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 .
Election/Restriction
Applicant’s election without traverse of group I, claims 1-5, 7-8, 23, 33-36, 39-41 and 50 in the reply filed on 06/15/2026 is acknowledged.
Claims 52-55 withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/15/2026.
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, 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 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.
Claim(s) 1-5, 7, 8, 23, 33-36, 39-41 and 50 is/are rejected under 35 U.S.C. 103 as being unpatentable over
Austedo® (deutetrabenazine) Label in view of Sommer et al. (US 20140336386). (2014Gant (US 2010/0130480 A1), Duffield (US 2012/0208773 A1), and further in view of Bosch (US 5,510,118).
The claims are drawn to A controlled release oral dosage form for twice daily administration of deutetrabenazine comprising a population of sustained release beads; wherein the sustained release beads comprise a core comprising a first amount of micronized deutetrabenazine and a first pharmaceutically acceptable excipient, and further comprising a first coat selected from a pH-independent polymer coat, a pH- dependent polymer coat, or a pH-independent polymer coat further coated with a pH-dependent polymer coat.
Austedo® is an FDA-approved drug known as deutetrabenazine (API) and the
label discloses oral dosage formulation, with known dose ranges (6-48 mg) in once a
day, twice a day and disclosed inactive ingredients: ammonium hydroxide, black iron
oxide, n-butyl alcohol, butylated hydroxyanisole, butylated hydroxytoluene, magnesium
stearate, mannitol, microcrystalline cellulose, polyethylene glycol, polyethylene oxide,
polysorbate 80, polyvinyl alcohol, povidone, propylene glycol, shellac, talc, titanium
dioxide (page 12, 1st II).
Regarding claims 1 and 2 as noted above, Austedo® label discloses deutetrabenazine (API) in oral administration, and known dosage range overlaps with instant dose range of 6-72 mg, and many of the inactive substances are known pharmaceutically acceptable excipient comprises an antioxidant (butylated hydroxyanisole, butylated hydroxytoluene); a binder (Povidone (Polyvinylpyrrolidone/PVP) a binder commonly used in wet granulation), Polyvinyl. Alcohol (PVA): commonly used as a binder and coating agent; a filler, mannitol, microcrystalline cellulose; a surfactant, polysorbate 80 (known to help with defoaming), polyethylene glycol (PEG) known to be used as foam control in some formulations. Moreover, Austedo® label discloses short half-life metabolites (page 13,1 Elimination), known safety issues of pharmacodynamics and pharmacokinetics tied to peak exposure (page 12, 12.2 and 12.3) and patients with hepatic impairment issues (T 8.6 and page 14).
Austedo® fails to specifically disclose extended-release formulation, sustained release beads, and pH-independent polymer coat, and pH-dependent polymer coat to further improve a composition comprising deutetrabenazine (API).
Sommer teaches a pharmaceutical composition comprising a deuterated analogue of tetrabenazine which yields, when orally administered to a subject. See Para [0022]. Sommer et al. in Example 34 teaches that sustained-release (SR) formulation that uses multiparticulate to improve solubility/delivery of the drug, and these drug-loaded particles are incorporated and released from a matrix tablet system by a combination of gelation and erosion of tablet. Drug-loaded particles can be ceform, shear form, extrusion-spheronization beads, layered beads, or other multiparticulate technology. Sommer teaches Compression of beads into tablets (either immediate release or SR matrix type tablets) is contemplated. d.sub.6-tetrabenazine-loaded beads made by using layering technique on sugar spheres are preferred, but one can use drug-loaded granules, floatable particles, extruded/spheronized pellets, Ceform microspheres, or other multiparticulates for drug core component as well. The typical bead size is from about 2 millimeters to about 0.1 mm in diameter or longest dimension before coating. Solubizers and acids (or absence thereof) can also be used in the core or in the coating component of the drug-loaded beads. See Para [0404]. Sommer teaches the functional coating polymers for SR coating can be solvent or aqueous-based, cellulosic, methacrylics, pH independent, or pH dependent in nature. In addition to polymer application on drug layered beads, d.sub.6-tetrabenazine beads manufactured by extrusion/spheronization can also be used as a substrate. See Para [0407]. It would have been obvious to a person skilled in the art to use Deuterobenzene in a sustained or immediate release motivated by the teachings of Sommer et al., which teaches the use of deutetrabenazine dosage form in a sustained or immediate release. The use of pH dependent and independent coating is also taught by Sommer et al. See Para [0407].
Regarding claims 3 and 4, Sommer teaches the functional coating polymers for SR coating can be solvent or aqueous-based, cellulosics, methacrylics, pH independent, or pH dependent in nature. In addition to polymer application on drug layered beads, d.sub.6-tetrabenazine beads manufactured by extrusion/spheronization can also be used as a substrate. See Para [0407]. The use of excipients in the coating is taught by Austedo® label and Sommer et al. The determination of number of coating would have been obvious to a person skilled in the art in the absence of evidence to the contrary.
