Methods of treating diseases associated with fibrosis using modified FGF-21 polypeptides and uses thereof
AssigneeBristol-Myers Squibb Company
InventorsPaul E. Morin, Daniel Cohen, Ranjan Mukherjee, Timothy P. Reilly, Rose C. Christian, Dasa Lipovsek, Ray Camphausen, John Krupinski
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Abstract
Modified FGF-21 polypeptides and uses thereof are provided, for example, for the treatment of diseases associated with fibrosis. Modified FGF-21 polypeptides are disclosed that contain an internal deletion and optionally replacement peptide, optionally modified with at least one non-naturally-encoded amino acid, and/or optionally fused to a fusion partner.
Claims30
A method of treating a disease associated with fibrosis selected from non-alcoholic steatohepatitis (NASH), liver fibrosis, or cirrhosis comprising administering to a patient in need thereof an effective amount of a modified FGF-21 polypeptide comprising the polypeptide of SEQ ID NO:201, wherein the para-acetyl-phenylalanine residue thereof is linked to a poly(ethylene glycol) moiety.
A method of treating NASH in a patient in need thereof, comprising administering to the patient an effective amount of a modified FGF-21 polypeptide comprising the polypeptide of SEQ ID NO:201, wherein the para-acetyl-phenylalanine residue thereof is linked to a poly(ethylene glycol) moiety having a molecular weight of between about 10 kDa and about 40 kDa.
A method of treating NASH in a patient in need thereof, comprising administering to the patient an effective amount of a modified FGF-21 polypeptide comprising the polypeptide of SEQ ID NO:201, wherein the para-acetyl-phenylalanine residue thereof is linked to a poly(ethylene glycol) moiety having a molecular weight of about 30 kDa, wherein said modified FGF-21 polypeptide is administered by subcutaneous injection about once per week at a dose of between about 0.05 mg/kg and about 1 mg/kg of patient body weight.
Dependencies are inferred from the claim text.