Ex Parte Nuijen et alDownload PDFPatent Trial and Appeal BoardSep 25, 201714173734 (P.T.A.B. Sep. 25, 2017) Copy Citation United States Patent and Trademark Office 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 APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 14/173,734 02/05/2014 Bastiaan Nuijen 1948361.00146 CON 7073 45200 7590 09/27/2017 K&L Gates LLP-Orange County 1 Park Plaza Twelfth Floor IRVINE, CA 92614 EXAMINER PAK, JOHN D ART UNIT PAPER NUMBER 1616 NOTIFICATION DATE DELIVERY MODE 09/27/2017 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): uspatentmail@klgates.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte BASTIAAN NUJIEN, ERNIE PFADENHAUER, JOS H. BEIJNEN, LUIGI LENAZ, SHANTA CHAWLA, and MARIO BEER1 Appeal 2017-003041 Application 14/173,734 Technology Center 1600 Before ULRIKE W, JENKS, JOHN E. SCHNEIDER, and RACHEL H. TOWNSEND, Administrative Patent Judges. SCHNEIDER, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 (a) involving claims to methods for treating bladder cancer which have been rejected for improper dependent form and/or as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. 1 Appellants identify the Real Party in Interest as Spectrum Pharmaceuticals, Inc. Appeal Br. 3. Appeal 2017-003041 Application 14/173,743 STATEMENT OF THE CASE Bladder cancer is one of the most common types of cancer in the world. Spec. 13. Management of bladder cancer may be achieved by transurethral resection where all visible lesions are removed. Spec. 1 6. “Transurethral resection of bladder tumor (TUR-BT) is often followed by a course of adjuvant intravesical chemotherapy or immunotherapy with the aim of both eradicating remaining tumor cells and preventing tumor recurrence.” Id. The Specification describes the use of Apaziquone as a treatment of bladder cancer following TUR-BT. Spec. H 11—14. Claims 1—3, 7—11, 13, and 16 are on appeal. Claims 1 and 16 are the sole independent claims and read as follow: 1. A method of treating bladder cancer comprising administering a therapeutic composition comprising a therapeutic amount of Apaziquone immediately after transurethral resection of bladder tumor (TUR-BT). 16. A method of treating bladder cancer comprising the steps of: (a) performing transurethral resection of a bladder tumor in patients in need thereof; and (b) administering via intravesical instillation a therapeutically effective amount of Apaziquone. 2 Appeal 2017-003041 Application 14/173,743 The claims stand rejected as follows: Claims 1—3, 7—11, 13, and 16 have been rejected under 35 U.S.C. § 103(a) as unpatentable over Nuijen2 in view of Oosterlinck3 and Wientjes.4 Claim 3 has been rejected under 35 U.S.C. § 112 fourth paragraph as being in improper dependent form.5 OBVIOUSNESS Issue The issue with respect to this rejection is whether a preponderance of evidence supports the Examiner’s finding that claims 1—3, 7—11, 13, and 16 would have been obvious over Nuijen combined with Oosterlinck and Wientjes. The Examiner finds that Nuijen discloses the use of Apaziquone to treat superficial bladder cancer following TUR-BT, but does “not specify administering their compositions ‘immediately after’ TUR-BT.” Final Act. 4—5. Oosterlinck teaches administration of a chemotherapeutic agent immediately following TUR. Final Act. 5. Wientjes teaches that administration of a chemotherapeutic agent following TUR reduces the likelihood of blabber cancer recurring by tumor cells dislodged by resection. 2 Nuijen et al., US 2003/0133954 Al, published July 17, 2003 (“Nuijen”). 3 Oosterlinck et al., Guideline on Bladder Cancer, 41 European Urology 105 (2002) (“Oosterlinck”). 4 Wientjes et al., Bladder Wall Penetration of Intravesical Mitomycin C in Dogs, 51 Cancer Res. 4347 (1991) (“Wientjes”). 5 Appellants also present arguments relating to a rejection of the claims as obvious over Mirejovsky et al., US 2007/0185188, published Aug. 9, 2007. We have not considered these arguments as the Examiner has noted that this rejection was not maintained in the Final Action. Ans. 2. 