Ex Parte BrownDownload PDFPatent Trial and Appeal BoardDec 17, 201814574989 (P.T.A.B. Dec. 17, 2018) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 14/574,989 12/18/2014 28977 7590 12/17/2018 MORGAN, LEWIS & BOCKIUS LLP (PH) 1701 MARKET STREET PHILADELPHIA, PA 19103-2921 UNITED ST A TES OF AMERICA FIRST NAMED INVENTOR Dennis Brown 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. 067716-5014-01-US 5284 EXAMINER THAKOR, DEV ANG K ART UNIT PAPER NUMBER 1619 MAIL DATE DELIVERY MODE 12/17/2018 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 DENNIS BROWN Appeal2017-004968 Application 14/574,989 Technology Center 1600 Before JEFFREYN. FREDMAN, MICHAEL J. FITZPATRICK, and RACHEL H. TOWNSEND, Administrative Patent Judges. FITZPATRICK, Administrative Patent Judge. DECISION ON APPEAL Appellant1 appeals under 35 U.S.C. § 134(a) from the Examiner's final decision rejecting claims 20-43. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. 1 The real party in interest is identified as Teva Pharmaceutical International, GmbH. Appeal Br. 3. Appeal2017-004968 Application 14/574,989 STATEMENT OF THE CASE The Specification "The invention relates to the use of cephalotaxines to ablate leukemic stem cells in treatment protocols using tyrosine kinase inhibitors (TKis) and other antileukemic agents." Spec. ,II. It discloses treating leukemia patients with a cephalotaxine followed by treatment with a tyrosine kinase inhibitor (TKI). Id. ,IS. In the prior art, treatment of leukemia, such as chronic myeloid leukemia (CML), involved administering to the patient imatinib, a TKI, known by its trade name as Gleevec. Id. ,I6. "This [prior art] treatment often results in remission of the disease. However, in many cases resistance to Gleev[e]c arises." Id. Second generation TKis include dasatinib and bosutinib. Id. ,I25. According to the invention, such TKI-resistant patients can be treated first with a cephalotaxine and then with a TKI. Id. i-f 6. The preferred cephalotaxine for the invention is homoharringtonine (HHT). Id. ,I7. HHT is also known as omacetaxine mepesuccinate, which is the terminology used in the rejected claims. Id. ,I42. The Rejected Claims Claims 20-43 stand rejected. Final Act. 1. All of the rejected claims recite, or incorporate by reference through their dependency on another claim, a "method for treating a patient with leukemia" comprising "administering omacetaxine mepesuccinate." Appeal Br. 22-24. Claims 20 and 27 are representative and reproduced below, with the only difference in their language italicized. 2 Appeal2017-004968 Application 14/574,989 20. A method for treating a patient with leukemia that is resistant to dasatinib, said method comprising: (a) administering omacetaxine mepesuccinate to said patient until said patient demonstrates a hematological or cytological response. 27. A method for treating a patient with leukemia that is resistant to bosutinib, said method comprising: (a) administering omacetaxine mepesuccinate to said patient until said patient demonstrates a hematological or cytological response. Appeal Br. 22-23 (Emphasis added). The Appealed Rejections The following rejections under 35 U.S.C. § I03(a) (pre-AIA) are before us for review: 1. claims 20-39 as unpatentable over Chen2 and Robin3 (as evidenced by Talpaz4 and Puttini)5 (Final Act. 3); 2. claims 40-43 as unpatentable over Chen, Robin, and Marin6 (id. at 11-12); 2 Rong Chen et al., A Sequential Blockade Strategy for the Design of Combination Therapies to Overcome Oncogene Addiction in Chronic Myelogenous Leukemia, 66 CANCER RES 10959---66 (2006) ("Chen"). 3 US 2004/0019036 Al, published Jan. 29, 2004 ("Robin"). 4 Moshen Talpaz et al., DASATINIB IN IMATINIB-RESISTANT PHILADELPHIA CHROMOSOME-POSITIVE LEUKEMIAS, 354(24) N. Engl. J. Med. 2531--41 (2006) ("Talpaz"). 5 Miram Puttini et al., In vitro and In vivo Activity of SKl-606, a Novel Src- Abl Inhibitor, against lmatinib-Resistant Ber-Ahl+ Neoplastic Cells, 66 CANCER RES 11314--22 (2006) ("Puttini"). 