Complement factor Bb antibodies
The present disclosure relates to antibodies and polynucleotides encoding the same, which may be used to prevent, control, or reduce the activity of the complement pathway. In addition, the disclosure is directed to compositions and methods for diagnosing and treating diseases mediated by or involving complement Factor Bb. Specifically, the disclosure is related to anti-complement Factor Bb antibodies.
1. A Factor Bb antibody, comprising a heavy chain and a light chain, wherein the antibody binds to Factor Bb with greater affinity than to Factor B; and inhibits complement dependent hemolysis; and wherein either:
a. the light chain comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 8-11; and wherein the heavy chain comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 12-15;
or
b. the light chain comprises an amino acid sequence selected from the group consisting of SEQ ID NO:24-27; and wherein the heavy chain comprises an amino acid sequence selected from the group consisting of SEQ ID NO:28-31.
2. The antibody of claim 1 , that binds Factor Bb with a K d of less than about 1 nM.
3. The antibody of claim 1 , wherein the antibody blocks formation of membrane attack complex (MAC) in a patient.
4. The antibody of claim 1 , wherein the antibody is an antibody comprising a light chain variable domain and a heavy chain variable domain selected from the light chain and heavy chain variable domain amino acid sequences: SEQ ID NO:8/SEQ ID NO: 12; SEQ ID NO:8/SEQ ID NO: 13; SEQ ID NO:8/SEQ ID NO:14; SEQ ID NO:8/SEQ ID NO:15; SEQ ID NO:9/SEQ ID NO:12; SEQ ID NO:9/SEQ ID NO:13; SEQ ID NO:9/SEQ ID NO:14; SEQ ID NO:9/SEQ ID NO:15; SEQ ID NO:10/SEQ ID NO:12; SEQ ID NO:10/SEQ ID NO:13; SEQ ID NO:10/SEQ ID NO:14; and SEQ ID NO:10/SEQ ID NO:15; SEQ ID NO:11/SEQ ID NO:12; SEQ ID NO:11/SEQ ID NO:13; SEQ ID NO:11/SEQ ID NO:14; and SEQ ID NO:11/SEQ ID NO:15.
5. The antibody of claim 1 , wherein the antibody is an antibody comprising a light chain variable domain and a heavy chain variable domain selected from the light chain and heavy chain variable domain amino acid sequences: SEQ ID NO:24/SEQ ID NO:28; SEQ ID NO:24/SEQ ID NO:29; SEQ ID NO:24/SEQ ID NO:30; SEQ ID NO:24/SEQ ID NO:31; SEQ ID NO:25/SEQ ID NO:28; SEQ ID NO:25/SEQ ID NO:29; SEQ ID NO:25/SEQ ID NO:30; SEQ ID NO:25/SEQ ID NO:31; SEQ ID NO:26/SEQ ID NO:28; SEQ ID NO:26/SEQ ID NO:29; SEQ ID NO:26/SEQ ID NO:30; and SEQ ID NO:26/SEQ ID NO:31; SEQ ID NO:27/SEQ ID NO:28; SEQ ID NO:27/SEQ ID NO:29; SEQ ID NO:27/SEQ ID NO:30; and SEQ ID NO:27/SEQ ID NO:31.
6. The antibody of claim 1 , wherein the antibody comprises a light chain variable domain amino acid sequence of SEQ ID NO:11 and a heavy chain variable domain amino acid sequence of SEQ ID NO: 15.
7. The antibody of claim 1 , wherein said antibody is a monoclonal antibody, a polyclonal antibody, a recombinant antibody, a humanized antibody, a chimeric antibody, a multispecific antibody, or an antibody fragment thereof.
8. The antibody of claim 7 , wherein said antibody fragment is a Fab fragment, a Fab′ fragment, a F(ab′)2 fragment, a Fv fragment, a diabody, or a single chain antibody molecule.
9. The antibody of claim 7 , wherein said antibody is of the IgG1-, IgG2-IgG3- or IgG4-type.
10. A pharmaceutical composition comprising the antibody of claim 1 and pharmaceutically acceptable carrier.
11. The antibody of claim 1 , wherein the antibody comprises a light chain variable domain amino acid sequence of SEQ ID NO:25 and a heavy chain variable domain amino acid sequence of SEQ ID NO: 30.