3 Appeal 2017-003041 Application 14/173,743 which may implant to form secondary tumors. Id. The Examiner concludes that the claimed invention, as a whole, would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made, because every element of the invention and the claimed invention as a whole have been fairly disclosed or suggested by the teachings of the cited references. Final Act. 6. Appellants contend that Nuijen does not teach or suggest administering Apaziquone in any specific time frame. Appeal Br. 9. Appellants contend that despite the teachings of Oosterlinck, one skilled in the art would not have been motivated to administer Apaziquone within 6 hours of TUR. Id. Appellants also argue that one skilled in the art would not have had a reasonable expectation of success that the use of Apaziquone within six hours of TUR would have been successful. Id. at 9—10. Appellants contend that the Examiner engaged in improper hindsight in reaching a conclusion of obviousness. Id. at 10. Findings of Fact We adopt the Examiner’s findings as our own, including with regard to the scope and content of, and motivation to modify or combine, the prior art. The following findings are included for emphasis and reference purposes. FF1. Nuijen discloses the use of Apaziquone for “intravesical instillation to treat bladder cancer.” Nuijen | 5. FF2. Nuijen teaches that while Apaziquone was reported to fail in several clinical trials, Nuijen teaches that the problems encountered using Apaziquone to treat systemic cancers 4 Appeal 2017-003041 Application 14/173,743 may be advantageous for treating cancers which arise in a third compartment such as superficial bladder cancer. In this scenario, drug delivery is not problematical via the intravesical route and the penetration of E09 into avascular tissue can be increased by maintenance of therapeutically relevant drug concentrations within the bladder (using a one hour instillation period for example). While this method of instilling E09 within the bladder may be useful, there still remains a need for drug delivery vehicles that are capable of delivering an effective amount of E09 within the bladder. Nuijen 14. FF3. Nuijen teaches that Apaziquone (E09) can be used in amounts ranging from 0.5 mg to about 16 mg. Nuijen 112. FF4. Nuijen states that “[t]he results of this study provide strong evidence in support of the proposal that intravesical administration of E09 may have activity against bladder tumors.” Nuijen 139. FF5. Oosterlinck teaches that Immediate instillation after TUR with a chemotherapeutic agent should be encouraged in all cases as it is able to reduce recurrence rate by about 50% [11,12], In intermediate risk tumours that needs a further instillation, an early instillation can reduce the need for maintenance therapy [13]. Low-risk tumours need no further treatment. Oosterlinck 106, col. 2. FF6. Oosterlinck goes on to teach that Tumours with a higher risk of recurrence should be treated with a 4—8-week-course of bladder instillation. Severe bladder irritation is a reason to delay or stop the treatment to avoid invalidating symptoms for the patient and later bladder contraction. Side effects are related to the intensity of the treatment regimen. 5 Appeal 2017-003041 Application 14/173,743 Id. FF7. Wientjes teaches that one type of target cells for intravesical chemotherapy is tumor cells which become dislodged during resection which may implant to form secondary tumors. Wientjes 4347. FF8. Wientjes also teaches that tumor classified as Ta respond more favorably to intravesical chemotherapy than Ti tumors. Id. Principles of Law “[T]he examiner bears the initial burden, on review of the prior art or on any other ground, of presenting a prima facie case of unpatentability. If that burden is met, the burden of coming forward with evidence or argument shifts to the applicant.” In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992). A proper § 103 analysis requires “a searching comparison of the claimed invention—including all its limitations—with the teaching of the prior art.” In re Ochiai, 71 F.3d 1565, 1572 (Fed. Cir. 1995). “The consistent criterion for determination of obviousness is whether the prior art would have suggested to one of ordinary skill in the art that this process should be carried out and would have a reasonable likelihood of success, viewed in the light of the prior art. Both the suggestion and the expectation of success must be founded in the prior art, not in the applicant’s disclosure.” In re Dow Chemical Co., 837 F.2d 469, 473 (Fed. Cir. 1988). “Non-obviousness cannot be established by attacking references individually where the rejection is based upon the teachings of a combination of references. . . . [The reference] must be read, not in isolation, but for what it fairly teaches in combination with the prior art as a whole.” In re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986). 