6 David Marin et al., Phase 1/11 Trial of Adding Semisynthetic 3 Appeal2017-004968 Application 14/574,989 3. claims 20-23, 25, 26, 34, 36, and 38 as unpatentable over Talpaz and Chen (id. at 13); 4. claims 21-26, 35-37, and 39 as unpatentable over Talpaz, Chen, and Robin (id. at 14); 5. claims 40-43 as unpatentable over Talpaz, Chen, Robin, and Marin (id. at 16); 6. claims 27-30, 32, 33, 34, 36, and 38 as unpatentable over Puttini and Chen (id. at 17); 7. claims 28-33, 35-37, and 39 as unpatentable over Puttini, Chen, and Robin (id. at 19); and 8. claims 40-43 as unpatentable over Puttini, Chen, Robin, and Marin (id. at 20-21 ). DISCUSSION Rejection 1 The Examiner rejects claims 20-39 under 35 U.S.C. § 103(a) as unpatentable over Chen and Robin, as evidenced by Talpaz and Puttini. Final Act. 3. Appellant argues all claims (i.e., claims 20-39) together under the same heading. Appeal Br. 9-17. Accordingly, we select independent claim 20 as representative. See 37 C.F.R. § 4I.37(c)(l)(iv). The Examiner found that Chen teaches in vitro administration of HHT ( which, again, is another name for omacetaxine mepesuccinate) to leukemia Homoharringtonine in Chronic Myeloid Leukemia Patients Who Have Achieved Partial or Complete Cytogenetic Response on Imatinib, AMERICAN CANCER Soc'y 1850-55 (2005) ("Marin"). 4 Appeal2017-004968 Application 14/574,989 cells containing the T315I mutation in the Bcr-Abl kinase in order to inhibit proliferation of the leukemia cells. Final Act. 4 ( citing Chen 10964 and Table 1 ). The Examiner found that Robin teaches treating leukemia patients in which the leukemia is resistant to imatinib with HHT. Final Act. 4 (citing Robin at [57], i-f20). The Examiner concluded that it "would have therefore been obvious to one of ordinary skill in the art to apply the steps of Robin to a patient with imatinib-resistant leukemia containing the T315I mutation in Bcr-Abl kinase, given that Chen teaches that HHT is effective against imatinib-resistant leukemia cells containing this mutation." Final Act. 4. With respect to independent claim 20, the preamble of which recites a "method for treating a patient with leukemia that is resistant to dasatinib," the Examiner cites Talpaz as evidence "that the T315I mutation confers resistance to dasitinib." Final Act. 4 ( citing Talpaz 2531 (Abstract)). Thus, a patient with imatinib-resistant leukemia containing the T315I mutation in Bcr-Abl kinase, which a person of ordinary skill in the art would have been motivated to treat with HHT, would also be resistant to dasatinib ( as well as bosutinib7). Final Act. 4--5. The Examiner explicitly addressed Appellant's arguments against the rejection and explained eloquently why they were not persuasive. Ans. 15- 38. We agree with the Examiner's explanations. As the Examiner noted, at 7 With respect to independent claim 27, which recites a "method for treating a patient with leukemia that is resistant to bosutinib," the Examiner cites Puttini as evidence "that the T315I mutation confers resistance to bosutinib." Final Act. 5 (citing Puttini 11321, left col.); see also Final Act. 17 (citing Puttini at Figs. 3 and 4). 5 Appeal2017-004968 Application 14/574,989 the heart of the Appellant's arguments is a misapprehension or mischaracterization of the Examiner's rejection. See Ans. 15-16. Appellant argues the following: Imatinib, dasatinib, and bosutinib are all tyrosine kinase inhibitors ("TKis") with distinct chemical structures and mechanisms of action. They each engage in different modes of binding to a protein known as BCR-ABL. Since different TKis bind differently to BCR-ABL, resistance to different TKis may be use to classify different types of leukemia. For example, as explained in Talpaz, "[ d]asatinib ... is an orally available ABL kinase inhibitor that differs from imatinib in that it can bind to both the active and inactive conformations of the ABL kinase domain. Dasatinib also inhibits a distinct spectrum of kinases that overlaps with the array of kinases that imatinib inhibits." Talpaz, p. 2532. Similarly, Puttini confirms that bosutinib (also known as SKI-606) is "in a class of its own" with respect to other kinase inhibitors, including imatinib, and is also differentiated from dasatinib. Puttini, p. 11321. Imatinib-resistant leukemia, dasatinib-resistant leukemia, and bosutinib-resistant leukemia are each recognized as individual species of the much larger class of cancers known as leukemia, which includes hundreds of different hematological malignancies affecting different tissues and cell types ( such as B cells, T cells, and myeloid cells). Methods of treating dasatinib- resistant leukemia or bosutinib-resistant leukemia using omacetaxine mepesuccinate, such as the methods claimed in Claims 20, 27, 34, and 39, are patentable over the prior art, which at best teaches only the treatment of imatinib-resistant leukemia. Appeal Br. 10-11 (footnote omitted). The Examiner responded to these arguments as follows: Appellant's argument appears to be that the method of the rejection is a method for treating