Anti-complement factor C1q antibodies and uses thereof
The present invention provides anti-C1q antibodies and methods of using the same.
1. An anti-C1q antibody, comprising;
(a) a light chain variable domain and a heavy chain variable domain, wherein the light chain variable domain comprises the hypervariable region (HVR)-L1, HVR-L2, and HVR-L3 of the monoclonal antibody M1 produced by a hybridoma cell line with ATCC Accession Number PTA-120399; and wherein the heavy chain variable domain comprises the HVR-H1, HVR-H2, and HVR-H3 of the monoclonal antibody M1 produced by a hybridoma cell line with ATCC Accession Number PTA-120399; or
(b) a heavy chain HVR selected from HVR-H1 comprising the amino acid sequence of SEQ ID NO: 9, HVR-H2 comprising the amino acid sequence of SEQ ID NO: 10, and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 11.
2. The antibody of claim 1 , wherein the antibody comprises a light chain variable domain comprising the amino acid sequence of SEQ ID NO:4.
3. The antibody of claim 1 , wherein the antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:8.
4. The antibody of claim 1 , which is a murine, humanized, or chimeric antibody.
5. The antibody of claim 1 , which is an antibody fragment, wherein the antibody fragment is a Fab, F(ab′) 2 or Fab′ fragment.
6. The antibody of claim 1 which binds specifically to human C1q, mouse C1q and rat C1q.
7. The antibody of claim 1 , which has a dissociation constant (K D ) for human C1q and mouse C1q less than about 30 nM.
8. The antibody of claim 1 which specifically binds to C1q and inhibits CH50hemolysis.
9. The antibody of claim 8 , wherein the CH50 hemolysis comprises human, mouse or rat CH50 hemolysis.
10. The antibody of claim 8 , which is capable of neutralizing at least 50%, at least 80%, or at least 90% of CH50 hemolysis.
11. The antibody of claim 8 , which is capable of neutralizing at least 50% of CH50hemolysis at a dose of less than 200 ng/ml, less than 100 ng/ml, less than 50 ng/ml, or less than 20 ng/ml.
12. A pharmaceutical composition comprising the antibody of claim 1 and a pharmaceutically acceptable carrier.
13. A diagnostic kit comprising an antibody of claim 1 .
14. A murine anti-human C1q monoclonal antibody having the same HVRs as an antibody produced by a hybridoma cell line with ATCC Accession Number PTA-120399.
15. A polynucleotide comprising a nucleic acid sequence encoding the antibody of claim 1 .
16. A host cell comprising the nucleic acid sequence of claim 15 .
17. A method of detecting synapses in an individual, the method comprising
(a) administering an antibody of claim 1 to the individual, and
(b) detecting antibody bound to synapses, thereby detecting synapses in the individual.
18. A method of detecting synapses in a biological sample, the method comprising
(a) contacting the biological sample with an antibody of claim 1 , and
(b) detecting antibody bound to synapses, thereby detecting synapses in the biological sample.
19. The antibody of claim 2 , wherein the antibody comprises a heavy chain variable domain comprising the amino acid sequence of SEQ ID NO:8.
20. The antibody of claim 2 which has a dissociation constant (KD) for human C1q and mouse C1q less than about 30 nM.
21. The antibody of claim 3 which has a dissociation constant (KD) for human C1q and mouse C1q less than about 30 nM.
22. The antibody of claim 2 , which is an antibody fragment, wherein the antibody fragment is a Fab, F(ab′) 2 or Fab′ fragment.
23. The antibody of claim 3 , which is an antibody fragment, wherein the antibody fragment is a Fab, F(ab′) 2 or Fab′ fragment.
24. The antibody of claim 19 , which is an antibody fragment, wherein the antibody fragment is a Fab, F(ab′) 2 or Fab′ fragment.
25. The antibody of claim 1 , wherein the antibody is of the IgG class.
26. The antibody of claim 25 , wherein the antibody has an IgG1, IgG2, IgG3, or IgG4 isotype.
27. The antibody of claim 14 , wherein the antibody has the same heavy chain variable domain as an antibody produced by a hybridoma cell line with ATCC Accession Number PTA-120399.
28. The antibody of claim 14 , wherein the antibody has the same light chain variable domain as an antibody produced by a hybridoma cell line with ATCC Accession Number PTA-120399.