DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . 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 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.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/28/2023 and 04/19/2023 have been considered by the examiner.
Status of the Claims
The claims filed 04/19/2023 are under consideration.
Claims 3 and 114-158 are pending.
The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application. Rejections not reiterated herein have been withdrawn.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
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 3 and 114-158 are rejected under 35 U.S.C. 103 as being unpatentable over Coulter, US 20120141531 and Kelm, US 5686106 as evidenced by Transcutol P, Pubchem, 2025.
Coulter teaches and exemplifies formulations comprising cyclosporin containing cores, wherein the core comprises a solid hydrocolloid hydrogel continuous phase containing a dispersed oil phase containing cyclosporin A, a medium chain triglyceride, e.g., MIGLYOL 810/MCT oil, polyethyoxylated castor oil, e.g., CRMOPHOR EL, and a solvent, e.g., TRANSCUTOL P; and wherein the continuous phase comprises an anionic surfactant, e.g., SDS, a hydrogel forming polymer, e.g., gelatin, and a plasticizer, e.g., d-sorbitol (Coulter, e.g., examples 48-50) and a coating containing a single polymer, e.g., ethylcellulose (Coulter, entire document, e.g., examples, e.g., example 24, e.g., 0359 table (SURELEASE), and 0278-0280).
Coulter teaches a number of cyclosporin A cores which are coated with a coating comprising a single polymer, e.g., ethylcellulose (Coulter, e.g., Ex-24-Ex 36, ¶ 0358-0372). This corresponds to the cores of claim 3 coated with the second coating of claim 3 comprising a single polymer, wherein the polymer is a delayed release pH independent polymer.
The coated cores exemplified in Coulter differ from the subject matter of claim 3 in that Coulter does not expressly exemplify cores of examples, e.g., examples 24-36, comprising a first coating comprising a water-soluble cellulose ether and a the first coating having a thickness of from 10 microns to 100 microns.
That is, Coulter’s exemplified hydrogel forming polymer matrix cores comprising cyclosporin A with an ethylcellulose coating do not explicitly include a “first coating” present on the core between the core and the second coating (ethylcellulose). However, Coulter expressly teaches modifying ethylcellulose cores with an HPMC coating directly on the core at ¶ 0294. For example, Coulter teaches formulations comprising a core having a first coating comprising hydroxypropyl methylcellulose on the core, and a second coating comprising ethylcellulose over the first coating (Coulter, e.g., 0294). The first coat may be used to protect the core and prevent leaching of core contents into the second coat (Coulter, e.g., 0294). Based on this teaching in Coulter, the skilled artisan would have been prompted to modify any of the exemplified cyclosporin A cores coated with ethylcellulose by including a first coating comprising hydroxypropyl methylcellulose to protect the core and prevent leaching of core contents into the ethylcellulose coating.
Coulter teaches the HPMC coating is effective to protect the core and prevent leaching of the core contents into the second coat. However, Coulter does not expressly teach a thickness ranging from 10-100 microns is effective to achieve this objective.
The teachings of Kelm cures this defect. In the pharmaceutical field, Kelm teaches barrier coatings, such as HPMC, are effective to separate the core from an additional coating when present on the core having a thickness from about 10 to 50 microns (Kelm, e.g., c8:6-20).
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). MPEP 2144.05.
The claimed thickness overlaps with and is within the range suggested by Kelm.
It would have been obvious before the effective filing date of the presently claimed invention to modify formulations comprising cyclosporin A cores and an ethylcellulose coating by including an HPMC layer between the core and the ethylcellulose coating and further to optimize the HPMC layer thickness in said modified dosage forms using the general conditions suggested by Kelm with a reasonable expectation of success. Since Coulter desires the HPMC layer is effective to act as a barrier between the core and the second coating, the skilled artisan would have been motivated to modify the thickness of Coulter’s first coating within the range of from about 10 to about 50 microns suggested by Kelm to achieve a desired barrier function. The skilled artisan would have had a reasonable expectation of success because both documents teach formulations effective to deliver cyclosporin to the colon.
Applicable to claims 3, 117, 122-123 (first coating): Coulter teaches the first coating comprises a water-soluble cellulose ether in contact with the core, e.g., hypromellose which is a water-soluble cellulose ether identified as hydroxypropyl methylcellulose (Coulter, e.g., 0294).
Applicable to claims 3, 118, 120-121 (second coating): Coulter teaches the second coating comprising ethylcellulose (surelease) applied on the first coating (Coulter, e.g., 0294). See also Coulter, e.g., pH-independent ethylcellulose (Coulter, e.g., 0278-0279), e.g., Surelease refers to ethylcellulose (Coulter, e.g., 0279).
Applicable to claims: 115-116, 119 and 124-125: Coulter teaches coatings may be applied to a weight gain of preferably in the range 0.1% to 50%, preferably from 1% to 15% of the dry weight of the bead, more preferably in the range 3% to 10% or in the range 5-12% or in the range 8-12% (Coulter, e.g., 0268).
Applicable to claim 126-128: Coulter teaches the polymer matrix is a hydrocolloid or non-hydrocolloid gum, or chitosan, or gelatin (Coulter, e.g., 0102-0107).
Applicable to claim 129: Coulter teaches the polymer matrix further comprising a plasticizer (Coulter, e.g., 0112).
Applicable to claims 130-133: Water soluble polymer matrix material (hydrogel forming polymer matrix/continuous phase) comprising dispersed oil droplets (hydrophobic phase/dispersed phase/liquid lipid) comprising active principle (Coulter, e.g., claim 1).
