in addition to the drug and SLSA such as water, thickening, gelling and/or solidifying polymers, fatty acid esters, parabens, solvents, carriers and the like [0068].
Hull et al. teaches that polymers which can be included are polyvinyl alcohol, (PVA), Gantrez® ES-425 (a monobutyl ester of the copolymer of methyl vinyl ether and maleic anhydride in ethanol), poly(2-hydroxyethyl methacrylate), Plastoid® B (a neutral copolymer based on butyl methacrylate and methyl methacrylate), and/or Eudragit® S100 (anionic copolymer based on methacrylic acid and methyl methacrylate) [0069]. Hull et al. teaches that generally, the polymer can comprise about 0.1 wt. % to about 15 wt. % of the formulation, from about 5 wt. % to about 15 wt. % of the formulation, or from about 6 wt. % to about 12 wt. % of the formulation [0069].
Hull et al. teaches that other suitable carriers that may be used in the topical formulations include solubilizers such as C2 to C8 straight or branched chain alcohols, diols and triols; moisturizers and humectants such as glycerine, amino acids and amino acid derivatives, polyaminoacids and derivatives, pyrrolidone carboxylic acids and their salts and derivatives; surfactants such as sodium laureth sulfate, sorbitan monolaurate; emulsifiers such as cetyl alcohol, stearyl alcohol; and thickeners such as methyl cellulose, ethyl cellulose, hydroxymethylcellulose, hydroxypropylcellulose, polyvinylpyrrolidone, polyvinyl alcohol and acrylic polymers [0072].
Hull et al. further teaches the topical formulation may also include ethanol and/or polyethylene glycol 300, or other similar low molecular weight alcohol [0072]. Hull et al. teaches that the ethanol may be present in the formulation at from about 1 wt. % to about 25 wt. % [0072]. The polyethylene glycol 300 or other low molecular weight alcohol may be present in the range at from about 1 wt. % to about 80 wt. % [0072]. In addition, the topical formulation may include at least one moisturizer/humectant [0072].
Hull et al. teaches that when not presented and applied to a skin surface in the form of a transdermal delivery system (e.g. patch), the present topical formulation may be applied to the skin by any method known in the art including, but not limited to: an aerosol, spray, pump-pack, brush, swab, or other applicator [0085]. The applicator provides either a fixed or variable metered dose application such as a metered dose aerosol, a stored-energy metered dose pump or a manual metered dose pump [0085]. Hull et al. teaches the application can be performed by means of a topical metered dose spray combined with an actuator nozzle shroud which together accurately control the amount and/or uniformity of the dose applied [0085].
Hull et al. does not specifically exemplify a composition as claimed.
The prior art does not appear to provide sufficient specificity, i.e., involves too much "picking and choosing" to give rise to anticipation. See Coming Glass Works v. Sumitomo Elec., 868 F.2d 1251, 1262 (Fed. Circ. 1989). That being said, it must be remembered that "[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect ....the combination is obvious". KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007)(quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). Consistent with this reasoning, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have selected the various combinations of features claimed from within the prior art disclosure to arrive at the instantly claimed subject matter, specifically, a topical formulation in the form of a liquid suitable for spraying comprising, lidocaine in an amount of 40 wt.% [0057], ethanol and polyethylene glycol 300, wherein the polyethylene glycol 300 may be present in the range at from about 1 wt. % to about 80 wt. % [0072], and one or more film forming excipients having the desired properties as claimed such as Gantrez® ES-425 (a monobutyl ester of the copolymer of methyl vinyl ether and maleic anhydride in ethanol), and/or Eudragit® S100 (anionic copolymer based on methacrylic acid and methyl methacrylate) in an amount of about 0.1 wt. % to about 15 wt. % of the formulation [0069], and a thickener such as hydroxypropylcellulose [0072], wherein the formulation is sealed in container fitted with a spray pump [0085]. With respect to the limitation that the formulation contains less than 10% w/w water, although Hull et al. teaches that in certain embodiments water can be included in the formulation, Hull et al. further teaches that the topical formulation may contain other suitable carriers including alcohols, and further specifically teaches including ethanol and/or polyethylene glycol 300, or other similar low molecular weight alcohol wherein the ethanol may be present in the formulation at from about 1 wt. % to about 25 wt. % and the polyethylene glycol 300 or other low molecular weight alcohol may be present in the range at from about 1 wt. % to about 80 wt. % [0072]. Accordingly, a person of ordinary skill in the art would contemplate a topical formulation comprising alcohols as the carrier in the absence of water based on these teachings of Hull et al.
