Ex Parte Liu et al

Patent Trial and Appeal BoardOct 12, 2016

11679630 (P.T.A.B. Oct. 12, 2016)

UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 111679,630 02/27/2007 52034 7590 10/14/2016 Parker Highlander PLLC 1120 South Capital of Texas Highway Bldg. 1, Suite 200 AUSTIN, TX 78746 FIRST NAMED INVENTOR YuyingLiu 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 ATTORNEY DOCKET NO. CONFIRMATION NO. CLFR:269US/10702383 3872 EXAMINER DUFFY, BRADLEY ART UNIT PAPER NUMBER 1643 NOTIFICATION DATE DELIVERY MODE 10/14/2016 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@phiplaw.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte YUYING LIU and MICHAEL G. ROSENBLUM 1 Appeal2015-001277 Application 11/679,630 Technology Center 1600 Before DEMETRA J. MILLS, FRANCISCO C. PRATS, and TIMOTHY G. MAJORS, Administrative Patent Judges. MAJORS, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. Â§ 134 involving claims to constructs comprising a cell targeting moiety and a polypeptide inhibitor of NF-KB. The Examiner rejected the claims as obvious. We have jurisdiction under 35 U.S.C. Â§ 6(b). We affirm. STATEMENT OF THE CASE "NF-kB activity may be specifically down-regulated in cells by directed delivery [of] compositions such as the protein inhibitor ofNF-kB, 1 Appellants identify the Real Party in Interest as Research Development Foundation. (App. Br. 3.) Appeal2015-001277 Application 11/679,630 IkB." (Spec. i-f 2.) According to the Specification, "[s]everal reports have also demonstrated that NF-kB is constitutively activated in human melanoma cells." (Id. at i-f 4.) In further describing the state of the art, Appellants disclose [g]iven the central role of NF-kB in immune response, autoimmune disease and cancer, many anti-inflammatory and chemotherapeutic agents are targeted to the NF-kB pathway ... . Previously it has been shown that IkB can be delivered to cells in nucleic acid form via an adenoviral vector [citing Batra] ... IkB can [also] be fused with a membrane translocating peptide [citing Rojas]. (Id. at i-f 5.) Appellants disclose "[t]he instant invention provides a significant improvement over the prior art methods of inhibiting NF-kB by enabling cell targeted delivery of IkB ... [that] enable[ s] cell targeted enhancement of apoptosis and thus can enhance the ability of known therapeutic agents to kill a targeted cell population." (Id. at i-f 6.) "A cell targeting construct according to the invention will desirably have two properties; (1) binding affinity for a specific population [of] cells and (2) the ability to be internalized into a specific population of cells." (Id. at i-f 13.) "[C]ell targeting moieties for use in the current invention are antibodies ... [including] a single chain antibody (scFv) ... [and] in some very specific embodiments the cell targeting construct is a fusion protein comprising IkB fused to scFvMEL." (Id. at i-f 14.) Claims 1, 10-16, 19, 20, and 28-35 are on appeal. Claim 1 is illustrative: 2 Appeal2015-001277 Application 11/679,630 1. A cell targeting construct compnsmg a polypeptide inhibitor of NF-kB (IkB) conjugated to cell targeting moiety, wherein the inhibitor has the sequence of SEQ ID N0:3, and further wherein the cell targeting construct is free of a membrane translocating peptide. (App. Br. 9 (Claims App'x).) In response to a species election requirement, Appellants elected "scfvMEL as the targeting moiety and cancer cell, and in particular, skin cancer cell, as the cell targeted by such a construct." (See 10/12/09 Resp. to Restriction Requirement 8; see also App. Br. 3.) We limit our analysis of claims to the patentability of the elected species. See Ex parte Ohsaka, 2 USPQ2d 1460, 1461 (BP AI 1987). The claims stand rejected as follows: I. Claims 1, 10-16, 19, 20, and 28-33 under 35 U.S.C. Â§ 103(a) over Rosenblum, 2 Rojas, 3 Haskill, 4 Batra, 5 and Meyskens. 6 IL Claims 34 and 35 under 35 U.S.C. Â§ 103(a) over Rosenblum, Rojas, Haskill, Batra, and Meyskens, in further view of Thorpe. 7 2 Rosenblum et al., US 2003/0086919 Al, published May 8, 2003 ("Rosenblum"). 3 Rojas et al., WO 2005/017188 A2, published Feb. 24, 2005 ("Rojas"). 4 Haskill et al., WO 92/20795, published Nov. 26, 1992 ("Haskill"). 5 Raj K. Batra et al., Ix:Ba Gene Transfer Is Cytotoxic to Squamous-Cell Lung Cancer Cells and Sensitizes Them to Necrosis Factor-a-Mediated Cell Death, 21 AM. J. RESPIR. CELL MOL. BIOL. 23 8-245 (1999) ("Batra"). 6 Frank L. Meyskens, Jr. et al., Activation of Nuclear Factor-KB in Human Metastatic Melanoma Cells and the Effect of Oxidative Stress, 5 CLINICAL CANCER RESEARCH 1197-1202 (1999) ("Meyskens"). 7 Thorpe et al., US 6,676,941 B2, issued Jan. 13, 2004 ("Thorpe"). 