Ex Parte Castan et alDownload PDFPatent Trial and Appeal BoardMay 29, 201810997836 (P.T.A.B. May. 29, 2018) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 10/997,836 11/24/2004 23347 7590 05/31/2018 GLAXOSMITHKLINE Global Patents UP4110 1250 South Collegeville Road Collegeville, PA 19426 FIRST NAMED INVENTOR Catherine Castan 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 ATTORNEY DOCKET NO. CONFIRMATION NO. PU60579A 9814 EXAMINER CHANNA V AJJALA, LAKSHMI SARADA ART UNIT PAPER NUMBER 1611 NOTIFICATION DATE DELIVERY MODE 05/31/2018 ELECTRONIC 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. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address(es): laura.m.mccullen@gsk.com US_cipkop@gsk.com eofficeaction@appcoll.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte CATHERINE CAST AN, PATRICK J. CROWLEY, FLORENCE GUIMBERTEAU, REMI MEYRUEIX, CHOOH K. OH, and GERARD SOULA Appeal2017-006250 Application 10/997, 83 6 1 Technology Center 1600 Before FRANCISCO C. PRATS, RICHARD J. SMITH, and KRISTI L. R. SA WERT, Administrative Patent Judges. SA WERT, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134(a) from the rejection of claims directed to a controlled release dosage form of carvedilol. The Examiner rejected the claims for obviousness. We have jurisdiction under 35 U.S.C. § 6(b ). We affirm. 1 Appellants identify SmithKline Beecham (Cork) Limited, Currabinny, Carrigaline, County Cork, Ireland, as the real party in interest. Br. 3. Appeal2017-006250 Application 10/997 ,83 6 STATEMENT OF THE CASE The following rejections are before us for review: ( 1) Claims 173, 17 4, 180, 181, 183, 185, and 186 as unpatentable under 35 U.S.C. § I03(a) for obviousness over Jain2 and Franchini3 in view of Clancy4 and/or Rudnic. 5 Final Act. 2. (2) Claims 175-78 and 182 as unpatentable under 35 U.S.C. § I03(a) for obviousness over Jain and Franchini in view of Clancy and/or Rudnic, and further in view of Chen 6 or Burke. 7 Id. at 11. Claim 173 is representative of the subject matter on appeal. See 37 C.F.R. § 4I.37(c)(l)(iv). Claim 173 recites: 173. A controlled release dosage form, which comprises the three different pellet, granule, or microparticle populations enumerated below: [ 1] a rapidly or early releasing pellet, granule, or microparticle population comprised of rapidly releasing pellets, granules, or microparticles; wherein the rapidly or early releasing pellets, granules, or microparticles comprise a pharmaceutically acceptable core and a coating comprising carvedilol free base or a carvedilol salt; 2 Girish Kumar Jain et al., WO 2004/056336 A2 (July 8, 2004) ("Jain"). 3 Mariam Franchini & Gopadi M. Venkatesh, US 6,515,010 Bl (Feb. 4, 2003) ("Franchini"). 4 Maurice Joseph Anthony Clancy & Kenneth Ian Cumming, US 6,110,494 (Aug. 29, 2000) ("Clancy"). 5 Edward M. Rudnic & George W. Belendiuk, US 5,326,570 (July 5, 1994) ("Rudnic"). 6 Pingyun Y. Chen et al., WO 2004/002472 Al (Jan. 8, 2004) ("Chen"). 7 Matthew D. Burke et al., WO 2005/051325 A2 (June 9, 2005) ("Burke"). 2 Appeal2017-006250 Application 10/997 ,83 6 [2] a first controlled release pellet, granule, or microparticle population comprised of first controlled release pellets, granules, or microparticles; wherein the first controlled release pellets, granules, or microparticles comprise a pharmaceutically acceptable core, a coating comprising a carvedilol salt, and a first release controlling coating layer which triggers a release of the carvedilol salt from the first controlled release pellets, granules, or microparticles at a pH of about 5.5 in the gastrointestinal tract of a human; [3] a second controlled release pellet, granule, or microparticle population comprised of second controlled release pellets, granules, or microparticles; wherein the second controlled release pellets, granules, or microparticles comprise a pharmaceutically acceptable core, a coating comprising a carvedilol salt, and a second release controlling coating layer which triggers a release of the carvedilol salt from the second controlled release pellets, granules, or microparticles at a pH of about pH > 6.4 in the gastrointestinal tract of a human. DISCUSSION Background The claimed invention is directed to controlled-release dosage forms of the known drug carvedilol. Spec. 1. Carvedilol, also known in the art as 1-( carbazol-4-yloxy-3-[[2-( o-methoxyphenoxy)ethyl]amino ]-2-propanol, has the following chemical structure: 3 Appeal2017-006250 Application 10/997 ,83 6 Id. Carvedilol is used to treat hypertension, congestive heart failure, and