Ex Parte Trivedi et al

Patent Trial and Appeal BoardOct 19, 2012

11176565 (P.T.A.B. Oct. 19, 2012)

UNITED STATES PATENT AND TRADEMARK OFFICE UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O. Box 1450 Alexandria, Virginia 22313-1450 www.uspto.gov APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 11/176,565 07/07/2005 Jay S. Trivedi 6102-000002/US 3940 28997 7590 10/22/2012 HARNESS, DICKEY, & PIERCE, P.L.C 7700 Bonhomme, Suite 400 ST. LOUIS, MO 63105 EXAMINER FINN, MEGHAN R ART UNIT PAPER NUMBER 1629 MAIL DATE DELIVERY MODE 10/22/2012 PAPER Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE PATENT TRIAL AND APPEAL BOARD __________ Ex parte JAY S. TRIVEDI and GAETAN MARCOUX __________ Appeal 2012-000210 Application 11/176,565 Technology Center 1600 __________ Before DONALD E. ADAMS, ERIC GRIMES, and STEPHEN WALSH, Administrative Patent Judges. GRIMES, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to a pharmaceutical composition, which the Examiner has rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. STATEMENT OF THE CASE “[T]he ACE inhibitor moexipril hydrochloride . . . is available by prescription in a coated tablet formulation containing 7.5 mg or 15 mg moexipril hydrochloride as the active agent” (Spec. 1, ¶ 2). The Appeal 2012-000210 Application 11/176,565 2 Specification discloses that “when using a tableting mix adapted for preparation of a standard tablet formulation of an ACE inhibitor to prepare a plurality of smaller micro-tablets, the resulting micro-tablets failed to release from tablet compressing equipment as cleanly or efficiently as standard tablets prepared from the same mix” (id. at 2, ¶ 9). The Specification discloses that “by increasing the amount of one or more lubricants in the mix, clean and efficient release of the micro-tablets from the compressing equipment can be restored” (id. at 4, ¶ 14). The lubricant can be magnesium stearate (id. at 8, ¶ 32). Claims 36-40 are on appeal. The claims have not been argued separately and therefore stand or fall together. 37 C.F.R. § 41.37(c)(1)(vii). Claim 36 is representative and reads as follows: 36. A pharmaceutical composition comprising a pharmaceutically acceptable capsule shell having enclosed therewithin a plurality of coated micro-tablets that collectively comprise (a) about 1 to about 30 mg moexipril hydrochloride, and (b) excipient ingredients that comprise magnesium stearate in an amount of about 0.8% to about 1.2%, said micro-tablets having an average uncoated weight of about 5 to about 20 mg. The Examiner has rejected claims 36-39 under 35 U.S.C. § 103(a) as obvious based on Stofik,1 Pich,2 Sasmal,3 and Bartholomaeus4 (Answer 5). The Examiner has also rejected claim 40 as obvious based on Stofik, Pich, 1 Stofik et al., Patent Application Publication US 2003/0215526 A1, Nov. 20, 2003. 2 Pich et al., US 4,828,843, May 9, 1989. 3 Sasmal et al., Patent Application Publication US 2005/0026992 A1, Feb. 3, 2005. 4 Bartholomaeus et al., Patent Application Publication US 2002/0156133 A1, Oct. 24, 2002. Appeal 2012-000210 Application 11/176,565 3 Sasmal, Bartholomaeus, and Laragh5 (Answer 9). The same issue is dispositive with respect to both rejections. The Examiner finds that Stofik discloses tablets (but not microtablets) comprising 15 mg moexipril hydrochloride and 0.5% magnesium stearate (Answer 6). The Examiner finds that Pich discloses that microtablets in capsules are useful with a wide range of active agents and are preferred to tablets (id.), and that Sasmal discloses ACE inhibitors formulated as microtablets in capsules (id.). Finally, the Examiner finds that Bartholomaeus discloses tramadol (an analgesic) in microtablets weighing 16.6 mg and comprising 0.2 mg, or 1.2% by weight, magnesium stearate (id. at 7). The Examiner concludes that “while the active agent in Bartholomaeus et al. is different than the ACE inhibitors of Stofik et al. and Sasmal et al., it would have been obvious to one of ordinary skill in the art that the microtablet formulation of Bartholomaeus et al. can be used for other active agents. Pich et al. clearly demonstrated that microtablets can be used for a wide variety of active agents.” (Id. at 7-8.) The Examiner also concludes that the dosage of moexipril hydrochloride recited in claim 36 would have been obvious because Stofik teaches a dosage of 7.5 to 30 mg (id. at 8). We agree with the Examiner that the cited references would have made obvious the composition of claim 36 to those of ordinary skill in the art. Stofik discloses that moexipril hydrochloride is an ACE inhibitor used at a dosage of 7.5 to 30 mg per day (Stofik 1, ¶ 6). Stofik also discloses that 5 Laragh, Patent Application Publication US 2005/0090752 A1, Apr. 28, 2005. Appeal 2012-000210 Application 11/176,565 4 magnesium stearate is a lubricant (id. at 2, ¶ 32) and exemplifies tablets comprising moexipril hydrochloride and magnesium stearate (id. at 3, ¶ 63). Pich discloses that formulating drugs as “pellets which can be introduced into, for example, capsules is generally preferred to the administration of compact tablets because very high local concentrations