DETAILED ACTION
Claims 1-2, 5-8, 10-14, 16-17, and 20 are pending and under consideration on the merits.
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 Rejections
The 112(b) rejections are withdrawn in view of the amendment.
The 103 rejection is maintained with respect to claim 13 and withdrawn with respect to the remaining claims in view of the amendment and accompanying arguments.
The provisional double patenting rejection is maintained.
A new claim objection is applied.
Notice of Subject Matter Free of the Prior Art
Claims 1-2, 5-8, 10-12, 14, 16-17, and 20 are free of the prior art. Base claims 1 and 12 have been amended to recite that the at least two hydrophilic polymers are present in the amount of 20-30 wt%, along with additional limitations on the amount of cladribine and the molar ratio of cladribine to cyclodextrin, and to the presence of plasticizers in specified amounts.
Patil et al. (Int. J. Pharm. Sci. Rev. Res., 65(2), November-December 2020; Article No. 03, Pages 14-21) is a comprehensive review of natural polymers for use in fast dissolving mouth films, and teaches that such films should comprise hydrophilic polymers, and that the hydrophilic polymers should be used in the amount of at least 45 wt%, but that “regularly 60 to 65%w/w of polymer is wanted to get wanted properties” (paragraph bridging pages 14-15). Chandramouli et al. (Biointerface Research in Applied Chemistry Volume 13, Issue 2, 2023, 177) is a review article on oral thin films for drug delivery, and teaches that the films should comprise at least 45 wt% of a polymer based on the total weight of the dry film (2nd paragraph of Section 1). Therefore, the art does not provide the skilled artisan with a motivation to reduce the amount of the at least two hydrophilic polymers to 20-30 wt% as recited by the claims as amended, but rather teaches that higher amounts in the 40-65 wt% range should be used.
Claim Objections
Claim 2 is objected to because of the following informalities:
In lines 2 and 3, “100 000” should be “100,000” to conform to conventions of U.S. English. Correction is required.
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 13 is rejected under 35 U.S.C. 103 as unpatentable over Schaneville (US Pat. Pub. 2020/0390837; of record in IDS) in view of Schultz et al. (US Pat. No. 6,194,395; of record in IDS) and Macphail et al. (US Pat. Pub. 2021/0267934; of record in IDS).
As to claim 13, Schaneville discloses sublingual orally dissolvable films for transmucosal delivery of an active (paragraphs 2, 28-29). The film comprises one or more film-forming agents (paragraph 41) such as pullulan and a starch polymer (paragraph 42)(“hydrophilic polymers” of claim 13). The composition further may comprise cyclodextrin as a taste masking agent (paragraph 40).
As to claim 13, Schaneville does not further expressly disclose that the two hydrophilic polymers represent at least 20 wt% of the total composition, nor that the active is cladribine, nor a method of treating MS, MG, or NMOSD comprising administering the composition.
Schultz teaches that cladribine is a pharmaceutical active known to be effective in the treatment of multiple sclerosis (column 1, 2nd paragraph). Schultz teaches that cladribine to date has been administered by intraveneous injection of saline solutions, but that cladribine is only slightly soluble in water and has limited stability in saline solutions, and that use of the compound orally has been limited since it would not be stable in the gastrointestinal system (column 1, 3rd paragraph). Schultz states that there is therefore a need for oral formulations that are stable against hydrolysis, and discloses compositions comprising cladribine in a complex with a cyclodextrin as a stabilizing/solubilizing agent to solve the foregoing issues (column 2, 1st and 2nd full paragraphs and Summary of the Invention at column 2). Schultz teaches that the composition is a solid oral dosage form that may be in the form of a fast-dissolving wafer (column 5, 5th full paragraph). Schultz teaches that particularly useful cyclodextrins are beta-cyclodextrins in hydroxypropyl, dimethyl, or sulfobutyl forms forms (column 3,5th full paragraph and column 6, 1st full paragraph) or carboxymethyl forms (column 3, 1st full paragraph). Schultz also expressly teaches that the cladribine/cyclodextrin complexes can be used to treat multiple sclerosis (column 6, lines 43-59).