angina. Id. at 2. The Specification states that "[ c ]arvedilol exhibits predictable solubility behavior in neutral or alkaline media." Id. Specifically, at a pH above 9, carvedilol has "relatively low(< 1 µm/mL)" solubility. Id. "The solubility of carvedilol increases with decreasing pH and reaches a plateau near pH= 5." Id. As pH further decreases, the solubility of carvedilol also decreases, as a result of protonation or the formation of its corresponding salt in situ. Id. The Specification also notes that "[ t ]he currently commercially available carvedilol product is a conventional[] tablet prescribed as a twice- a-day (BID) medication in the United States." Id. at 2. This "commercially available carvedilol formulation is in an immediate release or rapidly releasing carvedilol in its free base form." Id. But, "a desire to maintain a constant concentration of a pharmaceutical composition within the blood stream," results in a requirement for "a patient to take tablets frequently." Id. at 3. Thus, the present invention seeks to provide carvedilol in a controlled-release form that provides "greater aqueous solubility, chemical stability, prolonged residence time, [and] absorption in the gastrointestinal tract." Id. at 6. Statement of the Law As stated in In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992): [T]he examiner bears the initial burden ... of presenting a prima facie case of unpatentability. . . . After evidence or argument is submitted by the applicant in response, patentability is determined on the totality of the record, by a preponderance of evidence with due consideration to persuasiveness of argument. 4 Appeal2017-006250 Application 10/997 ,83 6 Obviousness of claims 173, 174, 180, 181, 183, 185, and 186 over Jain and Franchini in view of Clancy and/or Rudnic Appellants do not persuade us that the Examiner's conclusion of obviousness is not supported by a preponderance of the evidence. To the contrary, we adopt as our own the Examiner's findings as to the scope and content of the prior art, the Examiner's reasoning as to how and why an ordinary artisan would have combined the cited teachings of the references, and the Examiner's conclusion that representative claim 173 would have been prima facie obvious over the cited combination of references. See Ans. 2-10, 13-18. We provide the discussion below for emphasis. We agree with the Examiner that both Jain and Franchini disclose controlled-release formulations of carvedilol. Specifically, Jain discloses a controlled-release formulation of carvedilol comprising multiple units. Ans. 2-3; Jain 2: 16-17. Franchini discloses a controlled-release formulation of carvedilol comprising a priming dose of carvedilol and a sustained dose of carvedilol. Ans. 5; Franchini 2:63-3:1. We also agree with the Examiner that both Clancy and Rudnic teach controlled-release formulations of other drugs comprising three different pellet, granule, or microparticle populations. Ans. 7-9. Specifically, Clancy discloses controlled-release dosage forms of cisapride in a once-a-day formulation comprising: (1) mini- tablets that immediately release cisapride, (2) mini-tablets that release cisapride at pH 5.5 to 6.5, and (3) mini-tablets that release cisapride at pH 6.5 to 7.5. Ans. 7-8; Clancy 2:30-33. Similarly, Rudnic discloses controlled-release dosage forms of carbamazebine in a 12-hour formulation comprising: ( 1) pellet A for immediate release, (2) pellet B for sustained 5 Appeal2017-006250 Application 10/997 ,83 6 release in the GI tract, and (3) pellet C for sustained release in the lower GI tract. Ans. 8-9; Rudnic 2:5-11, 62---65, 3:51--4:50. We further find no reversible error in the Examiner's explanation that an ordinarily skilled artisan, looking to formulate a once-a-day controlled- release formulation of carvedilol would have looked to controlled-release formulations for drugs that exhibit similar solubility patterns in the GI tract. Ans. 9-10. For example, the solubility of cisapride, like carvedilol, decreases at higher pH levels, which reduces the dissolution of the drug in the distal regions of the GI tract. Clancy 2:1-7. Clancy solved the problem of providing a continuous release of cisapride throughout the GI tract by creating a dosage form with mini-tablets that release cisapride at different pH levels. Clancy 2:30-33. Jain and Franchini show that carvedilol can be successfully formulated in single dosage form having both immediate and delayed-release components. Jain 2: 16-17; Franchini 2:63-3: 1. Thus, we agree