DETAILED ACTION
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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 is a continuation of U.S. 18/832,936, filed on July 25, 2024, which is a national phase application, filed pursuant to 35U.S.C§371 of PCT Application No. PCT/IB2023/050766 filed on January 30, 2023, which claims foreign priority of Chinese Patent Application No. 202210107273.0 filed on January 28, 2022.
Claims Status
Claims 1-14 are pending and under examination.
Free of the Art
A search for the claim of claim 1 having the following formula:
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did not identify any prior art. As such, the compound is free of the art.
Terminal Disclaimer
The terminal disclaimer filed on 11/18/2025 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Action Summary
Claims 1-14 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-6, 9-14, 46, 49, 52, and 53 of copending Application No. 18/832,936, are withdrawn in light of the approved terminal disclaimer.
Claims 1-14 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4, 12, 22, 32, 35-36, 41-45, and 47 of copending Application No. 18/018,576, now allowed as U.S. patent 12/410,132 and over claims 1-14 of copending Application No. 19/262,108 in view of jacobs et al (Eur J Hosp Pharm. 2016 Apr 13;24(2):110–114) and U.S. Food and Drug Administration (Lyophilization of Parenteral (7/93), 11/11/2014), are maintained. Please note that the copending Application no. 18/018,576 has become U.S. Patent No. 12,410,132. The rejection to the copending application no. 18/018,576 has been changed to the corresponding U.S. patent No. 12,410,132.
Claims 1-14 are rejected on the ground of non-statutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 11,834,413 in view of jacobs et al (Eur J Hosp Pharm. 2016 Apr 13;24(2):110–114) and U.S. Food and Drug Administration (Lyophilization of Parenteral (7/93), 11/11/2014), are maintained, but revisited and modified to include U.S. patent No. 12,410,132.
Double Patenting
The non-statutory 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 non-statutory 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 non-statutory 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 non-statutory 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
Claims 1-14 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of copending Application No. 19/262,108 in view of jacobs et al (Eur J Hosp Pharm. 2016 Apr 13;24(2):110–114) and U.S. Food and Drug Administration (Lyophilization of Parenteral (7/93), 11/11/2014)
The copending claims teach a pharmaceutical composition comprising the following compound:
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or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, formulated for injection. (See claims 1-2, 4, 12, 22, 32, 35-36, 41-44.)
The copending claims do not teach the amount of the compound and beta-cyclodextrin claimed. The copending claims do not teach a solution, the claimed acid buffer, and the claimed pH.
Mosher teaches a ready to use injectable intravenous formulation (Solution) comprising:
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. (See Abstract and Table 1.) Moreover, Jacobs teaches amiodarone is commercially available at a concentration of 50 mg/ml. (See last paragraph of the left column.) If one were to make a 50 mg/ml amiodarone Hcl, the 50 mg/ml would be 27.8 times more than 1.80 mg/ml which. 27.8 time more than the 18.0 mg/mg cyclodextrin would give 500 mg/ml. Therefore, to make 50 mg/ml amiodarone, one would need 500 mg/ml cyclodextrin giving a weight ratio of 500:1 of cyclodextin to amioradone.
Food and Drug administration teaches Lyophilization or freeze drying is a process in which water is removed from a product after it is frozen and placed under a vacuum, allowing the ice to change directly from solid to vapor without passing through a liquid phase. The
The advantages of lyophilization include:
Ease of processing a liquid, which simplifies aseptic handling Enhanced stability of a dry powder
Removal of water without excessive heating of the product
Enhanced product stability in a dry state
Rapid and easy dissolution of reconstituted product. (See Introduction Section.)
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to modify the pharmaceutical composition taught by the copending claims by including sulfobutyl ether-β-cyclodextrin in the amount claimed with the amount of the compound used by Mosher and citric acid monohydrate in the amount claimed and the pH and further formulated said composition by lyophilization to give the claimed composition. One would have been motivated by the teaching of Mosher and Jacobs. One would reasonably expect the modified lyophilzed pharmaceutical composition to enhance dissolution and water solubility of the compound of the copending claims with success.
This is a provisional nonstatutory double patenting rejection.
Claims 1-14 are rejected on the ground of non-statutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 11,834,413 and over claims 1-14 of U.S. Patent No. 12,410,1321 in view of jacobs et al (Eur J Hosp Pharm. 2016 Apr 13;24(2):110–114) and U.S. Food and Drug Administration (Lyophilization of Parenteral (7/93), 11/11/2014). Although the claims at issue are not identical, they are not patentably distinct from each other.
