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 3-5, 7, 8, 12-16 are presented for examination.
The amendments and remarks filed on 07/28/2026 have been received and entered.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 3, 4, 7, 12 and 16 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 3, 4, 7, 12 and 16 are rejected as being indefinite in using improper Markush Language. The addition of “the group consisting of” after “selected from” will overcome the rejection.
Claims dependent on the rejected claims are also rejected, since they have all the limitations of the rejected claims.
Claim(s) 3-5, 7, 8 and 12-16 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sharma et al. (US 20200222326) in view of Liu et al. (CN 106176681 submitted by the applicant) and further in view of Darji et al. (Excipient Stability in Oral Solid Dosage Forms: A Review).
Sharma teaches a pharmaceutical composition comprising fixed dose combination of valsartan or pharmaceutically acceptable salts thereof and sacubitril or pharmaceutically acceptable salts thereof. See the abstract. Sharma teaches that he present invention provides a pharmaceutical composition, wherein valsartan is present in form of disodium salt. See Para [0031]. Sharma teaches that the first or second component is present in the form of powder, slugs, compacts, granules, beads, pellets, or minitablets. See Para [0035]. Sharma teaches the term "composition" or "dosage form" or "pharmaceutical composition" as used herein synonymously include tablet such as mono-layered/single layer tablets, bilayered tablets, trilayered tablet, multilayer tablet, drug layered tablet, caplets, minitablets, capsules, tablet in tablet, tablets in a capsule, granules in a capsule, pellets, pellets in a capsule, beads, powder, granules, sachets, suspension or any other suitable dosage form meant for oral administration. See Para [0090]. Sharma teaches that the pharmaceutical composition comprising valsartan and sacubitril and one or more pharmaceutically acceptable excipients, wherein said composition is a mono-layer table. See Para [0085]. Sharma teaches that the pharmaceutical composition comprises a film coating. See Para [0092]. Sharma teaches that the pharmaceutically acceptable excipients of the present invention may include filler, binder, disintegrant, lubricant, diluent, plasticizer, pH adjusting agent, pigment, opacifier, surfactant, glidant, and/or any combinations thereof. Some of the excipients may have two or more functions at the same time. See Para [0097]. Sharma teaches the core layer comprises sacubitril layer and valsartan layer. See Example 3, Para [0119]. Sharma teaches the use of microcrystalline cellulose, colloidal silicone dioxide and magnesium stearate in the drug layer. See Example 8, para [0161]. The use of mannitol, sorbitol, hydroxypropyl methylcellulose and povidone is taught in Para [0098] and [0099]. The use of a colorant is taught in Para [0107]. Sharma teaches the use of a tonicity adjusting agent, such as mannitol and sorbitol, the use of a thickener, such as hydroxypropyl methylcellulose, the use of a sweller, such as povidone, the use a colorant, such as iron oxide red, the use of a lubricant, such as silicone dioxide. See Para [0098], [0099] and table 1. Sharma teaches the amount of sacubitril 10-40% and the amount of valsartan 10- 40%. The combination of these two ingredients equals to 20-80% in the tablet. See Example 1, Para [0114]. The concentration of silicone dioxide as a lubricant is taught to be 0.1-5%. See Example 1. Sharma differs from the claimed invention in having a pore in one side of the drug -containing layer and the presence of sodium chloride as a tonicity agent. Liu teaches a composition for resisting cardiac failure LCZ696 (sacubitril/valsartan) oral sustained- release pellet and its preparation method. The slow-release micro-pill comprises is composed of slow- release material, pore-forming agent, plasticizer and ant sticking agent is comprised of LCZ696, diluent and adhesive pellet core and pellet core and outer coating, the weight of each component is as follows: LCZ696 2-55 parts, 15-90 parts of diluent, 1-15 parts of adhesive, 1-35 parts of slow release material, 0.1-5 parts of pore-forming agent, 0.1-5 parts of plasticizer and 0.1-25 parts of ant sticking agent. See the abstract. Liu teaches the pore-forming agent is one or more of hydroxypropyl methyl cellulose, polyethylene glycol 4000 and polyvinylpyrrolidone. See claims 1 and 6. Darji teaches the use of sodium chloride as an osmotic agent in an oral dosage form. See Page 20. The use of sorbitol, glycerol and lactose is also taught by Darji et al. See pages 13 and 21. Sharma teaches the use of a colorant, but does not teach the concentration of such agent. However, the determination of optimum proportions or amounts are considered to be within the skill of artisan in the absence of evidence to the contrary. Sharma does not teach the concentration of a tonicity agent. However, Liu teaches the concentration of mannitol being 5 g and the concentration of sucrose is 30 g. See Examples 2 and 3. Sharma teaches the use of sacubitril valsartan sodium, hydroxyethyl cellulose, colloidal silica and magnesium stearate and povidone. See Paras [0093] and [0098]. Sharma does not teach the concentration of each component. However, the determination of optimum proportions or amounts are considered to be within the skill of artisan in the absence of evidence to the contrary. Applicant's attention is drawn to In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955), wherein the court states "generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation". Sharma teaches the film-coating provides for immediate release, extended release, sustained release, delayed release, enteric release, or intestinal release of the active agent. See Para [0095].
