US2013085265A1PendingUtilityA1

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

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Assignee: JACKSON SIMON MARKPriority: Aug 23, 2007Filed: Mar 16, 2012Published: Apr 4, 2013
Est. expiryAug 23, 2027(~1.1 yrs left)· nominal 20-yr term from priority
Inventors:Simon Mark JacksonNigel Pelham Clinton WalkerDerek E. PiperBei ShanWenyan ShenJoyce Chi Yee ChanChadwick Terence KingRandal R. KetchemChristopher MehlinTeresa Arazas CarabeoQiong Cao
A61P 3/06A61P 7/00A61P 43/00A61P 9/00A61P 9/10A61P 25/28A61P 3/00C07K 16/40C07K 2299/00C07K 2317/34C12N 15/1137A61K 39/3955A61K 31/47A61K 31/505A61K 39/395A61K 2039/505A61K 31/66C07K 2317/76C07K 2317/14C07K 2317/92A61K 45/06A61K 31/44A61K 31/405A61K 31/366A61K 31/40A61K 31/22A61K 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 - 36 . (canceled) 
     
     
         37 . An antigen binding protein that competes for binding to PCSK9 with at least one of the following antigen binding proteins:
 a) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 79 and a light chain variable region of SEQ ID NO: 35;   b) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 80 and a light chain variable region of SEQ ID NO: 36;   c) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 76 and a light chain variable region of SEQ ID NO: 37;   d) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 77 and a light chain variable region of SEQ ID NO: 38;   e) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 78 and a light chain variable region of SEQ ID NO: 39;   f) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 83 and a light chain variable region of SEQ ID NO: 40;   g) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 67 and a light chain variable region of SEQ ID NO: 12;   h) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 483 and a light chain variable region of SEQ ID NO: 485;   i) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 459 and a light chain variable region of SEQ ID NO: 461; or   j) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 463 and a light chain variable region of SEQ ID NO: 465.   
     
     
         38 . The antigen binding protein of  claim 37 , wherein the antigen binding protein competes for binding to PCSK9 with at least one of:
 a) the antigen binding protein comprising the heavy chain variable region of SEQ ID NO: 67 and the light chain variable region of SEQ ID NO: 12;   b) the antigen binding protein comprising the heavy chain variable region of SEQ ID NO: 459 and the light chain variable region of SEQ ID NO: 461;   c) the antigen binding protein comprising the heavy chain variable region of SEQ ID NO: 483 and the light chain variable region of SEQ ID NO: 485; or   d) the antigen binding protein comprising the heavy chain variable region of SEQ ID NO: 463 and the light chain variable region of SEQ ID NO: 465.   
     
     
         39 . The antigen binding protein of  claim 38 , wherein the antigen binding protein competes for binding to PCSK9 with the antigen binding protein comprising the heavy chain variable region of SEQ ID NO: 67 and the light chain variable region of SEQ ID NO: 12. 
     
     
         40 . The antigen binding protein of  claim 38 , wherein the antigen binding protein competes for binding to PCSK9 with the antigen binding protein comprising the heavy chain variable region of SEQ ID NO: 459 and the light chain variable region of SEQ ID NO: 461. 
     
     
         41 . The antigen binding protein of  claim 38 , wherein the antigen binding protein competes for binding to PCSK9 with the antigen binding protein comprising the heavy chain variable region of SEQ ID NO: 463 and the light chain variable region of SEQ ID NO: 465. 
     
     
         42 . The antigen binding protein of  claim 38 , wherein the antigen binding protein competes for binding to PCSK9 with the antigen binding protein comprising the heavy chain variable region of SEQ ID NO: 483 and the light chain variable region of SEQ ID NO: 485. 
     
     
         43 . The antigen binding protein of  claim 37 , wherein the antigen binding protein that competes for binding is an antibody or a binding part thereof. 
     
     
         44 . An antigen binding protein that binds to an epitope on PCSK9 that is bound by at least one of the following antigen binding proteins:
 a) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 79 and a light chain variable region of SEQ ID NO: 35;   b) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 80 and a light chain variable region of SEQ ID NO: 36;   c) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 76 and a light chain variable region of SEQ ID NO: 37;   d) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 77 and a light chain variable region of SEQ ID NO: 38;   e) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 78 and a light chain variable region of SEQ ID NO: 39;   f) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 83 and a light chain variable region of SEQ ID NO: 40;   g) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 67 and a light chain variable region of SEQ ID NO: 12;   h) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 483 and a light chain variable region of SEQ ID NO: 485;   i) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 459 and a light chain variable region of SEQ ID NO: 461; or   j) an antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 463 and a light chain variable region of SEQ ID NO: 465.   
     