imatinib-resistant leukemia, from which it would be obvious to also treat dasatinib- and bosutinib-resistant leukemias because they [are] simply different species of the same genus of leukemia. However, this is 6 Appeal2017-004968 Application 14/574,989 incorrect; the rejections actually do not rely on genus-species obviousness to arrive at a method of treating dasatinib- and bosutinib-resistant leukemias from a method of treating imatinib- resistant leukemia. Rather, the rejection over Chen describes a method to treat a particular subpopulation of leukemia patients with the T315I mutation using omacetaxine mepesuccinate [(i.e., HHT)]. Because Chen teaches that this mutation gives rise to imatinib resistance, Talpaz provides evidence that this mutation gives rise to dasatinib resistance, and Puttini provides evidence that this mutation gives rise to bosutinib resistance, a method of effectively treating a leukemia patient carrying this mutation is necessarily a method of treating leukemia with imatinib, dasatinib, and bosutinib resistance. Appellant has provided no evidence that patients with the T315I mutation are not necessarily resistant to dasatinib and bosu[ti]ni[b] in addition to imatinib. [ 8] Appellant's arguments do not address the actual basis for rejection, which is the inherency of dasatinib and bosutinib resistance in patients with the T315I mutation, which is the population selected for treatment in the method of the rejection. Ans. 16-17. We agree that Appellant's arguments are not persuasive for the reasons explained by the Examiner. We also agree with the Examiner that many of Appellant's arguments attack the asserted prior art references individually and are thus not responsive to the rejection, which is based on a combination of prior art teachings. See Ans. 16 ("This argument is not persuasive both because it 8 In fact, Appellant concedes that the T315I mutation confers resistance to both dasatinib and bosutinib in addition to imatinib. Reply 5---6 ("Talpaz explains that, as related to wild-type Bcr-Abl, T315I mutants include a 'single mutation deep within the ATP-binding pocket of the ABL tyrosine kinase (T315I) that confers a high degree of resistance to imatinib and dasatinib[.]"' (quoting Talpaz 2532 left col.); Reply 6 ("Puttini indicates that bosutinib and imatinib may be less active against T315I Bcr-Abl mutants."). 7 Appeal2017-004968 Application 14/574,989 misses the basis for rejection and because it does not consider the teachings of the references as a whole." (emphasis added)); see also In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986) ("Non-obviousness cannot be established by attacking references individually where the rejection is based upon the teachings of a combination of references."). For example, Appellant states the following: "Chen is inapplicable because it discloses only in vitro treatment of imatinib-resistant leukemia" (Appeal Br. 11 ); "Robin provides no guidance as to the treatment of dasatinib- or bosutinib-resistant leukemias using omacetaxine mepesuccinate" (id. at 12); "Talpaz makes no mention of omacetaxine mepesuccinate" (id.); and "Puttini discloses no in vivo patient data and, like Talpaz, makes no mention of omacetaxine mepesuccinate" (id.). None of these alleged shortcomings are apposite given the rejection articulated by the Examiner (Final Act. 3-5) and recounted supra. Accordingly, the rejections based on these alleged shortcomings are not persuasive. See Merck, 800 F.2d at 1097. Finally, in the Reply, Appellant argues that the rejection should be reversed because it is based on an erroneous claim construction. Reply 2--4. More specifically, Appellant asserts that the Examiner has construed claim 20, for example, by reading the phrase "leukemia that is resistant to dasatinib" as meaning "leukemia containing the T315I mutation in a patient." Id. at 2. But this not the Examiner's construction. Nor is such a construction implicit in the Examiner's rejection, as Appellant suggest. See id. at 3 ("While the Examiner has asserted that the T315I mutation in Bcr- Abl may result in resistance to imatinib, dasatinib, and bosutinib the Examiner has not proven, and the cited prior art does not support, that every 8 Appeal2017-004968 Application 14/574,989 patient who has imatinib-, dasatinib-, or bosutinib-resistant leukemia carries the T315I mutant ofBcr-Abl."). For the foregoing reasons, we affirm the Examiner's rejection of claim 20 under 35 U.S.C. § 103(a) as unpatentable over Chen and Robin. For the same