DETAILED ACTION
Applicant's response filed on August 13, 2026 to the Non-Final rejection mailed on May 13, 2026 is acknowledged.
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 filed 11/07/2023 is a DIV of PAT 11844782 filed on 04/13/2018 which is a 371 of PCT/EP2016/075086 , International Filing Date: 10/19/2016 claims foreign priority to 15190601.3, filed 10/20/2015 and foreign priority to 16174999.9, filed 06/17/2016.
Information Disclosure Statement
The information disclosure statement(s) (IDS) filed on 7/24/26 is in compliance with the provisions of S7 CFR 1.97. Accordingly, the IDS is being considered by the Examiner.
Response to Arguments
Applicant’s arguments over the 35 U.S.C. 103 rejection of claims 1-21 and 26 over Chen (CN101254176 A) in view of Mueller (US 6407079 - IDS) is not persuasive. The rejection is herewith maintained. Applicant argues “Chen does not describe the amounts or proportions of the various formulation components, other than specifying in paragraph [0012] of the description that the "unit dose" of the formulation is a mass amount from 5 to 80 mg. Moreover, the formulations actually exemplified in Chen all refer to the use of "the prescribed amount' of dantrolene, without specifying the amount or proportion further; see the experimental examples in paragraphs [0027] onwards. This "prescribed amount" of dantrolene appears to relate to the same 5-80 mg dose disclosed in the description. Similarly, the pH adjusters and/or carriers exemplified in Chen are also said to be present in "the prescribed amount, but in this case without any further indication anywhere in the document as to what that amount might be. Therefore, Chen does not contain any teaching or suggestion that would motivate a person of ordinary skill in the art to select any particular molar ratio of dantrolene to cyclodextrin (or to any other formulation component), much less the specific molar ratio range of 1:5-1:18 for components A and B recited in amended claims 1 and 26.” “Chen does not teach or suggest the use of 2-HPBCD in a formulation of dantrolene, nor does it contain any specific motivation to select a cyclodextrin (in general) as an excipient for such a formulation. Chen also does not contain any teaching to motivate the skilled person to select a particular molar ratio of dantrolene to any other formulation component, let alone to a specific cyclodextrin. Mueller does not remedy the deficiencies of Chen in this regard, nor does it contain any teaching that would lead the skilled person to combine HPBCD (in particular) and an alkaline pH of 8-10 in a dantrolene formulation.
In response, the Examiner points out that the rejection is based on an obviousness not anticipatory type rejection. Since the general conditions of the claims are taught in the prior art, discovering optimum or workable ratios involves only routine skill in the art (In re Aller). Applicant has not provided any evidence of unexpected or surprising results with the ratio of component A to component B, molar substitution or molar ratio of component A to the pH adjuster claimed. Clearly, Mueller describes β-cyclodextrin esters in a molar ratio of drug to B-cyclodextrin ether is preferably about 1:6 to 4:1 increased water-solubility and improved stability. Additionally, the primary reference teaches the lyophilized powder injection is prepared by dissolving dantrolene sodium in water for injection, adding medicinal carrier, adjusting pH to 8.0-12.0. The arguments are not found persuasive.
The rejections are as below:
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, 5-6, 10-21, 26, and 29-30 are rejected under 35 U.S.C. 103 as being unpatentable over Chen (CN101254176 A) in view of Mueller (US 6407079 - IDS).
Chen teaches a lyophilized powder injection contains dantrolene sodium (with unit dose range of 5-80 mg) as active component, and medicinal adjuvant selected from carrier, pH regulator, and/or antioxidant, and/or chelating agent. The medicinal carrier is selected from mannitol, glucose, sorbitol, sodium chloride, dextran, and/or cyclodextrin and its derivatives, etc. The lyophilized powder injection is prepared by dissolving dantrolene sodium in water for injection, adding medicinal carrier, adjusting pH to 8.0-12.0. (The step of dissolving reads on at least two compartment kit).
While the reference teaches the dantrolene sodium, cyclodextrin carrier, pH of the claims, physiological-tolerable solvent, and pH adjusters, osmolality agents, the reference does not specify an example wherein the molar ratio of the formulation OR specify the container for the formulation.
Mueller teaches “inclusion of compounds of sparingly water-soluble or water-instable drugs with β-cyclodextrin ethers or β-cyclodextrin esters and process for the preparation thereof.” (abstract) Exemplified is hydroxypropyl-β-cyclodextrin, however, the reference generally teaches useful complex forming agents are especially the hydroxyethyl, hydroxypropyl and dihydroxypropyl ether, their corresponding mixed ethers, and further mixed ethers with methyl or ethyl groups, such as methyl-hydroxyethyl, methyl-hydroxypropyl, ethyl-hydroxyethyl and ethyl-hydroxypropyl ether of β-cyclodextrin. "The molar ratio of drug to B-cyclodextrin ether is preferably about 1:6 to 4:1. As a rule it is preferred to use the complex forming agent in a molar excess." (col. 2, lines 62-64). The water may further comprise physiologically compatible compounds such as sodium chloride, potassium nitrate, glucose, mannitol, sorbitol, xylitol or buffers such as phosphate, acetate or citrate buffer. Example 4 teaches the storage of the formulation in an ampule (reads, on glass or polymer).
It would have been obvious to one of ordinary skill in the art at the time of filing to incorporate the with β-cyclodextrin ethers or β-cyclodextrin esters in a molar ratio of drug to B-cyclodextrin ether is preferably about 1:6 to 4:1. The motivation to incorporate β-cyclodextrin ethers or β-cyclodextrin esters in a molar ratio of drug to B-cyclodextrin ether is preferably about 1:6 to 4:1 is because the reference teaches increased water-solubility and improved stability. Therefore, a skilled artisan would have had reasonable expectation of successfully achieving similar efficacy and results.
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 1, 5-6, 10-21, 26, and 29-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 11844782. Although the claims at issue are not identical, they are not patentably distinct from each other because the copending patents are directed to an aqueous composition, comprising: i) a component (A) selected from one or more members of the group consisting of dantrolene and a pharmaceutically acceptable salt of dantrolene; and ii) a component (B) selected from one or more members of the group consisting of 2-hydroxyethyl-β-cyclodextrin, sulfobutylether-β-cyclodextrin and 2-hydroxypropyl-β-cyclodextrin, wherein a pH of the composition is between 8.5 and 9.5, wherein a molar ratio of component (A) to component (B) ranges from 1:7 to 1:20, and wherein at least 90% of component (A) remains soluble for at least two days, whereas the claims herein are drawn to a powder obtained by drying an aqueous composition wherein the aqueous composition comprises: i) a component (A) selected from one or more members of the group consisting of dantrolene and a pharmaceutically acceptable salt of dantrolene; and ii) a component (B) selected from one or more members of the group consisting of cyclodextrin derivatives, wherein: the pH of the composition is greater than 7; and the molar ratio of component (A) to component (B) ranges from 1:2 to 1:30. The claims overlap having the same active dantrolene, cyclodextrin derivatives, molar ratio and pH.
Conclusion
No claims allowed.
The arguments are not persuasive and the rejection is made FINAL.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a). A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAYLA SOROUSH whose telephone number is (571)272-5008. The examiner can normally be reached on Monday thru Friday; 8:30 AM to 5:00 PM EST.
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/LAYLA SOROUSH/ Primary Examiner, Art Unit 1622
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