Ex Parte Newman et al

Patent Trials and Appeals BoardJun 21, 2016

12521965 - (D) (P.T.A.B. Jun. 21, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 12/521,965 06/02/2010 86738 7590 06/23/2016 MCCARTER & ENGLISH, LLP BOSTON 265 Franklin Street Boston, MA 02110 FIRST NAMED INVENTOR Walter Newman 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. 120485-00202 4431 EXAMINER SOROUSH, LAYLA ART UNIT PAPER NUMBER 1627 NOTIFICATION DATE DELIVERY MODE 06/23/2016 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): docket@mccarter.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte WALTER NEWMAN, ANJALI KUMAR, and LYNNE LIBERTINE1 Appeal2014-007157 Application 12/521,965 Technology Center 1600 Before MELANIE L. McCOLLUM, JEFFREY N. FREDMAN, and RICHARD J. SMITH, Administrative Patent Judges. McCOLLUM, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. Â§ 134 involving claims to a treatment method. The Examiner has rejected the claims for anticipation, obviousness, and/or obviousness-type double patenting. We have jurisdiction under 35 U.S.C. Â§ 6(b). We affirm. 1 Appellants identify the real party in interest as Cornerstone Therapeutics Inc. (App. Br. 3). Appeal2014-007157 Application 12/521,965 STATEMENT OF THE CASE Claims 1-16, 19-22, and 39 are on appeal and are set forth in the Claims Appendix to Appellants' Appeal Brief (App. Br. 24--27).2 Claims 1 and 3 are representative and read as follows: 1. A method of treating a condition selected from the group consisting of asthma, rheumatoid arthritis, gout, psoriasis, allergy, rhinitis, adult respiratory distress syndrome, chronic obstructive pulmonary disease, acne, atopic dermatitis, conjunctivitis, ischemia/reperfusion injury, atherosclerosis, aortic aneurysm, nasal polyposis, inflammatory bowel disease, irritable bowel syndrome, cancer, tumor, respiratory syncytial virus, Sjogren-Larsson syndrome, sickle cell disease, sepsis, endotoxin shock, myocardial infarction, cystic fibrosis and stroke in a patient suffering therefrom comprising administering to said patient a composition comprising: i) zileuton substantially free of (S)-zileuton; and ii) a pharmaceutically acceptable excipient, wherein said zileuton is administered at a daily dose from about 450 milligrams to about 1200 milligrams per day. 3. The method of Claim 1, wherein said zileuton is administered at a daily dose from about 500 milligrams to about 1000 milligrams per day. Claims 1, 2, 4, 5, 8-11, 13, 15, 16, 19-21, and 39 stand rejected under 35 U.S.C. Â§ 102(b) as anticipated by Gray3 (Ans. 2). Claims 3, 6, 7, 12, and 14 stand rejected under 35 U.S.C. Â§ 103(a) as obvious over Gray (id. at 5). Claim 22 stands rejected under 35 U.S.C. Â§ 103(a) as obvious over Gray in view of Rabe4 (id. at 6). 2 Claims 40 and 41 are also pending but have been withdrawn from consideration (App. Br. 27). 3 Gray, WO 94/26268 Al, Nov. 24, 1994. 4 Klaus F. Rabe et al., Worldwide Severity and Control of Asthma in Children and Adults: The Global Asthma Insights and Reality Surveys, 114 J. ALLERGY CLIN. lMMUNOL. 40-47 (2004). 2 Appeal2014-007157 Application 12/521,965 Claims 1-16 and 19-21 stand rejected on the ground ofnonstatutory obviousness-type double patenting as being unpatentable over claim 15 of US Patent No. 8,003,684 B2 to Hanko (patented Aug. 23, 2011) (hereinafter "Hanko") (id. at 7). Claim 22 stands rejected on the ground of nonstatutory obviousness- type double patenting as being unpatentable over claim 15 of Hanko in view of Rabe (id. at 9). I The Examiner finds that Gray anticipates representative claim 1 and renders representative claim 3 obvious (Ans. 2-5). Appellants have discussed these rejections together (App. Br. 5-19). We are, therefore, discussing these rejections together, although, as noted below, some of the arguments raised by Appellants do not appear to be applicable to the anticipation rejection. Findings of Fact 1. Gray discloses that, "[ c ]hemically, the active compound is the (+)isomer ofN-(1-benzo[b ]thien-2-ylethyl)-N-hydroxyurea, hereinafter referred to as zileuton[, which] appears to have the R absolute stereochemistry" (Gray 2: 3-7). 