Ex Parte Yla-HerttualaDownload PDFPatent Trial and Appeal BoardMar 23, 201713969763 (P.T.A.B. Mar. 23, 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. 13/969,763 08/19/2013 Seppo YLA-HERTTUALA FKD - 61/692,828 6511 22925 7590 03/27/2017 PHARMACEUTICAL PATENT ATTORNEYS, LLC 55 MADISON AVENUE 4THFLOOR MORRISTOWN, NJ 07960-7397 EXAMINER PAK, MICHAEL D ART UNIT PAPER NUMBER 1646 NOTIFICATION DATE DELIVERY MODE 03/27/2017 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): docket @ LicensingLaw. net administration @LicensingLaw.net PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte SEPPO YLA-HERTTUALA Appeal 2016-0073951 Application 13/969,763 Technology Center 1600 Before ERIC B. GRIMES, RICHARD M. LEBOVITZ, and JOHN E. SCHNEIDER, Administrative Patent Judges. LEBOVITZ, Administrative Patent Judge. DECISION ON APPEAL This appeal involves claims directed to treating cancer comprising administering a cytotoxic compound and a decoy receptor which binds to vascular endothelial growth factor (“VEGF”). The Examiner rejected the claims as anticipated under 35 U.S.C. §§ 102(b)/(e) and obvious under 35 U.S.C. § 103(a). We have jurisdiction under 35 U.S.C. § 134. The rejections are affirmed. STATEMENT OF THE CASE Appellant appeals from the Examiner’s final rejection of claims 1—11. The claims stand rejected by the Examiner as follows: 1 The Appeal Brief (“Appeal Br.”) at page 1 lists FKD Therapies Oy as the real-party-in-interest. Appeal 2016-007395 Application 13/969,763 1. Claims 1—6 and 8—10 under 35 U.S.C. § 102(e) as anticipated by Baldwin.2 Examiner’s Answer (“Ans.”) 3. 2. Claims 1—5 under 35 U.S.C. § 102(b) as anticipated by Hu.3 Ans. 3. 3. Claims 1—11 under 35 U.S.C. § 103(a) as obvious in view of Byrne,4 Hu, Sallinen,5 and Baldwin. Ans. 5. Claim 1, the only independent claim on appeal, is reproduced below: 1. In a method of treating cancer by administering a cytotoxic compound, the improvement comprising administering a decoy receptor which binds to Vascular Endothelial Growth Factor, wherein said decoy receptor is in a form adequate to ensure efficient dimerization of said decoy receptor, said cytotoxic compound and said decoy receptor administered in amounts which are together effective to treat said cancer. 1. REJECTION BASED ON BALDWIN The Examiner found that Baldwin describes treating ovarian cancer, 2 Megan E. Baldwin, U.S. Pat. App. Publ. 2013/0344065 Al, publ. Dec. 26, 2013. 3 Limin Hu, Hofmann, J., Holash, J., Yancopoulos, G.D., Sood, A.K., and Jaffe, R.B., Vascular Endothelial Growth Factor Trap Combined with Paclitaxel Strikingly Inhibits Tumor and Ascites, Prolonging Survival in a Human Ovarian Cancer Model, 11 Clin. Cancer Res., 6966—71 (2005). 4 Annette T. Byrne, Ross, L., Holash, J., Nakanishi, M., Hu, L., Hofmann, J.I., Yancopoulos, G.D., and Jaffe, R.B., Vascular Endothelial Growth Factor-Trap Decreases Tumor Burden, Inhibits Ascites, and Causes Dramatic Vascular Remodeling in an Ovarian Cancer Model, 9 Clin. Cancer Res., 5721-28 (2003). 5 Hanna Sallinen et al., Antiangiogenic Gene Therapy With Soluble VEGFR-1, -2, and -3 Reduces the Growth of Solid Human Ovarian Carcinoma in Mice, 17 Mol. Ther., 278—84 (2009). 2 Appeal 2016-007395 Application 13/969,763 as required by claim 1. Final Office Action (“Final Act.”) 5. The Examiner found that Baldwin describes administering a cytotoxic compound (taxane) and a soluble receptor trap from a VEGF receptor (VEGF-Trap) that serves as the claimed “decoy receptor which binds to Vascular Endothelial Growth Factor.” Id. The VEGF-Trap described in Baldwin comprises an Fc region which the Examiner found ensures efficient dimerization of said decoy receptor as required by the claims. Id. See Spec. 2:18—19 (“All constructs contain an immunoglobulin Fc domain to ensure efficient dimerization of the soluble decoy receptors”). The Examiner also found that Baldwin describes gene therapy using a viral vector comprising the VEGF-Trap as required by rejected claim 6. Id. The filing date of the Baldwin U.S. Application is August 29, 2013. Baldwin’s application is a continuation of an earlier filed application and a PCT Application filed April 5, 2011. It also claimed benefit of a provisional application filed April 15, 2010. The U.S. Application was published December 26, 2013. The corresponding PCT application published October 20, 2011.6 Neither the Examiner nor Appellant made an express determination as to whether Baldwin was entitled to the priority date of April 15, 2010. The instant application was filed August 19, 2013 and claims benefit to a provisional application filed August 24, 2012. Baldwin’s PCT application was published October 20, 2011 which is less than a year before the instant application’s provisional filing date and, thus, is not a statutory bar to patentability. 6 The Examiner did not cite the published PCT Application. 