Ex Parte Prater et alDownload PDFPatent Trial and Appeal BoardAug 2, 201811603766 (P.T.A.B. Aug. 2, 2018) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE FIRST NAMED INVENTOR 11/603,766 11/22/2006 Derek Allan Prater 26111 7590 08/06/2018 STERNE, KESSLER, GOLDSTEIN & FOX P.L.L.C. 1100 NEW YORK A VENUE, N.W. WASHINGTON, DC 20005 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. 1861.3300002/JMC 3704 EXAMINER VU, JAKE MINH ART UNIT PAPER NUMBER 1618 NOTIFICATION DATE DELIVERY MODE 08/06/2018 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): e-office@stemekessler.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte DEREK ALLAN PRATER, MOHAMMED HASSAN, CHRISTOPHER ROBERT BLAND 1 Appeal2017-008320 Application 11/603,7662 Technology Center 1600 Before TONI R. SCHEINER, RICHARD M. LEBOVITZ, and, TIMOTHY G. MAJORS, Administrative Patent Judges. LEBOVITZ, Administrative Patent Judge. DECISION ON APPEAL This appeal involves claims directed to a delayed release pharmaceutical composition that provides a lag in the delivery of a drug following administration. The Examiner finally rejected the claims as obvious under 35 U.S.C. § 103(a). Appellants appeal the rejections pursuant to 35 U.S.C. § 134. We have jurisdiction for the appeal under 35 U.S.C. § 6(b ). The rejections are reversed. 1 The Appeal Brief ("Appeal Br.") at page 3 lists Euro-Celtique S.A. as the real-party-in-interest. 2 The application is referenced as "the '766 Specification." Appeal2017-008320 Application 11/603,766 STATEMENT OF THE CASE Claims 24--33, 35, 37, 39, 42, and 45-53 stand finally rejected by the Examiner as unpatentable. The rejections are as follows: 1. Claims 24--33, 35, 37, 39-42, and 45-51 under 35 U.S.C. § I03(a) as obvious in view of Buxton et al. (EP O 527 638 Al, published Feb. 17, 1993) ("Buxton"), Katzhendler et al. (U.S. Pat. No. 5,980,942, issued Nov. 9, 1999) ("Katzhendler"), and Grimmett et al. (U.S. Pat. No. 6,358,528 Bl, issued Mar. 19, 2002) ("Grimmett"). Ans. 2. 2. Claims 24--33, 35, 37, 39-42, and 45-53 under 35 U.S.C. § I03(a) as obvious in view of Buxton, Katzhendler, Grimmett, and Curatolo et al. (U.S. Pat. No. 6,068,859, issued May 30, 2000) ("Curatolo"). Ans. 6. 3. Claims 24--33, 35, 37, 39, 42, and 45-53 are rejected under 35 U.S.C. § I03(a) as obvious in view of Curatolo as "evidenced" by Banjanac et al. (Pharmacol. Res., 66(4):357-62, 2012 (Abstract) ("Banjanac"). Ans. 7. There are two independent claims on appeal, composition claim 24 and method claim 46 which comprises administering the same composition of claim 24. Claim 24 is reproduced below: 2 Appeal2017-008320 Application 11/603,766 24. A delayed release pharmaceutical composition which provides a lag in delivery of a drug following administration, the composition comprising a multi-unit dosage of multiparticles, each unit of the composition comprising (a) a core which includes a drug and a disruption agent and (b) a regulatory membrane coating on the core formed from a mixture of a water-soluble gel-forming polymer and a water-insoluble film-forming polymer; wherein said water-soluble gel-forming polymer is a high viscosity grade hydroxyalkylcellulose or methyl cellulose, said water-insoluble film-forming polymer is an alkyl cellulose, and wherein there is a coating weight gain of said regulatory membrane coating of between 20% and 100%, and wherein said composition releases less than 10% of the drug in the lag period of up to 1 to 6 hours, and after said lag period, releases more than 90% of the drug over a release period of not greater than 6 hours. CLAIMS The claimed delayed release pharmaceutical composition recited in claims 24 and 46 comprises: (a) a core; and (b) a regulatory membrane coating on the core. The regulatory membrane comprises: (1) a water soluble gel-forming polymer which is a high viscosity grade hydroxyalkylcellulose or methyl cellulose; and (2) a water-insoluble film-forming polymer which is an alkyl cellulose. In claim 35, the water soluble gel-forming polymer is high viscosity grade hydroxypropylmethylcellulose. The composition has a functional limitation that the composition "releases less than 10% of the drug in the lag period of up to 1 to 6 hours, and after said lag period, releases more than 90% of the drug over a release period of not greater than 6 hours." 