6 Appeal 2017-003041 Application 14/173,743 “Any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning, but so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made and does not include knowledge gleaned only from applicant’s disclosure, such a reconstruction is proper.” In re McLaughlin, 443 F.2d 1392, 1395 (CCPA 1971). “A prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art.” In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003). Analysis We find the Examiner has established that the claims would have been obvious over Nuijen combined with Oosterlinck and Wientjes. Appellants have not produced evidence showing, or persuasively argued, that the Examiner’s determinations on obviousness are incorrect. Only those arguments made by Appellants in the Briefs have been considered in this Decision. Arguments not presented in the Briefs are waived. See 37 C.F.R. § 41.37(c)(l)(iv) (2015). We have identified claim 1 as representative; therefore, all claims, except those addressed below, fall with claim 1. We address Appellants’ arguments below. Appellants contend that the teachings of Oosterlinck as limited to the specific agents described in studies cited by Oosterlinck and do not apply to all chemotherapeutic agents. Appeal Br. 8—9. Appellants argue that Oosterlinck does not teach that the use of Apaziquone is safe and tolerable when administered immediately after TUR. Id. To support these arguments, Appellants point to the portion of Oosterlinck where it states that “[sjevere 7 Appeal 2017-003041 Application 14/173,743 bladder irritation is a reason to delay or stop treatment.” Id. (quoting Oosterlinck 106.) We are unpersuaded by Appellants’ arguments. We agree with the Examiner Ans. 4., that the teachings of Oosterlinck are not limited to the two agents specifically mentioned in the studies Oosterlinck cites as support for the statement with respect to treatment guidelines that “[ijmmediate instillation after TUR with a chemotherapeutic agent should be encouraged in all cases as it is able to reduce recurrence rate by about 50% [11,12]” FF5. We find that Oosterlink’s treatment guideline embraces all chemotherapeutic agents known to treat bladder cancer in light of the fact that. Oosterlinck recommends treatment with a chemotherapeutic agent and not the specific agents of the studies that Oosterlinck cites. FF5. Turning to the lack of teaching in Oosterlinck regarding Apaziquone, the Examiner does not rely on Oosterlinck to teach that Apaziquone was known to be used to treat bladder cancer. Appeal Br. 8. Nuijen teaches the use of Apaziquone to treat bladder cancer FF1, and is the reference the Examiner relied upon in that regard. Final Act. 4—5. Appellants’ argument that Oosterlinck teaches that immediate administration of a chemotherapeutic agent would cause irritation and that this would lead one skilled in the art not to use Apaziquone is misplaced. Appeal Br. 9. While Appellants correctly quote a portion of Oosterlinck, the paragraph from which the quote is taken does not address concerns with the immediacy of administration of a chemotherapeutic but refers to side effects which might occur during the course of a 4 to 8 week course of bladder instillation. FF6. We agree with the Examiner that the discussion of 8 Appeal 2017-003041 Application 14/173,743 possible side effects in Oosterlinck would not dissuade one skilled in the art from using a chemotherapeutic such as Apaziquone for immediate instillation following TUR. Ans. 5—7. Appellants argue that Nuijen is silent as to the time frame for application of Apaziquone and that one skilled in the art would not consider using Apaziquone for immediate instillation. We remain unpersuaded. Appellants’ argument is an attack on the teachings of Nuijen alone and not in context with teachings of Oosterlinck and Wientjes. We agree with the Examiner that the combined teachings of the references would lead one skilled in the art to administer Apaziquone immediately after TUR to prevent dislodged