3 Appeal 2016-007395 Application 13/969,763 The inventor, Seppo Yla-Herttuala, M.D., provided several declarations under 37 C.F.R. § 1.131 in an attempt to antedate the published U.S. application by establishing a reduction to practice of the claimed invention before Baldwin’s PCT filing date and before Baldwin’s provisional application filing date, respectively. Appellant argues that it was not necessary to provide evidence that the invention was reduced to practice prior to Baldwin’s provisional application’s filing date because the Examiner did not provide a copy of the provisional application7 nor establish that Baldwin’s published application was entitled to such date. Appeal Br. 5—6. We do not need to reach the issue of entitlement to the provisional application filing date because, as discussed in more detail below, the declarations filed to antedate Baldwin’s published application are ineffective. It is noted that the declarations filed March 13, 2015, July 17, 2015, and October 8, 2015 all contain the same information and all are ineffective in antedating Baldwin. The March 13, 2015 and July 17, 2015 declarations did not contain an English translation of the “laboratory animal printed form.” This was corrected in a declaration executed October 6, 2015 (“Yla-Herttuala Oct. 2015 Decl.”). We note that the Examiner indicated that the Oct. 2015 declaration was not considered, but yet commented that Appellant did not discuss the information within the Declaration. Ans. 8. We considered the declaration because it is the same as the other two declarations, differing only in having 7 It was not necessary for the Examiner to provide a copy of the provisional application because it was readily available to Appellant. See Ex parte Yamaguchi, 88 USPQ2d 1606, 2008 WL 4233306 (BPAI 2008)(Precedential Opinion). 4 Appeal 2016-007395 Application 13/969,763 attestments to different dates of the reduction to practice of the claimed invention and in being accompanied by an English translation of the laboratory animal printed form. Legal Principles 37 C.F.R. § 1.131(a): When any claim of an application or a patent under reexamination is rejected, the inventor of the subject matter of the rejected claim, the owner of the patent under reexamination, or the party qualified under § 1.42 or § 1.46, may submit an appropriate oath or declaration to establish invention of the subject matter of the rejected claim prior to the effective date of the reference or activity on which the rejection is based. 37 C.F.R. § 1.131(b): The showing of facts . . . shall be such, in character and weight, as to establish reduction to practice prior to the effective date of the reference, or conception of the invention prior to the effective date of the reference coupled with due diligence from prior to said date to a subsequent reduction to practice or to the filing of the application. Original exhibits of drawings or records, or photocopies thereof, must accompany and form part of the affidavit or declaration or their absence must be satisfactorily explained. Discussion Under 37 C.F.R. § 1.131(a), a publication can be antedated and eliminated as prior art by establishing “invention of the subject matter of the rejected claim prior to the effective date of the reference or activity on which the rejection is based.” “The showing of facts . . . shall be such, in character and weight, as to establish reduction to practice prior to the effective date of the reference.” 37 C.F.R. § 1.131(b). In this case, Seppo Yla-Herttuala, M.D., the named inventor of the instant application, provided a Declaration in which he declared that he 5 Appeal 2016-007395 Application 13/969,763 “conceived the claimed invention and reduced it to practice not later than 14 April 2010.” Yla-Herttuala Oct. 2015 Decl. 1. The experiments described in his declaration were performed in Kuopio, Finland and recorded in Finnish. Id. at 1—2. The laboratory animal printed form which accompanied his Declaration is an English translation. Id. Dr. Yla-Herttuala stated that a tumor was formed by injection of an ovarian cancer line into a mouse. Id. at 2. The mouse was administered soluble VEGF receptors (“decoy receptor which binds to Vascular Endothelial Growth Factor”) and paclitaxel (“cytotoxic compound”). Id. Dr. Yla-Herttuala testified that the soluble receptors form dimers as required by the claim. Id. Claim 1 is directed to “a method treating cancer” by administering “said cytotoxic compound and said decoy receptor administered in amounts which are together effective to treat said cancer.” Consequently, in order to show reduction to practice of the claimed invention, it must be shown in the Declaration that soluble receptor and cytotoxic compound treated the cancer (e.g., reduced tumor volume, weight; reduced tumor microvessels; prolonged survival) (see Spec. 3:9-22; 4: 1—11). However, Dr. Yla- Herttuala did not make a statement in his declaration that the cancer was treated. He stated that “[assessment includes