Applicable to claim 134-136: Oils include triglycerides, e.g., caprylic/capric triglyceride (Coulter, e.g., 0084). Alternative oils include linoleoyl macrogolglycerides (polyoxylglycerides) and caprylocaproyl macrogolglycerides (Coulter, e.g., 0086).
Applicable to claim 137, 139, and 140: oil phase further comprises a solvent (Coulter, e.g., 0095-0096).
Applicable to claim 138: oil phase is present in the composition in an amount ranging form 1-085% by dry weight (Coulter, e.g., 0082).
Applicable to claim 141: Specification teaches: One example of a surfactant with high HLB which may be used in a low HLB oil includes polyethoxylated castor oils (polyethylene glycol ethers), for example the commercial product Kolliphor EL (0360). Coulter teaches wherein the surfactant may be high HLB, e.g., polyethoxylated castor oils (polyethylene glycol ethers) or poloxamers (Coulter, e.g., 0074).
Applicable to claims 142-145: Coulter teaches wherein the oil phase comprises an oil having an HLB in the range of 0-10 (Coulter, e.g., 0089), e.g., a triglyceride (Coulter, e.g., 0090), e.g., caprylic/capric triglyceride (Coulter, e.g., 0090).
Applicable to claim 146: Coulter teaches wherein the solvent is TRANSCUTOL P (Coulter, e.g., example 49) which is diethylene glycol monoethyl ether, aka, 2-(2-ethyoxyethoxy)ethanol as evident from Pubchem. See TRANSCUTOL P, Pubchem, 2025.
Applicable to claim 147 and claims 153-155: Coulter teaches the core comprising a solid hydrocolloid hydrogel continuous phase containing a dispersed oil phase containing cyclosporin A, a medium chain triglyceride, e.g., MIGLYOL 810/MCT oil, polyethyoxylated castor oil, e.g., CRMOPHOR EL, and a solvent, e.g., TRANSCUTOL P; and wherein the continuous phase comprises an anionic surfactant, e.g., SDS, a hydrogel forming polymer, e.g., gelatin, and a plasticizer, e.g., d-sorbitol (Coulter, e.g., examples 48-50).
Applicable to claim 148: The limitations of claim 148 are found in Coulter, e.g., example 49, 0388, Table.
Applicable to claim 149 and 151: Coulter teaches the form of a minibead (Coulter, e.g., 0262, 0293-0294). Formulations contain a multiplicity of minibeads (Coulter, e.g., 0041 and 0267).
Applicable to claim 150: Coulter teaches minibeads having a cross section within the claimed range, e.g., 1.4 to 2 mm diameter (Coulter, e.g., 0388).
Applicable to claim 156: Coulter teaches formulations in the form for oral administration comprising cyclosporin A in an amount within the claimed range (Coulter, e.g., 0232 and examples)
Applicable to claims 157-158: Coulter teaches the second coating comprising at least one excipient, e.g., pectin (Coulter, e.g.., 0286). Coulter teaches SURLEASE is ethylcellulose in combination with a plasticizer, e.g., dibutyl sebacate (Coulter, e.g., 0280).
Accordingly, the subject matter of claims 3 and 114-158 would have been prima facie obvious before the effective filing date of the presently claimed invention, absent evidence to the contrary.
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 claims at issue 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); and 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claim(s) 3 and 114-158 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim(s) 1-18 of US 9278070 in view of Kelm, US 5686106 and WO 2010133609 A2.
Although the claims at issue are not identical, they are not patentably distinct from each other because:
The reference claims teach a formulation containing cores comprising cyclosporin A cyclosporin A in an amount of about 10.9%; 2-(2-ethoxyethoxy)ethanol at 99.9% purity in an amount of about 16.5%; polyethoxylated castor oil in an amount of about 9.3%; caprylic/capric triglyceride in an amount of about 4.6%; sodium dodecyl sulphate in an amount of about 4.0%; D-sorbitol in an amount of about 5.6%; and gelatin in an amount of about 49.0% wherein the % are % by weight as a proportion of the dry weight of the composition (claims 1 and 2). The cores further comprise two coatings, e.g., HPMC and ethylcellulose (claims 11-12).
The reference claims do not expressly teach the thickness of the first coating. However, the teachings of Kelm enumerated above cures this defect.
It would have been obvious before the effective filing date of the presently claimed invention to modify formulations of the reference claims using the general conditions suggested by Kelm with a reasonable expectation of success. The skilled artisan would have ben motivated to optimize the thickness of the HPMC layer as suggested by Kelm to achieve an effective separation of the outer release layer from the core. The skilled artisan would have had a reasonable expectation of success because both documents teach formulations of cyclosporin A.
The reference claims do not expressly teach the hydrogel core comprising chitosan. However, the ‘609 document teaches chitosan was known and used as a core hydrogel polymer as an alternative for gelatin (‘609, e.g., 0102 and 0106)
It would have been obvious before the effective filing date of the presently claimed invention to modify formulations suggested by the reference claims and Kelm by incorporating chitosan in the core with a reasonable expectation of success. The ‘609 document provides an express teaching which would have prompted the skilled artisan to make this modification with a reasonable expectation of success.
Accordingly, the subject matter of claims 3 and 114-158 would have been prima facie obvious before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WILLIAM A CRAIGO whose telephone number is (571)270-1347. The examiner can normally be reached on Monday - Friday, 9am - 6pm, PDT.
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/WILLIAM CRAIGO/Examiner, Art Unit 1615