tumor cells from forming secondary tumor and to significantly reduce the recurrence of bladder cancer. Ans. 4; FF 4, 5, 7, and 8. Appellants argue that one skilled in the art would not have a reasonable expectation of success in using Apaziquone for immediate instillation following TUR. Appeal Br. 9—10. This argument is unpersuasive. Nuijen clearly teaches the efficacy of Apaziquone against bladder tumors and recommends its use. FF4. Oosterlinck teaches that administration of a chemotherapeutic agent immediately after TUR has significant benefits. FF5. Moreover, as the Examiner points out, Nuijen teaches that Apaziquone is effective at reduced doses which reduces toxicity and the risk of adverse side effects. Ans. 5; Nuijen 139. In light of these facts, we agree with the Examiner that there would have been a reasonable probability of success. Id. 9 Appeal 2017-003041 Application 14/173,743 Appellants contend that the Examiner has engaged in impermissible use of hindsight. Appeal Br. 10. Appellants argue that since Oosterlinck only describes the use of two agents for immediate instillation, the motivation to use Apaziquone for immediate instillation came from Appellants’ Specification. Appeal Br. 10. We find this argument unpersuasive. As discussed above, the recommendation in Oosterlinck is not limited to the two agents used in the studies referenced but is directed to using chemotherapeutic agents generally. Nuijen teaches that Apaziquone is an effective chemotherapeutic agent for treating bladder cancer. FF3. Thus, the motivation to use Apaziquone stems from the references not from Appellants’ disclosure. Claim 2 Appellants argue that claim 2 is separately patentable for the reasons argued above and because the references do not teach or suggest intravesical installation as required by claim 2. Appeal Br. 11. We are unpersuaded. Nuijen specifically teaches intravesical instillation. Nuijen | 5 (“the compositions of the present invention comprise pharmaceutical products formulated for intravesical instillation to treat bladder cancer”) and ]fl 2 (“The embodiments of the present invention are directed to compositions for treating bladder cancer via intravesical instillation. . . . instillation doses range from. . . .). Claims 7—10 Appellants contend that claims 7—10 are separately patentable in that the references do not teach or suggest treating bladder cancer where the cancer is non-invasive cancer, a transition cell carcinoma, TNM stage Ta or 10 Appeal 2017-003041 Application 14/173,743 Tl, or histologic grade G1 or G2. Appellants’ argument is unpersuasive. As the Examiner points out, treatment of these types of bladder cancer is specifically taught by Oosterlinck. Ans. 9—11; Oosterlinck 106 section 3 (referring to treating non-invasive bladder cancer with instillation of a chemotherapeutic), 106 (disclosing treatment of TNM stage Ta and Tl lesions and histologic Gl, G2, and G3 tumors), 105—106 (disclosing immediate instillation of a chemotherapeutic agent after TUR-BT is encourage in transitional cell carcinoma bladder cancers).. Claims 11 and 13 In addition to the arguments discussed above, Appellants argue that claims 11 and 13 are patentable in that the references do not teach the specific dosage ranges recited in the claims. Appeal Br. 13. We are not persuaded. The claims recite dosage limits of from 1 to 8 mg (claim 11) and 3 to 5mg (claim 13). Appeal Br. 18 (Claims App’x). These values fall within the range taught by Nuijen of .5 to 13mg (FF3). Thus, the claimed ranges are prima facie obvious. In re Peterson, 315 F.3d at 1329. Claim 16 In addition to the arguments presented above, Appellants argue that claim 16 is patentable as Nuijen raises doubts about the efficacy of Apaziquone. Appeal Br. 14. In support of their argument, Appellants cite to paragraph 4 of Nuijen where the reference discusses failures that have occurred in clinical trials using Apaziquone. Id. We find this argument unpersuasive. Once again, we find Appellants have taken a quote out of context. While Nuijen does note there have been failures to treat some cancers using systemic delivery of Apaziquone, it points out the failures 11 Appeal 2017-003041 Application 14/173,743 “may be the result of poor drug delivery” to those tumors, rapid plasma elimination, and poor penetration through