Ex Parte Kelley

Patent Trial and Appeal BoardNov 28, 2012

11754082 (P.T.A.B. Nov. 28, 2012)

UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE PATENT TRIAL AND APPEAL BOARD __________ Ex parte SUSAN KELLEY __________ Appeal 2012-000290 Application 11/754,082 Technology Center 1600 __________ Before TONI R. SCHEINER, DEMETRA J. MILLS, and ERIC GRIMES, Administrative Patent Judges. GRIMES, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to drug combinations for treating cancer. The Examiner has rejected the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. STATEMENT OF THE CASE Claims 1-24 and 29-31 are on appeal. Claim 1 is representative and is directed to a “combination which is therapeutically effective for the treatment of mammalian cancer” comprising a “substituted-diaryl urea of Appeal 2012-000290 Application 11/754,082 2 Formula I” such as Sorafenib1 (Spec. 10:21-23), or a pharmaceutically acceptable salt thereof; a taxane such as paclitaxel (id.), “wherein said therapeutically effective amount of said taxane in said combination is between 100 mg/m2 to 175 mg/m2 of surface body area;” and a “platinum complex antineoplastic nucleic acid binding agent” such as carboplatin (Spec. 10:18-19). The full text of claim 1 is reproduced in the Claims Appendix of the Appeal Brief. The Examiner has rejected all of the claims on appeal under 35 U.S.C. § 103(a) based on Flaherty2 and Drug Facts,3 alone (claims 1-10, 23, 24, and 29-31) or combined with Riedl4 (claim 11) or Grewal5 (claims 12-22). We will consider these rejections together since Appellant has waived any arguments based on Riedl or Grewal. The Examiner finds that Flaherty discloses “a combination of BAY 43-9006, carboplatin, and paclitaxel … for treating human patients with cancer,” but teaches a paclitaxel dose of 225 mg/m2 rather than the claimed dosage of 100-175 mg/m2 (Answer 5). The Examiner finds that Drug Facts discloses “regimens for treating cancer of various types comprising combinations of chemotherapeutic drugs including paclitaxel in doses of 135 mg/m2 … and 200 mg/m2” (id. at 6), and discloses that the paclitaxel dose 1 Sorafenib is “a drug which contains the tosylate salt of BAY 43-9006 as an active ingredient” (Spec. 9:11-12). 2 Flaherty et al., 2004 ASCO Annual Meeting Proceedings (Post Meeting Ed.), 22 J. CLIN. ONCOL. (July 15 Supp.), abstract 7507 (2004). 3 Drug Facts and Comparisons, 58th ed., pp. 2150-2151 (2004). 4 Riedl et al., US 7,351,834, Apr. 1, 2008. 5 Grewal, US 2002/0197256 A1, Dec. 26, 2002. Appeal 2012-000290 Application 11/754,082 3 “can be varied depending on the cancer being treated and the other drugs used in combination with paclitaxel” (id.). The Examiner concludes that it would have been obvious “to adjust the dose of paclitaxel, in order to optimize the therapeutic efficacy of the treatment depending on patient factors such as age, weight, cancer type, stage of cancer, patient tolerance to the drug, and the other drugs used in combination with paclitaxel” (id.). The Examiner reasons that one of ordinary skill in the art would have recognized “the advantages of reducing the dosage of harsh chemotherapeutic agents as much as possible to reduce or avoid the well-known negative side effects of such drugs” (id.), and that “adjusting the dosages of active agents” is conventional and routine (id.). Appellant contends that the cited references would not have made obvious the claimed taxane amount of 100 mg/m2 to 175 mg/m2 of surface body area (Appeal Br. 19-21). Appellant also argues that unexpected results outweigh the evidence supporting the prima facie case of obviousness (id. at 20-21). The issues presented are: Does the evidence of record support the Examiner’s conclusion that the therapeutic agent combination of claim 1, with a taxane amount of between 100 mg/m2 to 175 mg/m2 of surface body area, would have been obvious in view of Flaherty and Drug Facts? If so, has Appellant provided evidence of unexpected results that outweighs the evidence supporting the prima facie case of obviousness? Appeal 2012-000290 Application 11/754,082 4 Findings of Fact 1. The Specification discloses that Sorafenib is a compound within the scope of Formula I of claim 1 (Spec. 10:29) and that Sorafenib “contains the tosylate salt of BAY 43-9006 as an active ingredient” (id. at 9:11-12). 