2. Gray also discloses that the "separation of racemic zileuton into (+) zileuton and(-) zileuton has not been described; however, the enantioselective synthesis of ( + )-zileuton from L-( +)-lactic acid has been described by Hsiao and Kolasa [Tetra. Letters 33, 2629-2632 (1992)]" (id. at 3: 20-25). 3 Appeal2014-007157 Application 12/521,965 3. In addition, Gray discloses that it "has now been discovered that the optically pure ( +) isomer of zileuton is an effective agent for treating asthma, ulcerative colitis, rheumatoid arthritis, psoriasis, [and] allergic rhinitis" (id. at 6: 2-5). 4. In particular, Gray discloses "a method of treating asthma, which comprises administering to a human in need of such therapy, an amount of ( + )-zileuton, or a pharmaceutically acceptable salt thereof, substantially free of its(-) stereoisomer, said amount being sufficient to alleviate the symptoms of asthma" (id. at 6: 20-26). 5. Gray also discloses that the "term 'substantially free of its (-) stereoisomer' as used herein means that the compositions contain at least 90% by weight of ( + )-zileuton and 10% by weight or less of(-) zileuton" (id. at 10: 31 to 11: 1 ). 6. In addition, Gray discloses: The magnitude of a prophylactic or therapeutic dose of ( + )-zileuton in the acute or chronic management of disease will vary with the severity and nature of the condition to be treated and the route of administration. The dose and perhaps the dose frequency will also vary according to the age, body weight and response of the individual patient. In general, the total daily dose range for ( + )-zileuton for the conditions described herein is from about 200 mg to about 2 gin single or divided doses. Preferably a daily dose range should be about 400 mg to about 1600 mg in single or divided doses, while most preferably a daily dose range should be about 600 mg to about 1200 mg in single or divided doses. In managing the patient, the therapy should be initiated at a lower dose, perhaps at about 400 mg to about 600 mg, and increased up to about 1200 mg or higher depending on the patient's global response. It is further recommended that children and patients over 65 years and those with impaired renal 4 Appeal2014-007157 Application 12/521,965 or hepatic function initially receive low doses and that they be titrated based on individual response(s) and blood level(s). (Id. at 13: 4--26.) 7. Appellants' Specification discloses that "a tablet comprising 600 milligrams (mg) of zileuton [ racemate] (ZYFLOÂ® and ZyfloÂ® CR zileuton tablets) is currently marketed for the treatment of asthma" and that the "current recommended dosing regimen for zileuton [ racemate] is administration four times a day for a total daily dose of 2400 mg (as well as twice daily ZyfloÂ® CR at 1200 mg each dose)" (Spec. 1: 22 to 2: 18). 8. A 2009 ZYFLOÂ® Patient Information Leaflet provided by Appellants indicates that the "recommended dosage of ZYFLO for the symptomatic treatment of patients with asthma is one 600-mg tablet four times a day for a total dose of 2400 mg" (App. Br. Evidence Appendix G). Analysis In view of the foregoing findings of fact (FF), we conclude that the Examiner has set forth a prima facie case that representative claim 1 is anticipated and that representative claim 3 would have been obvious. In particular, Gray discloses "a daily dose range should be about 600 mg to about 1200 mg" (FF 6). This range is encompassed by and, therefore, clearly anticipates the range recited in claim 1. In addition, this range overlaps and, therefore, provides a prima facie case that the range of claim 3 would have been obvious. We recognize Appellants' argument that the Federal Circuit has held, in Sanofi-Synthelabo v. Apotex, Inc., 550 F.3d 1075 (2008), that enantiomers can be "patentable, even in view of prior knowledge of the racemate" (App. Br. 7). However, in that case, the Federal Circuit found that the "district 5 Appeal2014-007157 Application 12/521,965 court correctly held that neither the [applied] patent nor its Canadian counterpart contains an anticipating disclosure of the [claimed enantiomer]." 