US 7,754,208 B2 · Binding domain-immunoglobulin fusion proteins

Abstract

The invention relates to novel binding domain-immunoglobulin fusion proteins that feature a binding domain for a cognate structure such as an antigen, a counterreceptor or the like, a wild-type IgG1, IGA or IgE hinge region polypeptide or a mutant IgG1 hinge region polypeptide having either zero, one or two cysteine residues, and immunoglobulin CH2 and CH3 domains, and that are capable of ADCC and/or CDC while occurring predominantly as polypeptides that are compromised in their ability to form disulfide-linked multimers. The fusion proteins can be recombinantly produced at high expression levels. Also provided are related compositions and methods, including cell surface forms of the fusion proteins and immunotherapeutic applications of the fusion proteins and of polynucleotides encoding such fusion proteins.

Claims8

Dependent claims

A fusion protein, comprising:

(a) a binding domain polypeptide that binds CD20, wherein the binding domain comprises amino acids 23-265 of SEQ ID NO:397 except that leucine at position 155 of SEQ ID NO:397 is substituted with a serine,
(b) a human IgG1 hinge peptide comprising a mutated core sequence as set forth in amino acids 279-282 of SEQ ID NO:397, 398 or 582,
(c) an immunoglobulin heavy chain CH2 constant region polypeptide as set forth in amino acids 284-393 of SEQ ID NO:397 fused to the hinge peptide,
(d) an immunoglobulin heavy chain CH3 constant region polypeptide as set forth in amino acids 39-500 of SEQ ID NO:397 fused to the CH2 polypeptide, and
wherein the fusion protein promotes antibody dependent cell-mediated cytotoxicity, complement fixation, or both.

2 more elements

Dependencies are inferred from the claim text.

Binding domain-immunoglobulin fusion proteins

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Binding domain-immunoglobulin fusion proteins

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Abstract

Claims8