# US 8,465,737 B2 · Three-dimensional structure of complement receptor type 2 and uses thereof

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- Number: US 8,465,737 B2
- Document ID: US8465737B2
- Status: Granted
- Kind: B2
- Application number: 11/786,788
- Filed: 2007-04-12
- Published: 2007-09-27
- Granted: 2013-06-18
- Earliest claimed: 2001-04-11
- Assignees: The Regents of the University of Colorado
- Applicants: Xiaojiang Chen; Vernon Michael Holers
- Inventors: Xiaojiang Chen; Vernon Michael Holers
- Web page: https://patentgrep.com/patent/US8465737B2

## CPC

- C07K 16/28: against receptors, cell surface antigens or cell surface determinants
- A61K 31/00: Medicinal preparations containing organic active ingredients
- C07K 14/70596: {Molecules with a "CD"-designation not provided for elsewhere}
- C07K 16/2896: {against molecules with a "CD"-designation, not provided for elsewhere}
- G16B 15/00: ICT specially adapted for analysing two-dimensional [2D] or three-dimensional [3D] molecular structures, e.g. structural or functional relations or structure alignment
- G16B 15/30: Drug targeting using structural data; Docking or binding prediction
- C07K 2299/00: Coordinates from 3D structures of peptides, e.g. proteins or enzymes
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- G16B: BIOINFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR GENETIC OR PROTEIN-RELATED DATA PROCESSING IN COMPUTATIONAL MOLECULAR BIOLOGY

## Abstract

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.

## Claims

### Claim 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.

### Claim 2 (depends on 1)

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.

### Claim 3 (depends on 1)

The isolated antibody or antigen binding fragment thereof of claim 1, wherein the antigen binding fragment is selected from the group consisting of an Fv fragment, an Fab fragment, an Fab′ fragment, and an F(ab)2 fragment.

### Claim 4 (depends on 1)

The isolated antibody or antigen binding fragment thereof of claim 1, wherein the antibody is a monoclonal antibody.

### Claim 5 (depends on 1)

The isolated antibody or antigen binding fragment thereof of claim 1, wherein the antibody is a single chain antibody.

### Claim 6 (depends on 1)

The isolated antibody or antigen binding fragment thereof of claim 1, wherein the antibody is mAb171 (produced by ATCC deposit PTA-12091).

### Claim 7 (depends on 1)

The isolated antibody or antigen binding fragment thereof of claim 1, wherein the antibody is mAb1048 (produced by ATCC deposit PTA-12093).

### Claim 8 (depends on 1)

The isolated antibody or antigen binding fragment thereof of claim 1, wherein the antibody is mAb629 (produced by ATCC deposit PTA-12092).

### Claim 9 (depends on 1)

A composition comprising the antibody or antigen binding fragment thereof of claim 1 and a pharmaceutically acceptable carrier.

### Claim 10 (depends on 1)

The isolated antibody or antigen binding fragment thereof of claim 1, wherein the antibody or antigen binding fragment thereof is chimeric.

### Claim 11 (depends on 1)

The isolated antibody or antigen binding fragment thereof of claim 1, wherein the antibody or antigen binding fragment thereof is CDR grafted.

### Claim 12 (depends on 1)

The isolated antibody or antigen binding fragment thereof of claim 1, wherein the antibody or antigen binding fragment thereof is humanized.