550 F.3d at 1084. Here, we do not find Appellants' argument persuasive that Gray does not anticipate the claimed enantiomer. In particular, Appellants argue that "Gray et al. does not indicate which enantiomer of zileuton would have surprising and unexpected properties, or even ![one enantiomer of zileuton is better than the other enantiomer" (App. Br. 8). However, Appellants have not adequately explained why this would be necessary to a prima facie case of anticipation or obviousness. In addition, Appellants argue that "the disclosure of Gray et al. is not properly enabled" (id. at 9 (emphasis omitted)). In support of this position, Appellants cite to Impax Labs., Inc. v. Aventis Pharms. Inc., 545 F.3d 1312 (Fed. Cir. 2008), and refer to WO 94/26269 Al published November 24, 1994 (hereinafter "the '269 publication") (App. Br. 9-12), which was filed on the same day as Gray by the same Applicant and inventor and is directed to (-)-zileuton (the '269 publication, cover page). We are not persuaded. "In order to anticipate a claimed invention, a prior art reference must enable one of ordinary skill in the art to make the invention without undue experimentation." Impax Labs., 545 F.3d at 1314. However, "a prior art printed publication cited by an examiner is presumptively enabling barring any showing to the contrary by a patent applicant." In re Antor Media Corp., 689 F.3d 1282, 1288 (Fed. Cir. 2012). In the present case, we do not find that Appellants have provided sufficient basis to conclude that Gray is not enabled. 6 Appeal2014-007157 Application 12/521,965 Gray discloses that it "has now been discovered that the optically pure ( +) isomer of zileuton is an effective agent for treating asthma, ulcerative colitis, rheumatoid arthritis, psoriasis, [and] allergic rhinitis" (FF 3 ). We understand Appellants' argument that Gray does not provide data supporting this statement. However, although "working examples are desirable in complex technologies ... examples are not required to satisfy [the enablement requirement]." In re Strahilevitz, 668 F.2d 1229, 1232 (CCPA 1982) (emphasis in original). In addition, we do not agree with Appellants that the filing of the '269 publication in and of itself is sufficient to demonstrate that undue experimentation would have been required to practice Gray's method. Appellants also argue that, "similar to Impax, the dosage guidelines of Gray et al. are broad and general without sufficient direction or guidance to prescribe the specifically claimed treatment regimen" (App. Br. 13). However, unlike Impax, where "the dosage guidelines [were] ... not specific to any of the hundreds of [prior art] compounds" (545 F.3d at 1315), Gray specifically discloses amounts for ( + )-zileuton (FF 6). Appellants have not adequately explained why it would have required undue experimentation to practice the invention using these dosage guidelines. In addition, Appellants argue that, "since the data are merely speculative, Gray ... fail[ s] to provide a reasonable expectation of success for the ordinary skilled artisan to arrive at the presently claimed invention" (App. Br. 14). However, we conclude that Appellants have not adequately shown that there was not a reasonable expectation for success. We note Appellants' evidence that the "recommended dosage of ZYFLO for the 7 Appeal2014-007157 Application 12/521,965 symptomatic treatment of patients with asthma is one 600-mg tablet four times a day for a total dose of 2400 mg" (FF 8). However, to the extent that this argument is even relevant to the anticipation rejection, we do not agree that this evidence is sufficient to demonstrate that there would not have been a reasonable expectation for success in the amounts recited in claim 1, nor do we agree that this evidence is sufficient to demonstrate that there would not have been a reasonable expectation for success in the amounts recited in claim 3. Appellants also argue that, "similar to Sanofi, it is clear that the claimed methods exploiting the unexpected properties of zileuton substantially