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US 2016/0108115 A1Published application
Anti-c5 antibodies having improved pharmacokinetics
AssigneeAlexion Pharmaceuticals, Inc.
InventorsBruce A. ANDRIEN, JR., Douglas L. SHERIDAN, Paul P. TAMBURINI
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Abstract
The disclosure provides antibodies that are useful for, among other things, inhibiting terminal complement (e.g., the assembly and/or activity of the C5b-9 TCC) and C5a anaphylatoxin-mediated inflammation and, thus, treating complement-associated disorders. The antibodies have a number of improved properties relative to eculizumab, including, e.g., increased serum half-life in a human.
Claims22
1-36. (canceled)
An isolated antibody, or antigen-binding fragment thereof, that:
- (a) binds to complement component human C5;
- (b) inhibits the cleavage of C5 into fragments C5a and C5b;
- and
- (c) comprises:
- (i) a heavy chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:23, (ii) a heavy chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:19, (iii) a heavy chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:3, (iv) a light chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:4, (v) a light chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:5, and (vi) a light chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:6.
2 more elements
An isolated antibody, or antigen-binding fragment thereof, that:
- (a) binds to complement component human C5;
- (b) inhibits the cleavage of human C5 into fragments C5a and C5b;
- and
- (c) comprises:
- (i) a heavy chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:23, (ii) a heavy chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:19, (iii) a heavy chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:3, (iv) a light chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:4, (v) a light chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:5, and (vi) a light chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:6,
- wherein the [(KD of the antibody or antigen-binding fragment thereof for human C5 at pH 6.0 and at 25° C.)/(KD of the antibody or antigen-binding fragment thereof for human C5 at pH 7.4 and at 25° C.)] is greater than 25, and
- and wherein the antibody has a serum half-life in humans that is at least 25 days.
4 more elements
Dependencies are inferred from the claim text.