Single chain fusionconstructs comprising multimeric antibody fragments fused to collagen trimerization domains
AssigneeLeadartis, S.L.
InventorsLuis Álvarez Vallina, Laura Sanz Alcober
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Abstract
The present invention relates to the field of biomedicine and antibody engineering. Specifically, it relates to mono and multispecific multivalent single chain polypeptide molecules and derivatives thereof, preferably to multispecific single chain (tandem) trimerbodies with defined stoichiometry, to nucleic acid sequences and vectors encoding thereof, and host cells expressing the same. It further relates to methods of producing thereof, pharmaceutical compositions, kits, methods of treatment, use as diagnostics or imaging reagents and combination therapies using thereof.
Claims23
A molecule according to formula (I) which comprises or consists of:
- (A)w-(L1)x-C1-L2-B1-L3-C2-L4-B2-L5-C3-(L6)y-(D)z
- wherein B1 and B2 are single-domain antibodies (sdAbs);
- wherein C1, C2 and C3 are a collagen XV trimerizing structural element (TSE) or a collagen XVIII TSE;
- wherein the collagen XV TSE is a polypeptide which comprises or consists of a polypeptide having the amino acid sequence shown in SEQ ID NO:
- 1;
- wherein the collagen XVIII TSE is a polypeptide which comprises or consists of a polypeptide having the amino acid sequence shown in SEQ ID NO:
- 2;
- wherein L1, L2, L3, L4, L5 and L6 are flexible peptide linkers, and wherein L2 and L4 have a length from 5 to 40 amino acids;
- wherein C1-L2-B1-L3-C2-L4-B2-L5-C3 is a recombinant single-chain polypeptide, C1 being located at the N-terminus and C3 at the C-terminus of the recombinant single-chain polypeptide;
- wherein w, x, y and z can be 1 or 0;
- wherein when w is 1 and A is a moiety with binding, detection and/or effector properties, then A is directly or indirectly covalently linked to the N-terminus of said recombinant single-chain polypeptide;
- and
- wherein when z is 1 and D is a moiety with binding, detection and/or effector properties then D is directly or indirectly covalently linked to the C-terminus of said recombinant single-chain polypeptide;
- wherein the flexible peptide linker comprises 2 or more amino acids selected from the group consisting of Gly, Ser, Ala and Thr.
Dependencies are inferred from the claim text.