Ex Parte BURGERDownload PDFPatent Trial and Appeal BoardSep 17, 201812879347 (P.T.A.B. Sep. 17, 2018) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 12/879,347 09/10/2010 20277 7590 09/19/2018 MCDERMOTT WILL & EMERY LLP The McDermott Building 500 North Capitol Street, N.W. WASHINGTON, DC 20001 FIRST NAMED INVENTOR Angelika BURGER 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. 075389-0013 6801 EXAMINER CHOI, FRANK I ART UNIT PAPER NUMBER 1616 NOTIFICATION DATE DELIVERY MODE 09/19/2018 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): ipdocketmwe@mwe.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte ANGELIKA BURGER Appeal2017-005423 Application 12/879,347 1 Technology Center 1600 Before ULRIKE W. JENKS, TA WEN CHANG, and DAVID COTTA, Administrative Patent Judges. COTTA, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to a method of enhancing the efficacy of an anti-cancer agent selected from docitaxel and paclitaxel in a patient suffering from docitaxel-resistant or paclitaxel- resistant prostate cancer. The Examiner rejected the claims on appeal under 35 U.S.C. § 103(a) as obvious. We affirm. 1 According to Appellant, the real party in interest is Kominox, Inc. Br. 2. Appeal2017-005423 Application 12/879,347 STATEMENT OF THE CASE The Specification discloses: The major problem in developing effective and ultimately curative treatments for cancer lies in the fact that cancers are heterogeneous and contain mature cells as well as cells that are responsible for self-renewal, termed stem cells. Current cytotoxic anticancer agents are mainly aimed toward killing the mature cell population, but can not eradicate cancer stem cells. As a result, cancer often relapses and tumors then comprise more aggressive stem cell-like drug resistant cancer cells (Chumsri, S. et al., Curr. Opin. Mol. Ther. 10: 323-333, 2008). Therefore, there is a need for new therapeutic agents and/or regimens that can inhibit telomerase or target telomere to reduce or eliminate both mature and stem-like cancer cells including drug resistant cancer stem cells and mature cancer cells. Spec. ,r 4. The Specification further discloses: "The present invention provides methods and pharmaceutical compositions for preventing, treating, reducing, or eliminating cancer cells; more particularly the present invention provides a prophylactically and/or therapeutically effective amount or regimen of sodium meta arsenite for reducing or eliminating cancer stem cells and drug resistant cancer cells." Id. ,r 2. Claims 1, 9, 11, and 22 are on appeal. Claim 1 is illustrative and reads as follows: 1. A method of enhancing the efficacy of an anti-cancer agent selected from docitaxel and paclitaxel in a patient suffering from docitaxel-resistant or paclitaxel-resistant prostate cancer, said method comprising administering to the patient a unit dose of from 0.1 to 20 mg of sodium meta arsenite one or more times a day and a therapeutically effective amount of the anti-cancer agent. 2 Appeal2017-005423 Application 12/879,347 App. Br. 10 (Claims App'x). The Examiner rejected claims 1, 9, 11, and 22 under 35 U.S.C. § I03(a) as obvious over the combination of Ellison,2 Hawley's, 3 and EP 1721615.4 FINDINGS OF FACT 1. Sodium arsenite is also called sodium metaarsenite. Hawley's 1137; see also App. Br. 3 n.1. 2. The Examiner finds, and Appellant does not dispute, that taxol is also called paclitaxel. Ans. 7. 3. EP 1 721615 discloses that "there are three chemotherapy drugs approved by the U.S. Food and Drug Administration for use in prostate cancer-Taxotere® ( docetaxel), Novantrone® (mitoxantrone hydrochloride) and Emcyt® (estramustine sodium phosphate)." EP 1721615 ,r 34. 4. EP 1721615 discloses: Accordingly, the present invention provides a pharmaceutical composition intended for the treatment of urogenital diseases and bone metastasis in a human, wherein said pharmaceutical composition contains an effective amount of arsenous acid alkaline or earth alkaline metal salt and/or a pharmaceutically acceptable adjuvant. According to the present invention, said alkaline arsenous acid metal salt is sodium meta-arsenite (As02Na) or potassium meta-arsenite (As02K). Id. ,I,I 41--42. 