Nucleic acids encoding polyvalent protein complexes

摘要

The invention provides for a polyvalent protein complex (PPC) comprising two polypeptide chains generally arranged laterally to one another. Each polypeptide chain typically comprises 3 or 4 “v-regions”, which comprise amino acid sequences capable of forming an antigen binding site when matched with a corresponding v-region on the opposite polypeptide chain. Up to about 6 “v-regions” can be used on each polypeptide chain. The v-regions of each polypeptide chain are connected linearly to one another and may be connected by interspersed linking regions. When arranged in the form of the PPC, the v-regions on each polypeptide chain form individual antigen binding sites.

主权项

1. An episome comprising:
(a) a first promoter operationally connected to a first nucleic acid encoding a first polypeptide comprising a polypeptide chain represented by the formula α-factor-a1-l1-a2-l2-a3, wherein a1, a2, and a3 are immunoglobulin variable domains and l1 and l2 are peptide linkers, and wherein the first polypeptide comprises the amino acid sequence of h679VH (residues 8 to 126 of SEQ ID NO:1), (b) a second promoter operationally connected to a second nucleic acid encoding a polypeptide comprising a second polypeptide chain represented by the formula α-factor-b1-l3-b2-l4-b3, wherein b1, b2 and b3 are immunoglobulin variable domains and l3 and l4 are peptide linkers and the second polypeptide comprises the amino acid sequence of h679VK (residues 243 to 357 of SEQ ID NO:2), wherein said first and second polypeptide bind together form a complex comprising at least three antigen binding sites, wherein each of said antigen binding sites comprises a variable domain from said first polypeptide chain and a variable domain from said second polypeptide chain, wherein each of said polypeptides does not bind to itself to form an antigen binding site, wherein said first nucleic acid and said second nucleic acid are coexpressed when the episome is transformed into a host cell.