Polynucleotides encoding novel pcsk9 variants

Abstract

The present invention provides novel polynucleotides encoding PCSK9b and PCSK9c polypeptides, fragments and homologues thereof. Also provided are vectors, host cells, antibodies, and recombinant and synthetic methods for producing said polypeptides. The invention further relates to diagnostic and therapeutic methods for applying these novel PCSK9b and PCSK9c polypeptides to the diagnosis, treatment, and/or prevention of various diseases and/or disorders related to these polypeptides. The invention further relates to screening methods for identifying agonists and antagonists of the polynucleotides and polypeptides of the present invention.

What is claimed is: 
     
         1 - 22 . (canceled) 
     
     
         23 . A method for preventing, treating, or ameliorating a medical condition, comprising the step of administering to a mammalian subject a therapeutically effective amount of a polypeptide or a modulator thereof wherein said polypeptide comprises an isolated polypeptide comprising a sequence selected from the group consisting of: (a) an isolated polypeptide comprising amino acids 1 to 315 of SEQ ID NO:2; (b) an isolated polypeptide comprising amino acids 2 to 315 of SEQ ID NO:2; (c) an isolated polypeptide encoded by nucleotides 250 to 1194 of SEQ ID NO:1; and (d) an isolated polypeptide encoded by nucleotides 253 to 1194 of SEQ ID NO:1. 
     
     
         24 . The method for preventing, treating, or ameliorating a medical condition of  claim 23 , wherein the medical condition is selected from the group consisting of: a disorder related to aberrant PCSK9 signaling and/or activity; cardiovascular disorder; hypercholesterolemia; autosomal dominant hypercholesterolemia; disorders associated with aberrant LDL receptor function; disorders associated with apolipoprotein B; disorders associated with autosomal recessive hypercholesterolemia; disorders associated with elevated cholesterol; disorders associated with elevated LDL; disorders associated with reduced clearance rate of LDL in the liver; disorders associated with elevated LDL apoB production; familial hypercholesterolemia; lipid metabolism disorders; elevated LDL; cholesterol depositions; tendon xanthomas; atheroma; premature arteriosclerosis; coronary heart disease; famialial defective apolipoprotein B; statin hypersensitivity; disorders associated with accelerated LDLR degradation; neural differentiation disorders; a metabolic disorder; a metabolic disorder selected from the group consisting of dyslipidemia; diabetic dyslipidemia; mixed dyslipidemia; hypercholesteremia; hypertriglyceridemia; type II diabetes mellitus; type I diabetes; insulin resistance; hyperlipidemia; obesity; and anorexia nervosa.