2. Flaherty discloses that “BAY 43-9006 (BAY) is a novel signal transduction inhibitor that prevents tumor cell proliferation and angiogenesis” (Flaherty, abstract). 3. Flaherty discloses that a “Phase I/II trial of BAY 43-9006, carboplatin (C) and paclitaxel (P) demonstrates preliminary antitumor activity” (id., title). 4. Flaherty discloses that “BAY was given from day 2 to 19 of a 21 day cycle,” and carboplatin and paclitaxel (225 mg/m2) were each administered on day 1 (id.). 5. Flaherty discloses that the “combination of BAY with C [carboplatin] and P [paclitaxel] has demonstrated activity in melanoma with a favorable safety profile” (id.). 6. Drug Facts discloses chemotherapy regimens for different types of cancer (Drug Facts 2150-2151). 7. Drug Facts discloses that paclitaxel is administered to treat cancer, in combination with other drugs, in dosages of 135 mg/m2 (in combination with vinorelbine to treat breast cancer (id. at 2150) or with carboplatin to treat lung cancer (id. at 2151)) and 175 mg/m2 (in combination with cisplatin to treat lung cancer (id.), with cisplatin and fluorouracil to treat esophageal cancer (id.), or with ifosfamide, mesna, and cisplatin to treat esophageal cancer or head and neck cancer (id.)). Appeal 2012-000290 Application 11/754,082 5 Analysis Claim 1 is directed to a combination that comprises a compound of Formula I (e.g., BAY 43-9006), a taxane (e.g., paclitaxel) in the amount of 100 mg/m2 to 175 mg/m2 of surface body area, and a platinum complex antineoplastic agent (e.g., cisplatin). Flaherty discloses treating melanoma patients with BAY 43-9006 in combination with carboplatin and paclitaxel. Flaherty discloses that the combination demonstrated activity and had a favorable safety profile. Flaherty’s combination differs from claim 1 in that it included a paclitaxel dose of 225 mg/m2. Drug Facts discloses that paclitaxel is used in combination with other therapeutic agents at dosages of 175 mg/m2 and 135 mg/m2. In view of these disclosures, it would have been obvious to one of skill in the art to modify Flaherty’s combination of BAY 43-9006, paclitaxel, and carboplatin to include a paclitaxel dose within the range of 100 mg/m2 to 175 mg/m2 of surface body area, as recited in claim 1, since Drug Facts discloses that dosages in this range are routinely used for cancer treatment and, as the Examiner pointed out (Answer 6), a person of ordinary skill in the art would strive to use the lowest effective dose in order to minimize side effects. Appellant argues that “Flaherty discloses a higher dosage of taxane than presently claimed, and does not suggest that a lower dosage can be used,” and that the disclosure in Drug Facts of different drug combinations with lower doses of taxane does not cure this deficiency because the combinations in Drug Facts are different from the claimed combination (Appeal Brief 19-20). Appellant also argues that “Drug Facts and Comparisons further discloses a three drug combination in which 200 Appeal 2012-000290 Application 11/754,082 6 mg/m2/day Paclitaxel is administered” and “by teaching the full dosage of taxane, both Flaherty and the three drug combination taught by Drug Facts and Comparisons teach away from the claimed invention” (Appeal Br. 20). This argument is not persuasive. We agree with the Examiner that it would have been obvious to adjust the dose of paclitaxel, in order to optimize the therapeutic efficacy of the treatment depending on patient factors such as “the particular drug(s) used, adverse drug effects or toxicity, clinical response to treatment, etc.” (Answer 5-6). Although Flaherty teaches a higher dose of paclitaxel of 225 mg/m2 to treat melanoma, Drug Facts makes clear that dosages of paclitaxel within the