Monoclonal antibodies against claudin-18 for treatment of cancer
AssigneesAstellas Pharma Inc., Tron - Translationale Onkologie An Der UniversitäTsmedizin Der Johannes Gutenb
InventorsUgur Sahin, Özlem Türeci, Dirk Usener, Stefan Fritz, Christoph Uherek, Gunda Brandenburg, Harald-Gerhard Geppert, Anja Kristina Schröder, Phillippe Thiel
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Abstract
The present invention provides antibodies useful as therapeutics for treating and/or preventing diseases associated with cells expressing CLD18, including tumor-related diseases such as gastric cancer, esophageal cancer, pancreatic cancer, lung cancer, ovarian cancer, colon cancer, hepatic cancer, head-neck cancer, and cancer of the gallbladder.
Claims23
1-26. (canceled)
An antibody that binds to CLD18A2, the antibody comprising a heavy chain variable region (VH), a human heavy chain constant region (CH), a light chain variable region (VL), and a human light chain constant region (CL), wherein each of the VH and VL comprise a set of complementarity-determining regions CDR1, CDR2 and CDR3:
- VH:
- CDR1:
- positions 45-52 of SEQ ID NO:
- 118, CDR2:
- positions 70-77 of SEQ ID NO:
- 118, CDR3:
- positions 116-126 of SEQ ID NO:
- 118, VL:
- CDR1:
- positions 47-58 of SEQ ID NO:
- 125, CDR2:
- positions 76-78 of SEQ ID NO:
- 125, CDR3:
- positions 115-123 of SEQ ID NO:
- 125.
An antibody that binds to CLD18A2 and mediates killing of cells expressing CLD18A2, wherein said antibody comprises a heavy chain variable region (VH) and a light chain variable region (VL), each of the VH and VL comprising a set of complementarity-determining regions CDR1, CDR2 and CDR3 selected from one of sets (i) to (viii):
- (i) VH:
- CDR1:
- positions 45-52 of SEQ ID NO:
- 115, CDR2:
- positions 70-77 of SEQ ID NO:
- 115, CDR3:
- positions 116-125 of SEQ ID NO:
- 115, VL:
- CDR1:
- positions 49-53 of SEQ ID NO:
- 122, CDR2:
- positions 71-73 of SEQ ID NO:
- 122, CDR3:
- positions 110-118 of SEQ ID NO:
- 122,
- (ii) VH:
- CDR1:
- positions 45-52 of SEQ ID NO:
- 116, CDR2:
- positions 70-77 of SEQ ID NO:
- 116, CDR3:
- positions 116-126 of SEQ ID NO:
- 116, VL:
- CDR1:
- positions 47-58 of SEQ ID NO:
- 121, CDR2:
- positions 76-78 of SEQ ID NO:
- 121, CDR3:
- positions 115-123 of SEQ ID NO:
- 121,
- (iii) VH:
- CDR1:
- positions 45-52 of SEQ ID NO:
- 117, CDR2:
- positions 70-77 of SEQ ID NO:
- 117, CDR3:
- positions 116-124 of SEQ ID NO:
- 117, VL:
- CDR1:
- positions 47-52 of SEQ ID NO:
- 123, CDR2:
- positions 70-72 of SEQ ID NO:
- 123, CDR3:
- positions 109-117 of SEQ ID NO:
- 123,
- (iv) VH:
- CDR1:
- positions 44-51 of SEQ ID NO:
- 119, CDR2:
- positions 69-76 of SEQ ID NO:
- 119, CDR3:
- positions 115-125 of SEQ ID NO:
- 119, VL:
- CDR1:
- positions 47-58 of SEQ ID NO:
- 126, CDR2:
- positions 76-78 of SEQ ID NO:
- 126, CDR3:
- positions 115-122 of SEQ ID NO:
- 126,
- (v) VH:
- CDR1:
- positions 45-53 of SEQ ID NO:
- 120, CDR2:
- positions 71-78 of SEQ ID NO:
- 120, CDR3:
- positions 117-128 of SEQ ID NO:
- 120, VL:
- CDR1:
- positions 47-58 of SEQ ID NO:
- 124, CDR2:
- positions 76-78 of SEQ ID NO:
- 124, CDR3:
- positions 115-123 of SEQ ID NO:
- 124,
- (vi) VH:
- CDR1:
- positions 45-53 of SEQ ID NO:
- 120, CDR2:
- positions 71-78 of SEQ ID NO:
- 120, CDR3:
- positions 117-128 of SEQ ID NO:
- 120, VL:
- CDR1:
- positions 47-58 of SEQ ID NO:
- 127, CDR2:
- positions 76-78 of SEQ ID NO:
- 127, CDR3:
- positions 115-123 of SEQ ID NO:
- 127,
- (vii) VH:
- CDR1:
- positions 45-53 of SEQ ID NO:
- 120, CDR2:
- positions 71-78 of SEQ ID NO:
- 120, CDR3:
- positions 117-128 of SEQ ID NO:
- 120, VL:
- CDR1:
- positions 47-58 of SEQ ID NO:
- 128, CDR2:
- positions 76-78 of SEQ ID NO:
- 128, CDR3:
- positions 115-123 of SEQ ID NO:
- 128, and
- (viii) VH:
- CDR1:
- positions 45-53 of SEQ ID NO:
- 120, CDR2:
- positions 71-78 of SEQ ID NO:
- 120, CDR3:
- positions 117-128 of SEQ ID NO:
- 120, VL:
- CDR1:
- positions 47-52 of SEQ ID NO:
- 129, CDR2:
- positions 70-72 of SEQ ID NO:
- 129, CDR3:
- positions 109-117 of SEQ ID NO:
- 129,
- wherein the VH and VL domains of the antibody are expressed on a single polypeptide chain.
Dependencies are inferred from the claim text.