Polypeptide linkers for production of biosynthetic proteins
AssigneeCreative BioMolecules, Inc.
InventorsJames S. Huston, Hermann Oppermann
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AssigneeCreative BioMolecules, Inc.
InventorsJames S. Huston, Hermann Oppermann
Estimating the term…
Disclosed are a family of synthetic proteins having binding affinity for a preselected antigen, and multifunctional proteins having such affinity. The proteins are characterized by one or more sequences of amino acids constituting a region which behaves as a biosynthetic antibody binding site (BABS) The sites comprise V.sub.H -V.sub.L or V.sub.L -V.sub.H -like single chains wherein the V.sub.H and V.sub.L -like sequences are attached by a polypeptide linker, or individual V.sub.H or V.sub.L -like domains. The binding domains comprise linked CDR and FR regions, which may be derived from separate immunoglobulins. The proteins may also include other polypeptide sequences which function, e.g., as an enzyme, toxin, binding site, or site for attachment to an immobilization media or radioactive atom. Methods are disclosed for producing the proteins, for designing BABS having any specificity that can be elicited by in vivo generation of antibody for producing analogs thereof, and for producing multifunctional synthetic proteins which are self-targeted by virtue of their binding site region.
A biosynthetic single chain polypeptide comprising a linking sequence connecting first and second non-naturally peptide-bonded, biologically active polypeptide domains to form a single polypeptide chain comprising at least two biologically active domains, connected by said linking sequence, said linking sequence comprising hydrophilic, peptide-bonded amino acids comprising at least 10 amino acid residues, said linking sequence being cysteine-free, having a flexible unstructured polypeptide configuration essentially free of secondary structure in aqueous solution, having a plurality of glycine or serine residues and defining a polypeptide of a length sufficient to span the distance between the C-terminal end of the first domain and the N-terminal end of the second domain.
Dependencies are inferred from the claim text.