claimed range are routinely used in combination with other chemotherapeutic agents to treat different types of cancer, and therefore would have been an obvious modification of Flaherty’s method. We do not agree with Appellant’s argument that the references teach away from the claimed dosage of paclitaxel. The fact that, for some uses, a higher dosage of paclitaxel is used does not teach away from using a lower dose in cases where that would be expected to be effective, and Drug Facts makes clear that dosages of paclitaxel within the claimed range are art- recognized for the treatment of cancer. Claim 1 is not limited to treatment of any specific type of cancer. Appellant also argues that evidence of unexpected results has overcome the prima facie case of obviousness (Appeal Br. 20). Appellant argues that “it was an unexpected result that the dosage of taxane could be reduced, as the higher dosage as a monotherapy was far less effective, and even the higher dosage in combination with carboplatin did not yield ORR Appeal 2012-000290 Application 11/754,082 7 [sic]” (id., citing Spec. 44, 50). Appellant argues that “it was unexpectedly found that the taxane dosage could be reduced and still have synergistic effectiveness” (id. at 21). This argument is not persuasive. The burden of demonstrating unexpected results rests on the party asserting them. In re Klosak, 455 F.2d 1077, 1080 (CCPA 1972). That burden has not been carried here because Appellant has not pointed to any evidence in the record to establish that the claimed paclitaxel dosage provides results that are superior to what would have been expected. Although the Appeal Brief asserts that the results of the combination were unexpected, attorney argument is not evidence. In re Pearson, 494 F.2d 1399, 1405 (CCPA 1974). Appellant points to pages 44 and 50 of the Specification as providing support for the assertion of unexpected results, but those passages provide no comparative data, much less a comparison to the closest prior art, that would show that the claimed dosage range provides unexpectedly superior results. See In re Baxter-Travenol Labs., 952 F.2d 388, 392 (Fed. Cir. 1991) (“[W]hen unexpected results are used as evidence of nonobviousness, the results must be shown to be unexpected compared with the closest prior art.”). In particular, although the Specification acknowledges that Flaherty’s combination was used in clinical trials (see Spec. 55:30-34), it provides no comparison of the claimed combination to Flaherty’s. Conclusion of Law The evidence of record supports the Examiner’s conclusion that the therapeutic agent combination of claim 1 would have been obvious in view of Flaherty and Drug Facts. Appellant has not provided evidence of Appeal 2012-000290 Application 11/754,082 8 unexpected results that outweighs the evidence supporting the prima facie case of obviousness. Thus, we affirm the rejection of claim 1 as being obvious in view of Flaherty and Drug Facts. Claims 2-10, 23-24 and 29-31 have not been argued separately and therefore fall with claim 1.6 37 C.F.R. § 41.37(c)(1)(vii). We also affirm the rejection of claim 11 as being obvious in view of Flaherty, Drug Facts and Riedl, and the rejection of claims 12-22 as being obvious in view of Flaherty, Drug Facts and Grewal, since Appellant has not provided any arguments based on Riedl or Grewal. SUMMARY We affirm the rejection of claims 1-24 and 29-31 under 35 U.S.C. § 103(a). 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 lp 6 Appellant raises an argument in the Reply Brief regarding claims 7 and 22, but “[t]he reply brief is not an opportunity to make arguments that could have been made during prosecution, but were not. Nor is the reply brief an opportunity to make arguments that could have been made in the principal brief on appeal to rebut the Examiner’s rejections, but were not.” Ex parte Borden, 2010 WL 191083 at *2 (BPAI 2010) (informative). “Any bases for asserting error, whether factual or legal, that are not raised in the principal brief are waived.” Id.