Ex Parte Edelman et alDownload PDFBoard of Patent Appeals and InterferencesOct 13, 200910059261 (B.P.A.I. Oct. 13, 2009) Copy Citation UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE BOARD OF PATENT APPEALS AND INTERFERENCES ____________ Ex parte LENA EDELMAN, ETIENNE DANIEL FRANCOIS JACOTOT, and JEAN-PAUL BRIAND ____________ Appeal 2009-003878 Application 10/059,261 Technology Center 1600 ____________ Decided: October 13, 2009 ____________ Before DONALD E. ADAMS, LORA M. GREEN, and JEFFREY N. FREDMAN, Administrative Patent Judges. ADAMS, Administrative Patent Judge. DECISION ON APPEAL This appeal under 35 U.S.C. § 134 involves claims 85-90, 94, and 95. Pending claims 57, 60, 61, 73-84, 91-93, and 96-105 have been withdrawn (Ans. 2; App. Br. 4; Reply Br. 1). We have jurisdiction under 35 U.S.C. § 6(b). Appeal 2009-003878 Application 10/059,261 STATEMENT OF THE CASE The claims are directed to a chimeric, bifunctional molecule (claims 85-90) and a pharmaceutical composition comprising a chimeric bifunctional molecule (claims 64 and 95). Claim 85 is illustrative: 85. A chimeric, bifunctional molecule that can enter into a cell to induce death of the cell by apoptosis, wherein the chimeric, bifunctional molecule comprises a first functional molecule covalently linked to a second functional molecule, wherein the first functional molecule targets and enters into the cell and the second functional molecule targets and induces the death of the cell by apoptosis by regulating opening of a permeability transition pore complex (PTPC) of mitochondria or a fragment of the PTPC, wherein the chimeric, bifunctional molecule has the formula: TARG-TOX, wherein TOX is a peptide chosen from Vpr 71-82 (SEQ ID NO: 225), Vpr 71-82 [R73, 77, 80K] (SEQ ID NO: 226), Vpr 71-96 (SEQ ID NO: 227), Vpr 71- 96 [R73, 77[,] 80K] (SEQ ID NO: 228), Vpr 52-96 (SEQ ID NO: 229), Vpr 52-96 [R73,77, 80K) (SEQ ID NO: 230), Vpr 52-96 [L60, 67A] (SEQ ID NO: 231), Vpr 52-82 (SEQ ID NO: 232), Vpr 52-82 [R73, 77, 80K] (SEQ ID NO: 233), Vpr 52-96 [C76S] (SEQ ID NO: 256), and TARG is chosen from HIV-1 tat 48-59 transduction domain (SEQ ID NO: 269), HIV-1 tat 49-57 (SEQ ID NO: 270), and pep-1 (SEQ ID NO[:] 271), and wherein the TARG peptide is optionally covalently linked to the TOX peptide by a peptide linker of 2-18 amino acids. The Examiner relies on the following evidence: Sherman et al. US 6,664,040 B2 Dec. 16, 2003 Arunagiri et al., A C-terminal domain of HIV-1 accessory protein Vpr is involved in penetration, mitochondrial dysfunction and apoptosis of human CD4+ lymphocytes, 2 APOPTOSIS 69-76 (1997). Kim et al., Introduction of soluble proteins into the MHC class I pathway by conjugation to an HIV tat peptide, 159 J. IMMUNOL 1666-1668 (1997) (PubMed Abstract No. 9257826). 2 Appeal 2009-003878 Application 10/059,261 Sela et al., Different roles of D-amino acids in immune phenomena, 11 FASEB J. 449-456 (1997) (PubMed Abstract No. 9194525). The rejection presented by the Examiner is as follows: Claims 85-90, 94, and 95 stand rejected under 35 U.S.C § 103(a) as unpatentable over the combination of Sherman, Kim, Arunagiri, and Sela. We reverse. ISSUE Have Appellants established error in the Examiner’s prima facie case of obviousness? FINDINGS OF FACT FF 1. The Examiner finds that Sherman teaches “a chimeric, bifunctional molecule that enters a cell and induces cellular death via apoptosis” (Ans. 5). FF 2. “Because sVpr rapidly and strongly transduces freshly isolated primary human cells at nanomolar concentrations, the methods of the invention provide an attractive and effective means for delivery of a molecule into a cell” Sherman’s “invention provides a method for delivering a molecule into a cell . . . compris[ing] contacting the cell with a conjugate comprising a Vpr polypeptide conjugated to the molecule” (Sherman, col. 7, ll. 40-47). FF 3. “Because sVpr can induce apoptosis, those cells which are more susceptible than non-target cells to transduction by Vpr are selectively killed,” therefore, “[i]n an alternative embodiment [of Sherman’s invention], the method of killing a target cell population comprises administration of a 3 Appeal 2009-003878 Application 10/059,261 Vpr polypeptide, without necessarily conjugating the Vpr polypeptide to a toxin or other molecule” (Sherman, col. 8, ll. 6-12). FF 4. Sherman defines “transduction” as “the ability to cross a biological membrane in a receptor-, energy-independent process” (Sherman, col. 19, ll. 59-60). FF 5. The Examiner finds that Arunagiri teaches “that the crucial peptide sequence of Vpr required in order to evoke mitrochondrial dysfunction and apoptotic death is a conserved H(F/S)RIG repeat motif” (Ans. 5). FF 6. The Examiner finds that neither Sherman nor Arunagiri teach SEQ. ID. NO. 232 of Appellants’ claimed invention. Nevertheless, the Examiner finds that Appellants’ Specification “fails to disclose any unique or novel contributions, such as, a change of function to the additional amino acids that are adjacent to the . . . [H(F/S)RIG] essential motifs in SEQ ID NO[ ]: 232” (Ans. 5). FF 7. Sherman teaches “that full-length sVpr, or at least more than only the putative transducing domain, is necessary for efficient protein transduction” (Sherman, col. 20, ll. 29-31). In this regard, Sherman teaches that “HIV-1 Vpr is optimized for protein transduction, including apparent receptor independence and rapid uptake under conditions of limited energy” (Sherman, col. 20, ll. 51-54). FF 8. The Examiner finds that Kim teaches “the unique ability of HIV-1 tat to transport macromolecules into cells is well known in the prior art” (Ans. 5). FF 9. The Examiner finds that Kim teaches “the use of tat-conjugated proteins for the treatment of tumors” (id.). 