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US 2023/0416366 A1Published application
Anti-cd3/anti-cd28 bispecific antigen binding molecules
AssigneeHoffmann-La Roche Inc.
InventorsPeter BRUENKER, Martina GEIGER, Thomas HOFER, Christian KLEIN, Pablo UMAÑA
Life of this patent
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Abstract
The present invention relates to anti-CD3/anti-CD28 bispecific antigen binding molecules and masked protease activated forms thereof, methods for their production, pharmaceutical compositions containing these molecules, and their use as immunomodulators and/or costiumulators in the treatment of a disease, in particular cancer.
Claims29
A bispecific agonistic CD28 antigen binding molecule characterized by monovalent binding to CD28, comprising
- (a) a first antigen binding domain capable of specific binding to CD28,
- (b) a second antigen binding domain capable of specific binding to CD3, and
- (c) a Fc domain composed of a first and a second subunit capable of stable association comprising one or more amino acid substitution that reduces the binding affinity of the antigen binding molecule to an Fc receptor and/or effector function,
- wherein said second antigen binding domain capable of specific binding to CD3 comprises
- (i) a heavy chain variable region (VHCD3) comprising a heavy chain complementary determining region CDR-H1 of SEQ ID NO:
- 2, a CDR-H2 of SEQ ID NO:
- 3, and a CDR-H3 of SEQ ID NO:
- 4, and a light chain variable region (VLCD3) comprising a light chain complementary determining region CDR-L1 of SEQ ID NO:
- 5, a CDR-L2 of SEQ ID NO:
- 6 and a CDR-L3 of SEQ ID NO:
- 7;
- or
- (ii) a heavy chain variable region (VHCD3) comprising a heavy chain complementary determining region CDR-H1 of SEQ ID NO:
- 10, a CDR-H2 of SEQ ID NO:
- 11, and a CDR-H3 of SEQ ID NO:
- 12, and a light chain variable region (VLCD3) comprising a light chain complementary determining region CDR-L1 of SEQ ID NO:
- 13, a CDR-L2 of SEQ ID NO:
- 14 and a CDR-L3 of SEQ ID NO:
- 15;
- wherein the Fc domain is of human IgG1 subclass and comprises the amino acid mutations L234A, L235A and P329G, in each case as numbered according to the Kabat EU index.
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Dependencies are inferred from the claim text.