With respect to the amount of the components as claimed, as detailed above, Hull et al. specifically teaches 40 wt.% of lidocaine and overlapping amounts of the other claimed components. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%." The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.); In re Geisler, 116 F.3d 1465, 1469-71, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997) (Claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms" considered prima facie obvious in view of prior art reference teaching that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." The court stated that "by stating that ‘suitable protection’ is provided if the protective layer is ‘about’ 100 Angstroms thick, [the prior art reference] directly teaches the use of a thickness within [applicant’s] claimed range.").
Furthermore, it has been held that it is within the skill in the art to select optimal parameters, such as amounts of ingredients, in a composition in order to achieve a beneficial effect. See In re Boesch, 205 USPQ 215 (CCPA 1980).
With respect to claim 5 which claims the composition comprises a unit dose of a volume of about 200 ml or less, it is within the skill of an ordinary artisan to determine the amount of the formulation to include in a unit dose. Thus in the absence of secondary considerations such as a demonstration of criticality or unexpected results, optimizing the unit dose volume as claimed in claim 5 is rendered obvious.
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here 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, 456, 105 USPQ 233, 235 (CCPA 1955); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438 (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."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying "the need for caution in granting a patent based on the combination of elements found in the prior art.").
Thus the cited claims of the instant application are rendered obvious in view of the cited prior art teachings.
Claims 1-6 are rejected under 35 U.S.C. 103 as being unpatentable over Kottayil et al. U.S. Publication No. 2017/0296484 A1 in view of Campbell et al. U.S. Publication No. 2009/0048296 A1.
Claims 1-6 of the instant application claim a composition comprising at least 40% w/w lidocaine; an aliphatic solvent; about 0.1% w/w to about 10% w/w of a washability enhancer; and about 0.1% w/w to about 10% w/w one or more film forming excipients, wherein said film forming excipient (i) has a solubility in water, at a pH between 1 and 10, that requires 30 parts or less of water to dissolve one part of said film forming excipient, (ii) has a solubility in ethanol that requires 30 parts or less of ethanol to dissolve one part of said film forming excipient; and (iii) can prevent crystallization of said lidocaine and maintain said lidocaine in an amorphous state during solvent evaporation when said composition is applied to skin; wherein said composition is a sprayable liquid solution; and wherein said composition contains less than 10% w/w water.
According to page 15 paragraph [0055] of the instant specification, examples of film forming excipients that have the desired characteristics as claimed in (i), (ii) and (iii) of claim 1, include Hydroxypropyl Cellulose (HPC or Hypromellose), Ethyl Cellulose, Hydroxypropyl Methyl Cellulose (HPMC), Eudragit® E100 (Amino Methacrylate Copolymer), Eudragit® L100 (Methacrylic Acid and Methyl Methacrylate Copolymer 1:1) (which dissolves above pH 6.0), Eudragit®S100 (Methacrylic Acid and Methyl Methacrylate Copolymer 1:2) (which dissolves above pH 7.0), Eudragit®E100 (Poly(butylmethacrylate-co-(2- dimethylaminoethyl)methacrylate-co-methyl methacrylate 1:2:1) (which dissolves below pH 5.0), Methyl Vinyl Ether-Maleic Anhydride Copolymers such as Gantrez® ES-435, a Butyl Ester of Methyl Vinyl Ether/Maleic Anhydride Copolymer; and Polyvinyl Acetate-Povidone Polymer. Thus the claims read on a liquid composition comprising at least 40% w/w lidocaine; an aliphatic solvent; about 0.1% w/w to about 10% w/w of a washability enhancer; and about 0.1% w/w to about 10% w/w one or more film forming excipients selected from the components listed above; wherein said composition contains less than 10% w/w water and further comprising one or more penetration enhancers and one or more viscosity increasing agents.
