US2015031870A1PendingUtilityA1

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

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Assignee: AMGEN INCPriority: Aug 23, 2007Filed: Sep 16, 2014Published: Jan 29, 2015
Est. expiryAug 23, 2027(~1.1 yrs left)· nominal 20-yr term from priority
Inventors:Simon Mark JacksonNigel Pelham Clinton WalkerDerek E. PiperWenyan ShenChadwick Terence KingRandal R. KetchemChristopher MehlinTeresa Arazas Carabeo
A61P 43/00A61P 3/06A61P 9/00A61P 7/00A61P 9/10A61P 3/00A61P 25/28A61K 31/405C07K 2317/92A61K 31/44A61K 45/06A61K 31/66C07K 2317/76C07K 16/40C07K 2299/00C07K 2317/34C12N 15/1137A61K 31/505A61K 31/40A61K 31/47A61K 2039/505A61K 31/22A61K 39/3955C07K 2317/14A61K 31/366A61K 39/395A61K 2300/00C07K 2317/24
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Claims

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.

Claims

exact text as granted — not AI-modified
1 . (canceled) 
     
     
         2 . A monoclonal antibody, wherein, when bound to human PCSK9, at least one amino acid residue of said monoclonal antibody is positioned at a location 8 angstroms or less from at least one of the following human PCSK9 residues: S153, I154, P155, W156, N157, L158, E159, H193, R194, E195, H229, R237, D238, A239, G240, K243, D367, I368, I369, G370, A371, S372, S373, D374, C375, S376, T377, C378, F379, V380, S381, or Q382 of SEQ ID NO: 3. 
     
     
         3 . The monoclonal antibody of  claim 2 , wherein, when bound to human PCSK9, the monoclonal antibody is positioned within 8 angstroms or less from at least one of the following residues: S153, I154, P155, R194, D238, A239, I369, S372, D374, C375, T377, C378, F379, V380, or S381. 
     
     
         4 . The monoclonal antibody of  claim 2 , wherein, when bound to human PCSK9, the monoclonal antibody is positioned within 8 angstroms or less from at least one of the following residues: W156, N157, L158, E159, H193, E195, H229, R237, G240, K243, D367, I368, G370, A371, S373, S376, or Q382. 
     
     
         5 . The monoclonal antibody of  claim 2 , wherein, when bound to human PCSK9, the monoclonal antibody is positioned within 5 angstroms or less from at least one of the following residues: S153, I154, P155, R194, D238, A239, I369, S372, D374, C375, T377, C378, F379, V380, or S381. 
     
     
         6 . The monoclonal antibody of  claim 2 , wherein, when bound to human PCSK9, the monoclonal antibody is positioned at a location 8 angstroms or less from at least two of the following residues: S153, I154, P155, R194, D238, A239, I369, S372, D374, C375, T377, C378, F379, V380, and S381. 
     
     
         7 . The monoclonal antibody of  claim 2 , wherein, when bound to human PCSK9, the monoclonal antibody is positioned at a location 5 angstroms or less from at least two of the following residues: S153, I154, P155, R194, D238, A239, I369, S372, D374, C375, T377, C378, F379, V380, and S381. 
     
     
         8 . The monoclonal antibody of  claim 2 , wherein, when bound to human PCSK9, the monoclonal antibody is positioned at a location 8 angstroms or less from at least one of the following residues: S153, I154, H193, R194, E195, R237, D238, A239, K243, I369, S372, S373, D374, C375, S376, T377, C378, and F379. 
     
     
         9 . The monoclonal antibody of  claim 2 , wherein, when bound to human PCSK9, the monoclonal antibody is positioned at a location 5 angstroms or less from at least one of the following residues: S153, R194, D238, D374, T377, and F379. 
     
     
         10 . The monoclonal antibody of  claim 2 , wherein, when bound to human PCSK9, the monoclonal antibody is positioned at a location 8 angstroms or less from at least one of the following residues: S153, R194, D238, D374, T377, and F379. 
     
     
         11 . The monoclonal antibody of  claim 2 , wherein, when bound to human PCSK9, the monoclonal antibody is positioned at a location 8 angstroms or less from at least two of the following residues: S153, R194, D238, D374, T377, and F379. 
     
     
         12 . The monoclonal antibody of  claim 2 , wherein, when bound to human PCSK9, the monoclonal antibody is positioned at a location 8 angstroms or less from at least three of the following residues: S153, R194, D238, D374, T377, and F379. 
     
     
         13 . The monoclonal antibody of  claim 2 , wherein, when bound to human PCSK9, the monoclonal antibody is positioned at a location 8 angstroms or less from all the following residues: S153, R194, D238, D374, T377, and F379. 
     