Macphail discloses an oral dispersible film comprising an active for delivery along with a film former such as pullulan or starch in the amount of 40-65 wt%, which is within the range of claim 13(paragraphs 1, 27, 30).
It would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of the present invention to modify the composition of Schaneville by selecting cladribine in complex with a hydroxypropyl, dimethyl, or sulfobutyl beta-cyclodextrin, because Schaneville does not limit the identity of the active to any particular compound and Schultz teaches that cladribine may be delivering using a fast dissolving dosage form and further that complexing the cladribine with the foregoing cyclodextrins stabilizes the compound and allows the cladribine to be delivered orally such that the skilled artisan reasonably would have expected that the oral sublingual dispersible film of Schaneville could be used to deliver cladribine to a subject orally when it is complexed with a cyclodextrin. Such a modification is merely the combining of known prior art elements according to known methods to yield predictable results, which is prima facie obvious. MPEP 2143. The skilled artisan would have been motivated to select an oral delivery dosage form for cladribine such as the Schaneville dosage form because oral dosage forms are more convenient and have higher patient acceptance than injectable formulations.
It further would have been prima facie obvious to select amounts of the two hydrophilic polymers (i.e., pullulan and starch), such that they represent at least 20 wt% of the total composition as recited by claim 13, because MacPhail teaches that oral dispersible films comprising an active for delivery suitably comprise pullulan or starch in the amount of 40-65 wt%, which is within the claimed ranges, such that the skilled artisan reasonably would have expected that such amounts would be suitable for use in the Schaneville oral dispersible film.
It further would have been prima facie obvious to administer an effective amount of the transmucosal delivery composition to a subject to treat multiple sclerosis, because Schultz expressly teaches that cladribine/cyclodextrin complexes are useful for treating multiple sclerosis.
Response to Applicant’s Arguments
Applicant argues that the claims have been amended to include limitations to the amount of the hydrophilic polymers and that the range of 40-60wt% taught by MacPhail is impossible to reach based upon the practical limits of the claimed film which needs to include specified amounts of cladribine, plasticizers, and molar ratio of cladribine to cyclodextrin.
In response, this argument is not relevant to independent claim 13, which has not been amended to include any of the foregoing limitations upon which Applicant’s argument relies. Therefore, the rejection is maintained with respect to claim 13.
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).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) 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 www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-2, 5-8, 10-14, 16-17, and 20 are provisionally rejected on the ground of nonstatutory double patenting as unpatentable over all claims of US Pat. Appl. No. 18/873,809.
Although the reference claims are not identical to the present claims, they are not patentably distinct because they recite a transmucosal delivery composition in the form of a sublingual orally dispersible film comprising cladribine as the sole active in the same amounts recited by the claims, and which is present in a complex with a cyclodextrin such as hydroxypropyl-beta-cyclodextrin, the composition further comprising at least two hydrophilic polymer in a total amount of at least 20 wt%, one being a structure forming polymer that is a starch polymer and the other being a binding and/or intercalating polymer that is pullulan, wherein each polymer has a molecular weight within the recited ranges, the complex comprising cladribine and cyclodextrin in the same molar ratio recited by the claims, wherein the starch may be the same starch recited by the present claims such as a hydroxypropyl pea starch, the two hydrophilic polymers being used in the same ratios recited by the claims, the composition further comprising a surfactant and plasticizer, the composition further comprising glycerol, the composition being formulated for use in a method of treating MS, MG, or NMOSD, the composition being formed by mixing the cladribine-cyclodextrin complex with film forming polymers by stirring with at least 100 rpm for at least 10 minutes at a temperature of at least 30 degrees Celsius.
Response to Applicant’s Arguments
Applicant has not provided any substantive arguments against the rejection, which is therefore maintained.
Conclusion
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/GAREN GOTFREDSON/Examiner, Art Unit 1619
/ANNA R FALKOWITZ/ Primary Examiner. Art Unit 1600
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