measurement of tumor size by MRI,” but there was no statement in the Declaration of the results of the assessment. Yla-Herttuala Oct. 2015 Decl. 2. In the English translation of the Laboratory Animal Printed Form, we observe recorded weights and MRI information, but none of this is explained. It is also not evident whether any kind of control was performed. In sum, the Declaration is not effective to antedate Baldwin because Dr. Yla-Herttuala did not establish that the combination of the soluble 6 Appeal 2016-007395 Application 13/969,763 VEGF receptor and taxane achieved the result required by claim 1, namely, treatment of cancer. As indicated by the Examiner, there is no discussion in the Appeal Brief as to why the Yla-Herttuala Declaration is effective to antedate Baldwin. Appellant did not provide any other basis to distinguish Baldwin. Consequently, we affirm the rejection of claims 1—6 and 8—10 as anticipated by Baldwin. 2. REJECTION BASED ON HU The Examiner found that Hu describes administering VEGF-Trap (“decoy receptor which binds to Vascular Endothelial Growth Factor”) and paclitaxel (“cytotoxic compound”) to treat cancer in a human ovarian cancer model OVCAR-3 cell in mice as required by claim 1. Final Act. 6. Hu states that the VEGF-Trap was obtained from Regeneron Pharmaceuticals. Hu 6967. The Examiner cited Holash8 as evidence that the Regeneron VEGF-Trap utilized in Hu contained the Fc region to achieve the claimed dimerization and did “not initiate VEGF signal transduction” as recited in claim 5. Final Act. 6—7. Appellant contends: Neither Hu nor Byrne, however, say exactly what fragments are included in VEGF-Trap™, nor whether these fragments have been modified to include dimer binding sites, nor modified to be soluble in normal saline. Appeal Br. 9. 8 Jocelyn Holash et al., J., Davis, S., Papadopoulos, N., Croll, S.D., Ho, L., Russell, M., Boland, P., Leidich, R., Hylton, D., Burova, E., Ioffe, E., Huang, T., Radziejewski, C., Bailey, K., Fandl, J.P., Daly, T., Wiegand, S.J., Yancopoulos, G.D., and Rudge, J.S .VEGF-Trap: A VEGF blocker with potent antitumor effects, 99 Proc. Natl. Acad. Sci., 11393—98 (2002). 7 Appeal 2016-007395 Application 13/969,763 Appellant’s argument is not supported by adequate evidence. Hu discloses: Specifically, we showed that a novel, soluble VEGF decoy receptor, the VEGF Trap, comprised of fragments of VEGF receptor (VEGFR)-1 (fltl) and VEGFR2 (flkl, KDR), could markedly decrease visible ascites formation and reduce tumor burden by—63% in a xenogeneic nude mouse model of advanced human ovarian cancer (4). Hu 6966. Thus, Hu describes the fragments present in its decoy receptor. Reference 4 cited in Hu (“(4)”) is Byrne which has similar disclosure to Hu regarding the use of VEGF-Trap to treat an ovarian cancer model. Because Appellant questioned the structure of VEGF-Trap, the Examiner identified a reference cited in Byrne — Holash — for the description of its structure. Byrne is authored by a group of scientists which included Holash from Regeneron. Holash discloses three different constructs of VEGF Trap, each which has an Fc region. Holash Fig. 1. One of these constructs, VEGF Trap R1R2, comprises both VEGFR-1 and VEGFR-2 {id), which, thus, would be reasonably understood to the version of the VEGF-Trap utilized by Hu and Byrne because both publications mention the presence of VEGFR1 and VEFGR2 fragments. Appellant has given no reason to doubt that the VEGF-Trap would include the Fc region, when all the constructs of it shown in Regeneron’s publication by Holash have it. In fact, each of Hu, Byrne, and Holash include inventors from Regeneron, the supplier of VEGF-Trap. Holash from Regeneron is a named co-author on all three publications. Appellant also argues that “[i]n teaching that VEGF-Trap™ includes tyrosine kinases, Hu (2005) implies that VEGF Trap™ initiates [signal] transduction.” Appeal Br. 9. Appellant did not identity disclosure in Hu that “implies” that VEGF-Trap initiates signal transduction. Hu describes 8 Appeal 2016-007395 Application 13/969,763 utilizing “fragments” of the VEGF receptors, but does not state that such fragments possessed tyrosine kinase activity. Figure 1 of Holash clearly shows that the kinase domain of the receptor is absent from VEGF Trap. As explained by Holash: The clinical promise of initial anti-VEGF approaches highlights the need to optimize blockade of this pathway. Previous studies have found that one of the most effective ways to block the VEGF signaling pathway is to prevent VEGF from binding to its normal receptors by administering decoy VEGF receptors .... The highest-affmity VEGF blocker described to date is a soluble decoy receptor created by fusing the first three Ig domains of VEGFR1 to the constant region (Fc portion) of human IgGl, resulting in a forced homodimer that has picomolar binding affinity.... Holash 11393 (endnotes omitted). Thus, it is counter intuitive to utilize