4 Appeal 2009-003878 Application 10/059,261 FF 10. Kim teaches that “[p]rotection against most intracellular pathogens requires T cells that recognize pathogen-derived peptides in association with MHC class I molecules on the surface of infected cells” (Kim, PubMed Abstract). FF 11. Kim teaches a HIV-1 tat (residues 49-57) – OVA protein conjugate and that “[w]hen APC were exposed in vitro to such protein conjugates, they processed and presented the peptides in association with MHC class I molecules and stimulated CD8+ Ag-specific T cells” (id.). FF 12. The Examiner finds that Sela teaches “that ‘the inclusion of D-amino acids may be an advantage in terms of both specificity and efficacy, the latter because of longer persistence in an undigested form because they resist enzymatic degradation’” (Ans. 5-6). PRINCIPLES OF LAW “In proceedings before the Patent and Trademark Office, the Examiner bears the burden of establishing a prima facie case of obviousness based upon the prior art.” In re Fritch, 972 F.2d 1260, 1265 (Fed. Cir. 1992). On appeal to this Board, Appellants must show that the Examiner has not sustained the required burden. See Ex parte Yamaguchi, 88 USPQ2d 1606, 1608 and 1614 (BPAI 2008) (precedential); Ex parte Fu, 89 USPQ2d 1115, 1118 and 1123 (BPAI 2008) (precedential). “The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). However, it can be important to identify a reason that would have prompted a person of ordinary skill in the relevant field to combine the elements in the way the claimed new invention 5 Appeal 2009-003878 Application 10/059,261 does . . . because inventions in most, if not all, instances rely upon building blocks long since uncovered, and claimed discoveries almost of necessity will be combinations of what, in some sense, is already known. Id. at 418-419. ANALYSIS Appellants contend that “the type of chimeric, bifunctional molecules envisioned by . . . [Sherman] relate to linking unspecified molecules with Vpr in order to deliver the molecules into the cell by exploiting Vpr’s ability to pass through cell membranes” (App. Br. 14). Appellants contend that “the cited art does not consider whether the three-dimensional structure of the Targ component of the claimed bifunctional molecule would interfere with the three-dimensional structure of the Tox component, and thus disturb the function of the Tox component” (App. Br. 13-14). Further, Appellants contend “that there is no teaching in Arunagiri [or Sherman] . . . that links apoptosis of cells to regulation of PTPC by Vpr-derived peptides” (App. Br. 12). We agree. The Examiner finds that neither Sherman nor Arunagiri teach SEQ. ID. NO. 232 of Appellants’ claimed invention. Nevertheless, the Examiner finds that Appellants’ Specification “fails to disclose any unique or novel contributions, such as, a change of function to the additional amino acids that are adjacent to the . . . [H(F/S)RIG] essential motifs in SEQ ID NO[ ]: 232” (FF 6). However, Sherman teaches that “HIV-1 Vpr is optimized for protein transduction, including apparent receptor independence and rapid uptake under conditions of limited energy” (FF 7). 6 Appeal 2009-003878 Application 10/059,261 Nevertheless, Sherman teaches that Vpr can: (1) be used to deliver molecules conjugated to Vpr into a cell in a receptor independent manner (FF 2); and (2) induce apoptosis without necessarily conjugating the Vpr polypeptide to a toxin or other molecule (FF 3). Sherman teaches that when conjugated to another molecule, Vpr is the targeting component of the conjugate and is responsible for taking the conjugate into a cell where the other component of the conjugate will exhibit its function (see e.g., FF 2). Notwithstanding this teaching in Sherman, the Examiner asserts that a person of ordinary skill in the art would have found it prima facie obvious to conjugate tat to Vpr effectively producing a conjugate with two targeting components. The Examiner reasons that in such a conjugate the tat component of the conjugate will be responsible for delivering the conjugate into a cell where Vpr will induce apoptosis. We do not find, and the Examiner failed to identify, a teaching in Sherman or Arunagiri of Vpr’s ability to induce apoptosis when conjugated to another molecule, particularly another “delivery” molecule. Further, it is unclear from the Examiner’s statement of the rejection why a person of ordinary skill in this art would modify Vpr, which can induce apoptosis on its own (FF 3) and is “optimized for protein transduction” in a receptor independent manner (FF 7), by conjugating it to tat. Kim teaches that a tat based conjugate is processed and presented in association with MHC class I molecules (FF 11). The Examiner fails to explain why a person of ordinary skill in the art would have expected the Vpr component of such a conjugate to induce apoptosis when it is processed and presented in association with MHC class I molecules as taught by Kim. 7 Appeal 2009-003878 Application 10/059,261 For the foregoing reasons we find that the Examiner failed to provide the evidence necessary to establish a prima facie case of obviousness. CONCLUSION OF LAW Appellants established error in the Examiner’s prima facie case of obviousness. REVERSED cdc FINNEGAN, HENDERSON, FARABOW, GARRETT & DUNNER, L.L.P. 1300 I STREET, NW WASHINGTON DC 20005-3315 8 Copy with citationCopy as parenthetical citation