10518523 (B.P.A.I. Feb. 28, 2011)

Ex Parte Haynes et al

Board of Patent Appeals and InterferencesFeb 28, 2011

10518523 (B.P.A.I. Feb. 28, 2011)

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. 10/518,523 08/17/2005 Barton Haynes 1579-968 7798 23117 7590 03/01/2011 NIXON & VANDERHYE, PC 901 NORTH GLEBE ROAD, 11TH FLOOR ARLINGTON, VA 22203 EXAMINER HUMPHREY, LOUISE WANG ZHIYING ART UNIT PAPER NUMBER 1648 MAIL DATE DELIVERY MODE 03/01/2011 PAPER 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. PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE __________ BEFORE THE BOARD OF PATENT APPEALS AND INTERFERENCES __________ Ex parte BARTON HAYNES and DAVID C. MONTEFIORI __________ Appeal 2010-008027 Application 10/518,523 Technology Center 1600 __________ Before DEMETRA J. MILLS, ERIC GRIMES, and MELANIE L. McCOLLUM, Administrative Patent Judges. GRIMES, Administrative Patent Judge. DECISION ON APPEAL1 This is an appeal under 35 U.S.C. § 134 involving claims to a fusion protein comprising an HIV envelope component. The Examiner has rejected 1 The two-month time period for filing an appeal or commencing a civil action, as recited in 37 C.F.R. § 1.304, or for filing a request for rehearing, as recited in 37 C.F.R. § 41.52, begins to run from the “MAIL DATE” (paper delivery mode) or the “NOTIFICATION DATE” (electronic delivery mode) shown on the PTOL-90A cover letter attached to this decision. Appeal 2010-008027 Application 10/518,523 2 the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. STATEMENT OF THE CASE The Specification discloses “an immunogen that induces broadly reactive neutralizing antibodies that are necessary for an effective AIDS vaccine. The immunogen … comprises at least one fusion protein that comprises at least 3 components: i) an IgG Fc component, ii) an HIV envelope component, and iii) a C3d component” (Spec. 3). The Specification discloses that the IgG Fc component provides the fusion protein with a longer serum half-life (id. at 4). Claims 1-17 are on appeal. Claims 1 and 13 are representative and read as follows: 1. A fusion protein comprising: i) an IgG Fc component, ii) an HIV envelope component, and iii) a C3d component. 13. A complex comprising a fusion protein, said fusion protein comprising: i) an IgG Fc component, ii) an HIV envelope component, and iii) a C3d component wherein said HIV envelope component of said fusion protein is activated so that intermediate conformations of conserved neutralization epitopes of said HIV envelope component are exposed. The claims stand rejected under 35 U.S.C. § 103(a) as follows: Appeal 2010-008027 Application 10/518,523 3 • claims 1-12 in view of Ross,2 Shearer,3 and Rizzuto;4 • claims 13, 14, 16 and 17 in view of Ross, Shearer, DeVico,5 and Rizzuto; and • claims 13-15 in view of Ross, Shearer, Wyatt,6 and Rizzuto. I. Issue The Examiner has rejected claims 1-12 as obvious in view of Ross, Shearer, and Rizzuto.7 Claims 2-12 have not been argued separately and therefore stand or fall with claim 1. 37 C.F.R. § 41.37(c)(1)(vii). The Examiner finds that Ross discloses a “DNA vaccine expressing a fusion protein of murine C3d fused to the C-terminus of HIV Env gp120” and discloses that C3d “amplifies B cell activation and antibody production” (Answer 4). The Examiner finds that “Shearer discloses a fusion protein by fusing the gp120 binding domain of CD4 to the Fc portion of the human 2 Ted M. Ross et al., Enhanced Avidity Maturation of Antibody to Human Immunodeficiency Virus Envelope: DNA Vaccination with gp120-C3d Fusion Proteins, 17 AIDS RES HUM RETROVIRUSES, 829-835 (2001). 3 William T. Shearer et al., Transport of Recombinant Human CD4- Immunoglobulin G across the Human Placenta: Pharmacokinetics and Safety in Six Mother-Infant Pairs in AIDS Clinical Trial Group Protocol 146, 2 CLIN. DIAG. LAB. IMMUNOL., 281-285 (1995). 4 Carlo D. Rizzuto et al., A Conserved HIV gp120 Glycoprotein Structure Involved in Chemokine Receptor Binding, 280 SCIENCE 1949-1953 (1998). 5 DeVico et al., US 5,518,723, May 21, 1996 6 Richard Wyatt et al., Involvement of the V1/V2 Variable Loop Structure in the Exposure of Human Immunodeficiency Virus Type 1 gp120 Epitopes Induced by Receptor Binding, 69 J. VIROLOGY, 5723-5733 (1995). 7 For each of the rejections on appeal, Rizzuto was cited for evidence that relates to dependent claim limitations. Since the dependent claims were not argued separately, Rizzuto will not be further discussed. Appeal 2010-008027 Application 10/518,523 4 IgG1 … heavy chain.