Please note that “In determining whether the invention as a whole would have been obvious under 35 U.S.C. 103, we must first delineate the invention as a whole. In delineating the invention as a whole, we look not only to the subject matter which is literally recited in the claim in question... but also to those properties of the subject matter which are inherent in the subject matter and are disclosed in the specification. . . Just as we look to a chemical and its properties when we examine the obviousness of a composition of matter claim, it is this invention as a whole, and not some part of it, which must be obvious under 35 U.S.C. 103.” In re Antonie, 559 F.2d 618, 620, 195 USPQ 6,8 (CCPA 1977). See also Ex parte Novitski, 26 USPQ2d 1389 (Bd. Pat. App. & Inter. 1993) (The Board rejected a claim directed to a method for protecting a plant from plant pathogenic nematodes by inoculating the plant with a nematode inhibiting strain of P. cepacia. A U.S. patent to Dart disclosed inoculation using P. cepacia type Wisconsin 526 bacteria for protecting the plant from fungal disease. Dart was silent as to nematode inhibition but the Board concluded that nematode inhibition was an inherent property of the bacteria. The Board noted that applicant had stated in the specification that Wisconsin 526 possesses an 18% nematode inhibition rating.).
Kottayil et al. teaches a polymeric bio-adhesive film forming topical spray formulation providing a modified, pulsatile (e.g., biphasic) release of the active agent(s) once the solvent evaporates and the film sets, e.g., on human skin (abstract and [0002]). Kottayil et al. teaches a polymeric film forming topical spray formulation, comprising a hydrophilic film forming polymer, the hydrophilic film forming polymer being present in the formulation in an amount from about 1% to about 50%, or about 2% to about 50% by weight; a drug crystal precipitation inhibiting agent in an amount effective to prevent or substantially prevent the active agent(s) included in the formulation from precipitating a pharmaceutically acceptable permeation enhancer for the active agent(s) and wherein the hydrophilic film forming polymer and the drug crystal precipitation inhibiting agent are the same or different; an active agent(s); a pharmaceutically acceptable permeation enhancer for the active agent(s); and a volatile solvent in a concentration from about 20 to about 99% of the formulation, by weight, the formulation when sprayed on and set on human skin provides a breathable, bioadhesive and microporous film [0010].
Kottayil et al. teaches a pharmaceutical formulation comprising a polymeric solution, emulsion or suspension of a hydrophilic polymer; an active agent(s); and a pharmaceutically acceptable permeation enhancer dispersed in a pharmaceutically acceptable hydroalcoholic solvent, the formulation capable of being sprayed via a pump spray into droplets having a diameter from about 5 microns to about 1000 microns and setting as a microporous, breathable and bioadhesive film when the hydroalcoholic solvent evaporates, and releasing from about 0.001% to about 25% of the active agent within about 2 hours, and further providing a biphasic release of the active agent(s) when the formulation sets as a film on human skin [0012].
Kottayil et al. teaches that the formulation is used for the treatment of neuropathic pain ([0016], [0018]-[0020]). Kottayil et al. teaches in certain embodiments, the methods further comprise using a metered pump delivering, e.g., from about 40 μl to about 350 μl volume per spray to deliver the active agent onto the skin of the human [0021]. Kottayil et al. teaches that these compositions can either be liquids or semisolids with a hydrophobic and/or hydrophilic film forming polymer as basic material for the matrix [0049]. The polymeric solution is sprayed to the skin as a liquid and forms an almost invisible film in situ by volatile solvent evaporation [0049].
Kottayil et al. teaches in certain preferred embodiments, the film forming topical spray formulation comprises from about 1% to about 50% hydrophilic film forming polymer(s), from about 0.05% to about 35% active agent(s), from about 0.05% to about 50% permeation enhancer, and from about 0.01% to about 30% optional additional pharmaceutically acceptable excipients (as described therein), in a hydroalcoholic solvent [0065]. In certain preferred embodiments, the film forming topical spray formulation comprises from about 2% to about 10% by weight hydrophilic film forming polymer(s), or from about 2.5% to about 7.5% by weight hydrophilic film forming polymer(s), and from about 1% to about 15% by weight permeation enhancer(s) or from about 2% to about 12% by weight permeation enhancer(s), or most preferably from about 2.5% to about 10% permeation enhancer [0065].
