Ex Parte Pesenti et alDownload PDFPatent Trial and Appeal BoardJan 29, 201613054868 (P.T.A.B. Jan. 29, 2016) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 13/054,868 01119/2011 23389 7590 02/02/2016 SCULLY SCOTT MURPHY & PRESSER, PC 400 GARDEN CITY PLAZA SUITE 300 GARDEN CITY, NY 11530 FIRST NAMED INVENTOR Enrico Pesenti 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. 23034 1502 EXAMINER PAGONAKIS, ANNA ART UNIT PAPER NUMBER 1628 NOTIFICATION DATE DELIVERY MODE 02/02/2016 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@SSMP.COM PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte ENRICO PESENTI, DARIO BALLINARI, and JUERGEN MOLL 1 Appeal2013-008868 Application 13/054,868 Technology Center 1600 Before DONALD E. ADAMS, JEFFREY N. FREDMAN, and RICHARD J. SMITH, Administrative Patent Judges. SMITH, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to a therapeutic combination comprising a compound and one or more antineoplastic agents. (Br. 11-12.) We have jurisdiction under 35 U.S.C. § 6(b ). We affirm. 1 According to Appellants, the real party in interest is N erviano Medical Sciences, S.R.L. (Br. 2.) Appeal2013-008868 Application 13/054,868 STATEMENT OF THE CASE Claims on Appeal Claims 12-14, 17, and 19 are on appeal. 2 (Br. 11-12.) Claim 12 is illustrative and reads as follows: 12. A therapeutic combination comprising (a) Compound 1 of formula (A): (A) and (b) one or more antineoplastic agents selected from the group consisting of bevacizumab and bortezomib, wherein the active ingredients of the combination are present in each case in free form or in the form of a pharmaceutically acceptable salt thereof. Examiner's Rejections 1. Claims 12-14 and 17 stand rejected under 35 U.S.C. § 103(a) as unpatentable over Fancelli '212 3 in view ofDai. 4 (Ans. 3.) 2 Claims 1-11 and 18 are cancelled, and claims 15 and 16 are withdrawn. (Br. 11-12.) 3 WO 2007/113212 A2, published Oct. 11, 2007 ("Fancelli '212"). 4 Dai, et al., Bortezomib and flavopiridol interact synergistically to induce apoptosis in chronic myeloid leukemia cells resistant to imatinib mesylate through both Ber/Ahl-dependent and -independent mechanisms, 104 BLOOD 2, at 509-18 (2004) ("Dai"). 2 Appeal2013-008868 Application 13/054,868 2. Claims 12-14, 17, and 19 stand rejected under 35 U.S.C. § 103(a) as unpatentable over Fancelli '427 5 and the Fancelli Article 6 in view of Dai. (Ans. 6.) 3. Claim 12 stands rejected on the ground of nonstatutory obviousness- type double patenting as unpatentable over claims 1-5 ofFancelli '628. 7 (Ans. 9.) 4. Claim 12 stands rejected on the ground of nonstatutory obviousness- type double patenting as unpatentable over claims 4---6 ofFancelli '568. 8 (Ans. 10.) Appellants have presented arguments for the patentability of claims 12-14, 17, and 19 as a group. (Br. 4--10.) In accordance with 37 C.F.R. § 41.37(c)(l)(iv), we select claim 12 as the representative claim to decide the appeal of the rejection of these claims. FINDINGS OF FACT We adopt the Examiner's findings and analysis concerning the scope and content of the prior art. The following findings are included for emphasis and reference convenience. FF 1. The Examiner finds that F ancelli '212, F ancelli '4 2 7, the F ancelli Article, claim 1 of Fancelli '628, and claim 4 of Fancelli '568 disclose or 5 WO 2005/005427 Al, published Jan. 20, 2005 ("Fancelli '427"). 6 Fancelli, et al., l,4,5,6-Tetrahydropyrrolo[3,4-c]pyrazoles: Identification of a Potent Aurora Kinase Inhibitor with a Favorable Antitumor Kinase Inhibition Profile, 49 J. MED. CHEM. 24, at 7247-51 (2006) ("the Fancelli Article"). 7 U.S. Patent No. 7,582,628 B2, issued Sept. 1, 2009 ("Fancelli '628"). 8 U.S. Patent No. 7,141,568 B2, issued Nov. 28, 2006 ("Fancelli '568"). 3 Appeal2013-008868 Application 13/054,868 encompass Compound 1 of formula (A) as claimed. (Ans. 4 and 6-10.) Appellants do not dispute this finding. FF 2. The Examiner finds that the compounds disclosed by Fancelli '212 are useful in the treatment of imatinib-resistant chronic myelogenous leukemia, and may be used alone or in combination with other cytostatic or cytotoxic agents. (Ans. 5.) FF 3. The Examiner finds that Dai teaches a method of "synergistically interacting to induce apoptosis in chronic myeloid leukemia cells resistant to imatinib mesylate with administration of bortezomib and flavopiridol." (Ans. 4.) DISCUSSION Issues The issues presented are whether a preponderance of evidence of record supports the Examiner's conclusion that (a) claim 12 is obvious based on Fancelli '212 and Dai, (b) claim 12 is obvious based on Fancelli '427, the Fancelli Article, and Dai, (c) claim 12 is unpatentable on the ground of nonstatutory obviousness-type double patenting over claims 1-5 of Fancelli '628,and ( d) claim 12 is unpatentable on the ground of nonstatutory obviousness-type double patenting over claims 4---6 of Fancelli '568. 