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US 9,315,577 B2Granted
Anti-hepcidin antibodies and methods of use
AssigneeAmgen Inc.
InventorsIan Foltz, Michael Gallo, Keegan Cooke, Randal R. Ketchem, Christopher Mehlin
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Abstract
The invention relates to monoclonal antibodies that bind hepcidin and methods of making and using such antibodies. Also provided are methods of treating hepcidin-related disorders.
Claims2
An isolated antibody comprising SEQ ID NOs:
- 334-339 wherein the antibody binds to human hepcidin of SEQ ID NO:
- 9 with an affinity KD of less than about 10−8M and which exhibits at least one of the properties selected from the group consisting of:
- (a) at least about a 50-fold higher KD at a pH of about 5.5 compared to its KD for said hepcidin at a pH of about 7.4;
- (b) at least about a 5-fold faster clearance of said hepcidin compared to antibody 1S1 having the heavy chain variable region of SEQ ID NO:
- 202 and the light chain variable region of SEQ ID NO:
- 128;
- and
- (c) an off rate of about 6×10−2 s−1 or higher at about pH 5.5.
5 more elements
An isolated antibody comprising the amino acid sequence SEQ ID NOs:
- 334-339 that binds to human hepcidin of SEQ ID NO:
- 9, with an affinity KD of at least 10−8M and said antibody has at least about a 50-fold higher KD at about pH 5.5 compared to its KD for said hepcidin at about pH 7.4 or said antibody has an off rate of about 6×10−2 s−1 or higher at about pH 5.5, wherein said antibody is obtained by:
- (a) replacing an amino acid in the heavy or light chain of said antibody with a histidine;
- (b) screening the antibody obtained in (a) for differential pH binding;
- (c) replacing another amino acid in the heavy or light chain of said antibody with a histidine;
- and
- (d) screening said antibody for having at least one of the properties selected from the group consisting of:
- (i) at least about 50-fold higher KD at about pH 5.5 compared to its KD for said hepcidin at about pH 7.4;
- and
- (ii) an off rate of about 6×10−2 s−1 or higher at about pH 5.5.
7 more elements
Dependencies are inferred from the claim text.