Kottayil et al. further teaches in certain preferred embodiments, the formulation further comprises from about 1% to about 50%, or from about 2% to about 20%, or more preferably from about 2.5 to about 10% of a drug crystal precipitation inhibiting agent which prevents or substantially prevents the drug(s) included in the formulation from precipitating [0076]. In certain preferred embodiments, the drug crystal precipitation inhibiting agent is selected from cellulose derivatives such as hydroxypropyl methylcellulose (HPMC), hydroxypropylmethylcellulose acetate succinate (HPMCAS), methylcellulose (MC), hydroxypropyl cellulose (HPC), and vinyl polymers such as polyvinyl pyrrolidone (also known as PVP, povidone or copovidone) or a derivative thereof, polyvinylalcohol (PVA), poly(acrylic acid) (PAA), polyvinylpyrrolidone vinyl acetate (PVPVA), or mixtures of any of the foregoing [0076].
Kottayil et al. teaches up to about 35% of the film forming polymer may be comprised of a hydrophobic polymer, wherein suitable hydrophobic polymers include acrylate copolymers, methacrylic polymers and copolymers, acrylate/octylacrylamide copolymer, methyl cellulose, ethyl cellulose, methacrylic polymer, Polyurethane-14 and AMP-acrylates copolymer, Poly(butyl methacrylate,(2-dimethylaminoethyl) methacrylate,methyl methacrylate) 1:2:1, Poly(ethyl acrylate, methyl methacrylate) 2:1, Poly(ethyl acrylate, (2-trimethylaminoethyl)methacrylate, methyl methacrylate) 1:0.2:2 chloride, Poly(methacrylic acid, methyl methacrylate) 1:2, Polyisobutylene, silicon gum, silicon dioxide, microcrystalline cellulose, sodium carboxyl cellulose, and the like [0077]. Kottayil et al. teaches in preferred embodiments the hydrophobic polymer comprises acrylic polymers or copolymers, methacrylic polymers and copolymers, including ethoxyethyl methacrylates, cynaoethyl methacrylate, poly(acrylic acid), poly(methacrylic acid), methacrylic acid alkylamide copolymer, poly(methyl methacrylate), polymethacrylate, poly(methyl methacrylate) copolymer, polyacrylamide, aminoalkyl methacrylate copolymer, poly(methacrylic acid anhydride), and glycidyl methacrylate copolymers [0078]. Preferred film-formers include a non-ionic copolymer of methyl methacrylate and butyl methacrylate (Plastoid B®), a copolymer of dimethylamine ethyl methacrylate and a neutral methacrylic acid ester (Eudragit E100®), ammonio methacrylate copolymer type B (Eudragit RS®), ammonio methacrylate copolymer type A (Eudragit RL®), methacrylic acid copolymer type A (Eudragit L100®), methacrylic acid copolymer type B (Eudragit S100®), and the like [0078].
Kottayil et al. teaches in certain preferred embodiments, the polymeric film forming topical spray formulation further comprises an effective amount one or more permeation enhancers which allows a sufficient amount of the dose of the drug(s) to permeate through the skin, wherein preferred permeation enhancers include isopropyl myristate, Oleic acid, Capric acid, Lauric acid, Lauric acid, pharmaceutically acceptable glycol derivatives (e.g., propylene glycol, diethylene glycol monoethyl ether), methyloleate, lysophosphatidylcholine, phosphatidylcholine, aprotinin, azone, cyclodextrin, dextran sulfate, menthol, polysorbate 80, sulfoxides and various alkyl glycosides, urea, ethanol, caprylic alcohol, oleyl alcohol, n-methyl-2-pyrrolidone, sodium lauryl sulfate, isostearic acid, oleth-2, polyethylene glycol, polyoxyl cetostearyl ether, polyoxyl oleyl ether, polyoxyl lauryl ether, polyoxyl stearyl ether, benzyl alcohol, mixtures of any of the foregoing, and the like [0083]. In certain preferred embodiments, the permeation enhancer is selected from isopropyl myristate, oleth-2, oleic acid, 2-pyrolidone, isostearic acid, oleyl alcohol, polysorbate 80, polyethylene glycol 600, and mixtures of any of the foregoing [0083].
