Ex Parte Rosenblum et alDownload PDFBoard of Patent Appeals and InterferencesOct 23, 200910964195 (B.P.A.I. Oct. 23, 2009) Copy Citation UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE BOARD OF PATENT APPEALS AND INTERFERENCES ____________ Ex parte MICHAEL ROSENBLUM and LAURA K. SHAWYER ____________ Appeal 2009-008350 Application 10/964,195 Technology Center 1600 ____________ Decided: October 23, 2009 ____________ Before TONI R. SCHEINER, DONALD E. ADAMS, and DEMETRA J. MILLS, Administrative Patent Judges. ADAMS, Administrative Patent Judge. DECISION ON APPEAL This appeal under 35 U.S.C. § 134 involves claim 24. The Examiner has indicated that pending claims 3-10, 23, and 25 are allowable (App. Br. 3). We have jurisdiction under 35 U.S.C. § 6(b). Appeal 2009-008350 Application 10/964,195 2 STATEMENT OF THE CASE The claims are directed to an antibody-toxin conjugate composition. Claims 7, 23, and 24 are reproduced below: 7. (Allowed) A composition comprising a conjugate of an antibody exhibiting binding specificity for an extracellular epitope of c-erbB-2 protein and a plant derived toxin, wherein said toxin is pharmacologically effective against neoplastic cells and is selected from the group consisting of gelonin, full length recombinant gelonin and functional gelonin fragments, wherein said conjugate is a fusion protein between said antibody and said toxin. 23. (Allowed) The composition of claim 7, wherein the antibody is a portion of a full length antibody. 24. (Under Appeal) The composition of claim 23, wherein the antibody portion is an antibody fragment selected from the group consisting of Fab; F(ab’)2; a CDR; a VL or a VH. The Examiner relies on the following evidence: Rudikoff, et al., Single amino acid substitution altering antigen-binding specificity, 79 Proc. Natl. Acad. Sci. USA 1979-1983 (1982). MaCallum, et. al., Antibody-antigen Interactions: Contact Analysis and Binding Site Topography, Journal of Molecular Biology, Vol. 262, 732-745 (1996). De Pascalis et al.,[hereinafter Pascalis] Grafting of “Abbreviated” Complementarity-Determining Regions Containing Specificity-Determining Residues Essential for Ligand Contact to Engineer a Less Immunogenic Humanized Monoclonal Antibody, The Journal of Immunology, Vol. 320, 415-428 (2002). Holm et al., Functional mapping and single chain construction of the anti- cytokeratin 8 monoclonal antibody TS 1, Molecular Immunology, Vol. 44, 1075-1084 (2007). Appeal 2009-008350 Application 10/964,195 3 Chen et al., Selection and Analysis of an Optimized Anti-VEGF Antibody: Crystal Structure of an Affinity-matured Fab in Complex with Antigen, Journal of Molecular Biology, Vol. 293, 865-881 (1999). Wu et al., Humanization of a Murine Monoclonal Antibody by Simultaneous Optimization of Framework and CDR Residues Journal of Molecular Biology, Vol. 294, 151-162 (1999). Casset et al., A peptide mimetic of an anti-CD4 monoclonal antibody by rational design, Biochemical and Biophysical Research Communications, 2003, Vol. 307, 198-205 (2003). Appellants rely on the following evidence: Michael G. Rosenblum and Laura K. Shawver Declaration, executed June 6 and 18, 2007. The rejection presented by the Examiner is as follows: Claim 24 stands rejected under the enablement provision of 35 U.S.C. § 112, first paragraph. We affirm. ISSUE Have Appellants established error in the Examiner’s conclusion that Appellants’ Specification fails to provide an enabling disclosure commensurate in scope with the claimed invention? FINDINGS OF FACT FF 1. The Examiner finds that the composition of claim 24 encompasses, inter alia, an antibody portion that is a “Fab, [F](ab’)[2], a CDR, a VL or a VH (Ans. 4). Appeal 2009-008350 Application 10/964,195 4 FF 2. The Examiner finds that while Appellants’ Specification provides an enabling disclosure of “an antibody portion which is a Fab or F(ab’)2 fragment, [it] does not reasonably provide enablement for an antibody portion which is a CDR, VL or VH” (id.). FF 3. The Examiner finds that Rudikoff “teaches that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope” (id.). FF 4. The Examiner finds that “a ‘CDR’ can be any one of the constant regions (CH1-3), and the art recognizes that the different CDR domains do not contribute equally to epitope binding, and that less than a full antibody paratope results in a dramatically decreased affinity for any given antigen” (Ans. 5). FF 5. The Examiner finds that MaCallum, Pascalis, Casset, Vajdos, Holm, Chen, and Wu teach that the conformation of the “CDRs as well as framework residues influence binding” (Ans. 5-6). PRINCIPLES OF LAW “[T]o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation.’” Genentech, Inc. v. Novo Nordisk, A/S, 108 F.3d 1361, 1365 (Fed. Cir. 1997) (quoting In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993)). Appeal 2009-008350 Application 10/964,195 5 ANALYSIS We adopt the Examiner's reasoning as our own in sustaining the rejections of record, and we add the following for emphasis only. Appellants contend that “[m]erely showing