with the Examiner that "a skilled artisan would have expected to achieve a continuous release of [ carvedilol] from a single dosage form for a prolonged period of time and avoid administration of multiple doses." Ans. 10. We are not persuaded by Appellants' arguments to the contrary. Appellants first argue that "[ n Jone of the cited references alone, and no combination of the cited references, suggest even [in] general a 3-component composition of carvedilol." Br. 6. Appellants point out that Jain teaches a "multiple units" that are the same, and Franchini teaches a two-component formulation. Id. at 7. And, finally, Appellants state that neither Clancy nor Rudnic "are directed to any type of carvedilol formulation at all." Id. 6 Appeal2017-006250 Application 10/997 ,83 6 Although Appellants correctly note that no reference explicitly teaches a three-component composition of carvedilol, the obviousness "analysis need not seek out precise teachings directed to the specific subject matter of the challenged claim," because "a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ." KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398,418 (2007). Here, we are satisfied that the Examiner set forth a prima facie case of obviousness based on the combination of the references' teachings. Appellants next argue that Clancy and Rudnic are irrelevant because their respective disclosures are "only directed to the needs of a single drug"----cisapride or carbamazepine. Br. at 8. Appellants assert that "cisapride is a different drug from carvedilol with different solubility characteristics, different uses, different modes of action, different risks, and different benefits," and repeats this assertion with respect to carbamazepine. Id. at 7-8. We are not persuaded, however, that Appellants' assertions demonstrate reversible error in the Examiner's analysis. In this regard, Appellants present no specific evidence or persuasive scientific reasoning that different uses, different modes of action, different risks, and different benefits would dissuade the ordinarily skilled artisan would looking to the three-component formulations of these drugs as a model for a controlled-release formulation of carvedilol. Johnston v. IVAC Corp., 885 F.2d 1574, 1581 (Fed. Cir. 1989) (attorney argument no substitute for evidence). Appellants also present no factual evidence that cisapride and carbamazepine have such different solubility characteristics that an ordinarily skilled artisan would have expected those drugs to behave differently from carvedilol in a controlled-release formulation. In fact, 7 Appeal2017-006250 Application 10/997 ,83 6 Clancy teaches that cisapride is poorly soluble, and that the solubility of cisapride is pH dependent. Clancy 1:16-20, 2:1---6. Thus, like carvedilol, cisapride becomes less soluble as it travels down the GI tract. Id. 2: 1---6; see also Spec. 2. Finally, Appellants argue that the "presently claimed formulation does not produce uniform controlled concentrations of carvedilol" whereas Clancy and Rudnic "have as their goal a uniform release of drug." Br. 8-9. As pointed out by the Examiner, however, representative claim 173 is silent as to whether drug release is uniform or non-uniform. See Ans. 16-17; Br. 11 ( claim 173). 8 Obviousness of claims 175-178 and 182 over Jain and Franchini in view of Clancy and/or Rudnic, and further in view of Burke and/or Chen As to dependent claims 17 5-17 8 and 182, Appellants states that "Applicants are happy to ignore Burke and Chen because Applicants are not arguing that the claimed invention is non-obvious because of any particular salts but rather because of the 3 specifically claimed populations of carvedilol." Br. 6. Thus, for the reasons discussed above and those provided by the Examiner in the Answer, we find that the Examiner has established a prima facie showing of obviousness with respect to claims 175-178 and 182, which Appellants have failed to rebut. Accordingly, we affirm the rejection of these claims. 8 The Examiner acknowledges that claim 182 recites non-uniform release of carvedilol. Ans. 16. The Examiner relied on Burke, however, to teach carvedilol salts and compositions that provide biphasic release of carvedilol. Id. Appellants do not challenge that finding. 8 Appeal2017-006250 Application 10/997 ,83 6 DECISION We affirm the Examiner's rejections under 35 U.S.C. § 103. No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a)(l)(iv). See 37 C.F.R. § 4I.50(f). AFFIRMED 9 Copy with citationCopy as parenthetical citation