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(12) Unlted States Patent (10) Patent No.: US 7,740,847 B2 Allan Et Al

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(12) Unlted States Patent (10) Patent No.: US 7,740,847 B2 Allan Et Al US007740847B2 (12) Unlted States Patent (10) Patent No.: US 7,740,847 B2 Allan et al. (45) Date of Patent: Jun. 22, 2010 (54) VARIANT FC REGIONS 5,550,362 A 8/1996 Sherman 5,595,721 A 1/1997 Kaminski et a1. (75) Inventors: Barrett Allan, Encinitas, CA (US); 5,624,321 A 4/1997 winter et a1, Weidong Jiallg, Sunnyvale, CA(US); 5,648,260 A 7/1997 Winter etal. Yillg Tang, San Die/g9’ CA (Us); Jeffry 5,677,180 A 10/1997 Robinson et a1. Dean Watkins’ Enclmtas, CA (Us) 5,721,108 A 2/1998 Robinson et a1. (73) Assignee: Applied Molecular Evolution, Inc., San 5’736’l37 A 4/1998 Anderson et al' Diego’ CA (Us) 5,776,456 A 7/1998 Anderson et a1. 5,843,398 A 12/1998 Kaminski et a1. ( * ) Notice: Subject to any disclaimer, the term of this 5,843,439 A 12/1998 Anderson et a1. patent is extended or adjusted under 35 5,985,599 A 11/1999 McKenzie et a1. U-S-C- 154(1)) by 195 days- 6,015,542 A 1/2000 Kaminskietal. 6,090,365 A 7/2000 Kaminski et a1. (21) Appl' NO‘: 11/572’634 6,120,767 A 9/2000 Robinson et a1. (22) PCT FiladZ Jul- 18, 2005 6,121,022 A 9/2000 Presta et a1. 6,165,745 A 12/2000 Ward et a1. (86) PCT No.: PCT/US2005/025276 6,171,586 B1 1/2001 Lam etal. 6,183,744 B1 2/2001 Goldenberg §371 (0X1), 6,187,287 B1 2/2001 Leung etal. (2)’ (4)132“: Jan- 25’ 2007 6,194,551 B1 2/2001 Idusogie et a1. (87) PCT Pub‘ NO‘: W02006/020114 6,204,023 B1 3/2001 Robinson et a1. 6,224,866 B1 5/2001 Barbera-Guillem PCT pub Date; Feb 23, 2006 6,242,195 B1 6/2001 Idusogie et a1. 6,277,375 B1 8/2001 Ward (65) Prior Publication Data 6,287,537 B1 9/2001 Kaminski et a1. Us 2007/0224188 A1 Sep. 27, 2007 6,306,393 B1 10/2001 Goldenberg Related US. Application Data (60) Provisional application No. 60/ 598,855, ?led on Aug. 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Cl. ............ .. 424/1331; 424/1441; 424/1531; Primary ExamineriROn schwadron 424/1551; 424/1561; 424/1731; 424/1741; (74) Anomeyl Agem, 0r FirmiROben L, Sharp; MaryAnn 424/1431; 435/69.6; 435/320.1; 435/325; wiskerchen 435/326; 435/328; 435/343.1; 435/344; 435/344.1; 435/358; 530/387.3; 530/388.22; 530/388.73; (57) ABSTRACT 530/38.8; 530/388.85; 536/2353 (58) Field of Classi?cation Search ..................... .. None See application ?le for complete search history. The present invention provides humanized anti-CD20 anti (56) References Cited bod1es compr1s1ng a human IgG1 Fc reg1on compnsmg an isoleucine at position 247 and a glutamine at position 339 as US. PATENT DOCUMENTS Well as nucleic acids encoding the antibodies and methods of using the antibodies for treating lymphoma. 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W0 WO 98/52975 11/1998 Hong, K, et a1 , “Simple quantitative live cell and anti-idiotypic based W0 WO 98/56418 12/1998 ELISA for humanized antibody directed to cell surface protein W0 WO 98/58964 12/1998 CD20,” Journal of Immunological Methods vol. 294, pp. 189-197 W0 WO 99/22764 5/1999 (2004). W0 WO 99/51642 10/1999 Idusogie, EE, et al., “Mapping of the Clq Binding Site on RituXan, A W0 WO 99/58572 11/1999 Chimeric Antibody With a Human IgGl Fc,” Journal of Immunology, W0 WO 00/09160 2/2000 vol. 164, No. 8, pp, 4178-4184 (2000). W0 WO 00/09560 2/2000 Idusogie, EE, et al., “Engineered Antibodies With Increased Activity W0 WO 00/20864 4/2000 to Recruit Complement,” Journal of Immunology, vol. 166, No. 4, pp, W0 WO 00/27428 5/2000 2571-2575 (Feb. 15,2001). W0 WO 00/27433 5/2000 Jones, PT, et al., “Replacing the Complementarity-Determining W0 WO 00/29584 5/2000 Regions in a Human Antibody With Those From a Mouse” Nature W0 WO 00/42072 7/2000 321:522-525 (May 29, 1986). W0 WO 00/44788 8/2000 Liu, AY, et al., “Production of a Mouse-Human Chimeric Monoclonal W0 WO 00/67795 11/2000 Antibody to CD20 With Potent Fc-Dependent Biologic Activity,” W0 WO 00/67796 11/2000 Journal ofImmunology, vol. 139, No. 10, pp. 3521-3526 (1987). W0 WO 00/74718 12/2000 Longo, DL, “Immunotherapy for non-Hodgkin’s lymphoma”, Cur W0 WO 00/76542 A1 12/2000 rent Opinion in Oncology, vol. 8, pp. 353-359, 1996. W0 WO 01/03734 A1 1/2001 Maloney, DG, et al., “Newer Treatments for Non-Hoggkin’s W0 WO 01/10460 A1 2/2001 Lymphoma: Monoclonal Antibodies”, Oncology, vol. 12, No. 10, W0 WO 01/10462 2/2001 Supplement No. 8, pp, 63-76, (Oct. 1998). W0 WO 01/13945 A1 3/2001 Martin, F, et al., “Pathogenic roles of B cells in Human Autoim W0 WO 01/74388 10/2001 munity; Insights from the Clinic,” Immunity, vol. 20, No. 5, pp. W0 WO 01/79299 10/2001 517-527 (May 2004). 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