differences exist between what Pascalis, Caseet [sic] and Chen report compared to what Appellant claims does not indicate that Appellant’s Claim is not enabled” (App. Br. 8; Reply Br. 3-5). Similarly, Appellants contend that: The same applies to Holm . . .; that residues from both CDR2 and 3 were involved in binding in Holm does not indicate unpredictability or support an enablement rejection. . . . The Examiner also admits that Wu . . . successfully identified important residues that were sought. Thus, the totality of the evidence the Examiner cites does not indicate unpredictability, but rather weighs in favor of enablement. (App. Br. 8.) We are not persuaded. Claim 24 reads on an antibody-toxin conjugate composition wherein the antibody component of the conjugate is a single CDR. Contrary to Appellants’ contentions, the evidence on this record supports the Examiner’s conclusion that at the time the invention was made an “antibody portion which consists of less than the antibody paratope as defined by the three hypervariable regions of an antibody in the appropriate three dimensional shape would not be expected to exhibit binding specificity for an extracellular epitope of c-erbB2” (Ans. 4; FF 3-5). We are not persuaded by Appellants’ intimation that since the references do not discuss an antibody directed against c-erbB2 they are not pertinent to the invention of claim 24. Appellants failed to identify the unique features or properties of an antibody – c-erbB2 interaction that exempt this specific interaction from the antibody-antigen interaction Appeal 2009-008350 Application 10/964,195 6 dynamics taught by the prior art relied upon by the Examiner (see e.g., Ans. 7 (Rudikoff, Pascalis, Casset, Chen, and Holm are cited for “teaching the complexity of the interaction between an[ ] antibody and an antigen and therefore the unpredictability of alterations of a known antibody with respect to retention of antigen-binding.”)). In addition, we recognize Appellants’ contention that “Figure 9 specifically discloses the functional CDRs . . . of an exemplary antibody. The Specification also provides a description of CDRs and provides outside references to the manipulation of functional CDRs” (App. Br. 8 (emphasis added)). Conspicuous by its absence is a statement from Appellants regarding a disclosure or teaching in their Specification or the prior art of record that a person of ordinary skill in the art, at the time the invention was made, would have expected a single CDR to exhibit “binding specificity for an extracellular epitope of c-erbB2” (Ans. 4). We recognize Appellants’ intimation that their disclosure of Fab or F(ab’)2 fragments is representative and sufficient to support the full scope of claim 24 (App. Br. 9; Reply Br. 5-6). We are not persuaded. “[T]o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation.’” Genentech, Inc. v. Novo Nordisk, A/S, 108 F.3d at 1365 (emphasis added). The Examiner has established an evidentiary basis to support the conclusion that CDRs (plural), in addition to their associated framework regions are responsible for antigen binding specificity (FF 3-5). An intact antibody, Fab, and F(ab’)2 each contain CDRs (plural) and associated Appeal 2009-008350 Application 10/964,195 7 framework regions. Therefore, the Examiner has found that Appellants’ Specification provides an enabling disclosure of these reagents. In contrast, a single CDR, for example, does not have a complete set of CDRs or associated framework regions. Cf. FF 5 (“CDRs [(plural)] as well as framework residues influence binding”). Accordingly, based on the evidence relied upon by the Examiner, the Examiner has found that a single CDR, for example, would not be expected to exhibit “binding specificity for an extracellular epitope of c-erbB2” (Ans. 4). We find no error in the Examiner’s conclusion on this record. For the foregoing reasons, we disagree with Appellants’ contention that a disclosure of a Fab and/or F(ab’)2 is sufficient on this record to support a conclusion that a single CDR would be expected to exhibit binding specificity for an extracellular epitope of c-erbB2 as required by Appellants’ claim 24. For the foregoing reasons we are not persuaded by Appellants’ contentions regarding the Rosenblum and Shawver Declaration (App. Br. 10 and Declaration). Appellants have not identified and we do not find a discussion of the ability of a single CDR to exhibit binding specificity for an extracellular epitope of c-erbB2 in this Declaration. CONCLUSION OF LAW Appellants failed to establish error in the Examiner’s conclusion that Appellants’ Specification fails to provide an enabling disclosure commensurate in scope with the claimed invention. The rejection of claim 24 under the enablement provision of 35 U.S.C. § 112, first paragraph is affirmed. Appeal 2009-008350 Application 10/964,195 8 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 alw FULBRIGHT & JAWORSKI, L.L.P. 600 CONGRESS AVENUE SUITE 2400 AUSTIN TX 78701 Copy with citationCopy as parenthetical citation