… This chimeric protein retains certain properties of human IgG, including a prolonged half-life in serum.” (Id. at 5.) The Examiner concludes that it “would have been prima facie obvious … to add Shearer’s human IgG Fc component to … Ross’ fusion protein of gp120- C3d for the purpose of increasing the serum half-life of gp120-C3d” (id.). Appellants contend that the cited references would not have suggested modifying Ross’s fusion protein to contain Shearer’s IgG Fc component, or provided a reasonable expectation of success (Appeal Br. 10). The issue with respect to this rejection is: Does the evidence of record support the Examiner’s conclusion that it would have been obvious to modify Ross’s fusion protein to contain Shearer’s IgG Fc component, with a reasonable expectation of success? Findings of Fact 1. Ross discloses that “DNA vaccines expressing the envelope (Env) protein of human immunodeficiency virus (HIV) have been relatively ineffective at generating high titer, long-lasting, neutralizing antibodies” (Ross, abstract). 2. Ross discloses plasmids that “expressed a secreted form of Env (sgp120) from three isolates of HIV and these same forms fused to … the murine homologue of C3d” (id.). 3. Ross discloses that the “fusion constructs induced higher antibody responses to Env and a faster onset of avidity maturation than did the respective wild-type gp120 sequences. These results suggest that the efficacy of DNA vaccines for raising antibody can be significantly improved by fusing proteins with C3d.” (Id. at 2.) Appeal 2010-008027 Application 10/518,523 5 4. Ross discloses that C3d supports “antibody responses by directly stimulating antibody-producing B cells through complement receptor 2 (CD21) and expanding the pool of anti-Env-specific B cells” (id. at 6). 5. Shearer discloses a protein “produced by fusing the gp120 binding domain of CD4 to the Fc portion of the human IgG1 heavy chain” (Shearer, abstract). 6. Shearer discloses that the “chimeric protein retains certain properties of human IgG, including a prolonged half-life in serum” (id. at 281). Analysis Claim 1 is directed to a fusion protein comprising an IgG Fc component, an HIV envelope component, and a C3d component. Ross discloses DNA encoding a fusion protein comprising HIV gp120 (Env) and C3d. Ross discloses that the fusion protein generated higher antibody responses to Env in inoculated mice than did the HIV envelope component alone. Shearer discloses that fusion proteins comprising the Fc portion of the human IgG1 heavy chain have a prolonged serum half-life. In view of these disclosures, it would have been obvious to modify Ross’s fusion construct to also contain an IgG Fc component to prolong the protein’s serum half-life and enhance antibody production. Appellants argue that “nothing in the [cited] references … would have suggested their combination …, nor would the references have provided any basis for a reasonable expectation of generating a successful product” (Appeal Br. 10). These arguments are not persuasive. Although Shearer does not disclose the IgG Fc component as part of an antigen-containing fusion Appeal 2010-008027 Application 10/518,523 6 protein, it states that its “chimeric protein retain[ed] certain properties of human IgG, including a prolonged half-life in serum” (FF 6). Since a prolonged serum half-life is a property of IgG that was conferred on a fusion protein by the IgG Fc component, a skilled worker would have reasonably expected that the IgG Fc component would prolong the serum half-life of other fusion proteins. Therefore, it would have been obvious to combine Shearer’s IgG Fc component with Ross’s fusion protein with a reasonable expectation that the resulting fusion protein would have a prolonged serum half-life, prolonged antigen persistence, and greater antibody response. Conclusion of Law The evidence of record supports the Examiner’s conclusion that it would have been obvious to modify Ross’s fusion protein to contain Shearer’s IgG Fc component, with a reasonable expectation of success. II. Issue The Examiner has rejected claims 13, 14, 16 and 17 as obvious in view of Ross, Shearer, DeVico, and Rizzuto, and has rejected claims 13-15 as obvious in view of Ross, Shearer, Wyatt, and Rizzuto. With respect to both rejections, the claims have not been argued separately and therefore stand or fall with claim 13. 37 C.F.R. § 41.37(c)(1)(vii). The Examiner relies on Ross and Shearer as discussed above. The Examiner finds that “DeVico teaches an immunogen, called gp120-CD4 complex, which is the recombinant HIV envelope protein gp120 chemically crosslinked to a soluble CD4 ligand” (Answer 6), and that DeVico discloses “that the gp120-CD4 immunogen exposes cryptic epitopes on gp120 that Appeal 2010-008027 Application 10/518,523 7 induce[ ] neutralizing antibodies to gp120” (id.). The Examiner finds that Wyatt discloses that “binding of the A32 antibody to the wild type envelope glycoprotein gp120 activates the gp120 so that [other] mAbs … recognize and bind to the exposed conformational epitopes” (id. at 8). The Examiner concludes that it would have been obvious to modify the fusion protein suggested by Ross and Shearer either by “crosslinking a CD4 molecule to the