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(12) United States Patent (10) Patent No.: US 7,829,086 B2 Hilbert Et Al

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(12) United States Patent (10) Patent No.: US 7,829,086 B2 Hilbert Et Al US007829086B2 (12) United States Patent (10) Patent No.: US 7,829,086 B2 Hilbert et al. (45) Date of Patent: Nov. 9, 2010 (54) HUMANIZED ANTI-CD22 ANTIBODIES AND 2004/0202658 A1 10/2004 Benyunes THEIR USE IN TREATMENT OF 2004/021915.6 A1 11/2004 Goldenberg et al. ONCOLOGY, TRANSPLANTATION AND 2005, 0118182 A1 6/2005 Pastan et al. AUTOIMMUNE DISEASE 2007,0264260 A1 11/2007 Tuscano et al. (75) Inventors: David M. Hilbert, Bethesda, MD (US); 2008.0118505 A1 5/2008 Tedder Tarran Jones, Radlett (GB); David G. Williams, Epsom (GB) (73) Assignees: Medimmune, LLC, Gaithersburg, MD FOREIGN PATENT DOCUMENTS (US); Aeres Biomedical, Ltd., London EP O 660 721 B1 10, 2008 (GB) WO WOO3,O93320 A2 11/2003 (*) Notice: Subject to any disclaimer, the term of this patent is extended or adjusted under 35 U.S.C. 154(b) by 132 days. OTHER PUBLICATIONS (21) Appl. No.: 11/715,308 MacCallum et al. (J. Mol. Biol. (1996) 262:732-745).* De Pascalis et al. (The Journal of Immunology (2002) 169, 3076 (22) Filed: Mar. 6, 2007 3084).* (65) Prior Publication Data Casset et al. (2003) BBRC 307, 198-205).* Vajdos et al. (2002) J. Mol. Biol. 320, 415-428).* US 2007/O258981 A1 Nov. 8, 2007 Holmetal ((2007) Mol. Immunol. 44: 1075-1084).* Related U.S. Application Data Chen et al. (J. Mol. Bio. (1999) 293, 865-881).* Wu et al. (J. Mol. Biol. (1999) 294, 151-162).* (60) Provisional application No. 60/779,806, filed on Mar. Brummell et al. (Biochemistry 32:1180-1187 (1993)).* 6, 2006. (Continued) (51) Int. Cl. A 6LX 39/395 (2006.01) Primary Examiner Lynn Bristol C07K 6/8 (2006.01) (74) Attorney, Agent, or Firm Jones Day CO7H21/04 (2006.01) (52) U.S. Cl. ................................. 424/133.1: 530/388.1 (57) ABSTRACT (58) Field of Classification Search .............. 424/133.1; 530/388.1, 138.1 See application file for complete search history. The present invention provides chimeric and humanized ver sions of anti-CD22 mouse monoclonal antibody, HB22.7. (56) References Cited The anti-CD22 antibodies of the invention comprise four human or humanized framework regions of the immunoglo U.S. PATENT DOCUMENTS bulin heavy chain variable region (“VH’) and four human or 4,816,567 A 3/1989 Cabilly et al. humanized framework regions of the immunoglobulin light 5,484,892 A 1/1996 Tedder et al. chain variable region (“VK). The invention further com 5,595,721 A 1/1997 Kaminski et al. prises heavy and/or light chain FW regions that contain one or 5,686,072 A 11, 1997 Uhr et al. more backmutations in which a human FW residue is 5,789,554 A 8/1998 Leung et al. exchanged for the corresponding residue present in the paren 5,831,142 A 11/1998 Tedder 5,843,398 A 12, 1998 Kaminski et al. tal mouse heavy or light chain. Human or humanized VH 6,015,542 A 1/2000 Kaminski et al. framework regions of antibodies of the invention may com 6,022,521 A 2/2000 Wahl et al. prise one or more of the following residues: a valine (V) at 6,090,365 