Kottayil et al. teaches in embodiments where the permeation enhancer is polyethylene glycol, all grades of polyethylene glycol are contemplated for use in preparation of the local anesthetic stock, for example, polyethylene glycol is available as PEG 200; PEG 300; PEG 400; or PEG 600, and in certain embodiments the polyethylene glycol is preferably PEG 300 [0084].
Kottayil et al. teaches in certain preferred embodiments of the invention, the active agent comprises a local anesthetic, such as mepivacaine, lidocaine, mepivacaine, etidocaine and prilocaine; ester type local anesthetics, such as procaine, chloroprocaine, and tetracaine; and antihistamine-like anesthetics, such as Benadryl [0096]. Preferred local anesthetic agents include, e.g., bupivacaine, ropivacaine or lidocaine [0097].
Kottayil et al. teaches that the film forming sprays were prepared by adding target drug, non-volatile solvent and permeation enhancer to the solvent while stirring the solution to ensure complete dissolution of the drug and other excipients, wherein the solvent used was ethanol (95%) [0127]. To the clear solution obtained, the polymers were added and other optional excipients and after addition of all excipients the solution was stirred to ensure complete dissolution and or hydration of polymer prior to use [0127]. The formulation was stored in glass vials sealed tightly with a cap or spray pump [0127].
Kottayil et al. specifically teaches in Example 1 on TABLE 1, the preparation of a local anesthetic composition comprising the penetration enhancer Transcutol® P (diethylene glycol monoethyl ether); the combination of polymethacrylate hydrophobic polymers Plastoid® B and Eudragit® EPO; the washability enhancer Propylene Glycol; and the aliphatic solvent Ethanol 95% and no added water ([0126]-[0129]).
Thus Kottayil et al. specifically teaches preparing a sprayable liquid solution local anesthetic formulation (which may be chosen as lidocaine) comprising the same combination of components in overlapping amounts as claimed, which are an aliphatic solvent, a washability enhancer, one or more film forming excipients having the desired properties as claimed, wherein the composition contains less than 10% w/w water, and also comprising a penetration enhancer.
Kottayil et al. does not specifically exemplify a composition as claimed having the same components in the same amounts. Kottayil et al. does not specifically teach at least 40% w/w lidocaine.
The prior art does not appear to provide sufficient specificity, i.e., involves too much "picking and choosing" to give rise to anticipation. See Coming Glass Works v. Sumitomo Elec., 868 F.2d 1251, 1262 (Fed. Circ. 1989). That being said, it must be remembered that "[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect ....the combination is obvious". KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007)(quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). Consistent with this reasoning, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have selected the various combinations of features claimed from within the prior art disclosure to arrive at the instantly claimed subject matter, specifically, as detailed above, Kottayil et al. teaches in certain preferred embodiments, the film forming topical spray formulation comprises from about 1% to about 50% hydrophilic film forming polymer(s)/crystallization inhibition which may be selected as hydroxypropylcellulose, from about 0.05% to about 35% active agent(s) which may be selected as lidocaine, from about 0.05% to about 50% of permeation enhancer which may be one or more permeation enhancers selected as Transcutol P (diethylene glycol monoethyl ether) and polyethylene glycol such as PEG 300 or PEG 400 or PEG 600, and from about 0.01% to about 30% optional additional pharmaceutically acceptable excipients (as described therein), in a hydroalcoholic solvent which is selected as 95% ethanol. Kottayil et al. further teaches up to about 35% of the film forming polymer may be comprised of a hydrophobic polymer, wherein suitable hydrophobic polymers include Poly(butyl methacrylate,(2-dimethylaminoethyl) methacrylate,methyl methacrylate) 1:2:1 (Eudragit® E100). Kottayil et al. further teaches wherein the formulation is sealed in a container fitted with a spray pump and that the formulation contains less than 10% w/w water.
