Antagonistic cd40 monoclonal antibodies and uses thereof
AssigneeBristol-Myers Squibb Company
InventorsAaron YAMNIUK, Mary STRUTHERS, Suzanne J. SUCHARD
Life of this patent
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Abstract
The disclosure provides for antibodies that bind CD40, including a humanized antibody and a chimeric antibody with different Fc domains. The antibodies bind CD40 and do not exhibit CD40 agonist activity. The antibodies may comprise a modified IgG1 Fc domain, and exhibit minimal activation of immature dendritic cells. Compositions comprising antibodies, methods of use for treatment of diseases involving CD40 activity, and use in the preparation of a medicament for treatment of a disease involving CD40 activity are provided.
Claims19
1-13. (canceled)
A nucleic acid encoding an isolated antibody or antigen binding portion thereof, that specifically binds to human CD40, wherein said antibody comprises a heavy chain, and a light chain, wherein:
- said heavy chain comprises a CDR1 comprising GYTFTDLSMHW (SEQ ID NO:
- 1), a CDR2 comprising YITPSSGYTAYNQKFKG (SEQ ID NO:
- 2), a CDR3 comprising LILQRGAY (SEQ ID NO:
- 3) and a human heavy chain constant region;
- and
- said light chain comprises a CDR1 comprising RASKNVDSYGNSFMHW (SEQ ID NO:
- 4), a CDR2 comprising RASNLES (SEQ ID NO:
- 5), and a CDR3 comprising QQSNEDPLT (SEQ ID NO:
- 6) and a human light chain constant region, and
- said human heavy chain constant region is a human IgG1 Fc domain comprising either (1) a mutation at Kabat position 238 that reduces binding to Fc-gamma-receptors (FcgRs), wherein proline 238 (P238) is mutated to one of the residues selected from the group consisting of lysine, serine, alanine, arginine and tryptophan, and wherein the antibody or antigen binding portion has reduced FcgR binding;
- or (2) or an alanine substituted at Kabat position 297.
18-20. (canceled)
Dependencies are inferred from the claim text.