5. EP 1721615 discloses: Surprisingly, oral arsenous acid sodium salt showed a 2 Ellison et al., US Patent No. 6,875,451 B2, issued Apr. 5, 2005 ("Ellison"). 3 HAWLEY'S CONDENSED CHEMICAL DICTIONARY 1137 (15th ed. 2007) ("Hawley's). 4 Lee et al., EP 1 721 615 Al, published Nov. 15, 2006 ("EP 1721615"). 3 Appeal2017-005423 Application 12/879,347 high therapeutic efficacy in cancer patients suffering from urogenital cancer, mainly prostate and bone metastasis, following treatment with 2.5, 10, 12.5, 15, 17.5 and 20 mg of arsenous acid sodium salt capsules for 14 consecutive days. Surprisingly the patients all tolerated the arsenous acid sodium salt extremely well with no adverse events (AE's) or serious adverse events (SAE's) occurring. Id. ,I,I 52-53. 6. EP 17216165 discloses: The compounds of the invention may be used alone or in combination. Additionally the treated compounds may be utilised with other types of treatments. For example, the subject compounds may be used with other chemotherapies e.g. tamoxifen, taxol, methothrexate, biologicals such as antibodies, growth factors or lymphokines, radiation etc. Combination therapies may result in synergistic results. The preferred indication is cancer especially the cancers identified previously. Id. ,I 88. 7. EP 1721615 discloses examples in which patients suffering from prostate cancer "not amenable to any established methods of therapy" were effectively treated with arsenous acid sodium salt at seven different dosing levels with "no adverse events" and a "high level of efficacy." Id. ,r,r 99-129 (quoted phrases drawn from ,r,r 99, 105). 8. Ellison discloses: the present invention relates to novel chemotherapeutic methods-novel uses of arsenic compounds for treating primary and metastatic tumors; primary and metastatic tumors of the central nervous system; refractory primary and metastatic tumors of the central nervous system; breast, lung, bladder and prostate cancer; and refractory breast, lung, bladder and prostate cancer to mention a few. Ellison, col. 1, 11. 17-24. 4 Appeal2017-005423 Application 12/879,347 9. Ellison discloses: "The arsenic compound of the invention may be utilized in ... a variety of known forms. . . . The inorganic salt forms of arsenic are preferred. For example ... sodium arsenite ... may be used." Id. at col. 8, 11. 48---60. 10. Ellison discloses: In accordance with the present invention, arsenic compounds can be used alone or in combination with other known therapeutic agents (including chemotherapeutics, radioprotectants and radiotherapeutics) or techniques to either improve the quality of life of the patient, or to treat the primary neoplastic disease. For example, the arsenic compounds can be used before, during or after the administration of one or more known antitumor agents including but not limited to ... taxol. Id. at col. 6, 11. 36-47. ANALYSIS In concluding that claims 1, 9, 11, and 22 would have obvious, the Examiner found that Ellison disclosed that "arsenic compounds, such as sodium arsenite, can be used to treat refractory primary and metastatic tumors of the prostate ... including remission thereof' and that the arsenic compounds could be administered "before, during or after chemotherapeutic agents, such as taxol and cisplatin." Final Act. 5 3--4. The Examiner acknowledged, however, that Ellison did not expressly disclose treatment of prostate cancer which is resistant to docetaxel or paclitaxel. Id. at 4. The Examiner found that EP 1721615 disclosed that "oral sodium meta-arsenite is well tolerated and has greater therapeutic and safety advantages in comparison with arsenic trioxide." Id. EP 1721615 further 5 Office Action mailed April 20, 2016 ("Final Act."). 