Biosynthetic binding proteins for immuno-targeting

A composition for targeting an epitope on an antigen expressed in a mammal, wherein the composition comprises a pharmaceutically acceptable carrier in combination with,

• a dimeric biosynthetic construct for binding to a preselected antigen, wherein the construct comprises:
• (a) two separate polypeptide chains, each of which have an amino acid sequence defining
• (1) an sFv comprising two polypeptide domains connected by a polypeptide linker spanning the distance between the C-terminus of one domain and the N-terminus of the other, the amino acid sequence of each said domain comprising complementarity determining regions (CDRs) interposed between framework regions (FRs), the CDRs and FRs of each said sFv together defining a binding site immunologically reactive with a said preselected antigen, and
• (2) a C-terminal tail essentially free of helical character under physiological conditions and comprising at least one amino acid having a derivatizable amino acid side chain;
• and
• (b) an sFv coupler linking together each said sFv through the derivatizable amino acid side chain disposed within the C-terminal tail of each sFv to form a homodimeric construct,
• said homodimeric construct having a conformation which binds said preselected antigen in said mammal with an avidity greater than the avidity of either sFv individually.

A composition for targeting an epitope on an antigen expressed in a mammal, wherein the composition comprises a pharmaceutically acceptable carder in combination with,

• a dimeric biosynthetic construct for binding at least one preselected antigen, wherein the construct comprises:
• (a) two separate polypeptide chains, each of which have an amino acid sequence defining
• (1) an sFv comprising two polypeptide domains connected by a polypeptide linker spanning the distance between the C-terminus of one domain and the N-terminus of the other, the amino acid sequence of each said domain comprising complementarity determining regions (CDRs) interposed between framework regions (FRs), the CDRs and FRs of each said sFv together defining a binding site immunologically reactive with a said preselected antigen, and
• (2) an N-terminal tail comprising at least one amino acid having a derivatizable amino acid side chain;
• and
• (b) an sFv coupler linking together each said sFv through the derivatizable amino acid side chain disposed within the N-terminal tail of each sFv,
• said dimeric construct having a conformation wherein the binding site of each said sFv binds a preselected antigen when said dimeric construct is administered to said mammal.

A composition for targeting an epitope on an antigen expressed in a mammal, wherein the composition comprises a pharmaceutically acceptable carrier in combination with,

• a dimeric biosynthetic construct for binding at least one preselected antigen, wherein the construct comprises:
• (a) two separate polypeptide chains, wherein each of said polypeptide chains have amino acid sequence defining
• an sFv comprising two polypeptide domains connected by a polypeptide linker spanning the distance between the C-terminus of one domain and the N-terminus of the other, the amino acid sequence of each said domain comprising complementarity determining regions (CDRs) interposed between framework regions (FRs), the CDRs and FRs of each said sFv together defining a binding site immunologically reactive with a said preselected antigen,
• one of said polypeptide chains further comprising an amino acid sequence defining an N-terminal tail comprising at least one amino acid having a derivatizable amino acid side chain, and
• the other of said polypeptide chains further comprising an amino acid sequence defining a C-terminal tail comprising at least one amino acid having a derivatizable amino acid side chain;
• (b) an sFv coupler linking together each said sFv through the derivatizable amino acid side chain disposed within the N-terminal tail of one polypeptide chain and the derivatizable amino acid side chain disposed within the C-terminal tail of the other polypeptide chain,
• said dimeric construct having a conformation wherein the binding site of each said sFv binds a preselected antigen when said dimeric construct is administered to said mammal.