DETAILED ACTION
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
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. INDIA 20221 1006919, filed on 02/09/2022.
Information Disclosure Statement
At the time of this office action, an IDS has not been submitted for this application.
Status of claims
Claims 1-3, 5-9, 11, 13, 15-27, 29-31, 39 and 44-45 are pending in this application. Claim 1 has been amended. Claims 4, 10, 12, 14, 28, 32-38, and 40-43 a have been cancelled by applicant without prejudice or disclaimer. Claims 31, 39, and 44 are withdrawn from examination from the office action filed on 11/16/2023.
Applicant’s arguments in the office action filed 01/06/2026, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.
Claims 1-3, 5-9, 11, 13, 15-27, 29-30 and 45 are currently under examination, they constitute the complete set presently being applied to the instant application.
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.
Claim 18 is 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.
Claim 18, line 3 contains the trademark/trade name “starch 1500”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe an excipient comprising a partially pregelatinized maize starch and, accordingly, the identification/description is indefinite.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1-3, 5-9, 11, 13, 15-27, 29-30 and 45 are rejected under 35 U.S.C. 103 as being unpatentable over Berlia (WO 2021/181262 Al) in view of Nandi (US 2022/0040196 Al) and further in view of Van Lengerich (WO 2000/021504 A1).
The instant claims are directed to a fixed dose combination comprising drotaverine or a pharmaceutically acceptable salt thereof and at least one benzodiazepine formulated as a single stable medicine wherein the at least one benzodiazepine is chlordiazepoxide and fixed dose combination comprises a core with at least one layer.
Berlia et al. teach controlled release formulations comprising Drotaverine for administration once or twice a day controlled release formulations of Drotaverine which avoids fluctuations of plasma levels, reduces pill burden and side effects owing to simplified dosage schedule, thereby improving patient compliance and methods of preparation of controlled release formulations of Drotaverine or salt thereof. The invention further provides controlled-release formulations of Drotaverine or salt thereof for treating at least one symptom of gastrointestinal, biliary, urological and gynecological disorders characterized by spastic conditions of smooth muscles in a subject (Abstract). Berlia discloses the effectiveness of a fixed dose immediate release (IR) combination of Drotaverine hydrochloride (80 mg) and PCM (500 mg) for amelioration of abdominal pain associated with acute infectious gastroenteritis. (pg. 4, lines 25-30). Berlia also discloses formulations comprising drotaverine as immediate release (IR) and controlled release (CR) in “In some embodiments, the Drotaverine CR formulations disclosed herein can be dosed once a day leading to better patient convenience and compliance. They can be formulated as a single layer, bilayer or trilayer tablets or multicoated mini tablets or beads or pellets compressed as MUPS (Multiple-Unit Pellet System) tablets or filled in capsules. The capsule shells used can be of gelatin or non-gelatin based materials.” (pg. 11, lines 20-33) Berlia teaches the use of Hydroxypropyl Cellulose, methyl cellulose, Carboxymethyl Cellulose and the acidifying agents of Citric acid, Fumaric acid, Lactic acid, maleic acid, malic acid and tartaric acid in a CR formulation (pg. 13, lines 16-25). Berlia also teaches the use of diluents, including microcrystalline cellulose, binders including polyvinylpyrrolidone as well as glidants and lubricants of talc, colloidal silicon dioxide, and magnesium stearate. (pg. 15, lines 26-33). Berlia also discloses “[i]n another embodiment the present invention discloses that the tablet or capsule is prepared by a wet granulation, dry granulation/slugging or direct compression process.” (pg. 16, lines 14-15). Berlia teaches “[t]he formulations of Drotaverine are capable of being manufactured by direct compression, dry granulation, wet granulation or fluidized bed processing methods.” (pg. 43, lines 10-12). Berlia discloses the use of polysorbate 80 as a surfactant (pg. 6, lines 28-33). Berlia also discloses an embodiment of a controlled release (CR) formulation of drotaverine in which an antioxidant is selected from butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), sodium metabisulfite, sodium thiosulfate, propyl gallate, ascorbic acid and cysteine (pg. 22, lines 23-25).