5 Appeal2017-005423 Application 12/879,347 disclosed that sodium meta arsenite could be used to treat prostate cancer which is resistant to traditional chemotherapy drugs and that sodium meta arsenite may be used with other chemotherapies, such as taxol. Id. Based on the combined disclosures ofEP 1721615, the Examiner concluded that claimed method would have been obvious and that the skilled artisan would reasonably have expected "that sodium meta arsenite would enhance the activity of docetaxel and paclitaxel against prostate cancer which is resistant to docetaxel or paclitaxel." Id. at 5. We adopt the Examiner's findings of fact and reasoning regarding the scope and content of the prior art (Ans. 2-7; Final Act. 3-8) and agree that the claims are obvious over Ellison, Hawley's, and EP 1721615. We address Appellant's arguments below. Appellant argues that "[ t ]he combination of cited prior art fails to provide a reasonable basis for an expectation of success in treating docetaxel or paclitaxel resistant prostate cancers with a combination of sodium meta arsenite and docetaxel or paclitaxel." App. Br. 3. We are not persuaded. Ellison and EP 1721615 both teach the use of sodium meta arsenite to treat prostate cancer. FFl, FF4, FF5, FF8, FF9. Ellison teaches that sodium meta arsenite can be used to treat refractory prostate cancer- i.e. cancer that does not respond to treatment. FF8. Similarly, EP 1721615 discloses examples in which patients suffering from prostate cancer not amenable to any established methods of therapy were effectively treated with arsenous acid sodium salt. FF7. Appellant fails to direct us to persuasive evidence demonstrating that docitaxel-resistant and paclitaxel-resistant prostate cancer differ materially from "refractory prostate cancer." Accordingly, we find that the skilled artisan would reasonably have expected that a compound that 6 Appeal2017-005423 Application 12/879,347 taught to be effective in treating "refractory prostate cancer" and prostate cancer that was "not amenable to any established methods of therapy" - i.e. sodium meta-arsenite - would also be effective in treating docitaxel-resistant or paclitaxel-resistant prostate cancer. In addition, both Ellison and EP 1721615 teach that sodium meta- arsenite may be used in combination therapy with other therapeutic agents. Both Ellison and EP 1721615 specifically identify taxol - i.e. paclitaxel (FF2)- among the therapeutic agents that can be used in combination their inventive arsenic compounds. FF6, FF 10. 6 This provides reason to administer sodium meta-arsenite in combination with paclitaxel. Appellant argues that the cited publications "do not suggest that sodium meta arsenite reverses taxane resistance of cancer cells, enabling use of both drugs ( sodium meta arsenite and the taxane) to treat the resistant forms of prostate cancer using lower effective concentration of each drug." App. Br. 3. We are not persuaded because, as discussed above, the prior art discloses that sodium meta arsenite would be effective to treat prostate cancers which are resistant to treatment (FF7, FF8), and suggests administering sodium meta arsenite in combination with other therapies, including paclitaxel. FF2, FF6, FFlO. As the Examiner explained, the advantage of reversing resistance to docetaxel and paclitaxel "would flow naturally from following the suggestion in the art to treat prostate cancer which is resistant to paclitaxel and docetaxel with the combination of sodium meta arsenite and paclitaxel or docetaxel." Ans. 5. 6 EP 1 721615 suggests that combination therapy "may result in synergistic results." FF6. 7 Appeal2017-005423 Application 12/879,347 Appellant argues that the record shows that "taxane resistance poses a significant challenge in the treatment of prostate cancer" and that even so, "taxanes remain the gold standard for treatment of prostate cancer." App. Br. 4 (citing Madan,7 Abstract). Accordingly, Appellant argues, "there is a long felt need for therapies that overcome taxane resistance of prostate cancer cells." Id. We are not persuaded. We acknowledge that Madan identifies a "need to overcome taxane resistance in prostate cancer." Madan, Abstract. This statement notwithstanding, we are not persuaded that Madan supports the existence of a long felt need because Madan also teaches, inter alia, that "[t]herapeutic combinations have ... been employed to overcome taxane resistance in prostate cancer." Madan 3 897; see also id. at Abstract ("[p ]reliminary evidence suggests that several treatment strategies