a kinase domain in VEGF Trap because the purpose of the construct is to block receptor kinase activity by trapping VEGF and preventing it from binding and stimulating the kinase activity of the endogenous receptor. Appellant states that Applicant has not been afforded the opportunity to provide rebuttal evidence to Holash. We disagree. Applicant petitioned to have the finality of the Final Office Action withdrawn, but the petition was denied and the decision stated that the citation of Holash was done in response to arguments and did not impact the original grounds of rejection. Decision on Petition (mailed Apr. 8, 2016). We have reviewed the record after the Final Rejection, and did not find an attempt by Applicant to rebut Holash nor did we find evidence regarding Holash that the Examiner had declined to consider. Appellant had the opportunity after the Final rejection was issued, as well as in the Appeal Brief, to explain why Holash is not 9 Appeal 2016-007395 Application 13/969,763 evidence of the structure of VEGF Trap. In the Reply Brief, Appellant states: I thus sense that the Examiner knows as well as I do that Holash doesn’t enable Hu’s proprietary fragment mixture, and arguably actively misrepresents how to make it, to make that proprietary mixture difficult for competitors to copy. This is, I sense, why the Examiner has adamantly refused to afford Applicant the opportunity to introduce rebuttal evidence. Reply Br. 8. Appellant did not explain how Holash misrepresented VEGF-Trap when Figure 1 clearly shows the structure of the various constructs with this name, including the construct comprising fragments of VEGF receptor (VEGFR)-1 (fltl) and VEGFR2 (flkl, KDR) that is referenced in Hu and in rejected claim 2. In sum, for the aforementioned reasons, we affirm the rejection of claims 1—5 as anticipated by Hu. 3. REJECTION BASED ON BYRNE, HU, SALLINEN, AND BALDWIN The Examiner found that Byrne describes administering an adenoviral vector comprising the nucleic acid encoding the VEGF-Trap high affinity soluble decoy receptor to treat cancer in OVCAR-3 model in mice, meeting the corresponding limitation of claim 6 of a gene therapy vector. Final Act. 9. The Examiner found Byrne did not administer the gene therapy vector in combination with a cytotoxic compound as required by the claim, but suggested it (“Currently, we are investigating the effects of combining VEGF-Trap treatment with a chemotherapeutic agent. ... We anticipate that by combining therapies, we will be able to further reduce tumor burden and 10 Appeal 2016-007395 Application 13/969,763 will prolong response and survival.” Byrne 5726.) Final Act. 9. The Examiner further cited the teachings in Hu and Baldwin of combination therapy using a VEGF-Trap and a cytotoxic drug as evidence of the obviousness of administering a cytotoxic drug with Byrne’s viral gene therapy vector prompted by his suggestion to do. Id. Sallinen was also cited by the Examiner for administering the same type of VEGFR gene therapy construct as in Byrne. Id. Appellant contends that the rejection is improper because Sallinen (misspelled in the Appeal Brief as “Salinnen”) “notes that the only phase III trial carried out so far combining chemotherapy and transgene therapy was closed prematurely because the combination ‘showed no clinical benefit’. See 278 col. 2. Salinnen [sic] accordingly teaches the claimed combination would have a reasonable expectation of failure, not success.” Appeal Br. 7. This argument is not persuasive. Sallinen’s discussion of a phase III trial had to do with p53 gene therapy, a different target than the claimed VEGF receptor target of the rejected claims and the cited prior art. See Sallinen 278. Sallinen’s own experiments show success with adenoviral gene therapy with three soluble VEGF receptors. Id. at 282, 283. Based on this success, Sallinen concluded: These results warrant further development of the combined antiangiogenic gene therapy to define the best dose and schedule for such a treatment, and suggest that this approach could be utilized in clinics along with other anticancer therapies. Id. at 283. Accordingly, Appellant’s argument about an expectation of failure is inconsistent with Sallinen’s own suggestion of combining gene therapy with other anticancer therapies. Appellant’s further statement that Sallinen “chose to use only the decoy receptor” (Appeal Br. 8) is misleading 11 Appeal 2016-007395 Application 13/969,763 because, as the above-quoted passage indicates, Sallinen, once having completed its experiments with the viral gene therapy vector alone, suggested combination therapy — the same combination therapy to which rejected claim 1 is directed. For the foregoing reasons, we affirm the obviousness rejection of claim 1, and dependent claims 2—11 which fall with claim 1 because they were not separately argued. 37 C.F.R. § 41.37(c)(l)(iv). 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