Stable and soluble antibodies inhibiting TNF alpha
AssigneeESBATech, an Alcon Biomedical Research Unit LLC
InventorsStefan Ewert, Alcide Barberis, David M. Urech, Adrian Auf Der Maur, Peter Lichtlen
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Abstract
The present invention relates to particularly stable and soluble scFv antibodies and Fab fragments specific for TNFα, which comprise specific light chain and heavy chain sequences that are optimized for stability, solubility, in vitro and in vivo binding of TNFα, and low immunogenicity. Said antibodies are designed for the diagnosis and/or treatment of TNFα-related disorders. The nucleic acids, vectors and host cells for expression of the recombinant antibodies of the invention, methods for isolating them and the use of said antibodies in medicine are also disclosed.
Claims18
An isolated nucleic acid sequence encoding a stable and soluble antibody which specifically binds TNFα, said antibody comprising a light chain variable domain (VL) comprising the protein sequence of SEQ ID NO:1 and a heavy chain variable domain (VH) comprising the protein sequence of SEQ ID NO:2, or an antigen-binding derivative thereof, wherein said derivative has at maximum up to five amino acid changes as compared to SEQ ID NO:
- 1 and/or at maximum up to nine amino acid changes as compared to SEQ ID NO:
- 2, wherein said changes occur at amino acid positions in framework regions of said VL comprising the protein sequence of SEQ ID NO:
- 1 and said VH comprising the protein sequence of SEQ ID NO:
- 2, and wherein said derivative does not comprise the entire protein sequences of SEQ ID NO:
- 3 and SEQ ID NO:
- 4.
An isolated nucleic acid sequence encoding a stable and soluble antibody which specifically binds TNFα, said antibody comprising the protein sequence of SEQ ID NO:
- 40, wherein the protein sequence of SEQ ID NO:
- 10 in the sequence of SEQ ID NO:
- 40 is a linker sequence.
An isolated nucleic acid sequence encoding a stable and soluble antibody which specifically binds TNFα, said antibody comprising a light chain variable domain (VL) comprising the protein sequence of SEQ ID NO:
- 1 and a heavy chain variable domain (VH) comprising the protein sequence of SEQ ID NO:
- 2 and a linker derived from the protein sequence of SEQ ID NO:
- 10.
Dependencies are inferred from the claim text.