COMBINATORIAL ANTIBODY LIBRARIES AND USES THEREOF
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Abstract
Methods for making a combinatorial antibody library from human germline segments are provided. Also provided are libraries of nucleic acid molecules compiled from germline segments encoding VL chains and libraries of nucleic acid molecules encoding VH chains, and resulting antibody libraries. The libraries are provided as addressable libraries. Methods for screening antibody libraries against a target protein antigen, and the identified or selected antibodies are provided.
37 Citations
318 Claims
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1-305. -305. (canceled)
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306. A combinatorial human antibody library selected from the group consisting of:
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A. a combinatorial human antibody library comprising a plurality of antibody or antigen-binding antibody fragment species, wherein; a) each antibody or antigen-binding antibody fragment species contains a variable light (VL) chain and a variable heavy (VH) chain or a sufficient portion thereof to form an antigen binding site;
wherein;i) each VL chain comprises a Vκ
and a Jκ
human germline segment or a Vλ
and a Jλ
human germline segment; andii) each VH chain comprises a human VH and a human JH germline segment; and b) the library comprises at least about or 50 or 100 or more different antibody or antigen-binding antibody fragment species; B. a combinatorial human antibody library comprising a plurality of antibody or antigen-binding antibody fragment species, wherein; a) each antibody or antigen-binding antibody fragment species contains a modified variable light (VL) chain and/or a modified variable heavy chain (VH) chain or a sufficient portion thereof to form an antigen binding site;
wherein;i) each VL chain comprises a Vκ
and a Jκ
human germline segment or a Vλ
and a Jλ
human germline segment;ii) each VH chain comprises a VH, DH and a JH human germline segment; and b) the VL chain and/or VH chain is/are modified by replacement or insertion of one amino acid, optionally the replacement or insertion of at least one amino acid into at least one complementarity determining region (CDR) selected from among a CDRH1, CDRH2, CDRH3, CDRL1, CDRL2, and CDRL3, wherein the CDR optionally is CDR is CDRH3; and c) the library comprises at least about or 50 or 100 or more different antibody or antigen-binding antibody fragment species; and C. a combinatorial human antibody library comprising a plurality of antibody or antigen-binding antibody fragment species, wherein; a) each antibody or antigen-binding antibody fragment species contains a variable light (VL) chain and a variable heavy (VH) chain or a sufficient portion thereof to form an antigen binding site;
wherein;i) each VL chain comprises a Vκ
and a Jκ
human germline segment or a Vλ
and a Jλ
human germline segment;ii) each VH chain comprises a human VH, DH, and a JH germline segment; and b) the library comprises at least about or 50 or 100 or more different antibody or antigen-binding antibody fragment species. - View Dependent Claims (307, 308, 309, 310, 311, 312, 313, 314, 315, 316, 317, 318)
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Specification