Multi specific molecules
The invention relates to proteins having multi-specific binding abilities by fusion of an OB-fold variant, in particular from the Sac7d family, to the light or heavy chain of an antibody.
1. A polypeptide comprising a variant OB-fold polypeptide having the amino acid sequence set forth in SEQ ID NO: 35, wherein the variant OB-fold polypeptide binds to IL17.
2. The polypeptide of claim 1 , comprising the amino acid sequence of SEQ ID NO: 36.
3. The polypeptide of claim 1 , comprising the amino acid sequence of SEQ ID NO: 37.
4. The polypeptide of claim 1 , comprising the amino acid sequence of SEQ ID NO: 38.
5. The polypeptide of claim 1 , wherein the variant OB-fold polypeptide is fused to another protein or polypeptide.
6. The polypeptide of claim 5 , wherein the other protein or polypeptide comprises another variant of an OB-fold protein derived from a Sac7d protein, wherein the other variant has between 4 and 20 or between 5 and 20 residues involved in the binding of said Sac7d protein with its native ligand mutated.
7. The polypeptide of claim 6 , wherein the mutated amino acid residues correspond to amino acids selected from V2, K3, K5, K7, Y8, K9, G10, E11, K13, E14, T17, K21, K22, W24, V26, G27, K28, M29, S31, T33, Y34, D35, D36, N37, G38, K39, T40, G41, R42, A44, S46, E47, K48, D49, A50 and P51 of the Sac7d protein set forth in SEQ ID NO: 1.
8. The polypeptide of claim 6 , wherein the other variant binds to TNF-alpha.
9. The polypeptide of claim 5 , wherein the other protein is an antibody.
10. The polypeptide of claim 9 , wherein the variant OB-fold polypeptide is fused to two heavy chains or to two light chains of the antibody.
11. The polypeptide of claim 9 , wherein the variant OB-fold polypeptide is fused to one heavy chain and to one light chain of the antibody.
12. The polypeptide of claim 6 , wherein the variant OB-fold polypeptide and the other variant of the OB-fold protein derived from the Sac7d protein are fused to the heavy chains and/or to the light chains of an antibody.
13. The polypeptide of claim 9 , wherein the antibody is a therapeutic antibody.
14. The polypeptide of claim 9 , wherein the antibody binds to a protein selected from TNFalpha, IL23, IL12, IL4, IL13, IL31, the receptor of IL31, and a tumor specific antigen.
15. The polypeptide of claim 1 , which is conjugated to an organic molecule.
16. A genetic construct comprising a DNA sequence coding for the polypeptide of claim 1 .
17. A genetic construct comprising a DNA sequence selected from:
(a) a sequence coding for a heavy chain of an antibody fused, at its 3′ end, with a sequence coding for the polypeptide of claim 1 ;
(b) a sequence coding for a heavy chain of an antibody fused, at its 5′ end, with a sequence coding for the polypeptide of claim 1 ;
(c) a sequence coding for a light chain of an antibody fused, at its 3′ end, with a sequence coding for the polypeptide of claim 1 ; and
(d) a sequence coding for a light chain of an antibody fused, at its 5′ end, with a sequence coding for the polypeptide of claim 1 .
18. A vector comprising the genetic construct of claim 16 .
19. A host cell comprising the genetic construct of claim 16 .
20. A method for producing the polypeptide of claim 1 , comprising:
(a) culturing a cell culture, wherein the cells have been transformed by a genetic construct comprising a DNA sequence coding for the polypeptide of claim 1 , and
(b) recovering the polypeptide.