Regarding claim 5, Sommer teaches Compression of beads into tablets (either immediate release or SR matrix type tablets) is contemplated. d.sub.6-tetrabenazine-loaded beads made by using layering technique on sugar spheres are preferred, but one can use drug-loaded granules, floatable particles, extruded/spheronized pellets, Ceform microspheres, or other multiparticulates for drug core component as well. See Para [0404].
Regarding claim 7, the use of excipients are taught by Austedo® label and Sommer in Paras [0298] and [0299]. The determination of using the same or different excipients in a drug dosage form is considered to be within the skill of artisan in the absence of evidence to the contrary.
Regarding claim 8, Sommer teaches the typical bead size is from about 2 millimeters to about 0.1 mm in diameter or longest dimension before coating. See Para [0404]. The particle size taught by Sommer is within the scope of the claimed diameter.
Regarding claim 23, Sommer teaches the functional coating polymers for SR coating can be solvent or aqueous-based, cellulosics, methacrylics, pH independent, or pH dependent in nature. See Para [0407].
Regarding claim 33, Sommer teaches between about 2 and about 18% of d.sub.6-tetrabenazine, which reads on 20 mg-180 mg. See Para [0057]. Such concentration overlaps with the claimed concentrations.
Regarding claims 33 and 34, Sommer et al. in Example 34 teaches that sustained-release (SR) formulation that uses multiparticulate to improve solubility/delivery of the drug, and these drug-loaded particles are incorporated and released from a matrix tablet system by a combination of gelation and erosion of tablet. Drug-loaded particles can be ceform, shear form, extrusion-spheronization beads, layered beads, or other multiparticulate technology.
Regarding claims 35 and 40, Austedo® label discloses deutetrabenazine (API) in oral administration, and known dosage range overlaps with instant dose range of 6-72 mg, and many of the inactive substances are known pharmaceutically acceptable excipient comprises an antioxidant (butylated hydroxyanisole, butylated hydroxytoluene); a binder (Povidone (Polyvinylpyrrolidone/PVP) a binder commonly used in wet granulation), Polyvinyl. Alcohol (PVA): commonly used as a binder and coating agent; a filler, mannitol, microcrystalline cellulose; a surfactant, polysorbate 80 (known to help with defoaming), polyethylene glycol (PEG) known to be used as foam control in some formulations. Austedo® label does not teach simethicone, hydroxypropyl cellulose and sodium lauryl adj sulfate. Sommer teaches the use of sodium lauryl sulfate as a surfactant. See Para [0310]. Sommer teaches In certain embodiments, sustained release polymers are selected from the group consisting of POLYOX.RTM. (poly(ethylene oxide), POLYOX.RTM. N60K grade, Kollidon.RTM. SR, HPMC, HPMC (high viscosity), HPC, HPC (high viscosity), and Carbopol.RTM. See Para [0313]. The use of simethicone is taught in table 30. It would have been obvious to a person skilled in the art to use sodium lauryl sulfate, hydroxypropyl cellulose and simethicone in the composition of Austedo® label, motivated by the teachings of Sommer, which teaches the use of such ingredients in deuterobenzene as old and well known. The use of pH dependent and pH independent coating is taught by Sommer. Sommer teaches that Formulations of the compounds disclosed herein suitable for oral administration may be presented as discrete units such as capsules, cachets or tablets each containing a predetermined amount of the active ingredient; as a powder or granules; as a solution or a suspension in an aqueous liquid or a non-aqueous liquid; or as an oil-in-water liquid emulsion or a water-in-oil liquid emulsion. The active ingredient may also be presented as a bolus, electuary or paste. See Para [0307]. The use of transitional phrase consisting essentially is the same as comprising, in the absence of showing that the addition of other ingredients, will materially affect the nature of the claimed invention. Additionally, the use of the phrase “beads” by Sommer reads on more than one bead.
Regarding claim 36, 39 and 41 Sommer teaches Compression of beads into tablets (either immediate release or SR matrix type tablets) is contemplated. d.sub.6-tetrabenazine-loaded beads made by using layering technique on sugar spheres are preferred, but one can use drug-loaded granules, floatable particles, extruded/spheronized pellets, Ceform microspheres, or other multiparticulates for drug core component as well. See Para [0404]. The use of excipients is taught in Para [0370].
Regarding claim 50, the amount released by the dosage form of claim 1, is the expected property of Sommer, which teaches the claimed ingredients in the dosage core and coating. The use of a device for measuring the released deutetrabenazine does not create a patentably distinct composition.
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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/ZOHREH A FAY/Primary Examiner, Art Unit 1617
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