Peptides targeting TNF family receptors and antagonizing TNF action, compositions, methods and uses thereof

摘要

The present invention provides modulators of TNF, particularly peptides and their derivatives, particularly GEP peptides, which antagonize TNF and TNF-mediated responses, activity or signaling. The invention provides methods of antagonizing TNF and the modulation of TNF-mediated diseases or responses, including inflammatory diseases and conditions. Compositions of GEP peptides, including in combination with other inflammatory mediators, are provided. Methods of treatment, alleviation, or prevention of TNF-mediated diseases and inflammatory conditions, including rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, psoriasis, inflammatory bowel diseases, Chrohn's disease, ulcerative colitis, uveitis, inflammatory lung diseases, chronic obstructive pulmonary disease, are provided.

主权项

1. An isolated peptide comprising
(a) one or more granulin units of Granulin/epithelin precursor (GEP) selected from the group consisting of: granulin units F (amino acids 126-178 of SEQ ID NO: 1), A (amino acids 284-335 of SEQ ID NO: 1), and C (amino acids 366-416 of SEQ ID NO: 1); and (b) one or more linker units of GEP, wherein the peptide antagonizes TNFR1 or TNFR2 signaling, and wherein the peptide consists of a mixed portion of the full-length GEP sequence.