3 Appeal2015-001277 Application 11/679,630 I Issue Has the Examiner established by a preponderance of the evidence that claims 1, 10-16, 19, 20, and 28-33 would have been obvious over Rosenblum, Rojas, Haskill, Batra, and Meyskens? Findings of Fact (FF) FF 1. The Examiner's findings of fact and statement of the rejection of claims 1, 10-16, 19, 20, and 28-33 may be found at pages 3-5 of the Final Rejection dated June 9, 2014. (See also Ans. 3-5, 7-12.) We adopt the Examiner's findings and provide the following for emphasis. FF 2. Rosenblum teaches chimeric polypeptides "comprised of at least two moieties: one moiety is the effectual component for killing of the cell; the second moiety is the delivery component ... to target the killing component to the cell of interest." (Rosenblum i-f 67.) Rosenblum teaches [D]elivery of granzyme B protein into the interior of target cells results in cell death through apoptotic mechanisms. Using recombinant ligand (VEGF) and recombinant antibody (scFvMEL), which bind to the cell-surface of tumor cells and internalize efficiently, the inventors designed two novel granzyme B-related fusion proteins: GrB-vegf121 to specifically target endothelial cells; and GrB-scFvMEL to specifically target the melanoma cells. (Id. at i-f 69 (emphases added); see also id. at i-f 19 .) FF 3. Rojas teaches "[i]n quiescent cells, NF-KB dimers are associated with certain inhibitory proteins called IKB proteins . . . . IKBa may be the best characterized IKB molecule." (Rojas 2:4---6.) Rojas further teaches "[t]he NF-KB family of transcription factors has also been 4 Appeal2015-001277 Application 11/679,630 demonstrated to play a role in regulating other cellular processes such as apoptotic cell death." (Id. at 2: 17-18.) Rojas teaches that "to affect intracellular cell signaling, inhibitors must access the cell interior." (Id. at 2:30-31.) Accordingly, Rojas teaches "fusion proteins that include a membrane-translocating peptide ... for preventing immune responses including a method for specifically inhibiting the NF-KB cascade within a cell." (Id. at 4:3-5.) For example, Rojas teaches "the MTS [membrane- translocating sequence] may be attached to the [inhibitory] IKB protein by means of a tag protein." (Id. at 15:5---6.) FF 4. Haskill discloses "experimental evidence shows that phosphorylation of IKB blocks its inhibitory effect on DNA binding activity ofNF-KB." (Haskill 2:27-29.) FF 5. Batra teaches "IKBa ... is a major regulator of NF-KB activity." (Batra at 238.) Batra teaches "inhibiting NF-KB activation may sensitize cells to anticancer therapy, thereby providing a more effective treatment for certain cancers." (Id. at Abstract.) Batra further teaches "IKBa gene transfer is cytotoxic to squamous-cell lung cancer cells and sensitizes them to tumor necrosis factor-a-mediated cell death." (Id. (emphasis omitted).) FF 6. Meyskens teaches "NF-KB is constitutively activated in melanoma cells compared with normal melanocytes." (Meyskens 1200; see also id. at Abstract.) Meyskens teaches "NF -KB is inactivated in the cytoplasm by inhibitor proteins (IKB)." (Id. at 1197.) Meyskens also discloses that in "melanoma cells, enhanced degradation of IKB-a contributed to exogenous activation ofNF-KB." (Id. at 1201.) 5 Appeal2015-001277 Application 11/679,630 Principles of Law "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). Analysis Appellants argue the patentability of claims 1, 10-16, 19, 20, and 28- 33 as a group. We select claim 1 as representative. The Examiner finds that "Rosenblum teaches immunoconjugates of an antibody designated scFvMEL ... that binds a gp240 antigen on melanoma cells and is internalized into the cells, wherein scFvMEL is conjugated to polypeptides [e.g., granzyme B, Bax, etc.] that are cytotoxic to cancer cells." (Ans. 3.) The Examiner finds that "Rosenblum do[ es] not expressly teach an IkB polypeptide ... that is cytotoxic to cancer cells." (Id.) The Examiner finds, however, that the "deficiencies [of Rosenblum J are made up for in the teachings of Rojas [], Haskill [], Batra [] and Meyskens []." (Id. at 4.) For example, the Examiner finds "Rojas [] teach[ es] immunoconjugates comprising IkB and an antibody ... the IkB as a therapeutic agent being able to treat cancer and that it can be fused to an antibody." (Id.) The Examiner further finds Haskill "teach[ es] that IkB having the SEQ ID N0:3 is an NF-kB inhibitor," Batra "teach[ es] IkBa is cytotoxic to cancer cells with increased NF-kB activity" and Meyskens "teach[ es] melanoma cells with increased NF-kB activity and that enhanced degradation of human IkBa in melanoma cells contributes to NF-kB activity." (Id.) 6 Appeal2015-001277 Application 11/679,630 The Examiner concludes, "in view of the references as a whole, it would have been prima facie obvious ... to make immunoconjugates of an antibody designated scFvMEL that binds a gp240 antigen on melanoma cells conjugated to the Il