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 .
Claims 1-18 are presented for examination.
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.
Claim(s) 1-18 are is/are rejected under 35 U.S.C. 103 as being unpatentable over Florin et al. (US 2013/0005749 submitted by the applicant) and Wang et al. (Design and Evaluation of hydrophilic Matrix System Containing Polyethylene Oxides for the Zero-order controlled Delivery of Water Insoluble Drugs) (submitted by the Applicant).
The claims are drawn to a pharmaceutical composition comprising 6-thioguanine (6-TG) and a homogeneous erodible hydrophilic polymer matrix, wherein the composition is formulated for oral
administration and to release at least 35% of the 6-TG in the distal intestine.
Regarding claim 1, Florin teaches the extended release formulation of 6-TG which is formulated to release 6-TG in the small intestine and colon. See Paras [0051], and [0052]. The use of a homogeneous erodible hydrophilic matrix is taught in Para [0084}. Florin teaches the oral administration formulation provides a 6-TG release of 30 +-.15% in the stomach in the first hour, 60 +-.15% of the 6-TG in the small intestine in the second hour and 80 +-.15% of the 6-TG in the small intestine in the third hour. See Para [0052]. Florin does not specifically teach the distal part of the intestine. However, the teaching of intestine encompasses any parts of intestine in the absence of evidence to the contrary. It would have been obvious to a person skilled in the art to use a composition released in the intestine taught by Florin with the expectation that such composition can travel to any parts of intestine in the absence of evidence to the contrary.
Regarding claim 2, Florin teaches upon exposure to the fluid in the stomach, small intestine and colon, hydrophilic polymers hydrate and form a hydrogel that acts as a barrier to drug release; hydrophobic polymers release drug through diffusion through pores and through erosion. See Para [0062].
Regarding claim 3, Florin teaches the Pharmaceutical preparations thioguanine for enteral use can be obtained by combining the active compounds with solid carriers. See Para [0099].
Regarding claim 4, Florin teaches a total daily dose of 6-TG of between 0.3 mg/kg body weight to 1.5 mg/kg body weight, where administered orally, where the dose is not administered as a bolus administration. Suitably, the 6-TG is administered in an extended-release formulation or as a divided dose. In other specific embodiments, it is considered that the optimal therapeutic protocol comprises a total daily dose of 6-TG of between 0.3 mg/kg body weight to 1.5 mg/kg body weight. See Paras [0013] and [0092]. The concentrations taught by Florin are within the scope or overlapping with the claimed concentrations.
Regarding claim 5, Florin teaches the composition comprises a film coating, or an enteric coat to prevent disintegration of the composition in the stomach. See Para [0053].
Regarding claim 6, Florin teaches that the composition can have an enteric coat to prevent disintegration of the composition in the stomach. See Para [0053].
Regarding claim 7, Florin teaches the extended-release formulation provides zero order kinetics of 6-TG delivery (i.e., a linear delivery with respect to the time of extended release). See Para [0050]. The release rate of between 12 hours and 24 hours is the inherent property of Florin composition, which comprises thioguanine and a homogeneous erodible hydrophilic polymer as claimed herein at the concentrations overlapping or within the scope of the claimed concentrations.
Regarding claim 8, low systemic concentration of 6-TG is the inherent property of Florin composition, which comprises thioguanine and a homogeneous erodible hydrophilic polymer as claimed herein at the concentrations within the scope or overlapping with the claimed concentrations.
Regarding claim 9, the amount of 6-TG release is the inherent property of Florin composition, which comprises thioguanine and a homogeneous erodible hydrophilic polymer as claimed herein.
Regarding claim 10, Florin teaches the oral administration formulation provides a 6-TG release of 30 +-.15% in the stomach in the first hour, 60 +-.15% of the 6-TG in the small intestine in the second hour and 80 +-.15% of the 6-TG in the small intestine in the third hour.
Regarding claim 11, Florin teaches the oral administration formulation provides a 6-TG release of 30 +-.15% in the stomach in the first hour, 60 +-.15% of the 6-TG in the small intestine in the second hour and 80 +-.15% of the 6-TG in the small intestine in the third hour.
Regarding claim 12, Florin teaches the oral administration formulation provides a 6-TG release of 30 +-.15% in the stomach in the first hour, 60 +-.15% of the 6-TG in the small intestine in the second hour and 80 +-.15% of the 6-TG in the small intestine in the third hour.
Regarding claim 13, Florin teaches the use of polymers, such as hydroxypropyl cellulose (HPC), hydroxyethyl cellulose (HEC), methylcellulose (MC) in a composition comprising thioguanine. See Para [0074].
Regarding Claim 14, Florin teaches the use of polyethylene oxide in Para [0056]. Furthermore, wang et al. teach that polyethylene oxide(PEO) matrix system with other hydrophilic materials were developed to zero order controlled release of water insoluble drugs. See conclusion.
Regarding claim 15, Florin teaches the presence of hydrophobic polymers in the matrix. Florin teaches that a matrix may comprise either or both hydrophilic polymers and hydrophobic polymers in order to achieve the appropriate release profile. See Para [00111].
Regarding claim 16, Florin teaches the use ethyl cellulose in the matrix in combination with thioguanine. See Para [0055].
Regarding claim 17, Florin teaches the composition comprises an enteric coat to prevent disintegration of the composition in the stomach. See Para [0053]. The use of an ethylene oxide is taught in Para [0056].
Regarding claim 18, florin teaches the use of polyethylene oxide and ethyl cellulose in a composition comprising thioguanine. See Paras [0056] and [0055]. The use of an enteric coating is taught in Para [0053]. Furthermore, wang et al. teach that polyethylene oxide(PEO) matrix system with other hydrophilic materials were developed to zero order controlled release of water insoluble drugs. See conclusion.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZOHREH A FAY whose telephone number is (703)756-1800. The examiner can normally be reached Monday-Friday 9:30AM-6:00.
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/ZOHREH A FAY/Primary Examiner, Art Unit 1617