     
         45 . The antigen binding protein of  claim 44 , wherein the antigen binding protein binds to the epitope on PCSK9 that is bound by at least one of:
 a) the antigen binding protein comprising the heavy chain variable region of SEQ ID NO: 67 and the light chain variable region of SEQ ID NO: 12;   b) the antigen binding protein comprising the heavy chain variable region of SEQ ID NO: 483 and the light chain variable region of SEQ ID NO: 485;   c) the antigen binding protein comprising a heavy chain variable region of SEQ ID NO: 459 and the light chain variable region of SEQ ID NO: 461; or   d) the antigen binding protein comprising the heavy chain variable region of SEQ ID NO: 463 and the light chain variable region of SEQ ID NO: 465.   
     
     
         46 . The antigen binding protein of  claim 45 , wherein the antigen binding protein binds to the epitope on PCSK9 that is bound by the antigen binding protein comprising the heavy chain variable region of SEQ ID NO: 67 and the light chain variable region of SEQ ID NO: 12. 
     
     
         47 . The antigen binding protein of  claim 45 , wherein the antigen binding protein binds to the epitope on PCSK9 that is bound by the antigen binding protein comprising the heavy chain variable region of SEQ ID NO: 459 and the light chain variable region of SEQ ID NO: 461. 
     
     
         48 . The antigen binding protein of  claim 45 , wherein the antigen binding protein binds to the epitope on PCSK9 that is bound by the antigen binding protein comprising the heavy chain variable region of SEQ ID NO: 463 and the light chain variable region of SEQ ID NO: 465. 
     
     
         49 . The antigen binding protein of  claim 45 , wherein the antigen binding protein binds to the epitope on PCSK9 that is bound by the antigen binding protein comprising the heavy chain variable region of SEQ ID NO: 483 and the light chain variable region of SEQ ID NO: 485. 
     
     
         50 . The antigen binding protein of  claim 44 , wherein the antigen binding protein that binds to the same epitope is an antibody or a binding part thereof. 
     
     
         51 . An antigen binding protein that binds to amino acids within amino acids 31-449 of PCSK9 of SEQ ID NO: 3. 
     
     
         52 . The antigen binding protein of  claim 51  that binds to amino acids within amino acids 300-400. 
     
     
         53 . The antigen binding protein of  claim 51 , wherein the antigen binding protein is an antibody or a binding part thereof. 
     
     
         54 . An antigen binding protein that binds at least one of the following residues of PCSK9: D374, V380, S381, D367, Q382, I369, S372, C378, F379, or S373 of SEQ ID NO: 3. 
     
     
         55 . The antigen binding protein of  claim 54 , wherein the antigen binding protein binds to at least one of the following residues: D374, V380, or S381. 
     
     
         56 . The antigen binding protein of  claim 54 , wherein the antigen binding protein binds to at least one of the following residues: D367 or Q382. 
     
     
         57 . The antigen binding protein of  claim 54 , wherein the antigen binding protein binds to at least one of the following residues: I369, S372, C378, or F379. 
     
     
         58 . The antigen binding protein of  claim 54 , wherein the antigen binding protein binds to S373 
     
     
         59 . The antigen binding protein of  claim 54 , wherein the antigen binding protein is an antibody or a binding part thereof. 
     
     
         60 . An antigen binding protein that blocks at least one of the following residues of PCSK9: D374, V380, S381, D367, Q382, I369, S372, C378, F379, or S373 of SEQ ID NO: 3. 
     
     
         61 . The antigen binding protein of  claim 60 , wherein the antigen binding protein blocks at least one of the following residues: D374, V380, or S381. 
     
     
         62 . The antigen binding protein of  claim 60 , wherein the antigen binding protein blocks at least one of the following residues: D367 or Q382. 
     
     
         63 . The antigen binding protein of  claim 60 , wherein the antigen binding protein blocks at least one of the following residues: I369, S372, C378, or F379. 
     
     
         64 . The antigen binding protein of  claim 60 , wherein the antigen binding protein blocks S373. 
     
     
         65 . The antigen binding protein of  claim 60 , wherein the antigen binding protein is an antibody or a binding part thereof. 
     
     
         66 . An antigen binding protein that binds to PSCK9, wherein the antigen binding protein binds 5 angstroms or less from at least two of the following residues of PCSK9: W72, F150, A151, Q152, T214, R215, F216, H217, A220, S221, K222, S225, H226, C255, Q256, G257, K258, N317, F318, T347, L348, G349, T350, L351, E366, D367, D374, V380, S381, Q382, S383, or G384, wherein PCSK9 comprises the amino acid sequence of SEQ ID NO:  3 . 
     
     
         67 . The antigen binding protein of  claim 66 , wherein the antigen binding protein is an antibody or a binding part thereof.

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