The U.S. patent claims teach a pharmaceutical composition comprising
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and a pharmaceutically acceptable carrier for oral or injection administration.
The U.S. patent claims do not teach the amount of the compound and beta-cyclodextrin claimed. The copending claims do not teach a solution, the claimed acid buffer, and the claimed pH.
Mosher teaches a ready to use injectable intravenous formulation (Solution) comprising:
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. (See Abstract and Table 1.) Moreover, Jacobs teaches amiodarone is commercially available at a concentration of 50 mg/ml. (See last paragraph of the left column.) If one were to make a 50 mg/ml amiodarone Hcl, the 50 mg/ml would be 27.8 times more than 1.80 mg/ml which. 27.8 time more than the 18.0 mg/mg cyclodextrin would give 500 mg/ml. Therefore, to make 50 mg/ml amiodarone, one would need 500 mg/ml cyclodextrin giving a weight ratio of 500:1 of cyclodextin to amioradone.
Food and Drug administration teaches Lyophilization or freeze drying is a process in which water is removed from a product after it is frozen and placed under a vacuum, allowing the ice to change directly from solid to vapor without passing through a liquid phase. The
The advantages of lyophilization include:
Ease of processing a liquid, which simplifies aseptic handling Enhanced stability of a dry powder
Removal of water without excessive heating of the product
Enhanced product stability in a dry state
Rapid and easy dissolution of reconstituted product. (See Introduction Section.)
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to modify the pharmaceutical composition taught by the U.S. patent claims by including sulfobutyl ether-β-cyclodextrin in the amount claimed with the amount of the compound used by Mosher and citric acid monohydrate in the amount claimed and the pH and further formulated said composition by lyophilization to give the claimed composition. One would have been motivated by the teaching of Mosher and Jacobs. One would reasonably expect the modified lyophilzed pharmaceutical composition to enhance dissolution and water solubility of the compound of the copending claims with success.
Acknowledgement is made of the receipt and entry of Applicant’s remarks/arguments filed on November 12, 2025.
Applicant argues that none of Application No. 18/018,576 (U.S. Patent No. 12,410,132), 19,262,108 and Patent No. 11,834,413 and Jacobs et al disclose, teach, or suggest that the pharmaceutical composition comprising the compound Ib-2 and cyclodextrin. Further, as shown in Tables 11 and 12, the present disclosure proved that compared with formulation without cyclodextrin, the claimed pharmaceutical composition exhibits improved exposure of the formulations and increased inhibition rate in experimental animals, thereby resulting in faster speed of onset of therapeutic effect and better drug effect. None of the cited references disclose, teach or suggest such technical effect. Therefore, Applicant submits that claims 1-14 are non-obvious in view of the cited references.
In response, Applicant’s argument is not persuasive. Specifically, the copending Applications. 18/018,576 (U.S. Patent No. 12,410,132), 19,262,108 and Patent No. 11,834,413 and Jacobs et al clearly suggest compound Ib-2 and cyclodextrin. Moreover, formulations #1 comprising compound Ib-2 in the amount of 0.048 g, sulfobutylether-beta-cyclodextrin in the amount of 2.88 g, citric acid monohydrate in the amount of 0.126 g, and diluted in 0.12 mg/ml 0.9% sodium chloride injection; formulations #2 comprising compound Ib-2 in the amount of 0.048 g, sulfobutylether-beta-cyclodextrin in the amount of 4.8 g, citric acid monohydrate in the amount of 0.126 g, and diluted in 0.12 mg/ml 0.9% sodium chloride injection; and formulations #3 comprising compound Ib-2 in the amount of 0.048 g, sulfobutylether-beta-cyclodextrin in the amount of 9.6 g, citric acid monohydrate in the amount of 0.126 g, and diluted in 0.12 mg/ml 0.9% sodium chloride injection may well prove that compared with formulation without cyclodextrin, they exhibit improved exposure of the formulations and increased inhibition rate in experimental animals. However, said improved exposure of the formulations and increased inhibition rate in experimental animals are not commensurate in scope with the claimed invention. Specifically, the claim broadly recites any amount compound Ib-2, any amount of cyclodextrin, any cyclodextrin, and no citric acid and amount of citric acid. Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980).
Conclusion
Claims 1-14 are not allowed.
THIS ACTION IS MADE FINAL. 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 nonprovisional extension fee (37 CFR 1.17(a)) 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.
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/JEAN P CORNET/Primary Examiner, Art Unit 1628