4 Appeal2013-008868 Application 13/054,868 Analysis Appellants argue all of the rejections together, and group Fancelli '212, the Fancelli Article, Fancelli '628, and Fancelli '568 together as the "Fancelli References."9 (Br. 4--10.) Accordingly, we address the two obviousness rejections and two obviousness-type double patenting rejections together. See Procter & Gamble Co. v. Teva Pharms. USA, Inc., 566 F.3d 989, 999 (Fed. Cir. 2009) ("In general, the obviousness analysis applies to double patenting"). Appellants argue that there is no motivation or reason to combine the compound of the Fancelli References (FF 1) with bortezomib as disclosed by Dai, and no reasonable expectation of success in doing so. (Br. 5-8.) Furthermore, Appellants argue that "[t]he circumstances strongly suggest that improper hindsight has been applied: that the combination only comes to mind by benefit of the instant specification." (Id. at 6.) We are not persuaded by Appellants' arguments. "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition which is to be used for the very same purpose." In re Kerkhoven, 626 F.2d 846, 850 (CCPA 1980). Here, the obviousness of using Compound 1 of formula (A) in combination with bortezomib is based on the fact that both are known in the prior art for the same purpose, and both are encouraged in 9 Appellants refer to Fancelli '212 rather than Fancelli '427 in connection with Rejection No. 2 (Br. 4), and do not list Fancelli '427 among the Fancelli References. (Br. 5.) However, although Appellants do not argue Fancelli '427, we include it as part of the Fancelli References for purpose of the appeal. 5 Appeal2013-008868 Application 13/054,868 the prior art to be used in combination therapy. (Ans. 4--5, 12; FF 2, 3.) Thus, the art provides a motivation to combine Compound 1 of formula (A) with bortezomib, and it is prima facie obvious to do so. We are also unpersuaded by Appellants' arguments regarding expectation of success and hindsight. Here, the reasonable expectation of success is shown in the art itself, which encourages both Compound 1 of formula (A) and bortezomib to be used with another agent. (FF 2, 3.) Furthermore, any concern regarding hindsight bias is overcome because the Examiner points to specific disclosures in the prior art that give a reason or motivation to make the claimed combination. See Otsuka Pharm. Co., Ltd. v. Sandoz, Inc., 678 F.3d 1280, 1292 (Fed. Cir. 2012). Accordingly, we find that the Examiner has established a prima facie case of obviousness and obviousness-type double patenting, and Appellants' arguments do not overcome that prima facie case. Unexpected Results Appellants argue that "the data presented in Tables 2 and 3 of the specification are compellingly indicative of an unexpected and surprisingly dramatic slowing in tumor growth, as indicated by a higher T-C number, 10 for administration of the claimed combination as opposed to administration of either agent singularly." (Br. 6.) Tables 2 and 3 are reproduced below. 10 According to Appellants, "[ t ]he T-C figure indicates the difference of time, in days, required for treatment group (T) and control group (C) tumors to reach a size of one gram. [] As an example, if the T-C was 2 days, it would take 2 days longer for treatment group tumors to reach one gram as compared to the time it takes for the control group tumors to reach one gram." (Br. 6.) 6 Appeal2013-008868 Application 13/054,868 Table 2 Trcattll('.lli Compound 1 15 mg/kg* Bevacizumab 20 mg/kg** Bcvacizumab 20mgikg + Compound I 15 mgikg*** Time to reach lg (days) 23,9 18.5 28.2 T-C (days) Toxicity 8.5 O//S 3.l 0/8 12.8 OiS *Treatments made intrnpcritonca!ly nvice at days 9,1OJIJ2,13)4)5, 16, l7, l8 and 19 **Treatment~ made intrapcritoncally at days 9, l 3 and ! 7 *** Days 9, 13 and l 7 bcvacizurm1b treatments; day~ 9, 10, l l, 12, 13, 14, 15, 16, 17, 18 and 19 Compound l treatments (Spec. 14.) Table 3 Treatment T in:ic to reach l g {days) T-C (days) Toxicity --~~);;~:;~1~; ___ 1 _____________________________ :~:~------------------- ____________________ ?:_! __________________________________ ?:/? ___________ Bo rtczon1 ·ib 0.5 mg/kg** 19 3.4 0/7 Bortczomib __ L_'.'.~~r~~},?-~~~'. ______________ ------------------=~:-~------------------- --------------------~:=-------------------- -----------~'..