Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Preliminary amendments dated 10/24/23 and 3/8/24 is acknowledged.
Claims 1-13 have been canceled.
Claims 14-32 are pending for consideration.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
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Claims 14, 19-21, 23, 27-30 and 32 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of U.S. Patent No. 10945984. Although the claims at issue are not identical, they are not patentably distinct from each other because both instant and the patented claims are directed to a method of treating psoriasis comprising administering to a subject a tablet comprising a core comprising (N,N-diethylcarbamoyl)methyl methyl (2E)but-2-ene-1,4-dioate and a compression coating layer comprising hydroxypropyl methyl cellulose. The patented claims recite administering the composition once to four times a day and the release rate of the active agent in an aqueous solution. Even though the patented claims fail to recite the claimed AUC, blood plasma level of the compound, IGA score and PASI, the claimed property is inherent because patented claims recite the same composition as that of the instant claims.
Claims 14-32 are rejected on the ground of nonstatutory double patenting as being unpatentable over EACH of claims 1-12 of U.S. Patent No. 10945984, claims 15-18 of US 10716760, claims 10-12 of US Patent 10940117, and claims 22-25 of US Patent 9999672, in view of US 20120034303 to Nilsson et al., Sangalli et al (European Journal of Pharmaceutical Sciences, 2004) and US 20140066505 to Joshi et al.
The above patented claims of U.S. Patent No. 10945984 fail to teach the limitations of instant claims 15-18, 22-26 and 31.
Each of the US Patent 10716760, claims 10-12 of US Patent 10940117, and claims 22-25 of US Patent 9999672 claims are directed to a method of treating psoriasis by administering an oral composition comprising the claimed active agent. However, the patent claims fail to recite the claimed compressed coating over a core comprising the claimed active agent.
Nilsson teaches pharmaceutical formulation comprising an erosion matrix comprising one or more fumaric acid esters as well as one or more rate-controlling agents (abstract), for treating psoriasis [0002] by providing a controlled or sustained release pharmaceutical formulation comprising fumaric acid ester(s) as active substance(s) which has an improved pharmacokinetic profile over prior art formulations [0008]. Nilsson teaches that the composition includes 30% to 60% by weight of fumaric acid esters, and 3-40% by weight of one or more rate controlling agents for providing the desired control release [0020]. Nilsson teaches additional excipients such as binder [0029] and further teaches that the composition provides 0-5% ww in the first 2 hours, whereas 70-100% w/w released after 5 hours [0035]. Nilsson teaches that the composition is in the form of a tablet with a core comprising the active agent and lactose and hydroxypropyl cellulose [0071, 0408, 0412]. Nilsson teaches that the daily dose of the active agent i.e., fumaric acid ester, is in the range of 200 to 2000 mg in one, two or three doses [0407].
Nilsson does not teach a prodrug of fumaric acid ester.
Joshi teaches dialkyl fumarates for the preparation of pharmaceutical preparations for treating autoimmune diseases, including psoriasis [0020-0021] and teaches the composition in the form of a tablet, capsule etc (examples). Joshi teaches compressed tablet comprising fumaric acid esters [example 1]. With respect to the prodrug, Joshi teaches administration of fumaric acid esters or their prodrug (see claims of the reference), and further teaches that the prodrugs improve resorption.
Therefore, it would have been obvious for one of an ordinary skill in the art before the effective filing date of the instant invention to choose optimum amounts of the active agent, optimize the amounts of the coating and the core active agents, and also include additional excipients in preparing the compressed tablets of the patented claims because the teachings of Nilsson suggests a range of fumaric acid ester amounts, and additional excipients for providing effective treatment of psoriasis, and further Joshi suggests equivalence of fumaric acid esters (etc., dialkyl fumarate) and a prodrug of methyl hydrogen fumarate. Further, Nilsson suggests rate controlling polymers, hydroxypropyl methylcellulose, hydroxypropyl cellulose, methyl cellulose and carboxymethyl cellulose and suggests release rate control as a function of viscosity [0154].
In this regard, Sangalli teaches HPMC of different viscosity grades as coating agents for oral time and/or site-controlled delivery system for the attainment of the system retarding hydrophilic layer.
Sangalli teaches a drug-containing core and a hydrophilic swellable polymeric coating capable of delaying drug release through slow interaction with aqueous fluids (abstract).
