Methods of treating or preventing cholesterol related disorders

Abstract

The present invention relates to methods of treating or preventing cholesterol related disorders, such as hypercholesterolemia, hyperlipidemia or dyslipidemia, using antibodies against proprotein convertase subtilisin/kexin type 9 (PCSK9). Formulations and methods of producing said formulations are also described.

1 . (canceled) 
     
     
         2 . A method of lowering serum LDL cholesterol in a patient, comprising administering at least one anti-PCSK9 antibody to a patient in need thereof at a dose of 45 mg to 90 mg and at a frequency of administration of once every two weeks, thereby lowering the patient's serum LDL cholesterol level by at least 15%,
 wherein the anti-PCSK9 antibody comprises:
 a light chain comprising a light chain complementarity determining region (CDRL) 1 of the CDRL1 sequence in SEQ ID NO: 23, a CDRL2 of the CDRL2 sequence in SEQ ID NO: 23, and a CDRL3 of the CDRL3 sequence in SEQ ID NO: 23; and 
 a heavy chain comprising a heavy chain complementarity determining region (CDRH) 1 of the CDRH1 sequence in SEQ ID NO: 49, a CDRH2 of the CDRH2 sequence in SEQ ID NO: 49, and a CDRH3 of the CDRH3 sequence in the SEQ ID NO: 49. 
   
     
     
         3 . The method of  claim 2 , wherein the heavy chain comprises: a CDRH1 comprising SEQ ID NO: 308 or 368, a CDRH2 comprising SEQ ID NO: 175, and a CDRH3 comprising SEQ ID NO: 180, and the light chain comprises: a CDRL1 comprising SEQ ID NO: 158, a CDRL2 comprising SEQ ID NO: 162, and a CDRL3 comprising SEQ ID NO: 395. 
     
     
         4 . The method of  claim 3 , wherein the heavy chain comprises a heavy chain variable region having an amino acid sequence at least 90% identical to SEQ ID NO: 49, and the light chain comprises a light chain variable region having an amino acid sequence at least 90% identical to SEQ ID NO: 23. 
     
     
         5 . The method of  claim 3 , wherein the heavy chain comprises a heavy chain variable region having an amino acid sequence at least 95% identical to SEQ ID NO: 49, and the light chain comprises a light chain variable region having an amino acid sequence at least 95% identical to SEQ ID NO: 23. 
     
     
         6 . The method of  claim 3 , wherein the heavy chain comprises a heavy chain variable region having an amino acid sequence at least 97% identical to SEQ ID NO: 49, and the light chain comprises a light chain variable region having an amino acid sequence at least 97% identical to SEQ ID NO: 23. 
     
     
         7 . The method of  claim 4 , wherein the serum LDL cholesterol level is lowered by a percentage in a range of 15% to 65%. 
     
     
         8 . The method of  claim 4 , wherein the anti-PCSK9 antibody is administered in a formulation comprising a sodium acetate buffer. 
     
     
         9 . The method of  claim 4 , wherein the anti-PCSK9 antibody is administered subcutaneously. 
     
     
         10 . A method of lowering serum LDL cholesterol in a patient, comprising administering at least one anti-PCSK9 antibody to a patient in need thereof at a dose of 70 mg to 120 mg and at a frequency of administration of once every two weeks, thereby lowering the patient's serum LDL cholesterol level by at least 15%,
 wherein the anti-PCSK9 antibody comprises:
 a light chain comprising a light chain complementarity determining region (CDRL) 1 of the CDRL1 sequence in SEQ ID NO: 23, a CDRL2 of the CDRL2 sequence in SEQ ID NO: 23, and a CDRL3 of the CDRL3 sequence in SEQ ID NO: 23; and 
 a heavy chain comprising a heavy chain complementarity determining region (CDRH) 1 of the CDRH1 sequence in SEQ ID NO: 49, a CDRH2 of the CDRH2 sequence in SEQ ID NO: 49, and a CDRH3 of the CDRH3 sequence in the SEQ ID NO: 49. 
   
     
     
         11 . The method of  claim 10 , wherein the serum LDL cholesterol level is lowered by a percentage in a range of 15% to 70%. 
     
     
         12 . A method of lowering serum LDL cholesterol in a patient, comprising administering at least one anti-PCSK9 antibody to a patient in need thereof at a dose of 120 mg to 160 mg and at a frequency of administration of no more frequently than once every two weeks, thereby lowering the patient's serum LDL cholesterol level by at least 15%,
 wherein the anti-PCSK9 antibody comprises:
 a light chain comprising a light chain complementarity determining region (CDRL) 1 of the CDRL1 sequence in SEQ ID NO: 23, a CDRL2 of the CDRL2 sequence in SEQ ID NO: 23, and a CDRL3 of the CDRL3 sequence in SEQ ID NO: 23; and 
 a heavy chain comprising a heavy chain complementarity determining region (CDRH) 1 of the CDRH1 sequence in SEQ ID NO: 49, a CDRH2 of the CDRH2 sequence in SEQ ID NO: 49, and a CDRH3 of the CDRH3 sequence in the SEQ ID NO: 49. 
   
     
     
         13 . The method of  claim 12 , wherein the serum LDL cholesterol level is lowered by a percentage in a range of 15% to 85%. 
     
