Polypeptides, antibody variable domains & antagonists
AssigneeDomantis Limited
InventorsLaurent JESPERS, Malgorzata Pupecka-Swider, Carolyn Enever, Ian Tomlinson
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Abstract
The invention relates to anti-TNFR1 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.
Claims19
An anti-TNFα receptor immunoglobulin single variable domain comprising an amino acid sequence that is at least 93% identical to the amino acid sequence shown in SEQ ID NO:
- 224.
A TNFα receptor type 1 antagonist that competes with an immunoglobulin single variable domain comprising the amino acid sequence shown in SEQ ID NO:
- 224 for binding to TNFR1.
A protease resistant immunoglobulin single variable domain comprising a TNFα receptor type 1 binding site, wherein the variable domain is resistant to protease when incubated with
- (i) a concentration (c) of at least 10 micrograms/ml protease at 37° C. for time (t) of at least one hour;
- or
- (ii) a concentration (c′) of at least 40 micrograms/ml protease at 30° C. for time (t) of at least one hour,
- wherein the variable domain comprises an amino acid sequence that is at least 90% identical to the amino acid sequence shown in SEQ ID NO:224.
An isolated or recombinant nucleic acid encoding the fusion protein of claim 19.
Dependencies are inferred from the claim text.