However, Berlia et al. fail to disclose the use of chlordiazepoxide.
Nandi et al. teach stable pharmaceutical compositions comprising a combination of chlordiazepoxide hydrochloride and clidinium bromide and one or more pharmaceutically acceptable excipients, wherein the com position is in the form of solid oral dosage and wherein the formulations are useful for the treatment of gastrointestinal disorders and various other therapeutic indications (Abstract). Nandi discloses Chlordiazepoxide hydrochloride is a versatile, therapeutic agent of proven value for the relief of anxiety and tension [0002]. Nandi discloses “The term "stable" refers to the compositions of the present invention, wherein substantially no analogues or degradation product of any active pharmaceutical excipient (API) is generated during storage of the dosage form for at least 1 month, preferably for at least 3 months, more preferably for at least 6 months. The stability of the solid oral composition may be evaluated at "long term" conditions 25° C./60% relative humidity, at intermediate condition 30° C./65% relative humidity, at "accelerated conditions" 40° C./75% relative humidity in the final container or pack either measured as the assay or drop in dissolution.” [0034]. Nandi discloses a dose of chlordiazepoxide is about 1-10 mg [0074]. Nandi teaches clidinium bromide is a synthetic anticholinergic agent, having an antispasmodic and antisecretory effect on the gastrointestinal tract [0003].
However, Nandi et al. fail to disclose the antispasmodic of drotaverine.
Van Lengerich et al. teach a continuous process for producing shelf stable, controlled release, discrete, solid particles from a liquid encapsulant component which contains a sensitive encapsulant, such as a heat sensitive or readily oxidizable pharmaceutically, biologically, or nutritionally active component (pg. 1, lines 5-9). Van Lengerich discloses exemplary active components which may be encapsulated or embedded in accordance with the present invention (pg. 18 line 6-7), include chlordiazepoxide (pg. 19 line 1) and drotaverine (pg. 19, line 25).
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art, prior to the effective filing date of the instant application, to combine the compounds of drotaverine using a wet or dry granulation or fluidized bed process taught by Berlia as a 80 mg dose and 1-10 mg dose of chlordiazepoxide and a stable dose combination at 40°C at 75% relative humidity for 6 months disclosed by Nandi in a multilayered fixed dose combination because both Berlia and Nandi taught the use of those compounds for the same purpose of treating a gastrointestinal disorder. Furthermore the combining the compounds of chlordiazepoxide and drotaverine were shown by Van Lengerich to be exemplary active ingredients ideal for combination into a single dose. See MPEP 2144.06.
It is noted that a hydroxypropyl cellulose coating agent, the acidifying agents of citric acid, fumaric acid, lactic acid, maleic acid, malic acid or tartaric acid, antioxidants of butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), sodium metabisulfite, sodium thiosulfate, propyl gallate, ascorbic acid and cysteine, glidants of talc, colloidal silicon dioxide, diluents of microcrystalline cellulose, binders including polyvinylpyrrolidone and a 20-300 mg drotaverine dose are all taught by Berlia. See MPEP 2143
A person of ordinary skill in the art would have been motivated to combine Berlia’s teachings of a single or multilayered stable fixed dose of drotaverine with Nandi’s disclosure of chlordiazepoxide wherein the dose is stable at 40°C and 75% relative humidity for an extended period of 6 months with the disclosures of Nandi’s chlordiazepoxide and teachings of stable formulations by Van Lengerich because a skilled artisan would have found it prima facie obvious to formulate a multilayered pharmaceutical composition comprising drotaverine and chlordiazepoxide, each compound identified by the prior art as useful for the same purpose of treating a gastrointestinal condition and would therefore have had a reasonable expectation of success in treating a gastrointestinal condition by the cumulative effects of combining chlordiazepoxide and drotaverine.
Conclusion
All claims are rejected. No claims are allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERNESTO VALLE JR whose telephone number is (703)756-5356. The examiner can normally be reached 0730-1700 M-F EST, 1st Friday off.
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/E.V./Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623