free of (S)-zileuton are patentable" (App. Br. 9). In particular, based on the data provided in their Specification, Appellants argue that "[ n ]either Gray et al. nor the '269 publication provide any indication that either enantiomer has superior properties to the racemic mixture and, therefore, neither reference provides the person of ordinary skill in the art with a reason to try the instantly claimed dosage regimen, using lower doses of ( + )-zileuton" (id. at 15). We are not persuaded. With regard to the anticipation rejection of claim 1, Gray teaches the claimed lower dosages (FF 6). In addition, evidence of unexpected results is not relevant to an anticipation rejection. In re Malagari, 499 F.2d 1297, 1302 (CCPA 1974); In re Wiggins, 488 F.2d 538, 543 (CCPA 1973). With regard to the obviousness rejection of claim 3, Appellants have not provided sufficient evidence indicating that the results are "unexpected compared with the closest prior art." In re Baxter Travenol Labs., 952 F.2d 388, 392 (Fed. Cir. 1991). 8 Appeal2014-007157 Application 12/521,965 In addition, Appellants argue that "there was a long-felt need for a more effective dosing strategy" (App. Br. 15 (emphasis omitted)). We are not persuaded. "[O]bjective evidence of nonobviousness includes ... long felt but unsolved need." In re Rouffet, 149 F.3d 1350, 1355 (Fed. Cir. 1998). "[L]ong-felt need is analyzed as of the date of an articulated identified problem and evidence of efforts to solve that problem." Texas Instruments, Inc. v. Int'! Trade Comm 'n, 988 F.2d 1165, 1178 (Fed. Cir. 1993). See also Leo Pharm. Products, Ltd. v. Rea, 726 F.3d 1346, 1359 (Fed. Cir. 2013), in which the Federal Circuit found: Here, the researchers were aware of the benefits of using both vitamin D and corticosteroids in the treatment of psoriasis as early as 1986 .... Yet, it was not until the ... patent's filing in 2000 ... that the solution to the long felt but unsolved need for a combined treatment of vitamin D and corticosteroid was created. In the present case, Appellants have not provided sufficient evidence that there was a recognized need for a more effective dosing strategy or of efforts to meet this need. We recognize that "Gray et al. was published on November 24, 1994, and the instant application was filed on January 4, 2008" (App. Br. 17), more than 13 years later. In addition, the Federal Circuit has stated that the "length of the intervening time between the publication dates of the prior art and the claimed invention can ... qualify as an objective indicator of nonobviousness." Leo Pharm., 726 F.3d at 1359. However, Appellants have provided no basis for the proposition that such evidence is relevant to an anticipation rejection. In addition, given that Appellants have not provided evidence of a recognized need or of efforts to meet this need, 9 Appeal2014-007157 Application 12/521,965 Appellants have not adequately shown that this time lag reflects problems in the art. For example, we note that Gray discloses that "the enantioselective synthesis of ( + )-zileuton from L-( +)-lactic acid has been described" (FF 2). However, the cost of the enantioselective synthesis of ( + )-zileuton may outweigh the benefit of a smaller dose, particularly given that Appellants have not pointed to evidence that this smaller dose would reduce side effects. Cf Sanofi-Synthelabo, 550 F.3d at 1081 ("the enantiomers ... had the rare characteristic of 'absolute stereoselectivity': the dextrorotatory enantiomer provided all of the favorable antiplatelet activity but with no significant neurotoxicity, while the levorotatory enantiomer produced no antiplatelet activity but virtually all of the neurotoxicity"). With regard to the anticipation rejection of claim 39, Appellants argue that "Gray et al. does not appreciate that ( + )-zileuton has greater potency over the racemic mixture such that it can be used at significantly lower doses than racemic zileuton" (App. Br. 18). However, as discussed above, Gray discloses the doses recited in claim 39 (via its dependency from claim 1). With regard to the