Section 2.2 of Sangalli teaches HPMC having different viscosities (E5, E50 and K4M) with 2% (w/v) solutions of which viscosity of 5, 50 and 4000 mPa.s respectively, used as coating agents. Table 1 shows different viscosities of HPMC and coating conditions and release behavior studied. Table 2 shows different concentrations of HPMC, coating thickness, crushing strength etc. Sangalli teaches that the coating thickness is a function of polymer viscosity (p 472). Even though Sangalli does not teach the claimed coating thickness of at least 0.5 mm and teaches in the range of 258 to 337 microns (Table 2), Sangalli teaches that the thickness is a function of viscosity and further all the HPMC grades found enabled a delayed release (p 472), with K4M showing highest capability of delaying the drug release (p 473, fig. 2 and table 3) and Methocel E50 enables modulation of lag time (col. 2, p 473). Sangalli studied the influence of ionizable groups on the dissolution of HPMC and states a mild influence on the in vitro performance at physiological values ranging 0.01-0.166 (paragraphs bridging p 474-475).
Therefore, it would have been obvious for one of an ordinary skill in the art before the effective filing date of the instant invention to prepare the oral composition of EACH of the patented claims, of claims 15-18 of US 10716760, claims 10-12 of US Patent 10940117, and claims 22-25 of US Patent 9999672, as well as the claims of U.S. Patent No. 10945984, i.e., the composition used for treating psoriasis, by employing optimum amounts of the prodrug in the core followed by a coating of hydroxypropyl methylcellulose in suitable amounts and include additional excipients, and further prepare compressed tablets because the teachings of Nilsson suggests a range of fumaric acid ester amounts, and additional excipients for providing effective treatment of psoriasis, and Joshi suggests equivalence of fumaric acid esters (etc., dialkyl fumarate) and a prodrug of methyl hydrogen fumarate. Nilsson also suggests rate controlling polymers hydroxypropyl methylcellulose, hydroxypropyl cellulose, methyl cellulose and carboxymethyl cellulose and suggests release rate control as a function of viscosity [0154]. Further, choosing an optimum amount of the claimed prodrug, the viscosity and amounts of HPMC as well as coating thickness of HPMC in the patented claims would have been obvious for one of an ordinary skill in the art with an expectation to provide a desired sustained release because one of an ordinary skill in the art would have recognized from Sangalli that the viscosity of HPMC determines the coating thickness, as well as controls the release rate, with the highest viscosity providing the most delayed release, and therefore one skilled in the art would have expected to achieve a desired release of the prodrug of the patented claims, by choosing an appropriate amount, viscosity and thickness of HPMC.
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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
3. Claims 14-32 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Gangakhedkar (U.S. 2012/0095003) in view of US 20120034303 to Nilsson et al., Sangalli et al (European Journal of Pharmaceutical Sciences, 2004) and US 20140066505 to Joshi et al.
Instant claims are directed to a method of treating psoriasis comprising orally administering a tablet to a subject in need thereof, wherein the tablet comprises: (A) a core comprising (N,N-diethylcarbamoyl)methyl methyl (2E)but-2-ene-1,4-dioate in a dose of about 100 mg or about 200 mg; and (B) a compressed coating layer surrounding the tablet core, wherein the compressed coating layer (i) comprises hydroxypropyl methyl cellulose; and (i1) is substantially free of ionizable polymer having carboxylic acid moieties; wherein (N,N-diethylcarbamoyl)methyl methyl (2E)but-2-ene-1,4-dioate is the sole active ingredient in the tablet; wherein the tablet, when subjected to an aqueous solution free of (N,N- diethylcarbamoyl)methyl methyl (2E)but-2-ene-1,4-dioate, releases at most 20% of the (N,N- diethylcarbamoyl)methyl methyl (2E)but-2-ene-1,4-dioate from the core over a period of 2 hours.
Gangakhedkar teaches using prodrugs of methyl hydrogen fumarate (MHF) meeting the requirements of Formula I, including (N,N-diethylcarbamoyl)methyl methyl (2E)but-2-ene-1,4-dioate [0105]. The compounds of formula I are provided as oral sustained release dosage forms to deliver the prodrug to the lower GI tract [0331]. These types of dosage forms are well known in the prior art and include erosion-controlled release [0331]. The prior art explicitly discussed in Gangakhedkar is the enteric coated of Fumaderm® formulation, which is administered TID to provide 1-2g/day in the treatment of psoriasis [0008]. MHF prodrugs of Formula I may be administered at 1 to 50mg/kg or from about 1 mg to about 5 g per day [0336].
Gangakhedkar does not teach the type of polymer used for coating, though it does teach such coating technology is well known in the art.
