Cd3 binding antibodies
AssigneeTeneoBio, Inc.
InventorsNathan Trinklein, Wim van Schooten, Shelley Force Aldred, Katherine Harris, Duy Pham
Life of this patent
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Abstract
The present invention relates to novel human CD3 antigen-binding polypeptides and their preparation and use in the treatment and/or diagnosis of various diseases, and also relates to bispecific antibody molecules capable of activating immune effector cells and their use in diagnosis and/or treatment of various diseases.
Claims37
An antigen-binding protein specific for CD3, comprising:
- a variable heavy chain domain comprising CDR1, CDR2 and CDR3 sequences in a human VH framework, where the CDR1 sequence has a formula:
- G1 F2 T3 F4 X5 X6 Y7 A8
- where X5, X6 may be any amino acid;
- the CDR2 sequence has the formula:
- I1′ S2′ W3′ N4′ S5′ G6′ S7′ I8′
- the CDR3 sequence has the formula
- A1″ K2″ D3″ S4″ R5″ G6″ Y7″ G8″ X9″ Y10″ X11″
- X12″ G13″ G12″ A15″ Y16″
- where X9″, X11″, X12″ may be any amino acid:
- and a variable light chain domains.
A method of producing an antigen-binding protein of any of claims 1-24, comprising growing a cell according to claim 29 under conditions permissive for expression of the protein, and isolating the protein from the cells.
The method of claim 30, wherein the individual is human.
A method of making an antigen-binding protein that specifically binds to CD3, comprising:
- immunizing OmniFlic or UniRat animals with CD3;
- and
- identifying antigen-specific heavy chain sequences.
A bispecific antigen-binding protein, wherein the protein comprises of a binding domain specific for CD3 and a binding domain specific for an antigen other than CD3;
- wherein when contacted with T cells in an activation assay the bispecific antigen binding protein induces release of reduced levels of one or both of IL-2 and IL-10 relative to a reference anti-CD3 antibody;
- and
- induces more than 30% tumor cytotoxicity in standard in vitro assays using tumor cells and human T cells.
A bispecific antibody comprising:
- (i) a CD3-binding variable region comprising CDR1, CDR2 and CDR3 sequences of SEQ ID NO:1 in a human VH framework;
- (ii) a variable light chain domain comprising CDR1, CDR2 and CDR3 sequences of SEQ ID NO:19 in a human VL framework;
- (iii) a single chain anti-BCMA variable region comprising CDR1, CDR2 and CDR3 sequences at positions 26-33;
- 51-58;
- 97-108, respectively, of SEQ ID NO:20 in single or in tandem configuration.
Dependencies are inferred from the claim text.