Lipoprotein lipase for treatment of hypertriglyceridemic-related conditions including acute pancreatitis

Abstract

A lipoprotein lipase (LPL) protein for treating and/or preventing HTG and its associated diseases, including but not limited to acute pancreatitis (AP), and in particular, acute pancreatitis secondary to or exacerbated by hypertriglyceridemia, and hypertriglyceridemia and its associated diseases in general, including cardiovascular and metabolic diseases, endocrine disorders, and fat embolism syndrome.

1 . A lipoprotein lipase (LPL) polypeptide for use in the treatment or prevention of a hypertriglyceridemia-related condition, in a subject. 
     
     
         2 . The LPL polypeptide of  claim 1 , wherein the LPL polypeptide is substantially resistant to proteolytic cleavage by proprotein convertase. 
     
     
         3 . The LPL polypeptide of  claim 1 , wherein the hypertriglyceridemia-related condition is secondary to or exacerbated by hypertriglyceridemia. 
     
     
         4 . The LPL polypeptide of  claim 1 , wherein the hypertriglyceridemia-related condition is selected from the group consisting of hypertriglyceridemia, acute pancreatitis, cardiovascular disease, a metabolic disorder, an endocrine disorder, and fat embolism syndrome. 
     
     
         5 . (canceled) 
     
     
         6 . The LPL polypeptide of  claim 4 , wherein the acute pancreatitis is secondary to or exacerbated by hypertriglyceridemia. 
     
     
         7 . The LPL polypeptide of  claim 1 , wherein the serum or plasma triglyceride level in the subject exceeds about 150 mg/dl. 
     
     
         8 . The LPL polypeptide of  claim 1 , wherein the LPL polypeptide comprises or consists of an amino acid sequence having 80%, 90%, 95%, 99%, 99.5% or 99.8% or more identity to SEQ ID NO: 1. 
     
     
         9 . The LPL polypeptide of  claim 1 , wherein the LPL polypeptide comprises or consists of the amino acid sequence of SEQ ID NO: 2. 
     
     
         10 . The LPL polypeptide of  claim 1 , wherein the LPL polypeptide exhibits a V max  of about 0.01-50 mmoles FA/hr/mg in a [ 3 H]-triolein liposome activity assay and/or a K m  value of about 0.01-1 μM. 
     
     
         11 . The LPL polypeptide of  claim 1 , wherein the LPL polypeptide is administered by oral, intravenous, intramuscular, intravenous, intranasal, intradermal, subcutaneous, or suppository route. 
     
     
         12 . The LPL polypeptide of  claim 1 , wherein the LPL polypeptide is administered by continuous infusion or by bolus injection. 
     
     
         13 . The LPL polypeptide of  claim 1 , wherein the LPL polypeptide is administered as a single dose or multiple doses. 
     
     
         14 . The LPL polypeptide of  claim 1 , wherein the LPL polypeptide is glycosylated. 
     
     
         15 . The LPL polypeptide of  claim 1 , wherein the LPL polypeptide is non-glycosylated. 
     
     
         16 . The LPL polypeptide of  claim 1 , wherein the LPL polypeptide is in aqueous form. 
     
     
         17 . The LPL polypeptide of  claim 1 , wherein the LPL polypeptide is in lyophilized form. 
     
     
         18 . A pharmaceutical composition comprising the LPL polypeptide of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         19 . (canceled) 
     
     
         20 . A method of treating or preventing a hypertriglyceridemia-related condition in a subject, comprising the step of administering to the subject an effective amount of the LPL polypeptide of  claim 1  or a pharmaceutical composition comprising the LPL polypeptide of  claim 1 . 
     
     
         21 . Use of the LPL polypeptide of  claim 1  or a pharmaceutical composition comprising the LPL polypeptide of  claim 1  in the preparation of a medicament for the treatment or prevention of a hypertriglyceridemia-related condition in a subject. 
     
     
         22 . A method of preparing the LPL polypeptide of,  claim 1  comprising performing the recombinant expression of the LPL polypeptide and LMF1 in a cell. 
     
     
         23 . (canceled)