With respect to the amount of the components as claimed, as detailed above, Kottayil et al. specifically teaches up to about 35 wt.% of the active agent which may be selected as lidocaine and since about 35 wt.% includes 40 wt.% the amount taught in the prior art overlaps with the claimed amount. In addition, the amounts of other claimed components overlap with the amounts as claimed. With respect to claim 5 which claims the composition comprises a unit dose of a volume of about 200 ml or less, Kottayil et al. teaches in certain embodiments, the methods further comprise using a metered pump delivering, e.g., from about 40 μl to about 350 μl volume per spray to deliver the active agent onto the skin of the human [0021] which overlaps with the unit dose volume as claimed in claim 5.
In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%." The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.); In re Geisler, 116 F.3d 1465, 1469-71, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997) (Claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms" considered prima facie obvious in view of prior art reference teaching that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." The court stated that "by stating that ‘suitable protection’ is provided if the protective layer is ‘about’ 100 Angstroms thick, [the prior art reference] directly teaches the use of a thickness within [applicant’s] claimed range.").
Furthermore, it has been held that it is within the skill in the art to select optimal parameters, such as amounts of ingredients, in a composition in order to achieve a beneficial effect. See In re Boesch, 205 USPQ 215 (CCPA 1980).
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here 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, 456, 105 USPQ 233, 235 (CCPA 1955); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438 (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."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying "the need for caution in granting a patent based on the combination of elements found in the prior art.").
In addition, with regard to the amount of lidocaine as claimed of at least 40% w/w lidocaine, Campbell et al. teaches that high concentration formulations of lidocaine are useful in treating neuropathic pain (abstract). Campbell et al. teaches a topical anesthetic formulation containing a high concentration of local anesthetic in a pharmaceutically acceptable carrier for topical application and method of use to ameliorate or inhibit pain, including neuropathic pain, has been developed, such that the target tissue (skin) is appropriately dosed with anesthetic [0011]. Campbell et al. teaches the local anesthetic is lidocaine, most preferably lidocaine free base, most preferably in a continuous phase gel, although creams, lotions, foams, sprays or ointments may also be used, and the dosage of the local anesthetic is effective in the painful area or immediately adjacent areas, to ameliorate or eliminate the pain [0011]. The formulations release the largest dose of drug shortly after administration, for example, from 0 to 6 hours after administration [0011]. This early time period release should result in a more rapid onset of pain relief for the patient [0011]. Campbell et al. teaches the concentration of the drug in the formulation is from about greater than 20% to about 40% or higher by weight of the formulation and preferably the concentration is about 40% and the formulation is applied to the site of, or adjacent to, the painful area for the treatment or alleviation of neuropathic pain [0011].
Accordingly, prior to the effective filing date of the claimed invention, it would have been obvious to a person of ordinary skill in the art to combine the teachings of Kottayil et al. which teach a film forming topical spray formulation comprising from about 0.05% to about 35% active agent(s) which may be selected as lidocaine for the treatment of neuropathic pain, with the teachings of Campbell et al. which teaches that high concentration formulations of lidocaine, specifically greater than 20% to about 40% or higher by weight of the formulation and preferably the concentration is about 40% are useful in treating neuropathic pain. Thus since Campbell et al. teaches that higher concentrations of lidocaine are effective for the treatment of neuropathic pain, a person of ordinary skill in the art would have been motivated to formulate the composition of Kottayil et al. comprising lidocaine in an amount greater than 20% to about 40% or higher by weight of the formulation with a reasonable expectation of providing an improved composition for the effective treatment of neuropathic pain.
Thus the cited claims of the instant application are rendered obvious in view of the cited prior art teachings.
Conclusion
Claims 1-6 are rejected. Claims 7, 9-11, 15-17, 26-29, 31, 42 and 54 are withdrawn. Claims 8, 12-14, 18-25, 30, 32-41, 43-53, and 55-77 are canceled. No claims are allowed.
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/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623
KRM