Multivalent binding protein compositions and methods for identifying variants of same
AssigneeAbbVie Inc.
InventorsJijie GU, Maria Cristina HARRIS, Lorenzo BENATUIL, Chung-Ming HSIEH
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Abstract
Provided are protein, nucleic acid, and cellular libraries of multivalent binding proteins (e.g., DVD-Fab or DVD-Ig molecules) and the use of these libraries for the screening of multivalent binding proteins using cell surface display technology (e.g., yeast display).
Claims38
A diverse library of binding proteins comprising a first polypeptide chain having the general formula VH1-(X1)n-VH2-C—(X2)n, wherein VH1 is a first heavy chain variable domain, X1 is a linker with the proviso that it is not a constant domain, VH2 is a second heavy chain variable domain, C is a heavy chain constant domain, X2 is a cell surface protein, and n is 0 or 1, and wherein the amino acid sequences of VH1, VH2 and/or X1 independently vary within the library.
The library of claim 2, wherein the binding proteins further comprise a second polypeptide chain having the general formula VL1-(Y1)n-VL2-C, wherein VL1 is a first light chain variable domain, Y1 is a linker with the proviso that it is not a constant domain, VL2 is a second light chain variable domain, C is a light chain constant domain, n is 0 or 1, wherein the VH1 and VH2 of the first polypeptide chain and VL1 and VL2 of second polypeptide chains of the binding protein combine form two functional antigen binding sites.
A method of selecting a binding protein that specifically binds to a first and a second target antigen simultaneously, the method comprising:
- a) providing a diverse library of transformed host cells expressing the diverse library of binding proteins, wherein the diverse library of binding proteins comprises a first polypeptide chain having the general formula VH1-(X1)n-VH2-C—(X2)n, wherein VH1 is a first heavy chain variable domain, X1 is a linker with the proviso that it is not a constant domain, VH2 is a second heavy chain variable domain, C is a heavy chain constant domain, X2 is a cell surface protein, and n is 0 or 1, and wherein the amino acid sequences of VH1, VH2 and/or X1 independently vary within the library;
- b) contacting the host cells with the first and second target antigen;
- and
- c) selecting a host cell that bind to the first and second target antigen, thereby identifying a binding protein that specifically binds to a first and a second target antigen simultaneously.
A multivalent binding protein having the general formula VH1-(X1)n-VH2-C—X2, wherein VH1 is a first heavy chain variable domain, X1 is a linker with the proviso that it is not a constant domain, VH2 is a second heavy chain variable domain, C is a heavy chain constant domain, X2 is an anchoring moiety, and n is 0 or 1.
Dependencies are inferred from the claim text.