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 .
DETAILED ACTION
Claims 44 and 46-66 are currently pending and amendments to the claims filed on 12/15/2025 is acknowledged. Claims 61-66 have been withdrawn by way of applicant’s election of 05/05/2025, and thus, claims 44 and 46-60 have been withdrawn. Consequently, claims 44 and 46-60 are being examined.
Withdrawn rejections:
Applicant's amendments and arguments filed 12/15/2025 are acknowledged and have been fully considered. The Examiner has re-weighed all the evidence of record. Any rejection and/or objection not specifically addressed below are herein withdrawn.
The following rejection and/or objection are either reiterated or newly applied. They constitute the complete set of rejection and/or objection presently being applied to the instant application.
New Grounds of the Rejections --- as necessitated by amendment
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 56 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 56 recites “the controlled-release formulation”, but which lacks sufficient antecedent basis because base claims 44 and 46 do not require “controlled-release formulation”, and instead, claim 44 recites “a formulation comprising a controlled-release portion …”
Appropriate correction is requested.
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.
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.
As indicated above, the present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 44, 49, 55 and 58 are rejected under 35 U.S.C. 103 as being obvious over Mullen et al. (US2013/0017262A1).
Applicant claims the below claim 44 filed on 01/27/2023
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Level of Ordinary Skill in the Art
(MPEP 2141.03)
MPEP 2141.03 (I) states: “The “hypothetical ‘person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988). The level of skill is that of a medical/pharmaceutical research scientist, as is the case here, then one can assume comfortably that such an educated artisan will draw conventional ideas from medicine, pharmacy, physiology and chemistry— without being told to do so.
In addition, the prior art itself reflects an appropriate level (MPEP 2141.03(II)).
Determination of the scope and content of the prior art (MPEP 2141.01); Ascertainment of the difference between the prior art and the claims(MPEP 2141.02) and Finding of prima facie obviousness Rational and Motivation (MPEP 2142-2143)
Mullen discloses immediate/delayed drug delivery (title); a formulation containing a pharmaceutically active agent is administered in a manner such that an immediate release followed by a delayed release of the pharmaceutically active ingredient could be achieved (e.g., [0009] and claim 17 of the prior art) that reads on the claimed formulation containing an immediate release portion and a controlled release portion, wherein the active ingredient includes drotaverine, etc. (e.g., claim 19) which reads on the claimed drotaverine, and the formulation is provided in the form of tablet wherein the tablet comprises a core comprising the active agent together with an excipient, a delayed release layer containing polymer such as L-HPC (hydroxypropyl cellulose) or LH-32 (low-substituted hydroxypropyl cellulose) (e.g., [0016]-[0017], [0080], [0095], and claim 17 of prior art), the prior art teaches any desired slow release rate can be achieved by adjusting the water soluble/hydrophilic material ([0049]) wherein the L-HPC or LH-32 delays the active agent within the core for between 2-8 hours (claim 17 of prior art) which reads on the claimed polymer, and a top-coating layer which reads on the claimed coating comprising the active agent together with one or more excipients, and that is, the formulation contains the active agent, lubricant excipient, hydroxypropyl cellulose (=HPC) polymer (claim 17 of prior art) and pH modifiers such as acids which reads on the claimed at least one acidifying agent (instant claims 44 , 49 and 58); the excipients include lubricant, binder, diluent, glidant, etc. ([0041]) and [0050](instant claim 55); the prior art teaches any desired slow release rate can be achieved by adjusting the water soluble/hydrophilic material ([0049]) wherein L-HPC or LH-32 delays the active agent within the core for between 2-8 hours (claim 17 of prior art).
In light of the foregoing, instant claims 44, 49, 55 and 58 are obvious over Mullen.
Claims 47, 48, 51-54 and 59 are rejected under 35 U.S.C. 103 as being obvious over Mullen et al. (US2013/0017262A1) in view of Bhambar et al.. “Formulation and Evaluation of Floating Matrix Tablets of Drotaverine Hydrochloride”, Journal of drug delivery and therapies, 2019; 9(3), pp. 200-206.
Mullen was discussed above.
However, Mullen does not expressly teach the amount of drotaverine of instant claim 47; drotaverine HCl of instant claim 48; the amount of polymer of instant claim 51; viscosity of HPMC of instant claims 52-53; species of acidifying agent of instant claim 54; and release rate of instant claim 59. The deficiencies are cured by Bharmbar.