     
         14 . A method of lowering serum LDL cholesterol in a patient, comprising administering at least one anti-PCSK9 antibody to a patient in need thereof at a dose of 160 mg to 250 mg and at a frequency of administration of no more frequently than once every two weeks, thereby lowering the patient's serum LDL cholesterol level by at least 15%,
 wherein the anti-PCSK9 antibody comprises:
 a light chain comprising a light chain complementarity determining region (CDRL) 1 of the CDRL1 sequence in SEQ ID NO: 23, a CDRL2 of the CDRL2 sequence in SEQ ID NO: 23, and a CDRL3 of the CDRL3 sequence in SEQ ID NO: 23; and 
 a heavy chain comprising a heavy chain complementarity determining region (CDRH) 1 of the CDRH1 sequence in SEQ ID NO: 49, a CDRH2 of the CDRH2 sequence in SEQ ID NO: 49, and a CDRH3 of the CDRH3 sequence in the SEQ ID NO: 49. 
   
     
     
         15 . The method of  claim 14 , wherein the serum LDL cholesterol level is lowered by a percentage in a range of 15% to 85%. 
     
     
         16 . A method of lowering serum LDL cholesterol in a patient, comprising administering at least one anti-PCSK9 antibody to a patient in need thereof at a dose of 250 mg to 400 mg and at a frequency of administration of no more frequently than once every two weeks, thereby lowering the patient's serum LDL cholesterol level by at least 15%,
 wherein the anti-PCSK9 antibody comprises:
 a light chain comprising a light chain complementarity determining region (CDRL) 1 of the CDRL1 sequence in SEQ ID NO: 23, a CDRL2 of the CDRL2 sequence in SEQ ID NO: 23, and a CDRL3 of the CDRL3 sequence in SEQ ID NO: 23; and 
 a heavy chain comprising a heavy chain complementarity determining region (CDRH) 1 of the CDRH1 sequence in SEQ ID NO: 49, a CDRH2 of the CDRH2 sequence in SEQ ID NO: 49, and a CDRH3 of the CDRH3 sequence in the SEQ ID NO: 49. 
   
     
     
         17 . The method of  claim 16 , wherein the serum LDL cholesterol level is lowered by a percentage in a range of 15% to 85%. 
     
     
         18 . The method of  claim 16 , comprising administering the at least one anti-PCSK9 antibody at a frequency of administration of once a month. 
     
     
         19 . The method of  claim 18 , wherein the serum LDL cholesterol level is lowered by a percentage in a range of 15% to 60%. 
     
     
         20 . A method of lowering serum LDL cholesterol in a patient, comprising administering at least one anti-PCSK9 antibody to a patient in need thereof at a dose of 400 mg to 480 mg and at a frequency of administration of no more frequently than once every two weeks, thereby lowering the patient's serum LDL cholesterol level by at least 15%,
 wherein the anti-PCSK9 antibody comprises:
 a light chain comprising a light chain complementarity determining region (CDRL) 1 of the CDRL1 sequence in SEQ ID NO: 23, a CDRL2 of the CDRL2 sequence in SEQ ID NO: 23, and a CDRL3 of the CDRL3 sequence in SEQ ID NO: 23; and 
 a heavy chain comprising a heavy chain complementarity determining region (CDRH) 1 of the CDRH1 sequence in SEQ ID NO: 49, a CDRH2 of the CDRH2 sequence in SEQ ID NO: 49, and a CDRH3 of the CDRH3 sequence in the SEQ ID NO: 49. 
   
     
     
         21 . The method of  claim 20 , wherein the serum LDL cholesterol level is lowered by a percentage in a range of 15% to 70%. 
     
     
         22 . The method of  claim 20 , wherein the anti-PCSK9 antibody is administered at a frequency of once every month. 
     
     
         23 . The method of  claim 20 , wherein the anti-PCSK9 antibody is administered at a frequency of once every two weeks. 
     
     
         24 . The method of  claim 20 , comprising subcutaneously administering the at least one anti-PCSK9 antibody at a dose of 420 mg and at a frequency of administration of once a month, thereby lowering the patient's serum LDL cholesterol level by a percentage in a range of 15% to 70%,
 wherein the light chain comprises: a CDRL1 comprising SEQ ID NO: 158, a CDRL2 comprising SEQ ID NO: 162, and a CDRL3 comprising SEQ ID NO: 395; and   wherein the heavy chain comprises: a CDRH1 comprising SEQ ID NO: 308 or 368, a CDRH2 comprising SEQ ID NO: 175, and a CDRH3 comprising SEQ ID NO: 180.   
     
     
         25 . The method of  claim 24 , wherein the heavy chain comprises a heavy chain variable region having an amino acid sequence at least 90% identical to SEQ ID NO: 49, and the light chain comprises a light chain variable region having an amino acid sequence at least 90% identical to SEQ ID NO: 23. 
     
     
         26 . The method of  claim 24 , wherein the heavy chain comprises a heavy chain variable region having an amino acid sequence at least 95% identical to SEQ ID NO: 49, and the light chain comprises a light chain variable region having an amino acid sequence at least 95% identical to SEQ ID NO: 23. 
     
     
         27 . The method of  claim 24 , wherein the heavy chain comprises a heavy chain variable region having an amino acid sequence at least 97% identical to SEQ ID NO: 49, and the light chain comprises a light chain variable region having an amino acid sequence at least 97% identical to SEQ ID NO: 23.