reasons, we also affirm the Examiner's rejection of claims 21- 39, which were not separately argued. See Appeal Br. 9-17; 37 C.F.R. § 4I.37(c)(l)(iv). Rejection 2 The Examiner rejects claims 40-43 under 35 U.S.C. § 103(a) as unpatentable over Chen, Robin, and Marin. Final Act. 11-12. Appellant argues these claims together under the same heading. Appeal Br. 17-18. Accordingly, we select dependent claim 41 as representative. See 37 C.F.R. § 4I.37(c)(l)(iv). Claim 40 depends from either claim 20 or claim 27 and further recites "wherein said administration is twice daily for seven days." Appeal Br. 24. Claim 41 depends from claim 40 and further recites "wherein the dose of said omacetaxine mepesuccinate is 1.25 mg/m2." Id. The Examiner rejects claim 41 over Chen and Robin as applied to claim 20 ( or claim 27) and additionally relies on Marin to teach twice daily administration and Robin for teaching a dosage range of .25 to 5 mg/m2 and a treatment duration range of 2 to 14 days. Final Act. 12 ( citing Marin 1851 right col.; Robin i-fi-fl3, 24). The Examiner concludes that claim 41 would have been obvious. Final Act. 12. In response, Appellant notes that the cited teachings do not disclose the specific duration of 7 days or dosage amount of 1.25 mg/m2 recited in 9 Appeal2017-004968 Application 14/574,989 claim 41, and summarily concludes that a person of ordinary skill in the art would not have had a reasonable expectation of success of discerning or implementing those species from the disclosed genera (2-14 days and 0.25 to 5 mg/m2) that encompass them. Appeal Br. 18 ( citing Medi chem, S.A. v. Rolabo, 437 F.3d 1157, 1165 (Fed. Cir. 2006)). Appellant does not explain why there would not have been a reasonable expectation of success. And the evidence of record is probative that there would have been a reasonable expectation of success. As noted by the Examiner in the Answer, Robin teaches a seven-day treatment of HHT. Ans. 38. Also, Marin teaches the specific dosage of" 1.25 mg/m2 twice daily." While not specifically called out by the Examiner, Appellants were nevertheless directed to this teaching by the Examiner when the Examiner cited to "page 1851, right column" of Marin regarding the "twice a day" teaching. In the Answer, the Examiner asserts that neither genus offers a substantially numerous selection of possible choices to render the species non-obvious and also points out that Appellant has not established the criticality of the species. Ans. 38-39. Given the evidence of reasonable expectation of success and that the species have not been shown to be critical, we agree that the species are obvious in view of the disclosed genera. See In re Petering, 301 F.2d 676, 681-82 (CCPA 1962) (a small genus may disclose the species within); In re Aller, 220 F.2d 454, 456, (CCPA 1955) ("[I]t is not inventive to discover the optimum or workable ranges by routine experimentation."). Moreover, [ s ]electing a narrow range from within a somewhat broader range disclosed in a prior art reference is no less obvious than identifying a range that simply overlaps a disclosed range. In fact, when ... the claimed ranges are completely encompassed 10 Appeal2017-004968 Application 14/574,989 by the prior art, the conclusion is even more compelling than in cases of mere overlap. The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages. In re Peterson, 315 F.3d 1325, 1329, 1330 (Fed. Cir. 2003). The same is true when the claims, as they do here, recite specific values ( as opposed to ranges) encompassed by the prior art. Appellants provide no evidence of any secondary considerations with regard to the claimed doses and administration protocols relative to the broader overlapping ranges disclosed in the prior art. For the foregoing reasons, we affirm the Examiner's rejection of claim 41 under 35 U.S.C. § 103(a) as unpatentable over Chen, Robin, and Marin. For the same reasons, we also affirm the Examiner's rejection of claims 40, 42, and 43, which were not separately argued. See Appeal Br. 17-18; 37 C.F.R. § 4I.37(c)(l)(iv). Re} ections 3---8 Appellant argues against these additional rejections based on reasons already considered above and deemed unpersuasive. Appeal Br. 18-20. Accordingly, these rejections are all also affirmed. CONCLUSION For the reasons discussed, we affirm the Examiner's rejections of claims 2 0-4 3 . 11 Appeal2017-004968 Application 14/574,989 TIME PERIOD 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). AFFIRMED 12 Copy with citationCopy as parenthetical citation