Nilsson teaches pharmaceutical formulation comprising an erosion matrix comprising one or more fumaric acid esters as well as one or more rate-controlling agents (abstract), for treating psoriasis [0002] by providing a controlled or sustained release pharmaceutical formulation comprising fumaric acid ester(s) as active substance(s) which has an improved pharmacokinetic profile over prior art formulations [0008]. Nilsson teaches that the composition includes 30% to 60% by weight of fumaric acid esters, and 3-40% by weight of one or more rate controlling agents for providing the desired control release [0020]. Nilsson teaches additional excipients such as binder [0029] and further teaches that the composition provides 0-5% ww in the first 2 hours, whereas 70-100% w/w released after 5 hours [0035]. Nilsson teaches that the composition is in the form of a tablet with a core comprising the active agent and lactose and hydroxypropyl cellulose [0071, 0408, 0412]. Nilsson teaches that the daily dose of the active agent i.e., fumaric acid ester, is in the range of 200 to 2000 mg in one, two or three doses [0407].
Nilsson does not teach a prodrug of fumaric acid ester.
Joshi teaches dialkyl fumarates for the preparation of pharmaceutical preparations for treating autoimmune diseases, including psoriasis [0020-0021] and teaches the composition in the form of a tablet, capsule etc (examples). Joshi teaches compressed tablet comprising fumaric acid esters [example 1]. With respect to the prodrug, Joshi teaches administration of fumaric acid esters or their prodrug (see claims of the reference), and further teaches that the prodrugs improve resorption.
Therefore, it would have been obvious for one of an ordinary skill in the art before the effective filing date of the instant invention to prepare the oral composition of Gangakhedkar by employing optimum amounts of the prodrug in the core followed by a coating of hydroxypropyl methylcellulose in suitable amounts and include additional excipients, and further prepare compressed tablets of Gangakhedkar because the teachings of Nilsson suggests a range of fumaric acid ester amounts, and additional excipients for providing effective treatment of psoriasis, and Joshi suggests equivalence of fumaric acid esters (etc., dialkyl fumarate) and a prodrug of methyl hydrogen fumarate. Further, Nilsson suggests rate controlling polymers hydroxypropyl methylcellulose, hydroxypropyl cellulose, methyl cellulose and carboxymethyl cellulose and suggests release rate control as a function of viscosity [0154].
In this regard, Sangalli teaches HPMC of different viscosity grades as coating agents for oral time and/or site-controlled delivery system for the attainment of the system retarding hydrophilic layer.
Sangalli teaches a drug-containing core and a hydrophilic swellable polymeric coating capable of delaying drug release through slow interaction with aqueous fluids (abstract).
Section 2.2 of Sangalli teaches HPMC having different viscosities (E5, E50 and K4M) with 2% (w/v) solutions of which viscosity of 5, 50 and 4000 mPa.s respectively, used as coating agents. Table 1 shows different viscosities of HPMC and coating conditions and release behavior studied. Table 2 shows different concentrations of HPMC, coating thickness, crushing strength etc. Sangalli teaches that the coating thickness is a function of polymer viscosity (p 472). Even though Sangalli does not teach the claimed coating thickness of at least 0.5 mm and teaches in the range of 258 to 337 microns (Table 2), Sangalli teaches that the thickness is a function of viscosity and further all the HPMC grades found enabled a delayed release (p 472), with K4M showing highest capability of delaying the drug release (p 473, fig. 2 and table 3) and Methocel E50 enables modulation of lag time (col. 2, p 473). Sangalli studied the influence of ionizable groups on the dissolution of HPMC and states a mild influence of the ionizable groups on the in vitro performance at physiological values ranging 0.01-0.166 (paragraphs bridging p 474-475).
Accordingly, choosing an optimum dose of the claimed prodrug, the viscosity and amounts, as well as coating thickness of HPMC in coating the prodrug core of Gangakhedkar would have been obvious for one of an ordinary skill in the art with an expectation to provide a desired sustained release because one of an ordinary skill in the art would have recognized from Sangalli that the viscosity of HPMC determines the coating thickness, as well as controls the release rate, with the highest viscosity providing the most delayed release, and therefore one skilled in the art would have expected to achieve a desired release of the prodrug of the patented claims, by choosing an appropriate amount, viscosity and thickness of HPMC.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAKSHMI SARADA CHANNAVAJJALA whose telephone number is (571)272-0591. The examiner can normally be reached Generally M- F 9 AM to 6 PM.
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/LAKSHMI S CHANNAVAJJALA/Primary Examiner, Art Unit 1611