Host cell specific binding molecules capable of neutralizing viruses and uses thereof
AssigneeCrucell Holland B.V.
InventorsMark Throsby, Cornelis Adriaan De Kruif
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Abstract
The present invention provides human binding molecules specifically binding to a host cell protein and having virus neutralizing activity, nucleic acid molecules encoding the human binding molecules, compositions comprising the human binding molecules and methods of identifying or producing the human binding molecules. The human binding molecules can be used in the diagnosis, prophylaxis and/or treatment of viral infections.
Claims58
A binding molecule capable of specifically binding to an intracellular host cell protein, which can be incorporated into a viral membrane, characterized in that the binding molecule has virus-neutralizing activity.
A binding molecule capable of specifically binding to a protein comprising an amino acid sequence selected from the group consisting of SEQ ID NO:2 and SEQ ID NO:4.
A method of identifying a binding molecule specifically binding to a host cell protein or a nucleic acid molecule encoding a binding molecule specifically binding to a host cell protein, wherein the method comprises the steps of:
- a) contacting a collection of binding molecules on the surface of replicable genetic packages with a virus, virus-like particle or fragment thereof under conditions conducive to binding,
- b) selecting at least once for a replicable genetic package binding to the virus, virus-like particle or fragment thereof, and
- c) separating and recovering the replicable genetic package binding to the virus, virus-like particle or fragment thereof from replicable genetic packages that do not bind.
An eukaryotic leader peptide, characterized in that the peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NO:150, SEQ ID NO:152 and SEQ ID NO:154.
An expression vector comprising a nucleic acid sequence selected from the group consisting of SEQ ID NO:155, SEQ ID NO:156 and SEQ ID NO:157.
A method for producing an expression vector for producing an immunoglobulin heavy chain, the method comprising the steps of:
- a. digesting an expression vector comprising the nucleic acid sequence of SEQ ID NO:155 and downstream thereof an XhoI-site and an immunoglobulin heavy chain constant region with the restriction enzymes SfiI and XhoI,
- b. digesting a phage display vector comprising an immunoglobulin heavy chain variable region with the restriction enzymes SfiI and XhoI,
- c. inserting the immunoglobulin heavy chain variable region into the expression vector, and
- d. isolating the expression vector.
A method for producing an expression vector for producing an immunoglobulin light chain, the method comprising the steps of:
- a. digesting an expression vector comprising the nucleic acid sequence of SEQ ID NO:156 or SEQ ID NO:157 and downstream thereof a NotI-site and an immunoglobulin light chain constant region with the restriction enzymes XhoI and NotI,
- b. digesting a phage display vector comprising an immunoglobulin light chain variable region with the restriction enzymes SalI and NotI, and
- c. inserting the immunoglobulin light chain variable region into the expression vector, and
- d. isolating the expression vector.
Dependencies are inferred from the claim text.