Bharmbar teaches drotaverine hydrochloride is effectively used in the treatment of management of spasticity, indicated in muscle pain as muscle relaxant (abstract on page 200)(instant claim 48); drotaverine hydrochloride approximately 95% bounds to plasma proteins and is metabolized by liver, and in the investigation, efforts were put to develop a sustained release floating matrix tablets of drotaverine hydrochloride, wherein gastro retentative dosage form will also greatly improve the pharmacotherapy of the stomach itself through local drug release leading to high drug concentrations at the gastric mucosa, which are sustained over a long period of time, and floating matrix tablets were prepared by direct compression method using sodium bicarbonate and citric acid as gas forming agents, and HPMC K100M and Ethyl cellulose were used in the formula to retard drug release wherein HPMC K100M reads on the claimed polymer and its identical viscosity, and floating matrix tablets were evaluated for different quality attributes; in vitro drug release showed that polymer percentage is enough to extend the release of the drug for at least 12 hr. The dissolution curve shows that formulation FT-6 shows maximum drug release 79.37% at the end of 12 hours (abstract on page 200) (instant claim 59); Table 1 on page 201 shows the below formulation: the formulation of Table 1 contains drotaverine HCl which reads on the claimed drotaverine salt, HPMC K100M which reads on the claimed polymer and K100M has a viscosity of 100,000 cP which is within the claimed viscosity of 100-150,000cP(instant claims 52-53), HPMC (FT-6) is used in an amount of 12.5% (=40/320) that is within the claimed range of 5-30%(instant claim 51), and citric acid which reads on the claimed acidifying agent species (instant claim 54); and magnesium stearate and sodium bicarbonate; the drotaverine HCl of FT-6 is used in an amount of 160mg which is within the claimed 10-300mg (instant claim 47); and the HPMC K100M is used in an amount of 40/320=12.5% (FT-6) and the range is within the claimed range of 5-30%; and the in vitro dissolution curve shows that formulation FT-6 has maximum drug release 79.37% at the end of 12 hours which is within the claimed dissolution profile in vitro of 60-85% after 8 hours (pages 200-201)(instant claims 47, 48, 51-54 and 59).
It would have been obvious to modify the teachings of Mullen with the amount of active agent/polymer, viscosity of the polymer, and release rate of Bhambar in order to enhance the properties of the formulation meet intended purpose of controlling release rate as taught by Bhambar.
In light of the foregoing, instant claims 47, 48, 51-54 and 59 are obvious over Mullen in view of Bhambar.
Claim 46 and 56-57 are rejected under 35 U.S.C. 103 as being obvious over Mullen et al. (US2013/0017262A1) in view of Krishnakant et al. (WO2016/075617A1, IDS of 09/08/2022).
Mullen was discussed above.
However, Mullen does not expressly teach antioxidant of instant claim 46 and its species of instant claims 56 and 57. The deficiencies are cured by Krishnakant.
Krishnakant discloses fixed does pharmaceutical formulation of analgesic and antispasmodic drugs (title) comprising NSAID such as ibuprofen, antispasmodic drug including drotaverine or its salt and the combination 200-800mg ibuprofen and about 20-about 100mg of drotaverine hydrochloride and pharmaceutically acceptable excipients (page 6); the excipients includes antioxidants, diluents, acidifiers, disintegrants, binders, surfactants, lubricants, glidants, wherein the acidifiers includes citric acid, fumaric acid, lactic acid, maleic acid, malic acid and tartaric acid (page 7, 5th para.) wherein the antioxidant is chosen from BHA, BHT, sodium metabisulphite, sodium thiosulfate, propyl gallate, ascorbic acid, etc. (page 7, 6th para.) (instant claims 46 and 57), wherein the diluents include sugar including lactose monohydrate, lactose anhydrous, mannitol, starches maize starch, corn starch, pregelatinized starches (page 7, last para.), wherein the disintegrant includes crospovidone, croscarmellose sodium, L-HPC and alginic acid (page 8, second para.), wherein the binders include HPMC (=hypromellose=Methocel products), HPC, PVP or povidone, carbomers (e.g., Carbopol), methylcellulose, polymethacrylate, and starches (page 8, third para.), wherein the surfactants includes POE-POP block copolymers, alkyl sulfates, polysorbates, etc. (page 8, 4th para.), and wherein the lubricants include magnesium stearate, stearic acid, silicon dioxide, etc. (page 8, 5th para.); the formulation can be prepared as monolithic layer tablet or bilayer tablet having tow distinguishable portions (page 6, first para.), which can be further coated with Opadry polymer from HPMC or HPC, Colorcon and others (page 12, third para.); in one embodiment (Example 1B), the formulation contains ibuprofen, citric acid, starch 1500, crospovidone XL-10, and stearic acid, ascorbic acid in an amount of 7% which is within the claimed range of up to 10%. MPEP 2144.05:“In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976).”(instant claim 56). Krishnakant further discloses bilayer containing two different drugs with excipients (Examples 4A/4B).
It would have been obvious to modify the teachings of Mullen with additions of antioxidant of Krishnakant. One of the ordinary artisan would have been motivated to do so because the antioxidant protects active ingredients from oxidative degradation and therefore enhance stability of the formulation (page 7, third para.), and selecting sodium metabisulphite species of Krishnakant would be a matter of choice or design and such selection would have yielded no more than the predictable results. Accordingly, in order to enhance the properties of the composition, it would be obvious to combine Mullen with Krishnakant.
