Anti-C5aR antibodies with improved properties

1. An antibody comprising:

(i) a variable heavy chain sequence as shown in SEQ ID NO:3;

(ii) a variable light chain sequence as shown in SEQ ID NO:4; or

(iii) a variable heavy chain region comprising the CDR1, CDR2, and CDR3 loop sequences of a variable heavy chain sequence as shown in SEQ ID NO:3 and a variable light chain region comprising the CDR1, CDR2, and CDR3 loop sequences of a variable light chain sequence as shown in SEQ ID NO:4;

wherein the antibody reduces or inhibits the binding of C5a to C5aR.

2. An antibody according to claim 1 , that binds to human C5aR, or a fragment thereof comprising the sequence set forth in SEQ ID NO: 27, with:

(i) an IC 50 value that is at least 1.5 fold lower than that of MAb7F3 (produced by a hybridoma deposited with ECACC under accession number 00110609) when determined under identical conditions; or

(ii) an association constant (Kon) that is at least 1.5 fold higher than that of MAb7F3 when determined under identical conditions; or

(iii) a K d affinity constant that is at least 1.3 fold lower than that of MAb7F3 when determined under identical conditions.

3. An antibody according to claim 1 that binds to human C5aR, or a fragment thereof, comprising the sequence set forth in SEQ ID NO: 27 with:

(i) an IC 50 value that is less than 500 pM; or

(ii) an association constant (Kon) that is at least 6.8×10 5 M −1 s −1 ; or

(iii) a K d affinity constant that is less than 1.4 nM.

4. An antibody according to claim 2 , wherein the fragment of C5aR is a peptide comprising the sequence LYRVVREEYFPPKVLCGVDYSHDKRRERAVAIV (SEQ ID NO: 2).

5. An antibody comprising:

(i) a variable heavy chain sequence as shown in SEQ ID NO:5;

(ii) a variable light chain sequence as shown in SEQ ID NO:6; or

(iii) a variable heavy chain region comprising the CDR1, CDR2, and CDR3 loop sequences of a variable heavy chain sequence as shown in SEQ ID NO:5 and a variable light chain region comprising the CDR1, CDR2, and CDR3 loop sequences of a variable light chain sequence as shown in SEQ ID NO:6;

wherein the antibody reduces or inhibits the binding of C5a to C5aR.

6. An antibody comprising:

(i) a variable heavy chain sequence as shown in SEQ ID NO:7;

(ii) a variable light chain sequence as shown in SEQ ID NO:8; or

(iii) a variable heavy chain region comprising the CDR1, CDR2, and CDR3 loop sequences of a variable heavy chain sequence as shown in SEQ ID NO:7 and a variable light chain region comprising the CDR1, CDR2, and CDR3 loop sequences of a variable light chain sequence as shown in SEQ ID NO:8;

wherein the antibody reduces or inhibits the binding of C5a to C5aR.

7. A monoclonal antibody selected from the group consisting of:

(i) an antibody comprising a variable heavy chain sequence as shown in SEQ ID NO: 3 and a variable light chain sequence as shown in SEQ ID NO: 4;

(ii) an antibody produced by a hybridoma deposited with ECACC under accession number 06081801;

(iii) an antibody comprising a variable heavy chain sequence as shown in SEQ ID NO: 5 and a variable light chain sequence as shown in SEQ ID NO: 6;

(iv) an antibody produced by a hybridoma deposited with ECACC under accession number 06081802;

(v) an antibody comprising a variable heavy chain sequence as shown in SEQ ID NO: 7 and a variable light chain sequence as shown in SEQ ID NO: 8; and

(vi) an antibody produced by a hybridoma deposited with ECACC under accession number 06081803.

8. A hybridoma as deposited with ECACC under accession number 06081801, 06081802, or 06081803.

9. An isolated nucleic acid molecule comprising a sequence encoding an antibody of claim 1 .

10. A composition comprising an antibody of claim 1 or claim 6 and a pharmaceutically acceptable carrier.

11. A method for detecting C5aR in a subject in a subject, the method comprising:

contacting a sample obtained from the subject in vitro with a conjugate comprising the antibody of claim 1 and a detectable label; and

detecting immunospecific binding between the conjugate and the sample by detecting the detectable label,

wherein said detecting indicates the presence of C5aR in the subject.

12. A method of inhibiting the interaction of a cell bearing C5aR with C5a comprising contacting the cell with an antibody of claim 1 .

13. A method of reducing or inhibiting interaction of C5aR with C5a in a subject having an autoimmune or inflammatory condition, comprising administering to the subject an antibody of claim 1 .

14. A method of inhibiting leukocyte trafficking in a mammal in need thereof, comprising administering to the mammal an antibody of claim 1 in an amount effect to inhibit the migration of leukocyte trafficking in the mammal.

15. The antibody of claim 1 , which is a monoclonal antibody, a recombinant antibody, a chimeric antibody or a humanized antibody.

16. The antibody of claim 5 , which is a monoclonal antibody, a recombinant antibody, a chimeric antibody or a humanized antibody.

17. The antibody of claim 6 , which is a monoclonal antibody, a recombinant antibody, a chimeric antibody or a humanized antibody.

18. A method of detecting and/or quantitating expression of C5aR by a cell, the method comprising:

contacting a composition comprising a cell or fraction thereof with a conjugate comprising the antibody of claim 1 and a detecting label; and

detecting immunospecific binding between the conjugate and the cell or fraction thereof by detecting the detecting label,

wherein detecting the immunospecific binding detects and/or quantitates expression of C5aR by the cell.