Polypeptides and uses thereof
The present invention provides polypeptides comprising or consisting of an amino acid sequence from thrombin, or a fragment, variant, fusion or derivative thereof, or a fusion of said fragment, variant or derivative thereof, for use in the treatment or prevention of inflammation and/or excessive coagulation of the blood. Related aspects of the invention provide isolated polypeptides comprising or consisting of an amino acid sequence of any one of SEQ ID NOs: 1 to 7, or a fragment, variant, fusion or derivative thereof, or a fusion of said fragment, variant or derivative thereof, which exhibit an anti-inflammatory activity, together with isolated nucleic acid molecules, vectors and host cells for making the same. Additionally provided are pharmaceutical compositions comprising a polypeptide of the invention, as well as methods of use of the same in the treatment and/or prevention of inflammation and/or excessive coagulation.
1. A method for treating inflammation and coagulation of the blood in a patient, the method comprising administering to the patient a therapeutically-effective amount of a polypeptide comprising the amino acid sequence selected from the group consisting of
[SEQ ID NO: 3]
GKYGFYTHVFRLKKWIQKVI;
and
[SEQ ID NO: 4]
KYGFYTHVFRLKKWIQKVID,
wherein the polypeptide has a length of 20 to 25 amino acids.
2. The method according to claim 1 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 3
[SEQ ID NO: 3]
GKYGFYTHVFRLKKWIQKVI.
3. The method according to claim 1 , wherein the polypeptide consists of the amino acid sequence of SEQ ID NOs: 3 or 4.
4. The method according to claim 1 , wherein said inflammation and coagulation of the blood in a patient is associated with a condition or indication selected from the following:
i) Acute systemic inflammatory disease, with or without an infective component, systemic inflammatory response syndrome (SIRS), acute respiratory distress syndrome (ARDS), erysipelas, meningitis, arthritis, appendicitis, pancreatitis, cholecystitis, colitis, cellulitis,;
ii) Chronic inflammatory diseases, cystic fibrosis, chronic obstructive pulmonary disease (COPD) pulmonary diseases, gastrointestinal disease, chronic skin and stomach ulcerations, epithelial inflammatory, oral ulcerations (aphtous ulcers), genital ulcerations and inflammatory changes, parodontitis, eye inflammations, conjunctivitis and keratitis, external otitis, mediaotitis, genitourinary inflammations;
iii) Postoperative inflammation, thrombosis, disseminated intravasal coagulation (DIC), postoperative coagulation disorders, coagulative disorders related to contact with foreign material, and vasculitis related inflammatory disease; or
iv) Excessive contact activation and/or coagulation in relation to stroke.
5. The method according to claim 1 , wherein said inflammation and coagulation of the blood in a patient is associated with acute inflammation, acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), cystic fibrosis, cutaneous and systemic vasculitis, thrombosis and disseminated intravascular coagulation (DIC).
6. The method according to claim 1 , wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 4
[SEQ ID NO: 4]
KYGFYTHVFRLKKWIQKVID.
7. The method according to claim 1 , wherein the polypeptide has a length of 20, 21, 22, 23, 24 or 25 amino acid residues.