3 Appeal2017-008320 Application 11/603,766 REJECTION BASED ON BUXTON, KATZHENDLER, AND GRIMMETT The Examiner found that Buxton describes a controlled delivery pharmaceutical composition with a spheroid core and controlled released coating material, which corresponds to the claimed (a) core and (b) regulatory membrane coating, respectively. Ans. 2-3. The Examiner also found that Buxton describes a coating comprising the same (1) water-soluble gel-forming and (2) water-insoluble film-forming polymers as claimed. Id. at 3. The Examiner acknowledged that Buxton does not disclose that the (1) water soluble gel-forming polymer is a high viscosity grade hydroxyalkylcellulose or methyl cellulose as required by all the claims. However, the Examiner found that Katzhendler teaches that hydroxypropylmethylcellulose ("HPMC"), a hydroxyalkylcellulose as claimed (see dependent claim 35), is available in "low, normal or high viscosity grades," making it obvious to have used the high viscosity grade. Id. The Examiner also cited Grimmett as teaching that binders such as hydroxypropylmethylcellulose and hydroxypropylcellulose, limitations recited in dependent claims 31 and 32, were known in the art. Id. at 4. With respect to the recited lag period, the Examiner found, citing the '766 Specification, that "the ratio of water insoluble to water soluble material will depend on the release rate required and the solubility of the material." Ans. 3. The Examiner also found that Appellants had stated in the Appeal Brief that "the claimed result is simply a 'desired release rate profile', wherein ... , the time of releasing a drug in a composition (release rate profile) is clearly a result effective parameter that a person of ordinary 4 Appeal2017-008320 Application 11/603,766 skill in the art would routinely optimize by changing/increasing/decreasing the polymers." Ans. 10. The Examiner stated that it would have been "customary for an artisan of ordinary skill to determine the optimal amount of each polymer to add in order to best achieve the desired results, such as amount of drug release and the timing of the drug release." Id. The issue in this rejection is not whether the ordinarily skilled person could have achieved the claimed lag period and release rate by routine optimization, but whether there would have been reason to optimize the cited prior art to arrive at the claimed lag period and release rate. In making an obviousness determination, "it can be important to identify a reason that would have prompted a person of ordinary skill in the relevant field to combine the elements in the way the claimed new invention does." KSR Int'! Co. v. Teleflex, Inc., 550 U.S. 398,418 (2007). The reason does not have to be explicit, and "may be found explicitly or implicitly: 1) in the prior art references themselves; 2) in the knowledge of those of ordinary skill in the art that certain references, or disclosures in those references, are of special interest or importance in the field; or 3) from the nature of the problem to be solved." Ruiz v. A.B. Chance Co., 234 F.3d 654, 665 (Fed. Cir. 2000). However, a reason must still be identified. In this case, the Examiner did not provide a reason to have achieved the claimed release rate and lag period. Buxton was cited for teaching a core and regulatory membrane as claimed. Ans. 2-3. Katzhendler was cited for teaching high viscosity grade HPMC as required by the claim. Id. at 3. The Examiner stated that it would be obvious to use Katzhendler' s material in Buxton "because it would allow the practitioner to adjust the drug release rate to the desired level." Id. at 4. However, the Examiner did not provide a 5 Appeal2017-008320 Application 11/603,766 reason that would have prompted the skilled worker to adjust the release rate such that the pharmaceutical "releases less than 10% of the drug in the lag period of up to 1 to 6 hours, and after said lag period, releases more than 90% of the drug over a release period of not greater than 6 hours" as recited in both independent claims. While it may be correct it is conventional to adjust polymer types and amounts to achieve a desired release rate, the Examiner did not point to any disclosure in the cited publications, or provide other sufficiently persuasive reasoning, that would have guided the skilled worker to the release profile which is claimed. The Examiner cited disclosure in Buxton that the core of its pharmaceutical composition is coated with a control release coating material, but did not explain how such a coating suggested the recited lag period or inherently possessed it. Ans. 3. The Examiner stated that "it has been held that the recitation that an element is 'capable of performing a function is not a positive limitation, but only requires the ability to so perform." Ans. 5. We do not agree that the recited lag period is not a "positive" limitation of the claims. The claims positively require that the composition have the recited release rate "following administration." To the extent that the claimed composition must only be "capable" of achieving the lag and release period when ingested, the Examiner is not relieved of the burden of providing a reason to have made a composition with such a property when administered. The Examiner also stated: the prior art's composition is inherently capable of a delay period of 1 to 2 hours and release the entire content of the drug over a period of not greater than 6 hours or a controlled release period of over 1 to 12 hours, since the prior art's ingredient in the composition is the same as Appellant's compositional ingredient. 