Antigen binding proteins to proprotein convertase subtilisin kexin type 9 (pcsk9)

Abstract

Antigen binding proteins that interact with Proprotein Convertase Subtilisin Kexin Type 9 (PCSK9) are described. Methods of treating hypercholesterolemia and other disorders by administering a pharmaceutically effective amount of an antigen binding protein to PCSK9 are described. Methods of detecting the amount of PCSK9 in a sample using an antigen binding protein to PCSK9 are described.

1 - 36 . (canceled) 
     
     
         37 . An isolated PCSK9-specific antagonist that antagonizes PCSK9's inhibition of cellular LDL uptake. 
     
     
         38 . An isolated PCSK9-specific antagonist that antagonizes PCSK9's inhibition of cellular LDL uptake and binds to human PCSK9 with an equilibrium dissociation constant (KD) of less than 1200 nM. 
     
     
         39 . The PCSK9-specific antagonist of  claim 38  that binds to human PCSK9 with a KD of less than 500 nM. 
     
     
         40 . The PCSK9-specific antagonist of  claim 38  that binds to human PCSK9 with a KD of less than 100 nM. 
     
     
         41 . The PCSK9-specific antagonist of  claim 38  that binds to human PCSK9 with a KD of less than 5 nM. 
     
     
         42 . An isolated PCSK9-specific antagonist that antagonizes PCSK9's inhibition of cellular LDL uptake at an IC 50  of less than 500 nM. 
     
     
         43 . The PCSK9-specific antagonist of  claim 42  that antagonizes PCSK9's inhibition of cellular LDL uptake at an IC 50  of less than 200 nM. 
     
     
         44 . The PCSK9-specific antagonist of  claim 42  that antagonizes PCSK9's inhibition of cellular LDL uptake at an IC 50  of less than 100 nM. 
     
     
         45 . An isolated PCSK9-specific antagonist that antagonizes PCSK9's inhibition of cellular LDL uptake by at least 20%. 
     
     
         46 . An isolated PCSK9-specific antagonist that antagonizes PCSK9's inhibition of cellular LDL uptake by at least 50%. 
     
     
         47 . An isolated PCSK9-specific antagonist that antagonizes PCSK9's inhibition of cellular LDL uptake by at least 60%. 
     
     
         48 . An isolated PCSK9-specific antibody molecule that antagonizes PCSK9's inhibition of cellular uptake by at least 20%. 
     
     
         49 . An isolated antigen binding molecule that binds to PCSK9 and reduces PCSK9's ability to inhibit cellular LDL uptake. 
     
     
         50 . The isolated antigen binding molecule of  claim 49 , wherein the antigen binding molecule is an isolated antigen binding protein. 
     
     
         51 . An isolated antigen binding molecule that reduces PCSK9's ability to inhibit LDL uptake by cells and binds to human PCSK9 with an equilibrium dissociation constant (K D ) of less than 10 −6 M. 
     
     
         52 . The isolated antigen binding molecule of  claim 51 , wherein the isolated antigen binding molecule is an antigen binding protein. 
     
     
         53 . The isolated antigen binding protein of  claim 52  that binds to human PCSK9 with a K D  of less than 10 −7 M. 
     
     
         54 . The isolated antigen binding protein of  claim 52  that binds to human PCSK9 with a K D  of less than 10 −8 M. 
     
     
         55 . The isolated antigen binding protein of  claim 52  that binds to human PCSK9 with a K D  of less than 10 −8  or less than 10 −9 M. 
     
     
         56 . An isolated antigen binding molecule that binds to PCSK9 and reduces PCSK9's inhibition of cellular LDL uptake at an IC 50  of no more than 100 nM. 
     
     
         57 . The isolated antigen binding molecule of  claim 56 , wherein the antigen binding molecule is an antigen binding protein, and where the IC 50  is 100 nM. 
     
     
         58 . The isolated antigen binding molecule of claim  21 , wherein the IC 50  is 28.7 nM, 18 nM, 13.3 nM, or 16.7 nM. 
     
     
         59 . An isolated antigen binding molecule that binds to PCSK9 and reduces PCSK9's inhibition of cellular LDL uptake by at least about 25%. 
     
     
         60 . The isolated antigen binding molecule of  claim 59 , wherein the antigen binding molecule is an antigen binding protein and wherein the antigen binding protein reduces PCSK9's inhibition of cellular LDL uptake by about 50%. 
     
     
         61 . The isolated antigen binding molecule of  claim 59 , wherein the antigen binding molecule is an antigen binding protein and wherein the antigen binding protein reduces PCSK9's inhibition of cellular LDL uptake by at least about 50%. 
     
     
         62 . An isolated PCSK9-specific antibody that binds to PCSK9 and reduces PCSK9's inhibition of cellular LDL uptake by at least about 25%. 
     
     
         63 . The isolated PCSK9-specific antibody of  claim 62  that binds to PCSK9 and reduces PCSK9's inhibition of cellular LDL uptake by about 25%. 
     
     
         64 . The isolated PCSK9-specific antibody of  claim 62  that binds to PCSK9 and reduces PCSK9's inhibition of cellular LDL uptake by at least about 50%. 
     
     
         65 . The isolated PCSK9-specific antibody of  claim 62  that binds to PCSK9 and reduces PCSK9's inhibition of cellular LDL uptake by about 50%.