~------------ Ho rtczom i b 0.5 mg/kg+ Cornpound l 29.2 B.5 0/7 ___ \_~--~~'.¥:'.~:\:l~-~~-------- ----------------------------------------------- ----------------------------------------------- ------------------------------ Bortezo mib l mg/kg+ Compound 1 15 mg/kg*** 51.4 35.7 3/7 *cfrci:(!n1cn-is-:111;at:-ii1-rri:;i;-crii(ii1cd-i>-:--i\\.:-r;:c -~;i:--ai:i):s--L2:-1IT{T5-Jl;:r;-:-rs:T9~-2 o, n , 22. 23. **Treatments made by intravenous route at days 12.16,20,24 "'** Day;; 12,l 6, 20 24 bortczornib treatments, 13, 14, l 5,l 7,18, 19, 2 l, 22, 23, 25, 26 and 27 Compound l treatments. (Spec. 15-16.) 7 Appeal2013-008868 Application 13/054,868 We do not find that the data in the Specification, as argued by Appellants and when weighed with the evidence supporting the prima facie case, provides sufficient evidence of unexpected results to rebut the prima facie case. Appellants state that "only the T-C column needs consideration," but then argue the results from the column entitled "Time to reach 1 g (days)." (Br. 6.) Furthermore, when arguing the T-C column results, Appellants refer to the "average" of the T-C results for compound 1 and bortezomib (or bevacizumab) independently, rather than the "addition" of the T-C results as referenced in the Specification. (See Br. 7 and Spec. 13, 1. 22; 15, 1. 14.) As pointed out by the Examiner, when the results of the individual components argued by Appellants are added rather than averaged, "the difference in actual delays in tumor growth is approximately 1 day for each combination." 11 (Ans. 16.) Also, Appellants do not sufficiently establish that a person of ordinary skill in the art would have found the data regarding the claimed therapeutic combination to be unexpected. See Pfizer, Inc. v. Apotex, Inc., 480 F .3d 1348, 1371 (Fed. Cir. 2007) ("any superior property must be unexpected to be considered as evidence of non-obviousness"). Here, some improved efficacy would not appear to be unexpected given that the effectiveness of both Compound 1 of formula (A) and bortezomib was already known in the 11 From Table 2, Appellants average 8.5 and 3.1 (yielding 5.8 days), but when the individual results are added, the result is 11.6 days (compared to 12.8 days for the combination). From Table 3, Appellants average 9.1 and 3.4 (yielding 6.25 days), but when the individual results are added, the result is 12.5 days (compared to 13.5 days for the combination). Appellants do not explain why they average the results in their argument when the Specification adds the results. 8 Appeal2013-008868 Application 13/054,868 art. (FF 1-3.) See Bristol-Myers Squibb Co. v. Teva Pharms. USA, Inc., 752 F.3d 967, 977-78 (Fed. Cir. 2014) (effectiveness of claimed compound was not unexpected in light of the activity of structurally similar compound in prior art reference). We also find that the data in the Specification regarding improved slowing in tumor growth reflects a difference in degree rather than a difference in kind. "[D]ifferences in degree" of a known and expected property are not as persuasive in rebutting obviousness as differences in "kind" (i.e., a new property dissimilar to the known property). Id. at 977; see also In re Merck, 800 F.2d 1091, 1099 (Fed. Cir. 1986) (finding evidence that the new drug was a more potent sedative and stronger anticholinergic effect than the prior art was insufficient to outweigh the evidence of obviousness). Accordingly, we find that Appellants' evidence of unexpected results is insufficient to rebut the prima facie case established by the Examiner. Conclusions of Law A preponderance of evidence of record supports the Examiner's conclusion that (a) claim 12 is obvious under 35 U.S.C. § 103(a) based on Fancelli '212 and Dai, (b) claim 12 is obvious under 35 U.S.C. § 103(a) based on Fancelli '427, the Fancelli Article, and Dai, (c) claim 12 is unpatentable on the ground ofnonstatutory obviousness- type double patenting over claims 1-5 of Fancelli '628, and (d) claim 12 is unpatentable on the ground of nonstatutory 9 Appeal2013-008868 Application 13/054,868 obviousness-type double patenting over claims 4---6 of Fancelli '568. Furthermore, Appellants have not provided sufficient evidence of unexpected results, that when weighed with the evidence of obviousness, is sufficient to support a conclusion of nonobviousness. Claims 13, 14, 17, and 19 were not argued separately and therefore fall with claim 12. SUMMARY We affirm all rejections of all appealed claims. 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 tc 10 Copy with citationCopy as parenthetical citation