Polypeptides comprising immunoglobulin single variable domains targeting IL-13 and TSLP
The present technology aims at providing a novel type of drug for treating a subject suffering from an inflammatory disease. Specifically, the present technology provides polypeptides comprising at least four immunoglobulin single variable domains (ISVDs), characterized in that at least two ISVDs bind to IL-13 and at least two ISVDs binds to TSLP. The present technology also provides nucleic acids, vectors and compositions.
1. A polypeptide comprising five ISVDs, wherein each of the ISVDs comprises three complementarity determining regions (CDR1 to CDR3, respectively), wherein:
a) a first ISVD specifically binds to IL-13 and comprises a CDR1 that comprises the amino acid sequence of SEQ ID NO: 7, a CDR2 that comprises the amino acid sequence of SEQ ID NO: 12 and a CDR3 that comprises the amino acid sequence of SEQ ID NO: 17;
b) a second ISVD specifically binds to IL-13 and comprises a CDR1 that comprises the amino acid sequence of SEQ ID NO: 8, a CDR2 that comprises the amino acid sequence of SEQ ID NO: 13 and a CDR3 that comprises the amino acid sequence of SEQ ID NO: 18;
c) a third ISVD specifically binds to TSLP and comprises a CDR1 that comprises the amino acid sequence of SEQ ID NO: 9, a CDR2 that comprises the amino acid sequence of SEQ ID NO: 14 and a CDR3 that comprises the amino acid sequence of SEQ ID NO: 19;
d) a fourth ISVD specifically binds to human serum albumin and comprises a CDR1 that comprises the amino acid sequence of SEQ ID NO: 10, a CDR2 that comprises the amino acid sequence of SEQ ID NO: 15 and a CDR3 that comprises the amino acid sequence of SEQ ID NO: 20; and
e) a fifth ISVD specifically binds to TSLP and comprises a CDR1 that comprises the amino acid sequence of SEQ ID NO: 11, a CDR2 that comprises the amino acid sequence of SEQ ID NO: 16 and a CDR3 that comprises the amino acid sequence of SEQ ID NO: 21.
2. The polypeptide according to claim 1 , wherein the five ISVDs are arranged in the order of, from the N-terminus to the C-terminus of the polypeptide, the first ISVD to the fifth ISVD.
3. A composition comprising the polypeptide according to claim 2 .
4. The polypeptide according to claim 1 , wherein:
a) the first ISVD comprises the amino acid sequence of SEQ ID NO: 2;
b) the second ISVD comprises the amino acid sequence of SEQ ID NO: 3;
c) the third ISVD comprises the amino acid sequence of SEQ ID NO: 4;
d) the fourth ISVD comprises the amino acid sequence of SEQ ID NO: 5; and
e) the fifth ISVD comprises the amino acid sequence of SEQ ID NO: 6.
5. The polypeptide according to claim 4 , wherein the five ISVDs are arranged in the order of, from the N-terminus to the C-terminus of the polypeptide, the first ISVD to the fifth ISVD.
6. A composition comprising the polypeptide according to claim 5 .
7. A composition comprising the polypeptide according to claim 4 .
8. A composition comprising the polypeptide according to claim 1 .
9. A polypeptide comprising the amino acid sequence of SEQ ID NO: 1.
10. A composition comprising the polypeptide according to claim 9 .
11. A polypeptide consisting of the amino acid sequence of SEQ ID NO: 1.
12. A composition comprising the polypeptide according to claim 11 .