发明名称 |
Humanized Anti-HLA-DR Antibodies |
摘要 |
The present invention concerns compositions and methods of use of humanized anti-HLA-DR antibodies. In preferred embodiments, the antibodies induce apoptosis and inhibit proliferation of lymphoma cells without inducing CDC or ADCC. In more preferred embodiments, the humanized anti-HLA-DR antibodies bind to the same epitope of HLA-DR as, or compete for binding to HLA-DR with, a murine L243 antibody. Most preferably, the humanized anti-HLA-DR antibody exhibits a higher affinity for HLA-DR than the parental murine antibody. The humanized HLA-DR antibody is of use for therapy of various diseases such as cancer, autoimmune disease or immune dysregulatory function, and is of particular use for therapy of B cell lymphomas and leukemias. In most preferred embodiments, the humanized anti-HLA-DR antibody is capable of inducing at least partial remission of lymphomas that are resistant to other B cell antibodies, such as rituximab. |
申请公布号 |
US2014227178(A1) |
申请公布日期 |
2014.08.14 |
申请号 |
US201414224866 |
申请日期 |
2014.03.25 |
申请人 |
Immunomedics, Inc. |
发明人 |
Goldenberg David M.;Hansen Hans J.;Chang Chien-Hsing |
分类号 |
A61K51/10;A61K47/48;A61K45/06;C07K16/28;A61K39/395 |
主分类号 |
A61K51/10 |
代理机构 |
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代理人 |
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主权项 |
1. A method of treating hematopoietic cancer comprising:
a) administering to a subject with hematopoietic cancer a humanized anti-HLA-DR antibody or antigen-binding fragment thereof that competes for binding to HLA-DR with a murine L243 antibody comprising the heavy chain complementarity determining region (CDR) sequences CDR1 (NYGMN (SEQ ID NO: 39)), CDR2 (WINTYTREPTYADDFKG (SEQ ID NO: 40)), and CDR3 (DITAVVPTGFDY (SEQ ID NO: 41)) and the light chain CDR sequences CDR1 (RASENIYSNLA (SEQ ID NO: 42)), CDR2 (AASNLAD (SEQ ID NO: 43)), and CDR3 (QHFWTTPWA (SEQ ID NO: 44)); wherein the humanized antibody is an IgG4 antibody comprising a Ser241Pro mutation, further comprising light chain murine L243 FR residues R37, K39, V48, F49, and G100 and heavy chain murine L243 FR residues F27, K38, K46, A68, and F91. |
地址 |
Morris Plains NJ US |