US2017362311A1PendingUtilityA1

Methods and compositions for regulating iron homeostasis by modulation of bmp-6

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Assignee: MASSACHUSETTS GEN HOSPITALPriority: Nov 13, 2008Filed: May 18, 2017Published: Dec 21, 2017
Est. expiryNov 13, 2028(~2.3 yrs left)· nominal 20-yr term from priority
Inventors:Herbert Y. LinJodie Babitt
C07K 16/18C07K 2317/34C07K 2319/30A61K 2039/505A61P 7/06C07K 2317/76C07K 16/22C12N 15/113G01N 33/53
51
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Claims

Abstract

Modulation of iron homeostasis by regulating BMP-6 activity is provided. Methods of using BMP-6 and BMP-6 protein-specific reagents, such as antibodies, for altering serum iron levels in humans are provided. Such antibodies are useful in pharmaceutical compositions for the prevention and treatment of hemochromatosis and anemia of inflammation.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A method of increasing serum transferrin saturation in a subject, the method comprising administering to said subject an effective amount of a pharmaceutical composition comprising a monoclonal antibody that specifically binds mature bone morphogenetic protein-6 (BMP-6) or fragments thereof. 
     
     
         2 . The method of  claim 1 , wherein administration of said composition inhibits liver hepcidin mRNA production. 
     
     
         3 . The method of  claim 1 , wherein administration of said composition inhibits hepatic hepcidin expression. 
     
     
         4 . The method of  claim 1 , wherein the subject is a human and administration of said composition inhibits hepcidin expression in human hepatic cells. 
     
     
         5 . The method of  claim 1 , wherein the antibody binds BMP-7. 
     
     
         6 . The method of  claim 5 , wherein the antibody specifically binds BMP-6 with higher affinity than BMP-7. 
     
     
         7 . The method of  claim 6 , wherein the antibody binds BMP-6 with at least 5-fold greater affinity than BMP-7. 
     
     
         8 . The method of  claim 6  wherein said BMP-6 is human BMP-6 and said BMP-7 is human BMP-7. 
     
     
         9 . The method of  claim 1 , wherein the antibody binds to said BMP-6 with a K a  greater than or equal to about 10 4  M −1 . 
     
     
         10 . The method of  claim 1 , wherein administration of said composition reduces BMP-6 signaling. 
     
     
         11 . The method of  claim 1 , wherein the mature BMP-6 comprises the amino acid sequence of SEQ ID NO: 2. 
     
     
         12 . The method of  claim 1 , wherein the method increases serum iron. 
     
     
         13 . The method of  claim 1 , wherein the composition is administered in an amount sufficient to inhibit an interaction between hemojuvelin and BMP-6. 
     
     
         14 . The method of  claim 1 , wherein the subject is a human and the antibody preferably inhibits human BMP-6 over BMP-2, 4, 5, 7 or 9. 
     
     
         15 . A method of inhibiting hepcidin expression in the liver of a subject, the method comprising administering to said subject an effective amount of a pharmaceutical composition comprising a monoclonal antibody that specifically binds bone morphogenetic protein-6 (BMP-6) or fragments thereof. 
     
     
         16 . The method of  claim 15 , wherein administration of said composition inhibits liver hepcidin mRNA production. 
     
     
         17 . The method of  claim 15 , wherein administration of said composition inhibits hepatic hepcidin expression. 
     
     
         18 . The method of  claim 15 , wherein the subject is a human and administration of said composition inhibits hepcidin expression in human hepatic cells. 
     
     
         19 . The method of  claim 15 , wherein administration of said composition increases serum transferrin saturation in the subject. 
     
     
         20 . The method of  claim 19 , wherein the inhibition is in the presence of BMP-6 and BMP-2, BMP-4, BMP-5, BMP-7, or BMP-9. 
     
     
         21 . The method of  claim 15 , wherein the antibody binds BMP-7. 
     
     
         22 . The method of  claim 21 , wherein the antibody specifically binds BMP-6 with higher affinity than BMP-7. 
     
     
         23 . The method of  claim 22 , wherein the antibody binds BMP-6 with at least 5-fold greater affinity than BMP-7. 
     
     
         24 . The method of any one of  claims 21 ,  22 , or  23  wherein said BMP-6 is human BMP-6 and said BMP-7 is human BMP-7. 
     
     
         25 . The method of  claim 15 , wherein the antibody binds to said BMP-6 with a K a  greater than or equal to about 10 4  M −1 . 
     
     
         26 . The method of  claim 15 , wherein administration of said composition reduces BMP-6 signaling. 
     
     
         27 . The method of  claim 15 , wherein the mature BMP-6 comprises the amino acid sequence of SEQ ID NO: 2. 
     
     
         28 . The method of  claim 15 , wherein the method increases serum iron. 
     
     
         29 . The method of  claim 15 , wherein the composition is administered in an amount sufficient to inhibit an interaction between hemojuvelin and BMP-6. 
     
     
         30 . The method of  claim 15 , wherein the subject is a human and the antibody preferably inhibits human BMP-6 over BMP-2, 4, 5, 7 or 9.

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