It would have been obvious to a person skilled in the art to create a pore in the tablet of Sharma, motivated by the teachings of Liu, which teaches the use of pore forming agents in the drug forming layer of a sacubitril valsartan sodium sustained release formulation as old and well known. The determination of the location of the pore is considered to be within the skill of artisan in the absence of evidence to the contrary. Darji teaches the use of sodium chloride as an osmotic agent in an oral dosage form. The relied upon references make clear that the claimed excipients have been previously used in a sacubitril valsartan composition or are well known excipients in an oral solid dosage form.
Response to arguments
Applicant’s arguments have been noted. Applicant in his remarks argues that “Applicant submits that Sharma discloses immediate-release tablets (100% released within 30 min), while Liu neither discloses nor addresses the synchronized slow release of valsartan and sacubitril.
With respect to Claim 3, Sharma provides an active ingredient that includes "valsartan or pharmaceutically acceptable salts thereof and sacubitril or pharmaceutically acceptable salts thereof". Office Action at 4 and Example 1 in Sharma”. It is the examiner’s position that Sharma teaches the film-coating provides for immediate release, extended release, sustained release, delayed release, enteric release, or intestinal release of the active agent. See Para [0095]. Furthermore, Liu teaches the slow release composition comprising sacubitril valsartan. Applicant in his remarks further argues that “Further, Sharma teaches that "The present invention provides a pharmaceutical composition of sacubitril and valsartan, wherein the composition is free from supramolecular complex of sacubitril and valsartan." Sharma, paragraph [0087].
In contrast, the claimed invention recites "the active pharmaceutical ingredient is sacubitril valsartan sodium" (see claim 1), which is a complex of sacubitril and valsartan”. It is the examiner’s position that Sharma in Para [0038] teaches the present invention provides a pharmaceutical composition comprising valsartan and sacubitril and one or more pharmaceutically acceptable excipients, wherein said composition is a mono-layer tablet. Sharma further teaches the present invention provides a process for preparing a pharmaceutical composition wherein said process comprises the steps of: (a) preparing a mix of valsartan and sacubitril and one or more pharmaceutically acceptable excipients; (b) lubricating the mixture of step (a) with lubricants; (c) granulating the mixture obtain in step (b); (d) lubricating the mixture of step (c) with lubricants; (e) formulating the lubricated granules of step (d) to form final dosage form. See Para [0108]. Applicant in his remark additionally argues that “Further, neither Sharma nor Liu discloses the tonicity adjusting agent that is "a mixture of lactose monohydrate and sodium chloride, or a mixture of sorbitol and sodium chloride", much less a content of tonicity adjusting agent that is "27.50% to 60.00%". It is the examiner’s position that Sharma teaches the use of lactose and sorbitol as tonicity adjusting agents. Darji teaches the use of lactose and sodium chloride as a tonicity agents being used in a solid dosage form. To combine well-known tonicity adjusting agents would have been obvious to a person skilled in the art in the absence of evidence to the contrary. Applicant in his remarks argues that “claim 4 recites "the pore is formed by laser on the side of the drug- containing layer core and has a size of 0.4 mm to 0.7 mm". Although Liu discloses a pore forming agent that can form pores, it discloses neither the size of the pores nor forming the pore using laser. “ It is the examiner’s position that the process by which the pore is formed does not create a patentably distinct composition. Furthermore, the specific size of the pore does not create a patentably distinct composition in the absence of evidence to the contrary.
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 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZOHREH A FAY whose telephone number is (703)756-1800. The examiner can normally be reached Monday-Friday 9:30AM-6:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sue Liu can be reached at 571-272-5539. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ZOHREH A FAY/Primary Examiner, Art Unit 1617
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