Polypeptides, antibody variable domains and antagonistsmethods for
AssigneeDomantis Limited
InventorsCarolyn Enever, Laurent Jespers, Malgorzata Pupecka, Ian Tomlinson, Armin Sepp
Life of this patent
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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.
Claims25
An anti-TNFα receptor type 1 (TNFR1;
- p55) immunoglobulin single variable domain comprising an amino acid sequence that is at least 95% identical to the amino acid sequence of DOM1h-131-511 (shown in FIG. 3).
An anti-TNFα receptor type 1 (TNFR1;
- p55) immunoglobulin single variable domain comprising an amino acid sequence that is identical to the amino acid sequence selected from the group consisting of DOM1h-131-511, DOM1h-131-201, DOM1h-131-202, DOM1h-131-203, DOM1h-131-204 and DOM1h-131-205 (shown in FIG. 3).
An anti-TNFα receptor type 1 (TNFR1;
- p55) immunoglobulin single variable domain encoded by a nucleotide sequence that is at least 80% identical to the nucleotide sequence of DOM1h-131-511 (shown in FIG. 19).
An anti-TNFα receptor type 1 (TNFR1;
- p55) immunoglobulin single variable domain encoded by a sequence that is identical to the nucleotide sequence of DOM1h-131-511, DOM1h-131-201, DOM1h-131-202, DOM1h-131-203, DOM1h-131-204 or DOM1h-131-205 (shown in FIG. 3).
10-12. (canceled)
An immunoglobulin single variable domain comprising a TNFα receptor type 1 (TNFR1;
- p55) 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 of DOM1h-131-511, DOM1h-131-201, DOM1h-131-202, DOM1h-131-203, DOM1h-131-204 and DOM1h-131-205.
23-25. (canceled)
A polypeptide comprising a sequence that is at least 95% identical to the amino acid sequence of DOM1h-131-511 (shown in FIG. 3).
A polypeptide encoded by a sequence that is at least 80% identical to the nucleotide sequence of the nucleotide sequence of DOM1h-131-511 (shown in FIGS. 19).
29-83. (canceled)
Dependencies are inferred from the claim text.