Antibodies to CCR2
Provided are antibodies including human antibodies and antigen-binding portions thereof that specifically bind to CCR2, specifically human CCR2, and that may function to inhibit CCR2. Anti-CCR2 antibodies include those which bind to the first and/or second extracellular loops of CCR2. Also provided are human anti-CCR2 antibodies and antigen-binding portions thereof. Isolated heavy and light chain immunoglobulins derived from human anti-CCR2 antibodies and nucleic acid molecules encoding such immunoglobulins are provided. Methods of making human anti-CCR2 antibodies or antigen-binding portions, compositions comprising these antibodies or antigen-binding portions, methods of using the antibodies and antigen-binding portions, and compositions for diagnosis and treatment are provided. Also provided are gene therapy methods using nucleic acid molecules encoding the heavy and/or light immunoglobulin molecules that comprise the human anti-CCR2 antibodies or antigen binding portions thereof.
1. An isolated human monoclonal antibody or an antigen-binding portion thereof that specifically binds to human CCR2, comprising a heavy chain variable (V H ) domain amino acid sequence comprising
a V H CDR1 as set forth in SEQ ID NO:84, a V H CDR2 as set forth in SEQ ID NO:85, and a V H CDR3 as set forth in SEQ ID NO:86; and a light chain variable (V L ) domain amino acid sequence comprising a V L CDR1 as set forth in SEQ ID NO:102, a V L CDR2 as set forth in SEQ ID NO:103, and a V L CDR3 as set forth in SEQ ID NO:104.
2. The isolated human monoclonal antibody or antigen-binding portion thereof according to claim 1 , comprising the heavy chain variable (V H ) domain amino acid sequence selected from the group consisting of: SEQ ID NO:83, SEQ ID NO:83 having a conservative amino acid substitution, SEQ ID NO:83 having a germline amino acid substitution compared to SEQ ID NO:160, and an amino acid sequence at least 90% identical to SEQ ID NO:83.
3. The isolated human monoclonal antibody or an antigen-binding portion thereof according to claim 1 , comprising the light chain variable (V L ) domain amino acid sequence selected from the group consisting of:
SEQ ID NO:101, SEQ ID NO:113, SEQ ID NO:101 having a conservative amino acid substitution, SEQ. ID NO: 113 having a conservative amino acid substitution, SEQ ID NO:101 having a germline amino acid substitution compared to SEQ ID NO:161, SEQ ID NO:113 having a germline amino acid substitution compared to SEQ ID NO: 161, an amino acid sequence at least 90% identical to SEQ ID NO:101, and an amino acid sequence at least 90% identical to SEQ ID NO:113.
4. An isolated human monoclonal antibody or an antigen-binding portion that specifically binds to CCR2, comprising: heavy chain CDR1, CDR2 and CDR3 from the heavy chain of a monoclonal antibody produced by the hybridoma designated ATCC Accession No. PTA-6981; and light chain CDR1, CDR2 and CDR3 from the light chain of the monoclonal antibody produced by the hybridoma designated ATCC Accession No. PTA-6981.
5. The isolated human monoclonal antibody or antigen binding portion according to claim 1 , the antibody having the heavy chain and the light chain selected from the group consisting of:
a) the heavy chain having an amino acid sequence of SEQ NO:82 and the light chain having an amino acid sequence of SEQ ID NO:100
and
b) the heavy chain having an amino acid sequence of SEQ ID NO:116 and the light chain having an amino acid sequence of SEQ ID NO:112.
6. The isolated human monoclonal antibody or antigen-binding portion according to claim 1 , wherein the heavy chain amino acid sequence is SEQ ID NO:116 and the light chain amino acid sequence is SEQ ID NO:112.
7. The isolated human monoclonal antibody or antigen-binding portion according to claim 1 , further comprising one or more V H FR1, FR2, FR3 or FR4 and/or V L FR1, FR2, FR3 or FR4 amino acid sequence of an antibody heavy or light chain sequence selected from the group consisting of: SEQ ID NO:82, SEQ ID NO:100, SEQ ID NO: 116, and SEQ ID NO:112.
8. The isolated human monoclonal antibody or antigen-binding portion according to claim 7 , further comprising a heavy chain constant domain.
9. The isolated human monoclonal antibody or antigen-binding portion according to claim 8 , further comprising a light chain constant domain.
10. A pharmaceutical composition comprising the antibody or antigen-binding portion according to claim 1 and a pharmaceutically acceptable carrier.
11. An isolated human monoclonal antibody or an antigen-binding portion thereof that specifically binds to human CCR2, comprising the heavy chain variable (V H ) domain amino acid sequence of SEQ ID NO:83 and the light chain variable (V L ) domain amino acid sequence of SEQ ID NO:113.