Novel tnf family ligand trimer-containing antigen binding molecules
AssigneeHoffmann-La Roche Inc.
InventorsHarald Duerr, Claudia Ferrara Koller, Guy Georges, Friederike Hesse, Sabine Imhof-Jung, Christina Claus, Wei Xu
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Abstract
The invention relates to novel TNF family ligand trimer-containing antigen binding molecules comprising two different fusion polypeptides that comprise a spacer domain, an antigen binding domain and three ectodomains of a TNF ligand member or fragments thereof, wherein two of said ectodomains are separated from each other by a spacer domain comprising at least 25 amino acids and wherein the two fusion polypeptides are covalently associated to each other in the spacer domain
Claims17
A TNF family ligand trimer-containing antigen binding molecule comprising
- (a) a first fusion polypeptide comprising a first ectodomain of a TNF ligand family member or a fragment thereof, a spacer domain and a second ectodomain of said TNF ligand family member or a fragment thereof, wherein
- the spacer domain is a polypeptide and comprises at least 25 amino acid residues,
- the first ectodomain of a TNF ligand family member or a fragment thereof is fused either directly or via a first peptide linker to the N-terminus of the spacer domain and
- the second ectodomain of said TNF ligand family member or a fragment thereof is fused either directly or via a second peptide linker to the C-terminus of the spacer domain,
- (b) a second fusion polypeptide comprising a first part of an antigen binding domain and a spacer domain, wherein
- the spacer domain is a polypeptide and comprises at least 25 amino acid residues, and
- wherein the second part of the antigen binding domain is fused either directly or via a third peptide linker to the C-terminus of the spacer domain or is present in form of a light chain, and
- (c) a third ectodomain of said TNF ligand family member or a fragment thereof that is fused either directly or via a fourth peptide linker to
- either the C-terminus of the second ectodomain of said TNF ligand family member in the first fusion polypeptide or to the C-terminus of the spacer domain in the second fusion polypeptide, or
- in case the second part of the antigen binding domain is fused to the C-terminus of the spacer domain of the second fusion protein, to the C-terminus of the second ectodomain of said TNF ligand family member in the first fusion polypeptide,
- wherein the spacer domain of the first fusion polypeptide and the spacer domain of the second fusion polypeptide are associated covalently to each other by a disulfide bond.
The TNF family ligand trimer-containing antigen binding molecule of any one of claims 1 to 14, wherein the antigen binding domain capable of specific binding to CD19 comprises
- (a) a heavy chain variable region (VHCD19) comprising (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 25, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 26, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 27, and a light chain variable region (VLCD19) comprising (iv) CDR-L1 comprising the amino acid sequence of SEQ ID NO:
- 28, (v) CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 29, and (vi) CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 30, or
- (b) a heavy chain variable region (VHCD19) comprising (i) CDR-H1 comprising the amino acid sequence of SEQ ID NO:
- 31, (ii) CDR-H2 comprising the amino acid sequence of SEQ ID NO:
- 32, and (iii) CDR-H3 comprising the amino acid sequence of SEQ ID NO:
- 33, and a a light chain variable region (VLCD19) comprising (iv) CDR-L1 comprising the amino acid sequence of SEQ ID NO:
- 34, (v) CDR-L2 comprising the amino acid sequence of SEQ ID NO:
- 35, and (vi) CDR-L3 comprising the amino acid sequence of SEQ ID NO:
- 36.
Dependencies are inferred from the claim text.