Polypeptides, antibody variable domains and antagonists methods for
The invention relates to anti-IL-1R1 polypeptides and antibody single variable domains (dAbs) that are resistant to degradation by a protease, as well as antagonists comprising these. The polypeptides, dAbs and antagonists are useful for as therapeutics and/or prophylactics that are likely to encounter proteases when administered to a patient, for example for pulmonary administration, oral administration, delivery to the lung and delivery to the GI tract of a patient, as well as for treating inflammatory disease, such as arthritis or COPD.
1. An isolated immunoglobulin single variable domain comprising an amino acid sequence with at least 98% identity to the amino acid sequence shown in SEQ ID NO: 238; wherein the immunoglobulin single variable domain binds Interleukin-1 Receptor Type 1.
2. The isolated immunoglobulin single variable domain of claim 1 comprising a serine at Kabat position 22, a serine at Kabat position 49, a serine at Kabat position 83 and a tyrosine at Kabat position 94.
3. The isolated immunoglobulin single variable domain of claim 1 comprising the amino acid sequence shown in SEQ ID NO: 238.
4. The isolated immunoglobulin single variable domain of claim 3 encoded by the nucleic acid sequence shown in SEQ ID NO: 50.
5. An isolated polypeptide comprising an immunoglobulin single variable domain that comprises an amino acid sequence with at least 98% identity to the amino acid sequence shown in SEQ ID NO: 238; wherein the immunoglobulin single variable domain binds Interleukin-1 Receptor Type 1.
6. The isolated polypeptide of claim 5 wherein the immunoglobulin single variable domain comprises a serine at Kabat position 22, a serine at Kabat position 49, a serine at Kabat position 83 and a tyrosine at Kabat position 94.
7. An isolated polypeptide comprising an immunoglobulin single variable domain that comprises the amino acid sequence shown in SEQ ID NO: 238; wherein the immunoglobulin single variable domain binds Interleukin-1 Receptor Type 1.
8. An isolated polypeptide comprising an immunoglobulin single variable domain that comprises the amino acid sequence shown in SEQ ID NO: 238; wherein the immunoglobulin single variable domain binds Interleukin-1 Receptor Type 1 and that is encoded by the nucleic acid sequence shown in SEQ ID NO: 50.
9. An isolated composition comprising the isolated immunoglobulin single variable domain of claim 1 and a pharmaceutically acceptable carrier.
10. An isolated composition comprising the isolated immunoglobulin single variable domain of claim 3 and a pharmaceutically acceptable carrier.
11. An isolated composition comprising the isolated polypeptide of claim 5 and a pharmaceutically acceptable carrier.
12. An isolated composition comprising the isolated polypeptide of claim 7 and a pharmaceutically acceptable carrier.