middle component, HIV Env gp120, … to raise neutralizing antibodies” (id. at 7), in view of DeVico, or by “binding an antibody to the middle component, HIV Env gp120, so as to raise more neutralizing antibodies” (id. at 8), in view of Wyatt. Appellants contend that one of skill in the art would not have been motivated to combine the cited references (Appeal Br. 12, 13), and that the references would not have provided a reasonable expectation of success (id.). The issue with respect to these rejections is: Does the evidence of record support the Examiner’s conclusion that one of ordinary skill in the art would have considered it obvious to modify the fusion protein suggested by Ross and Shearer to contain either a CD4 ligand or a monoclonal antibody bound to the gp120 protein, with a reasonable expectation of success? Additional Findings of Fact 7. DeVico discloses “overcom[ing] the shortcomings of type specific anti-gp120 antibodies and antibodies against CD4 by raising anti-HIV-1 neutralizing antibodies using as the immunogen a complex of gp120 chemically coupled to … soluble CD4” (DeVico, col. 1, ll. 54-59). Appeal 2010-008027 Application 10/518,523 8 8. DeVico discloses that the “complexed gp120 appears to undergo a conformational change that presents an array of epitopes that were hidden on the uncomplexed glycoprotein” (id. at col. 1, ll. 59-63). 9. DeVico discloses that a “portion of such epitopes elicit group- specific neutralizing antibodies, which are not strain limited like the type specific antibodies…. We have discovered that the covalently bonded CD4- gp120 complexes are useful for raising neutralizing antibodies against various isolates of HIV-1.” (Id. at col. 1, l. 63 to col. 2, l. 2.) 10. Wyatt discloses that “[c]onserved, discontinuous epitopes on the HIV-1 gp120 glycoprotein recognized by the 17b, 48d, and A32 antibodies are preferentially exposed upon the binding of soluble CD4 (sCD4). The binding of the 17b and 48d antibodies to the gp120 glycoprotein can also be enhanced by the binding of the A32 antibody.” (Wyatt, abstract.) 11. Wyatt discloses that the “increased exposure of the 17b and 48d epitopes represents an attractive candidate for a functionally relevant CD4- induced conformational change, since these epitopes are neutralization targets … and may be located in gp120 regions important for virus entry” (id. at 5729, right col.). Analysis Claim 13 is similar to claim 1 and further requires that the HIV envelope component of the fusion protein is activated so that “intermediate conformations of conserved neutralization epitopes of said HIV envelope component are exposed.” As discussed above, it would have been obvious to modify Ross’s gp120 fusion construct to contain Shearer’s IgG Fc component in order to prolong serum half-life to enhance antibody production. DeVico discloses Appeal 2010-008027 Application 10/518,523 9 that a complex of gp120 with soluble CD4 presents hidden epitopes on gp120, with the result that gp120 in these complexes is useful in generating neutralizing antibodies which are not type-specific. Wyatt discloses that binding of gp120 to soluble CD4 or antibody A32 can activate gp120 to expose conserved neutralization epitopes. In view of these disclosures, it would have obvious to one of ordinary skill in the art to activate the gp120-containing fusion protein made obvious by Ross and Shearer by binding the gp120 component to CD4, as taught by DeVico, or to antibody A32, as taught by Wyatt, in order to expose neutralization epitopes in order to generate additional neutralizing antibodies. Appellants argue that one of skill in the art would not have been motivated to combine the relevant disclosures of the cited references (Appeal Br. 12, 13). This argument is not persuasive for the reasons discussed above. Appellants also argue that those of skill in the art would not have had a reasonable expectation of success in assembling all of the components of claim 13 (Appeal Br. 12, 13), but provide no basis on which to conclude that combining the prior art components would have been unpredictable or would have required more than routine experimentation. Appellants therefore have not set forth any reason to doubt that a skilled worker would not have had a reasonable expectation of success in making the claimed fusion protein complex. Conclusion of Law The evidence of record support the Examiner’s conclusion that one of ordinary skill in the art would have considered it obvious to modify the Appeal 2010-008027 Application 10/518,523 10 fusion protein suggested by Ross and Shearer to contain either a CD4 ligand or a monoclonal antibody bound to the gp120 protein, with a reasonable expectation of success. SUMMARY We affirm the rejection of claims 1-17 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 NIXON & VANDERHYE, PC 901 NORTH GLEBE ROAD, 11TH FLOOR ARLINGTON VA 22203