of active compound in the gastrointestinal tract are avoided” (Pich, col. 1, ll. 12-17). Pich discloses that such pellets have disadvantages, including nonuniform size (id. at col. 1, ll. 42-58), that are not shared by microtablets (id. at col. 1, ll. 8-10; col. 2, ll. 8-11) weighing 1-20 mg (id. at col. 2, ll. 66- 67). Pich disclose that the microtablets are useful for pharmaceuticals (id. at col. 4, ll. 15-17). Sasmal discloses capsules comprising a combination of active agents, including a microtablet containing the ACE inhibitor enalapril maleate, as well as zinc stearate (Sasmal 4, ¶ 51; 3, ¶ 29). The Examiner finds that zinc stearate, like magnesium stearate, is a lubricant, and calculates that Sasmal’s microtablets contain 0.89% zinc stearate (Answer 7). Appellants do not dispute these finding (see Appeal Br. 12), and Stofik supports the Examiner’s finding that zinc stearate is a known lubricant (see Stofik 2, ¶ 32). Bartholomaeus discloses “an oral administration unit that contains the two active substances Tramadol and Diclofenac . . . , with the two active substances, respectively, contained in separately formulated subunits in the same administration unit” (Bartholomaeus 1, ¶ 9). “Preferably, the subunits are present in multiparticulate form, such as for example as microtablets” (id. at 1, ¶ 13). Bartholomaeus exemplifies capsules comprising coated Appeal 2012-000210 Application 11/176,565 5 microtablets weighing 16.6 mg that comprise tramadol hydrochloride and 0.2 mg magnesium stearate (id. at 4-5, ¶¶ 56-59). The Examiner finds that the exemplified microtablets contained 1.2% magnesium stearate (Answer 7). Appellants do not dispute the Examiner’s calculation. We agree with the Examiner that these disclosures would have made obvious the composition of claim 36. Specifically, it would have been obvious to substitute moexipril hydrochloride for the tramadol hydrochloride in Bartholomaeus’ microtablets, because Sasmal discloses microtablets containing any of a variety of ACE inhibitors and Pich discloses that capsules containing microtablets have advantages over both standard-sized tablets and capsules containing pellets of active agent. In addition, Stofik discloses that the standard dosage of moexipril hydrochloride is 7.5 to 30 mg per day, and therefore would have made it obvious to formulate capsules containing a total of 1-30 mg of moexipril hydrochloride, as recited in claim 36. Appellants argue that the cited references do not provide a teaching or suggestion to arrive at the claimed composition (Appeal Br. 10). Appellants point out that none of the cited references individually teaches all of the limitations of claim 36 (id. at 10-13). This argument is not persuasive. Appellants have not shown any error in the Examiner’s basis for combining the elements of claim 36, all of which are disclosed in the cited references. “The test for obviousness is what the combined teachings of the references would have suggested to one of ordinary skill in the art.” In re Young, 927 F.2d 588, 591 (Fed. Cir. 1991). Appeal 2012-000210 Application 11/176,565 6 Appellants also argue that “if too much lubricant is added to a tableting mix, the resulting tablets can be slow to disintegrate and/or dissolve, and/or have other deficiencies” (Appeal Br. 10). Appellants argue that “nowhere does the cited art provide any predictability that the specific formulation of Claim 36 would be able to provide (1) clean, efficient release of micro-tablets (2) but not retard disintegration and/or dissolution rate of the micro-tablets” (id. at 13). This argument is also unpersuasive. Bartholomaeus provides a working example of microtablets containing an active agent (tramadol hydrochloride) and 1.2% magnesium stearate. While Appellants argue that a skilled worker would not consider Bartholomaeus relevant to the present invention because of the difference in active agents (Appeal Br. 12-13), they have provided no evidence or sound technical reasoning to show that Bartholomaeus’ working example would not have provided a skilled worker with a reasonable expectation of success in making microtablets comprising moexipril hydrochloride and 1.2% magnesium stearate. In particular, Appellants have provided no persuasive evidence to show that a skilled worker would have expected 1.2% magnesium stearate to retard the disintegration or dissolution rate of microtablets containing moexipril hydrochloride. With regard to the rejection of claim 40, Appellants do not admit that Laragh is prior art (Appeal Br. 13) but do not provide evidence or reasoning to show that it is not. Appellants otherwise rely on the same arguments presented with respect to claim 36, which are unpersuasive for the reasons discussed above. Appeal 2012-000210 Application 11/176,565 7 SUMMARY We affirm the rejection of claims 36-39 under 35 U.S.C. § 103(a) based on Stofik, Pich, Sasmal, and Bartholomaeus; and the rejection of claim 40 under 35 U.S.C. § 103(a) based on Stofik, Pich, Sasmal, Bartholomaeus, and Laragh. TIME PERIOD FOR RESPONSE No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a). AFFIRMED lp