Antibodies to the C3D fragment of complement component 3
The present invention relates to methods and materials for modulating the complement alternative pathway (CAP), the complement classical pathway (CCP), the complement lectin/mannose pathway (CMP), or combinations thereof, as well as methods and materials for targeting diagnostic, prophylactic and therapeutic agents to localized areas of tissue within the body where they may more directly exert their effects upon the intended target cells or tissue, with reduced, associated systemic effects compared with administration of the same or similar agents in an untargeted, systemic manner. The methods and materials of the present invention may therefore allow for increased efficacy, lower threshold effective dosages and/or lower effective maintenance doses, and/or reduced associated undesired or adverse effects in terms of frequency or severity of occurrence, or both. The present invention also relates to methods and materials for modulating a host humoral immune response, especially reducing, inhibiting, or preventing a host humoral immune response.
1. An isolated antibody or antigen-binding fragment thereof, comprising the complementarity determining regions of an antibody selected from the group consisting of:
i) 3db8 3d8b produced by hybridoma cell line 3d-8b/2 (ATCC Deposit PTA-10999);
ii) 3d9a produced by hybridoma cell line 3d-9a/25 (ATCC Deposit PTA-10998);
iii) 3d29 produced by hybridoma cell line 3d-29/5/2 (ATCC Deposit PTA-11000);
iv) 3d11 produced by hybridoma cell line 3d-11/14 (ATCC Deposit PTA-10011);
v) 3d31 produced by hybridoma cell line 3d-31/A6/9 (ATCC Deposit PTA-11027);
vi) 3d3 produced by hybridoma cell line 3d-3/28/4 (ATCC Deposit PTA-11025);
vii) 3d15 produced by hybridoma cell line 3d-15A9 (ATCC Deposit PTA-11012);
viii) 3di0 produced by hybridoma cell line 3d-10/14/1 (ATCC Deposit PTA-11010); and
ix) 3d16 produced by hybridoma cell line 3d-16/3/3 (ATCC Deposit PTA-11026);
wherein said isolated antibody or antigen-binding fragment thereof is capable of specifically binding to a mammalian complement component C3d protein.
2. The isolated antibody or antigen-binding fragment thereof of claim 1 or 19, wherein said antibody or antigen-binding fragment thereof is a humanized, primatized, or chimerized antibody or antigen-binding fragment thereof.
3. The isolated antibody or antigen-binding fragment thereof of claim 1 or 19, wherein said antibody or antigen-binding fragment thereof is selected from the group consisting of: a monoclonal antibody or antibody fragment, a single chain antibody, an Fv, an Fab, an Fab′, and an F(ab′) 2 .
4. The isolated antibody of claim 3 , wherein said antibody is a monoclonal antibody.
5. The isolated antibody of claim 4 , wherein said antibody is selected from the group consisting of:
i) 3db8 3d8b produced by hybridoma cell line 3d-8b/2 (ATCC Deposit PTA-10999);
ii) 3d9a produced by hybridoma cell line 3d-9a/25 (ATCC Deposit PTA-10998);
iii) 3d29 produced by hybridoma cell line 3d-29/5/2 (ATCC Deposit PTA-11000);
iv) 3d11 produced by hybridoma cell line 3d-11/14 (ATCC Deposit PTA-10011);
v) 3d31 produced by hybridoma cell line 3d-31/A6/9 (ATCC Deposit PTA-11027);
vi) 3d3 produced by hybridoma cell line 3d-3/28/4 (ATCC Deposit PTA-11025);
vii) 3d15 produced by hybridoma cell line 3d-15A9 (ATCC Deposit PTA-11012);
viii) 3di0 produced by hybridoma cell line 3d-10/14/1 (ATCC Deposit PTA-11010); and
ix) 3d16 produced by hybridoma cell line 3d-16/3/3 (ATCC Deposit PTA-11026).
6. A hybridoma cell selected from the group consisting of: 3d-8b/2 (ATCC Deposit PTA-10999), 3d-9a/25 (ATCC Deposit number: PTA-10998), 3d-29/5/2 (ATCC Deposit number: PTA-11000), 3d-11/14 (ATCC Deposit number: PTA-11011), 3d-31/A6/9 (ATCC Deposit number: PTA-11027), 3d-3/28/4 (ATCC Deposit number: PTA-11025), 3d-15A9 (ATCC Deposit number: PTA-11012), 3d-10/14/1 (ATCC Deposit number: PTA-11010), and 3d-16/3/3 (ATCC Deposit number: PTA-11026).