6 Appeal2017-008320 Application 11/603,766 Ans. 5. As held in In re Swinehart, 439 F.2d 210, 212-13 (CCPA 1971) ( emphasis added): [W]here the Patent Office has reason to believe that a functional limitation asserted to be critical for establishing novelty in the claimed subject matter may, in fact, be an inherent characteristic of the prior art, it possesses the authority to require the applicant to prove that the subject matter shown to be in the prior art does not possess the characteristic relied on. Furthermore: Where, as here, the claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes, the PTO can require an applicant to prove that the prior art products do not necessarily or inherently possess the characteristics of his claimed product. See In re Ludtke, supra. Whether the rejection is based on "inherency" under 35 U.S.C. § 102, on "prima facie obviousness" under 35 U.S.C. § 103, jointly or alternatively, the burden of proof is the same, and its fairness is evidenced by the PTO's inability to manufacture products or to obtain and compare prior art products. See In re Brown, 459 F.2d 531, 59 CCPA 1036 (1972). In re Best, 562 F.2d 1252, 1255 (CCPA 1977). The Examiner did not establish that Buxton describes a composition that would inherently possess the functional limitation of the recited lag period. The Examiner did not identify a single example, range of values, or ratios of the recited polymers that would meet the claimed functional limitation to give rise to a reason to believe the composition inherently possessed the claimed release rate. See also Appeal Br. 11-13 ( explaining the failure of Buxton to disclose controlled release examples comprising the recited polymers). For example, while Buxton teaches both water-soluble 7 Appeal2017-008320 Application 11/603,766 and water-insoluble polymers (Buxton 3:38--45), the Examiner did not provide a reason for making a delayed release composition with a lag period, rather than a composition with sustained single-release rate. The Examiner states that the same polymers are disclosed in Buxton, but does not identify an example in which the same polymers are combined in such a way that they necessarily would have resulted in a composition with the claimed lag period and release rate. In addition, Buxton teaches that its core and coating have different drugs and different release rates. Buxton, Abstract (57). The Examiner did not explain why one of ordinary skill in the art would have used the same drug in both the core and coating. In sum, the Examiner did not provide adequate "reason to believe" that Buxton's core and coating inherently "releases less than 10% of the drug in the lag period of up to 1 to 6 hours, and after said lag period, releases more than 90% of the drug over a release period of not greater than 6 hours." With respect to Katzhendler, as discussed by the Appellants, Katzhendler teaches the person of ordinary skill in the art that its polymers are used in its compositions to provide a zero-order release rate. Katzhendler, Abstract, col. 1, 11-25. "Zero order release rate" is defined in column 3, lines 39--40, of Katzhendler as "a constant, linear, continuous sustained and controlled release rate." See Appeal Br. 15. Thus, we agree with Appellants that the evidence does not establish that Katzhendler would have guided the skilled worker to a release rate with a lag period as claimed. Id. at 16. Grimmett is relied upon by the Examiner for teaching that binders such as hydroxypropylmethylcellulose and hydroxypropylcellulose were 8 Appeal2017-008320 Application 11/603,766 known in the art. Ans. 4. Grimmett also describes a release retarding coating, including release after an initial delay. Grimmett, col. 1, 11. 16-22; Appeal Br. 16. However, the Examiner did not establish that this coating meets or suggests the claimed regulatory coating, and Appellants provided evidence that it does not. Appeal Br. 16-17. Because the Examiner did not meet the burden in establishing that the cited combination of Buxton, Katzhendler, and Grimmett suggests the composition recited in claims 24 and 46, and dependent claims 25-33, 35, 37, 39-42, 45, and 47-51, the obviousness rejection is reversed. REJECTION BASED ON BUXTON, KATZHENDLER, GRIMMETT, AND CURATOLO The Examiner relied on Buxton, Katzhendler, and Grimmett for the same reasons as discussed above. Ans. 6. The Examiner further cited Curatolo for teaching using high viscosity grade hydroxypropyl methylcellulose, such as K4M. It appears that Curatolo was additionally cited because claims 52 and 53 recite that the high viscosity grade gel forming polymer is, inter alia, hydroxypropylmethylcellulose K4M. We reverse the rejection of claims 24--33, 35, 37, 39-42, and 45-53, as well, because the Examiner did not cite Curatolo for making up the deficiencies described above for Buxton, Katzhendler, and Grimmett. REJECTION BASED ON CURATOLO AND BANJANAC The Examiner found that Curatolo describes a controlled delivery pharmaceutical composition with a spheronization core and coating material, which corresponds to the claimed (a) core