C5-specific antibodies for the treatment of inflammatory diseases
First Claim
1. An antibody comprising at least one antibody-antigen binding site, said antibody exhibiting specific binding to human complement component C5, said specific binding being targeted to the alpha chain of human complement component C5, wherein the antibody 1) inhibits complement activation in a human body fluid, 2) inhibits the binding of purified human complement component C5 to either human complement component C3 or human complement component C4, and 3) does not specifically bind to the human complement activation product free C5a.
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Abstract
The use of anti-C5 antibodies, e.g., monoclonal antibodies, to treat glomerulonephritis (GN) is disclosed. The administration of such antibodies at low dosage levels has been found to significantly reduce glomerular inflammation/enlargement and other pathologic conditions associated with GN. Also disclosed are anti-C5 antibodies and anti-C5 antibody-encoding nucleic acid molecules. These antibodies are useful in the treatment of GN and other inflammatory conditions involving pathologic activation of the complement system.
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Citations
23 Claims
- 1. An antibody comprising at least one antibody-antigen binding site, said antibody exhibiting specific binding to human complement component C5, said specific binding being targeted to the alpha chain of human complement component C5, wherein the antibody 1) inhibits complement activation in a human body fluid, 2) inhibits the binding of purified human complement component C5 to either human complement component C3 or human complement component C4, and 3) does not specifically bind to the human complement activation product free C5a.
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18. Antibody 5G1.1 scFv CB (humanized) having the amino acid sequence encoded by the nucleic acid sequence of SEQ ID NO:
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19. An isolated antigen binding protein comprising:
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1) a variable light region CDR1 comprising an amino acid sequence corresponding to amino acid residues 26-36 of SEQ ID NO;
8,2) a variable light region CDR2 comprising an amino acid sequence corresponding to amino acid residues 52-58 of SEQ ID NO;
8,3) a variable light region CDR3 comprising an amino acid sequence corresponding to amino acid residues 91 through amino acid 99 of SEQ ID NO;
8,4) a variable heavy region CDR1 comprising an amino acid sequence corresponding to amino acid residues 152 through amino acid 161 of SEQ ID NO;
8,5) a variable heavy region CDR2 comprising an amino acid sequence corresponding to amino acid residues 176 through amino acid 192 of SEQ ID NO;
8,6) a variable heavy region CDR3 comprising an amino acid sequence corresponding to amino acid residues 225 through amino acid 237 of SEQ ID NO;
8,said protein exhibiting specific binding to human complement component C5, said specific binding being targeted to the alpha chain of human complement component C5, wherein the protein inhibits complement activation in a human body fluid and does not specifically bind to the human complement activation product free C5a.
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20. A nucleic acid molecule comprising a nucleotide sequence encoding a polypeptide comprising a variable heavy chain region amino acid sequence corresponding to amino acid 1 through amino acid 122 of SEQ ID NO:
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- 21. Hybridoma 5G1.1 having ATCC designation HB-11625.
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23. An antibody comprising at least one antibody-antigen binding site, said antibody exhibiting specific binding to human complement component C5, said specific binding being targeted to the alpha chain of human complement component C5, wherein:
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(A) the antibody inhibits (i) C5b-9-mediated hemolysis and (ii) C5a generation in a fluid comprising human serum; and
(B) the antibody does not specifically bind to the human complement activation product free C5a.
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Specification