A 7/2000 Kaminski et al. position 24 of framework region 1, a glycine (G) at position 6,183,744 B1 2/2001 Goldenberg 49 of framework region 2, and an asparagine (N) at position 6,187,287 B1 2/2001 Leung et al. 73 of framework region3, numbered according to Kabat. The 6,251,362 B1 6, 2001 Wahl et al. invention further relates to pharmaceutical compositions, 6,254,868 B1 7/2001 Leung et al. immunotherapeutic compositions, and methods using thera 6,287,537 B1 9/2001 Kaminski et al. peutic antibodies that bind to the human CD22 antigen and 6,306,393 B1 10/2001 Goldenberg that preferably mediate human ADCC, CDC, and/or apopto 6,331.415 B1 12/2001 Cabilly et al. sis for: the treatment of B cell diseases and disorders inhuman 6,399,061 B1 6/2002 Anderson et al. Subjects. Such as, but not limited to, B cell malignancies, for 6,455,043 B1 9/2002 Grillo-Lopez the treatment and prevention of autoimmune disease, and for 6,921,846 B1 7, 2005 Tedder the treatment and prevention of graft-Versus-host disease 2002/0071807 A1 6/2002 Goldenberg (GVHD), humoral rejection, and post-transplantation lym 2003/O124058 A1 7/2003 Goldenberg 2003. O133930 A1 7/2003 Goldenberg et al. phoproliferative disorder in human transplant recipients. 2003/0202975 A1 10/2003 Tedder et al. 2004/0001828 A1 1/2004 Tuscano et al. 24 Claims, 53 Drawing Sheets US 7,829,086 B2 Page 2 OTHER PUBLICATIONS Linden et al., 2005, "Dose-fractionated radioimmunotherapy in non Hodgkin's lymphoma using DOTA-conjugated, 90Y-radiolabeled, Kobayashi et al. (Protein Engineering 12:879-844 (1999)).* humanized anti-CD22 monoclonal antibody, epratuzumab’. Clin. Burks et al. (PNAS 94:412–417 (1997)).* Cancer Res. 11(14):5215-5222. Jang et al. (Molec. Immunol. 35:1207-1217 (1998)).* Losman et al., 1997, “Generation of a high-producing clone of a Brorson et al. (J. Immunol. 163:6694-6701 (1999)).* humanized anti-B-cell lymphoma monoclonal antibody (hLL2)”. Coleman (Research in Immunol. 145:33-36 (1994)).* Cancer 80(12 Suppl):2660-2666. Dufner (Trends Biotechnol. 24(11):523-29 (2006)).* Maloney et al., 1997, “IDEC-C2B8: results of aphase I multiple-dose U.S. Appl. No. 1 1/715,307, filed Mar. 6, 2007, Jones et al. trial in patients with relapsed non-Hodgkin's lymphoma'. J. Clin. Friedberg, 2004, “Developing new monoclonal antibodies for Oncol. 15:3266-3274. aggressive lymphoma: a challenging road in the rituximab era'. Clin Maloney et al., 1994, "Phase I clinical trial using escalating single Cancer Res. 10(16):5297-5298. dose infusion of chimeric anti-CD20 monoclonal antibody (IDEC Ghetie et al., 1991, “Antitumor activity of Fab' and IgG-anti-CD22 C2B8) in patients with recurrent B-cell lymphoma'. Blood immunotoxins in disseminated human B lymphoma grown in mice 84(8):2457-2466. with severe combined immunodeficiency disease: effect on tumor Maloney et al., 1997, “IDEC-C2B8 (Rituximab) anti-CD20 cells in extranodal sites”. Cancer Res. 51(21):5876-5880. monoclonal antibody therapy in patients with relapsed low-grade Ghetie et al., 1992, “The antitumor activity of an anti-CD22 immunotoxin in SCID mice with disseminated Daudi lymphoma is non-Hodgkin's lymphoma'. Blood 90:2188-2195. enhanced