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 21-40 are pending in this application.
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.
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 21-40 are rejected under 35 U.S.C. 103 as being unpatentable over Nelson et al. (US 2005/0137198; hereinafter, Nelson) in view of Hydralazine hydrochloride injection, USP Safety Data Sheet and Albayrak (US 2017/0231957).
Nelson (US 2005/0137198) discloses sterile aqueous injectable pharmaceutical composition comprising hydralazine hydrochloride in a pharmaceutically acceptable carrier or diluent, wherein the hydralazine hydrochloride is essentially free of phthalazines, hydrazine, and metal ions (claim 1). Nelson discloses that hydralazine hydrochloride is commercially available in sterile injectable dosage forms to treat hypertension, but it is unstable in storage because it forms insoluble polymeric products by reacting with hydralazine and contaminating by-products of hydralazine manufacture during storage of hydralazine solutions (paragraphs 5-6, 12). By providing hydralazine hydrochloride that is free of contaminating by-products (paragraphs 13-15, 54-56, 62-64), the hydralazine hydrochloride does not degrade or produce particulates during extended storage (paragraph 16). 5-20 mg/mL concentration of hydralazine hydrochloride is disclosed (paragraph 65), with examples of 5 mg/mL and 20 mg/mL (Examples 3, 4, 5 on page 7). The sterile aqueous injection solution comprises pharmaceutically acceptable liquid carrier or diluent for parenteral administration such as water, glycols such as propylene glycol, and other carriers described in the standard reference texts in this field (paragraph 66). Nelson shows stability of hydralazine hydrochloride with 0.8% or less degradation after 118 days at 40° C with water and propylene glycol as the solvents or carriers (Table 3 in view of Examples 3, 5-7). Packaging in a bottle is disclosed (Examples 3-7, 9-10).
Hydralazine hydrochloride injection, USP Safety Data Sheet is cited to establish that injectable formulation of hydralazine hydrochloride for treating hypertension is known to contain, in addition to water, propylene glycol, and hydralazine hydrochloride, methyl paraben, sodium hydroxide, hydrochloric acid, and propyl paraben. See pages 1-3. Weight ratio of propylene glycol to hydralazine chloride is 5.2:1 (from 10.2/2). See pages 1-2.
Albayrak (US 2017/0231957) is cited to establish that ethanol, isopropanol, glycols, and vegetable oils are well-known pharmaceutically acceptable carriers or vehicles (paragraph 75).
Nelson does not explicitly exemplify an “about 10 mg/mL” concentration of hydralazine/salt, but Nelson teaches 5-20 mg/mL, which is amply suggestive of about 10 mg/mL.
Nelson does not explicitly disclose a weight ratio of the co-solvent to hydralazine/salt, but Nelson teaches that his hydralazine hydrochloride, which is essentially free of phthalazines, hydrazine, and metal ions, degrades less than 1% after 118 days in storage at 40° C. Because the source of degradation has been eliminated or substantially removed, the ordinary skilled artisan would have expected stability, including no more than about 10% loss after 2 months of storage at 60° C.
5.2:1 weight ratio of co-solvent to hydralazine hydrochloride is known from Hydralazine hydrochloride injection, USP Safety Data Sheet, so the ordinary skilled artisan would have found it obvious to similarly formulate a 10 mg/mL concentration with a comparable ratio of co-solvent to hydralazine.
Ethylene glycol, isopropanol, and vegetable oil are well-known pharmaceutically acceptable vehicles, and their use as the co-solvent would have been obvious from Nelson’s teaching and suggestion of such vehicles, further in view of Albayrak.
Presence of sodium hydroxide is known from Hydralazine hydrochloride injection, USP Safety Data Sheet, and its inclusion would have been obvious for pH adjustment purposes.
A pre-filled syringe comprising the sterile, ready-to-use pharmaceutical composition of hydralazine as discussed herein would have been obvious for the convenience and safety of direct use.
Method of treating hypertension comprising administering comprising the sterile, ready-to-use pharmaceutical composition of hydralazine as discussed herein would have been obvious because hydralazine hydrochloride is a known drug for hypertensive treatment.
Therefore, the claimed invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, because every element of the invention and the claimed invention as a whole have been fairly disclosed or suggested by the teachings of the cited references.
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 21, 26-31, and 36 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 12,109,211 in view of Hydralazine hydrochloride injection, USP Safety Data Sheet.
Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons.
Patented claims ae directed to a sterile, ready-to-use pharmaceutical composition comprising 10 mg/mL hydralazine/salt, water + propylene glycol as the co-solvent, wherein the weight ratio of the co-solvent and hydralazine/salt is “no more than about 7.5:1, and wherein the hydralazine and/or salt thereof has a change in concentration of no more than about 10% after 2 months of storage at 60° C” (claim 1), a pre-filled syringe comprising the same composition (claims 13, 18), and a method of treating hypertension comprising administering to a subject in need thereof the same composition (claim 17). Ratio of no more than about 6:1 is also claimed (claims 2, 15). Inclusion of a buffer (claims 4-5), chelating agent (claims 6-7), tonicity agent, e.g., salt (claims 8-9) is also claimed. See also claims 3, 10-12, 14, 16.
Hydralazine hydrochloride injection, USP Safety Data Sheet is cited to establish that injectable formulation of hydralazine hydrochloride for treating hypertension is known to contain, in addition to water, propylene glycol, and hydralazine hydrochloride, methyl paraben, sodium hydroxide, hydrochloric acid, and propyl paraben. See pages 1-3. Weight ratio of propylene glycol to hydralazine chloride is 5.2:1 (from 10.2/2). See pages 1-2.
Therefore, the ordinary skilled artisan would have recognized the instant invention as an obvious variation of the invention set forth in the patented claims of U.S. Patent No. 12,109,211.
For the foregoing reasons, all claims are rejected. No claim can be allowed at this time.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to JOHN PAK whose telephone number is (571)272-0620. The Examiner can normally be reached on Monday to Friday from 8:30 AM to 5 PM.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's SPE, Fereydoun Sajjadi, can be reached on (571)272-3311. The fax phone number for the organization where this application or proceeding is assigned is (571)273-8300.
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/JOHN PAK/Primary Examiner, Art Unit 1699
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