multicell layers (Nuijen 14), not that Apaziquone is ineffective as a general matter. Nuijen states that “[wjhile these undesirable characteristics are a serious setback for the treatment of systemic disease,. . . they may be advantageous” for treating cancers such as superficial bladder cancer. FF2. Nuijen explains that “drug delivery is not problematical via the intravesical route” for such a “third compartment cancer” and that, in such cancers, penetration into avascular tissue “can be increased by maintenance of therapeutically relevant drug concentrations within the bladder.” Nuijen 14. Moreover, Nuijen goes on to state that “The results of this study provide strong evidence in support of the proposal that intravesical administration of E09 may have activity against bladder tumors.” FF4. Thus, Nuijen sternly encourages the use of Apaziquone to treat balder cancer. It does not raise doubts about its efficacy. Conclusion of Law We conclude that a preponderance of the evidence supports the Examiner’s conclusion that claims 1, 2, 7—11, 13, and 16 would have been obvious over Nuijen combined with Oosterlinck and Wientjes. Claim 3 has not been argued separately and therefore falls with claim 1. 37C.F.R. §41.37(c)(l)(iv). 12 Appeal 2017-003041 Application 14/173,743 IMPROPER DEPENDENT FORM Issue The issue with respect to this rejection is whether a preponderance of the evidence supports the Examiner’s conclusion that claim 3 is in improper dependent form. The Examiner finds that claim 1 calls for the administration of Apaziquone “immediately after” TUR whereas claim 3 calls for administration within 6 hours of TUR. Final Act. 3. Using a dictionary definition, the Examiner defines immediately as not separated in time or without delay. Id at 4. The Examiner finds that a period of 6 hours later does not meet either condition and thus is not immediate. Id. Consequently, the Examiner concludes that claim 3 does not properly depend from claim 1. Id. Appellants contend that the Examiner has improperly ignored the teaching of the Specification where it teaches that immediate means within 6 hours. Appeal Br. 16. Findings of Fact FF9. The instant Specification states This study assessed the tolerability and safety of administering EOQUIN® immediately (i.g. [sic] within about 6 hours) following TUR-BT in patients with superficial bladder cancer. Plasma levels were measured in patients at selected sites to assess the degree of systemic absorption of EOQUIN® following intravesical instillation immediately (i.e. within about 6 hours) following TUR-BT. Spec. 1119. 13 Appeal 2017-003041 Application 14/173,743 Principles of Law “[T]he specification is always highly relevant to the claim construction analysis. Usually, it is dispositive; it is the single best guide to the meaning of a disputed term.” Vitronics Corp. v. Conceptronic, Inc., 90 F.3d 1576, 1582 (Fed. Cir. 1996). “[DJuring examination proceedings, claims are given their broadest reasonable interpretation consistent with the specification.” In re Hyatt, 211 F.3d 1367, 1372 (Fed. Cir. 2000). Analysis We find that Appellants have the better argument. When read in light of the Specification, one skilled in the art would understand the term immediate as used in the claimed method of treating bladder cancer to mean within 6 hours. The Specification clearly equates immediate administration of Apaziquone with administration within 6 hours of TUR-BT. The Examiner contends that since Appellants do not recite a specific definition of immediate in the Specification, there is no basis for interpreting the term to embrace delay of up to six hours. Ans. 13—14. We are unpersauded. The Specification clearly coveys to one skilled in the art that a period of up to six hours is within the meaning of immediate as used in the claims. FF9. To hold otherwise would be inconsistent with the teachings of the Specification. Conclusion of Law We conclude that a preponderance of the evidence does not support the Examiner’s conclusion that claim 3 improperly depends from claim 1. 14 Appeal 2017-003041 Application 14/173,743 SUMMARY We affirm the rejection under 35 U.S.C. § 103(a). We reverse the rejection under 35 U.S.C. § 112, fourth paragraph. 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 15 Copy with citationCopy as parenthetical citation