by either an anti-CD19 antibody or an anti-CD 19 May et al., 1986, "Selective killing of normal and neoplastic human immunotoxin', Blood 80(9): 2315-2320. B cells with anti-CD 19- and anti-CD22-ricin A chain Ghetie et al., 1996, “Combination immunotoxin treatment and che immunotoxins', Cancer Drug Delivery 3(4):261-272 (1986). motherapy in SCID mice with advanced, disseminated Daudi McLaughlin et al., 1998, "Clinical status and optimal use of lymphoma'. Int. J. Cancer 68(1):93-96. rituximab for B-cell lymphomas'. Oncology 12:1763-1769. Goldenberg et al., 1990, "Monoclonal antibody therapy of cancer', Onrust et al., 1999, “Rituximab, Drugs 58:79-88. N. J. Med. 87(11 Spec No):913-918. Poe et al., 2004, "CD22 Regulates B lymphocyte function in vivo Goldenberg, 1994, “New developments in monoclonal antibodies for through both ligand-dependent and ligand-independent mecha cancer detection and therapy”, CA Cancer J. Clin. 44(1):43-64. nisms”, Nat. Immunol. 5(10): 1078-1087. Haas et al., 2006, “CD22 regulates normal and malignant B survival Press et al., 2001, “Immunotherapy of Non-Hodgkin's lymphomas'. in vivo’, J. Immunol. 177:3063-3073. Hematology 221-240. Hekman et al., 1991, “Initial experience with treatment of human B Qu et al., 2005. “Development of humanized antibodies as cancer cell lymphoma with anti-CD19 monoclonal antibody”. Cancer therapeutics'. Methods 36(1):84-95. Immunol. Immunother, 32(6):364-372 (1991). Reffet al., 1994, "Depletion of B cells in vivo by a chimeric mouse Jacobsen et al., 1997, “Epidemiology and Estimated Population Bur human monoclonal antibody to CD20”. Blood 83:435-455. den of Selected Autoimmune Diseases in the United States', Clin Renner et al., 1997, “Monoclonal antibodies in the treatment of Immunol. Immunopathol. 84:223-243. non-Hodgkin's lymphoma: Recent results and future prospects'. Juweid et al., 1995, "Treatment of non-Hodgkin's lymphoma with Leukemia 11(Suppl): S55-S59. radiolabeled murine, chimeric, or humanized LL2, an anti-CD22 Sharkey et al., 1994, "Treatment of non-Hodgkin's lymphoma monoclonal antibody”. Cancer Res. 55(23 Suppl):5899s-5907s. (NHL) with LL2, an anti-CD22 monoclonal antibody”. J. Kaminski et al., 1993, "Radioimmunotherapy of B-Cell Lymphoma Immunother. 16(2):160 (abstract 48). with ''IlAnti-B1 (Anti-CD20) Antibody”. N. Eng. J. Med. Silverman et al., 2002, "Rituximab therapy and autoimmune disor 329:459465. ders: prospects for anti-B cell therapy”, Arthritis Rheum. 48: 1484 Khazaeli et al., 1994, "Low V-region immunogenicity of therapeutic 1492. doses of 1311-LL2 mouse monoclonal antibody in lymphoma Smith et al., 2003, "Rituximab (monoclonal anti-CD20 antibody): patients'. J. Immunother, 16(2): 170 (abstract No. 89). mechanisms of action and resistance'. Oncogene 22:7359-7368. Kreitman et al., 1993, "Pseudomonas exotoxin-based immunotoxins containing the antibody LL2 or LL2-Fab' induce regression of Sub St. Clair & Tedder, 2006, "New prospects for autoimmune disease cutaneous human B-cell lymphoma in mice'. Cancer Res. 53(4):819 therapy: B cells on deathwatch.” Arthritis and Rheumatism.54(1): 1-9. 825. 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