may improve the activity of taxanes in prostate cancer and perhaps enhance clinical outcomes"). Additionally, Madan was published after Appellant's Application was filed. Appellant does not provide evidence that the purported need identified in Madan was recognized at the time of Appellant's invention. To the extent there was a need to overcome taxane resistance at the time of Appellant's invention, Ellison, and EP 1721615 address that need. Ellison and EP 1721615 disclose that sodium meta-arsenite can be used to treat refractory prostate cancer and prostate cancer that was not amenable to any established methods of therapy. FF7, FF8. As discussed above, Appellant has not directed us to persuasive evidence suggesting that 7 Ravi A. Madan et al., Overcoming Chemotherapy Resistance in Prostate Cancer, 17(12) CLIN. CANCERRES. 3892, 3902 (2011) ("Madan"). Madan was cited by Appellant as evidence supporting a long felt need. 8 Appeal2017-005423 Application 12/879,347 docetaxel and paclitaxel resistant cancer would not be among the refractory cancers taught to be treatable with sodium meta-arsenite. More specifically, Appellant has not provided persuasive evidence or argument explaining why Ellison and EP 1 71615 do not address the purported need to overcome taxane resistance in prostate cancer. See Newell Companies, Inc. v. Kenney Mfg. Co., 864 F.2d 757, 768 (Fed. Cir. 1988) ("[o]nce another supplied the key element, there was no long-felt need or, indeed, a problem to be solved."). Accordingly, we are not persuaded that a long felt need demonstrates the non-obviousness of the claimed method. Appellant argues that unexpected results demonstrate the non- obviousness of the claimed method. According to Appellant, the Kim8 and Hussain9 Declarations show that: not only is drug resistance reversed by sodium meta arsenite, but the taxane-resistant prostate cancer cells are killed by the combination of sodium meta arsenite and the taxane at a surprisingly and significantly lower effective dose of each of the drugs in the combination than is required of each drug when used alone to treat wild type or resistant cells. App. Br. 6. We are not persuaded because we agree with the Examiner that the prior art provides a "general expectation of synergistic activity." Ans. 5; see also FF6. Particularly in view of this general expectation, Appellant has 8 Declaration of Dr. Su jong Kim, signed October 23, 2014 ("Kim Deel."). The record includes a second Kim declaration, signed October 6, 2014, however, this Declaration relates to treatment of lung cancer cells with sodium meta-arsenite. Appellant does not explain the relevance of this declaration to the present claims, which are directed to treatment of prostate cancer. 9 Declaration of Dr. Arif Hussain, signed December 19, 2011 ("Hussain Deel."). 9 Appeal2017-005423 Application 12/879,347 not provided persuasive evidence that the results described in the Kim and Hussain Declarations would have been unexpected. In addition, the claimed method requires administering a dose of "0.1 to 20 mg of sodium meta arsenite one or more times a day" to a patient together with a "therapeutically effective amount" docetaxel or paclitaxel. The Kim and Hussain Declarations describe administration of a 50%, 75%, and 90% of an effective dose to cultured prostate cancer cells. AppeUant does not explain how the dosages tested in the experiments described in the Kim and Hussain Declarations c01Telate with the claimed dosage. Nor does Appellant explain why the results from testing performed on a cell culture establish unexpected results for administration "to the patient" as claimed. Accordingly, the proffered evidence of unexpected results is not commensurate with the scope of the claims. DECISION For these reasons and those set forth in the Examiner's Answer and Final Office Action, we affirm the Examiner's rejection of claims 1, 9, 11, and 22 under 35 U.S.C. § 103(a) as obvious over the combination of Ellison, Hawley's, and EP 1721615. 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 ). See 37 C.F.R. § 1.136(a)(l )(iv). AFFIRMED 10 Copy with citationCopy as parenthetical citation