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 .
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.
Claims 5 and 22-34 are rejected under 35 U.S.C. 103 as being unpatentable over Bloemers et al. KR 20140048882 A (‘882), in view of Bloemers et al. CA 2835845 A1 (‘845).
Bloemers ‘882 teaches a dual drug delivery device comprising a time controlled, immediate release drug delivery system for oral administration of a first active ingredient, and further comprising a second coating comprising a second active ingredient. See Abstract. Preferred time-controlled, immediate release drug delivery systems according to the invention comprise an immediate release formulation comprising a compressed core comprising one or more active ingredients enclosed by a coating, wherein release of the active ingredient from the core is preliminary. See Description of Embodiments. The first coating is preferably sprayed with a nozzle, for example on the core. To this end, the hydrophobic polymer and the water-soluble and / or water-insoluble hydrophilic material are suspended or dissolved in, for example, water or an organic solvent or a mixture thereof and sprayed onto the core until a predetermined average thickness of the first coating is obtained. Preferred organic solvents are alcohols, for example ethanol. The amount of the first coating is preferably about 0.5 to 30% (w / w), more preferably about 1 to 20% (w / w) of the total weight of the time controlled, immediate release drug delivery system. The hydrophobic coating polymer according to the present invention is preferably selected from water-insoluble coating materials such as cellulose derivatives and polymethacrylates produced by copolymerization of methacrylate monomers with hydrophobic groups, for example. Preferred polymethacrylate hydrophobic polymers are EUDRAGIT RL, EUDRAGIT RS, EUDRAGIT NE, and EUDRAGIT S. Preferred cellulose derivatives are selected from ethylcellulose and derivatives thereof. The most preferred hydrophobic polymer of the first coating of the drug delivery system according to the present invention comprises ethylcellulose. Ethylcellulose forms a mechanically weak hydrophobic film that breaks easily. The core comprises a drug in combination with a water-insoluble, gel-forming disintegrant which disintegrates upon contact with an aqueous medium. Formation of pores in the hydrophobic film, and the influx of water into the pores, causes rupture of the ethylcellulose coating. When the coating ruptures, the core disintegrates in minutes after the release of the drug. The preferred ethyl cellulose is Ethocel S. See Description of Embodiments. As is known to those skilled in the art, factors (process conditions) that may affect the uniformity of the inter-internal tablet of the first coating are, for example, fan speed, spray rate, spray pattern, nozzle type, viscosity, drying temperature, air Flow rate and coating time. If necessary, a heat-controlled curing step, for example a heat treatment at 60-80°C. for 1-3 hours, is applied to the first coating after coating, preferably after spraying of the first coating.
Most preferred examples are preferred combination therapies for the treatment of men or women, such as sexual dysfunction, desire disability, or erectile dysfunction. Preferably the combination treatment is treatment of disorders of libido. Preferably by using a combination of testosterone or a functional analog thereof and the first active ingredient, the testosterone or functional analog thereof has a peak plasma level of testosterone of about 2-6 hours, more preferably before the peak plasma level of the first active ingredient. Preferably 3-4 hours. The first active ingredient is preferably provided in a time controlled, immediate release drug delivery system according to the present invention. Sildenafil and buspirone are the preferred ingredients for the first active ingredient for the treatment of me or women sexual dysfunction.
The present invention also provides a dual drug delivery device comprising a time controlled immediate release drug delivery system according to the present invention wherein the first coating of the time controlled immediate release drug delivery system comprises a second active ingredient. Is surrounded by a second coating. The second active ingredient may or may not be similar to the first active ingredient. In one embodiment, the second active ingredient, for example a steroid such as testosterone, is provided sublingually by the dual drug delivery device according to the invention in the absence of the first active ingredient. In this embodiment, the core of the dual drug delivery device does not contain the active ingredient. The second coating comprising a steroid such as testosterone or a functional analog thereof preferably comprises a carrier selected from hydroxypropyl-β-cyclodextrin, poly-β-cyclodextrin, γ-cyclodextrin and polyvinylpyrrolidone. Preferred polyvinylpyrrolidone is a low molecular weight polyvinylpyrrolidone having a molecular weight of up to 80000. Suitable polyvinylpyrrolidone is preferably selected from K10, K15, K25, K30, and K50. Most preferred carrier is hydroxypropyl-β-cyclodextrin. The presence of testosterone, such as cyclodextrin, and poorly soluble steroids, such as carriers, provide fast and efficient delivery of testosterone to the mucosa rather than being rapidly absorbed into the circulation. The drug delivery device further comprising carriers, and excipients such as flavorant, sweetener and the like. See Description and Examples.
It is noted that the Bloemers ‘882 does not expressly teach the claimed relative deviation. However, such limitation is known in pharmaceutical tableting art. See for example the teaching in Bloemers ‘845, which teaches a dual drug delivery device, comprising the time controlled, immediate release drug delivery system according to the invention, further comprising a second coating comprising a second active ingredient. See Abstract. Fig. 5 shows that for determining the end point for the coating process with the testosterone coat the weight of the second coating solution sprayed is an excellent indicator for the total amount of testosterone applied to the tablets. The testosterone content uniformity of three batches as described in Fig 5 was well within Pharmacopeial requirements with relative standard deviations of 4.2, 2.8 and 3.1% for batches M0R202/66, /71 and /75 respectively.
Thus, it would have been prima facie obvious to one of ordinary skill in the art to optimize the teaching in Bloemers ‘882 reference in view of the teaching from the Bloemers ‘845 reference with the expectation to obtain a tablet process having a relative standard deviation within 4%. See 2.8% and 3.1% relative standard deviation taught in the Bloemers ‘845 reference. The term “within” 4% allows value around 4%, which includes 4.2 and 3.1 taught in the prior art. As such, one of ordinary skill in the art would have been motivated to, by routine experimentation select a tablet processing parameter to provide a tableting process having a relative standard deviation that falls within the claimed range with the expectation to provide tablets exhibit improved uniformity.
Response to Arguments
Applicant’s arguments filed 08/14/2026 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
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.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUSAN T TRAN whose telephone number is (571)272-0606. The examiner can normally be reached Monday-Friday, 8:30 am-5:30 pm.
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/SUSAN T TRAN/Primary Examiner, Art Unit 1615
