Antibodies Blocking DLL4-Mediated Notch Signalling
AssigneeThe Brigham and Women's Hospital, Inc.
InventorsMasanori Aikawa, Toshiaki Nakano, Shunsuke Katsuki
Life of this patent
Estimating the term…
Abstract
The present invention is directed to antibodies that interact with DLL4 and inhibit it from binding to NOTCH receptors. The invention also includes nucleic acids encoding the antibodies and methods of using the antibodies in research and in the prevention or treatment of various diseases and conditions.
Claims34
An isolated IgG antibody that binds to human DLL4 with an affinity at least 1000 times higher than human DLL1, and which comprises:
- a) a heavy chain variable region at least 90% identical to the sequence of amino acids 1-114 of SEQ ID NO:14 and/or which includes one or more heavy chain complementarity determining regions (HCDRs) selected from the group consisting of:
- HCDR1-8C2, amino acids 31-35 of SEQ ID NO:14;
- HCDR2-8C2, amino acids 50-65 of SEQ ID NO:14;
- and HCDR3-8C2, amino acids 96-103 of SEQ ID NO:14;
- b) a light chain variable region at least 90% identical to the sequence of amino acids 1-106 of SEQ ID NO:16 and/or which includes one or more light chain complementarity determining regions (LCDRs) selected from the group consisting of:
- LCDR1-8C2, amino acids 23-34 of SEQ ID NO:16;
- LCDR2-8C2, amino acids 50-56 of SEQ ID NO:16;
- and LCDR3-8C2, amino acids 89-97 of SEQ ID NO:16.
An isolated IgG antibody that binds to human DLL4 with an affinity at least 1000 times higher than human DLL1, and which comprises:
- a) a heavy chain variable region at least 90% identical to the sequence of amino acids 1-115 of SEQ ID NO:18 and/or which includes one or more HCDRs selected from the group consisting of:
- HCDR1-8D2, amino acids 25-29 of SEQ ID NO:18;
- HCDR2-8D2, amino acids 44-60 of SEQ ID NO:18;
- and HCDR3-8D2, amino acids 93-104 of SEQ ID NO:18;
- b) a light chain variable region at least 90% identical to the sequence of amino acids 1-110 of SEQ ID NO:20 and/or which includes one or more LCDRs selected from the group consisting of:
- LCDR1-8D2, amino acids 23-37 of SEQ ID NO:20;
- LCDR2-8D2, amino acids 53-59 of SEQ ID NO:20;
- and LCDR3-8D2, amino acids 92-100 of SEQ ID NO:20.
-60. (canceled)
The antibody or fragment of claim 57, wherein said detectable label is selected from the group consisting of:
- a radioactive label;
- a fluorophore;
- a chemiluminescent label;
- an enzymatic label;
- biotin;
- avidin;
- and a heavy metal.
(canceled)
(canceled)
Dependencies are inferred from the claim text.