7. A pharmaceutical composition comprising the isolated antibody or antigen-binding fragment thereof of claim 1 or 19, and a pharmaceutically-acceptable excipient.
8. A therapeutic kit comprising: (i) the antibody or antigen-binding fragment thereof of claim 1 or 19, and (ii) means for delivering the antibody or antigen-binding fragment thereof to a human.
9. A pre-filled syringe comprising the antibody or antigen-binding fragment thereof of claim 1 or 19.
10. The isolated antibody or antigen-binding fragment thereof of claim 1 or 19, comprising the complementarity determining regions of the antibody 3db8 3d8b produced by hybridoma cell line 3d-8b/2 (ATCC Deposit PTA-10999).
11. The isolated antibody or antigen-binding fragment thereof of claim 1 or 19, comprising the complementarity determining regions of the antibody 3d9a produced by hybridoma cell line 3d-9a/25 (ATCC Deposit PTA-10998).
12. The isolated antibody or antigen-binding fragment thereof of claim 1 or 19, comprising the complementarity determining regions of the antibody 3d29 produced by hybridoma cell line 3d-29/5/2 (ATCC Deposit PTA-11000).
13. The isolated antibody or antigen-binding fragment thereof of claim 1 or 19, comprising the complementarity determining regions of the antibody 3d11 produced by hybridoma cell line 3d-11/14 (ATCC Deposit PTA-10011).
14. The isolated antibody or antigen-binding fragment thereof of claim 1 or 19, comprising the complementarity determining regions of the antibody 3d31 produced by hybridoma cell line 3d-31/A6/9 (ATCC Deposit PTA-11027).
15. The isolated antibody or antigen-binding fragment thereof of claim 1 or 19, comprising the complementarity determining regions of the antibody 3d3 produced by hybridoma cell line 3d-3/28/4 (ATCC Deposit PTA-11025).
16. The isolated antibody or antigen-binding fragment thereof of claim 1 or 19, comprising the complementarity determining regions of the antibody 3d15 produced by hybridoma cell line 3d-15A9 (ATCC Deposit PTA-11012).
17. The isolated antibody or antigen-binding fragment thereof of claim 1 or 19, comprising the complementarity determining regions of the antibody 3d10 produced by hybridoma cell line 3d-10/14/1 (ATCC Deposit PTA-11010).
18. The isolated antibody or antigen-binding fragment thereof of claim 1 or 19, comprising the complementarity determining regions of the antibody 3d16 produced by hybridoma cell line 3d-16/3/3 (ATCC Deposit PTA-11026).
19. An isolated antibody or antigen-binding fragment thereof, comprising all six of the complementarity determining region (CDR) of an antibody selected from the group consisting of:
i) 3d8b produced by hybridoma cell line 3d-8b/2 (ATCC Deposit PTA-10999);
ii) 3d9a produced by hybridoma cell line 3d-9a125 (ATCC Deposit PTA-10998);
iii) 3d29 produced by hybridoma cell line 3d-29/5/2 (ATCC Deposit PTA-11000);
iv) 3d11 produced by hybridoma cell line 3d-11/14 (ATCC Deposit PTA-10011);
v) 3d31 produced by hybridoma cell line 3d-31/A6/9 (ATCC Deposit PTA-11027);
vi) 3d3 produced by hybridoma cell line 3d-3/28/4 (ATCC Deposit PTA-11025);
vii) 3d15 produced by hybridoma cell line 3d-15A9 (ATCC Deposit PTA-11012);
viii) 3d10 produced by hybridoma cell line 3d-10/14/1 (ATCC Deposit PTA-11010); and
ix) 3d16 produced by hybridoma cell line 3d-16/3/3 (ATCC Deposit PTA-11026);
wherein said isolated antibody or antigen-binding fragment thereof is capable of specifically binding to a mammalian complement component C3d protein, and wherein said isolated antibody or antigen-binding fragment thereof optionally further comprises a complement modulator conjugated to said antibody or antigen-binding fragment.
20. The isolated antibody or antigen-binding fragment thereof of claim 1 or 19, which comprises the heavy chain variable region (VH) of any one of the antibodies of i)-ix).