     
         14 . The monoclonal antibody of  claim 2 , wherein, when bound to human PCSK9, the monoclonal antibody is positioned at a location 5 angstroms or less from at least two of the following residues: S153, R194, D238, D374, T377, and F379. 
     
     
         15 . The monoclonal antibody of  claim 2 , wherein, when bound to human PCSK9, the monoclonal antibody is positioned at a location 5 angstroms or less from all the following residues: S153, R194, D238, D374, T377, and F379. 
     
     
         16 . The monoclonal antibody of  claim 2 , wherein said monoclonal antibody comprises: a light chain variable region and a heavy chain variable region that comprises at least one amino acid in the specified position selected from the group consisting of T28, L29, T30, S31, Y32, G33, I34, S35, W47, W50, V51, S52, F53, Y54, N55, G56, N57, T58, N59, Y60, T72, R98, G99, Y100, G101, M102, and D103, as numbered sequentially in the direction from the amino acid terminus to the carboxy terminus of the heavy chain. 
     
     
         17 . The monoclonal antibody of  claim 2 , wherein said monoclonal antibody comprises: a heavy chain variable region and a light chain variable region that comprises at least one amino acid in the specified position selected from the group consisting of S26, V29, G30, G31, Y32, N33, S34, V35, Y51, E52, N55, S92, Y93, T94, S95, T96, S97, M98 and V99, as numbered sequentially in the direction from the amino acid terminus to the carboxy terminus of the light chain. 
     
     
         18 . The monoclonal antibody of  claim 17 , wherein said heavy chain variable region comprises at least one amino acid in the specified position selected from the group consisting of T28, L29, T30, S31, Y32, G33, I34, S35, W47, W50, V51, S52, F53, Y54, N55, G56, N57, T58, N59, Y60, T72, R98, G99, Y100, G101, M102, and D103, as numbered sequentially in the direction from the amino acid terminus to the carboxy terminus of the heavy chain. 
     
     
         19 . The monoclonal antibody of  claim 5 , wherein said monoclonal antibody comprises: a light chain variable region and a heavy chain variable region that comprises at least one amino acid in the specified position selected from the group consisting of T30, S31, Y32, G33, W50, S52, F53, Y54, N55, N57, N59, R98, G99, Y100, and G101, as numbered sequentially in the direction from the amino acid terminus to the carboxy terminus of the heavy chain. 
     
     
         20 . The monoclonal antibody of  claim 5 , wherein said monoclonal antibody comprises: a heavy chain variable region and a light chain variable region that comprises at least one amino acid in the specified position selected from the group consisting of G30, G31, Y32, N33, S34, E52, Y93, T94, S95, T96, and S97, as numbered sequentially in the direction from the amino acid terminus to the carboxy terminus of the light chain. 
     
     
         21 . The monoclonal antibody of  claim 2 , wherein said monoclonal antibody reduces binding of an EGFa domain of LDLR to human PCSK9. 
     
     
         22 . The monoclonal antibody of  claim 2 , wherein, when bound to human PCSK9, an antigen binding region of the monoclonal antibody is positioned at a location 8 angstroms or less from at least S153. 
     
     
         23 . The monoclonal antibody of  claim 2 , wherein, when bound to human PCSK9, an antigen binding region of the monoclonal antibody is positioned at a location 8 angstroms or less from at least R194. 
     
     
         24 . The monoclonal antibody of  claim 2 , wherein, when bound to human PCSK9, an antigen binding region of the monoclonal antibody is positioned at a location 8 angstroms or less from at least D238. 
     
     
         25 . The monoclonal antibody of  claim 2 , wherein, when bound to human PCSK9, an antigen binding region of the monoclonal antibody is positioned at a location 8 angstroms or less from at least D374. 
     
     
         26 . The monoclonal antibody of  claim 2 , wherein, when bound to human PCSK9, an antigen binding region of the monoclonal antibody is positioned at a location 8 angstroms or less from at least T377. 
     
     
         27 . The monoclonal antibody of  claim 2 , wherein, when bound to human PCSK9, an antigen binding region of the monoclonal antibody is positioned at a location 8 angstroms or less from at least F379. 
     
     
         28 . The monoclonal antibody of  claim 2 , wherein the monoclonal antibody comprises a humanized antibody. 
     
     
         29 . The monoclonal antibody of  claim 2 , wherein the monoclonal antibody comprises a human antibody. 
     
     
         30 . The monoclonal antibody of  claim 2 , wherein the monoclonal antibody comprises a lambda light chain. 
     
     
         31 . The monoclonal antibody of  claim 2 , wherein the monoclonal antibody comprises a light chain of SEQ ID NO: 157.

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