Three-dimensional structure of complement receptor type 2 and uses thereof
View Patent ↗Disclosed is a crystalline human CR2 protein in complex with C3d, and the three dimensional structure of the crystalline complex. Also disclosed are methods of use of the structure, particularly for structure-based identification of compounds that bind to CR2 and inhibit or enhance the binding of CR2 to a natural ligand, that bind to CR2 and agonize or antagonize the receptor, that bind to CR2 and inhibit or enhance CR2 dimerization, or that use the C3-binding ability of CR2 as a drug delivery vehicle. Also disclosed are therapeutic compounds obtained by such methods and uses for such compounds.
1. An isolated antibody or antigen binding fragment thereof, wherein the antibody or antigen binding fragment thereof binds to an epitope of human Complement Receptor Type 2 (CR2) at the interface between CR2 and C3d, wherein the antibody is mAb171 (produced by ATCC deposit PTA-12091), mAb1048 (produced by ATCC deposit PTA-12093), or mAb629 (produced by ATCC deposit PTA-12092), or a chimeric or humanized antibody thereof.
2. The isolated antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or antigen binding fragment thereof inhibits the binding of CR2 to C3d.
3. The isolated antibody or antigen binding fragment thereof of claim 1 , wherein the antigen binding fragment is selected from the group consisting of an F v fragment, an F ab fragment, an F ab′ fragment, and an F(ab) 2 fragment.
4. The isolated antibody or antigen binding fragment thereof of claim 1 , wherein the antibody is a monoclonal antibody.
5. The isolated antibody or antigen binding fragment thereof of claim 1 , wherein the antibody is a single chain antibody.
6. The isolated antibody or antigen binding fragment thereof of claim 1 , wherein the antibody is mAb171 (produced by ATCC deposit PTA-12091).
7. The isolated antibody or antigen binding fragment thereof of claim 1 , wherein the antibody is mAb1048 (produced by ATCC deposit PTA-12093).
8. The isolated antibody or antigen binding fragment thereof of claim 1 , wherein the antibody is mAb629 (produced by ATCC deposit PTA-12092).
9. A composition comprising the antibody or antigen binding fragment thereof of claim 1 and a pharmaceutically acceptable carrier.
10. The isolated antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or antigen binding fragment thereof is chimeric.
11. The isolated antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or antigen binding fragment thereof is CDR grafted.
12. The isolated antibody or antigen binding fragment thereof of claim 1 , wherein the antibody or antigen binding fragment thereof is humanized.