anticipation rejection of claims 4, 5, and 8, Appellants additionally argue that "there is no specific direction or guidance in Gray et al. to prescribe the specifically claimed daily dose required by the claims, i.e., ... from about 600 mg to about 900 mg per day (claim 4 ), about 600 mg per day (claim 5), ... or about 1200 mg per day (claim 8)" (id. at 13-14). We are not persuaded. Gray discloses that "most preferably a daily dose range should be about 600 mg to about 1200 mg" (FF 6). We are aware that, inAtofina v. 10 Appeal2014-007157 Application 12/521,965 Great Lakes Chem. Corp., the Federal Circuit indicated that disclosure of a range does not necessarily disclose any particular species within the range, even the endpoints. 441F.3d991, 1000 (Fed. Cir. 2006) ("the disclosure of a range of 150 to 350 Â°C does not constitute a specific disclosure of the endpoints of that range, i.e., 150 Â°C and 350 Â°C" and "the disclosure of a 0.001 to 1.0 percent range is not a disclosure of the end points of that range"). However, the Federal Circuit subsequently held that, "when the prior art discloses a range, rather than a point, the court must evaluate whether the patentee has established that the claimed range is critical to the operability of the claimed invention." Ineos USA LLC v. Berry Plastics Corp., 783 F.3d 865, 871 (Fed. Cir. 2015). Here, we conclude that Appellants have not adequately explained why the claimed range and points recited in claims 4, 5, and 8 are critical. Therefore, in view of recent case law, we conclude that Appellants have not adequately explained why claims 4, 5, and 8 are not anticipated by Gray. With regard to the obviousness rejection of claims 6 and 7, Appellants additionally argue that "there is no specific direction or guidance in Gray et al. to prescribe the specifically claimed daily dose required by the claims, i.e., ... about 900 mg per day (claim 6), [or] about 1000 mg per day (claim 7)" (App. Br. 13-14). However, Appellants do not adequately explain why these amounts would not have been obvious over the teachings in Gray (FF 6). Conclusion The evidence supports the Examiner's finding that Gray discloses the methods of claims 1, 4, 5, 8, and 39. We, therefore, affirm the anticipation 11 Appeal2014-007157 Application 12/521,965 rejection of these claims. Claims 2, 9-11, 13, 15, 16, and 19-21 have not been argued separately and, therefore, fall with claim 1. 37 C.F.R. Â§ 41.37(c)(l)(iv). The evidence also supports the Examiner's conclusion that Gray suggests the methods of claims 3, 6, and 7. We, therefore, affirm the obviousness rejection of claims 3, 6, and 7. Claims 12 and 14 have not been argued separately and, therefore, fall with claim 3. II In rejecting claim 22, which ultimately depends from claim 1, the Examiner relies on Gray "as discussed above" (Ans. 6). However, the Examiner finds that Gray "does not specify the condition is selected from the group consisting of moderate persistent asthma and severe persistent asthma" (id.). The Examiner relies on Rabe for teaching "moderate persistent asthma" (id.). The Examiner concludes that it would have been obvious "to treat moderate persistent asthma ... because Gray generally teaches the treatment of asthma" (id.). Analysis Appellants argue that Gray does not teach or suggest the invention for the reasons discussed above and that Rabe does not overcome the deficiencies of Gray (App. Br. 20-22). We are not persuaded by these arguments for the reasons discussed above. 12 Appeal2014-007157 Application 12/521,965 Conclusion The evidence supports the Examiner's conclusion that Gray and Rabe suggest the method of claim 22. We, therefore, affirm the obviousness rejection of claim 22. III On the ground of nonstatutory obviousness-type double patenting, the Examiner rejects claims 1-16 and 19-21 over claim 15 of Hanko and rejects claim 22 over claim 15 of Hanko in view of Rabe (Ans. 7 & 9). Appellants do not traverse these rejections (App. Br. 22-23). We, therefore, summarily affirm them. 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. Â§ 1.136(a). AFFIRMED 13