In light of the foregoing, instant claims 46, 56 and 57 are obvious over Mullen in view of Krishnakant.
Claim 50 is rejected under 35 U.S.C. 103 as being obvious over Mullen et al. (US2013/0017262A1) in view of Wang et al. (US2018/0325907A1).
Mullen was discussed above.
However, Mullen does not expressly teach HPMCAS of instant claim 50. The deficiency is cured by Wang.
Wang discloses pharmaceutical composition comprising drotaverine as an active agent (e.g., [0078], [0082] and claim 4 of prior art), HPC, HPMC or HPMCAS polymer (e.g., [0314] and [0323]) as an erodible matrix water-swellable polymers, organic acid such as citric acid as pH acidifier or osmogene ([0273] or [0320]), and excipients or carriers (e.g., [0031]-[0032]), and antioxidant such as BHT, BHA, propyl gallate, ascorbic acid, and sodium metabisulfite ([0279]).
It would have been obvious to replace HPC of Mullen with HPMCAS of Wang for delaying the release rate and such selection would be a matter of choice or design because HPC, HPMC, HPMCAS all polymers have equivalent function in controlling release rate of the composition and thus selecting HPMCAS from the teachings of Wang would have yielded no more than predictable results.
In light of the foregoing, instant claim 50 is obvious over Mullen in view of Wang.
Claim 60 is rejected under 35 U.S.C. 103 as being obvious over Bhambar et al.. “Formulation and Evaluation of Floating Matrix Tablets of Drotaverine Hydrochloride”, Journal of drug delivery and therapies, 2019; 9(3), pp. 200-206 in view of Wang et al. (US2018/0325907A1).
Bhambar discloses formulation containing drotaverine hydrochloride, HPMCK100, citric acid, and magnesium stearate (see Table 1 on page 201).
However, Bhambar does not expressly teach antioxidant sodium metabisulfite, and HPMCAS. The deficiencies are cured by Wang.
Wang discloses pharmaceutical composition comprising drotaverine as an active agent (e.g., [0078], [0082] and claim 4 of prior art), HPC, HPMC or HPMCAS polymer (e.g., [0314] and [0323]) as an erodible matrix water-swellable polymers, organic acid such as citric acid as pH acidifier or osmogene ([0273] or [0320]), and excipients or carriers (e.g., [0031]-[0032]), and antioxidant such as BHT, BHA, propyl gallate, ascorbic acid, and sodium metabisulfite ([0279]).
It would have been obvious to modify the teachings of Bhambar with sodium metabisulfite and HPMCAS of Wang, and such selection of polymer would be a matter of choice or design because HPC, HPMC, HPMCAS all polymers have equivalent function in controlling release rate of the composition and thus selecting HPMCAS from the teachings of Wang would have yielded no more than predictable results; and adding antioxidant sodium metabisulphite to the formulation of Bhambar would enhance the properties of the formulation as taught by Wang.
Further, the applied art alone or in combination does not provide embodiment of claim 60. However, one of ordinary skill would be motivated to provide this embodiment because a reference is analyzed using its broadest teachings. MPEP 2123 [R-5]. Where, as here, the specific combination of features claimed is disclosed within the broad teachings of the reference but the reference does not disclose the specific combination of elements in a specific embodiment or in a working example, “picking and choosing” within several variables does not necessarily give rise to anticipation. Corning Glass Works v. Sumitomo Elec., 868 F.2d 1251, 1262 (Fed. Circ. 1989). However, "when a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious". KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007)(quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976). "[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious", the relevant question is "whether the improvement is more than the predictable use of prior art elements according to their established functions." (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that "[a] person of ordinary skill is ... a person of ordinary creativity, not an automaton." Id. at 1742.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to rearrange the disclosed elements and embodiments of the cited references (selecting drotaverine hydrochloride, HPMC K4M polymer, HPMCAS, citric acid acidifier, and sodium metabisulphite) to prepare the instantly claimed composition. Such a rearrangement by a person of ordinary skill in the art who is not an automaton to yield the instantly claimed invention is within the purview of the ordinary skilled artisan upon reading the cited reference and would yield predictable results.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a).
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the combined references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant’s arguments have been fully considered, but are moot in view of new reference of Mullen. Further, it is noted that one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. In reKeller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In reMerck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). MPEP 2145.
Conclusion
No claims are allowed.
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 KYUNG S CHANG whose telephone number is (571)270-1392. The examiner can normally be reached M-F 8-5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Yong (Brian-Yong) S Kwon can be reached at 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KYUNG S CHANG/Primary Examiner, Art Unit 1613