Antibodies against PD-1
AssigneesWyeth, MedImmune, LLC
InventorsMary Collins, Clive R. Wood, Beatriz M. Carreno, Deborah Luxenberg, Jason Jussif, Laura L. Carter, Frances K. Bennett, Vila Valge-Archer, John Andrews, Caroline Russell
Life of this patent
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Abstract
This disclosure provides antibodies and antigen-binding fragments that can act as agonists and/or antagonists of PD-1 (Programmed Death 1), thereby modulating immune responses in general, and those mediated by TcR and CD28, in particular. The disclosed compositions and methods may be used for example, in treating autoimmune diseases, inflammatory disorders, allergies, transplant rejection, cancer, and other immune system disorders.
Claims23
An isolated antibody comprising:
- a VH domain comprising SEQ ID NO:6, SEQ ID NO:10 , SEQ ID NO:14 or SEQ ID NO:47,
- wherein the antibody specifically binds an epitope within the extracellular domain of human or mouse PD-1.
An isolated antibody comprising:
- a VL domain comprising SEQ ID NO:8, SEQ ID NO:12, SEQ ID NO:16 or SEQ ID NO:49,
- wherein the antibody specifically binds an epitope within the extracellular domain of human or mouse PD-1.
An isolated antibody comprising:
- a VH domain or an antigen-binding fragment thereof that comprises 3 CDRs;
- and a VL domain or an antigen-binding fragment thereof that comprises 3 CDRs;
- wherein the antibody comprises at least 3 VH domain CDRs having sequences of:
- SEQ ID NO:23, SEQ ID NO:24 and SEQ ID NO:25;
- or
- SEQ ID NO:29, SEQ ID NO:30 and SEQ ID NO:31;
- or
- SEQ ID NO:35, SEQ ID NO:36 and SEQ ID NO:37;
- or
- SEQ ID NO:50, SEQ ID NO:51 and SEQ ID NO:52;
- or at least 3 VL domain CDRs having sequences of:
- SEQ ID NO:26, SEQ ID NO:27 and SEQ ID NO:28;
- or
- SEQ ID NO:32, SEQ ID NO:33 and SEQ ID NO:34;
- or
- SEQ ID NO:38, SEQ ID NO:39 and SEQ ID NO:40;
- or
- SEQ ID NO:53, SEQ ID NO:54, and SEQ ID NO:55;
- and
- wherein the antibody specifically binds an epitope within the extracellular domain of human or mouse PD-1.
An antibody produced by steps comprising:
- (a) providing a nucleic acid encoding 3 VL domain CDRs having sequences of:
- SEQ ID NO:26, SEQ ID NO:27 and SEQ ID NO:28;
- or SEQ ID NO:32, SEQ ID NO:33 and SEQ ID NO:34;
- or SEQ ID NO:38, SEQ ID NO:39 and SEQ ID NO:40;
- or SEQ ID NO:53, SEQ ID NO:54, and SEQ ID NO:55;
- (b) combining a repertoire of nucleic acids encoding 3 VH domain CDRs with the nucleic acid encoding the 3 VL domain CDRs, so as to provide a product repertoire of nucleic acids encoding the 3 VL domain CDRs and the repertoire of 3 VH domain CDRs
- (c) expressing the nucleic acids of the product repertoire;
- (d) selecting an antigen-binding fragment comprising a variable domain that specifically binds to PD-1 and that is expressed from the nucleic acids of the product repertoire;
- and
- (e) producing an antibody comprising the antigen-binding fragment.
Dependencies are inferred from the claim text.