and (b) regulatory membrane 9 Appeal2017-008320 Application 11/603,766 coating, respectively. Ans. 7. The Examiner also found that Buxton describes a coating comprising the same (1) water-soluble gel-forming and (2) water-insoluble film-forming polymers as claimed. Id. With respect to the recited lag period, the Examiner, like in the Buxton rejection, asserts that Curatolo "teaches all the limitations as claimed by Appellant. Thus, adjusting the amount would have been a routine optimization step to attain any desired release rate." Ans. 28. However, as explained above, the issue is not whether the claimed release rates could have been achieved by optimizing the polymer amounts used, but whether the Examiner has provided a sufficient reason on this record for the ordinarily skilled person to obtain the claimed release rates To begin, we note that Curatolo describes a delayed release dosage which, e.g., "releases not more than about 10% of its incorporated azithromycin in the stomach, and which releases no more than an additional 10% during the first 15 minutes after the dosage form has entered the duodenum" and the rest after moving distally through the intestine. Curatolo, col. 2, 11. 32--44. However, as argued by Appellants, Curatolo also describes a sustained-released dosage formation which comprises different polymers than the delayed-release form. Appeal Br. 22. A sustained release dosage slowly releases drug, but does not necessarily have a delayed release with a lag period. Curatolo, vol. 5, 11. 30--46. The Examiner did not provide evidence that the sustained release formulations would have reasonably suggested the claimed composition with a lag or delay release period. The Examiner cited coatings from Curatolo's description of sustained- dosage formulations for teaching the claimed (b) regulatory membrane 10 Appeal2017-008320 Application 11/603,766 coating on (a) the core. Specifically, the disclosure cited by the Examiner at column 12 (Ans. 7) is a description of sustained dosage formulations. Curatolo, col. 10, 11. 48-50. The more specific discussion of the delayed release formulations begins at column 15, line 22 of Curatolo. The Examiner appeared to acknowledge this fact, but stated that "there is no need to go into the delay-release formulation section in CURATOLO, since most of Appellant's claim limitations are found in column 12 of the CURATOLO's reference." Ans. 21. We disagree with this statement because there is a "need" to establish that the sustained release formulation of Curatolo would result in the release rates required by the claims, particularly with a lag or delay period. The Examiner did not adequately address the lag/delay release limitation recited in the claims. The coatings for the delayed-release formulation of Curatolo include water soluble hydroxypropylmethylcellulose (Curatolo, col. 17, 1. 21 ), the (1) water soluble gel-forming polymer of the claims. However, as argued by Appellants, Curatolo does not disclose (2) a water-insoluble film-forming polymer which is an alkyl cellulose as required by the claims. Appeal Br. 23. The Examiner acknowledged this argument, but once again referred to the sustained release coatings. Ans. 23. Yet the Examiner did not establish that the sustained release coatings would achieve the claimed lag and release rates. Indeed, the fact that the polymers present in the sustained release coatings are different from the delayed release coating suggests that sustained release coatings would not achieve the claimed lag period and release rates. In sum, the Examiner did not provide adequate evidence that Curatolo describes the claimed "regulatory membrane" having the recited lag and 11 Appeal2017-008320 Application 11/603,766 drug release rate. In contrast, the Examiner stated it was not necessary to tum to the examples in Curatolo of delayed release formulations, but provided no persuasive evidence that the sustained release formations described in Curatolo enable or would achieve delayed release as claimed. In addition to this, as noted by Appellants, Curatolo does not describe (b) (1) a coating with high viscosity grade hydroxyalkylcellulose or methyl cellulose as claimed. Appeal Br. 23. The Examiner cited Example 14 of Curatolo for this limitation. Ans. 23. Example 14 of Curatolo describes a sustained release matrix made with a high viscosity HPMC, K4M-CR. Curatolo, col. 43 (Table 14-1 ). Example 14 does not contain a description of a coating. The Examiner did not explain why one of ordinary skill in the art would have used the high viscosity grade polymer in a coating, particularly when, as argued by Appellants, the delayed release formulations use a low viscosity HPMC. Appeal Br. 24, 27. Because the Examiner did not meet the burden in establishing that the cited Curatolo suggest the composition recited in claims 24 and 46, and dependent claims 25-33, 35, 37, 39, 42, 45, and 47-51, the obviousness rejection is reversed. REVERSED 12 Copy with citationCopy as parenthetical citation