Anti-RANTES antibodies
The invention relates to fully human monoclonal antibodies, and fragments thereof, that bind to the chemokine Regulated upon Activation, Normal T-cell Expressed, and Secreted (RANTES, CCL5), thereby modulating the interaction between RANTES and one of more of its receptors, such as, e.g., CCR1, CCR3, CCR4 and CCR5, and/or modulating the biological activities of RANTES. The invention also relates to the use of these or any anti-RANTES antibodies in the prevention or treatment of immune-related disorders and in the amelioration of one or more symptoms associated with an immune-related disorder.
1. An isolated fully human monoclonal antibody or fragment thereof that binds human Regulated upon Activation, Normal T-cell Expressed, and Secreted (RANTES), wherein said antibody comprises:
(a) a V H CDR1 region comprising the amino acid sequence of SEQ ID NO: 8;
(b) a V H CDR2 region comprising the amino acid sequence of SEQ ID NO: 9;
(c) a V H CDR3 region comprising the amino acid sequence of SEQ ID NO: 20;
(d) a V L CDR1 region comprising the amino acid sequence of SEQ ID NO: 14;
(e) a V L CDR2 region comprising the amino acid sequence of SEQ ID NO: 15; and
(f) a V L CDR3 region comprising the amino acid sequence of SEQ ID NO: 16,
wherein said antibody binds RANTES.
2. The antibody of claim 1 , wherein said antibody is an IgG isotype.
3. The antibody of claim 1 , wherein said antibody is an IgG1 isotype.
4. The antibody of claim 1 , wherein said antibody further comprises a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 18 and a light chain variable sequence comprising the amino acid sequence of SEQ ID NO: 4.
5. A pharmaceutical composition comprising the antibody of claim 1 and a carrier.
6. An isolated fully human monoclonal antibody comprising a heavy chain variable sequence comprising the amino acid sequence of SEQ ID NO: 18 and a light chain variable sequence comprising the amino acid sequence of SEQ ID NO: 4, wherein said antibody binds RANTES.
7. The antibody of claim 6 , wherein said antibody is an IgG isotype.
8. The antibody of claim 6 , wherein said antibody further comprises a heavy chain sequence comprising the amino acid sequence of SEQ ID NO:238 and a light chain sequence comprising the amino acid sequence of SEQ ID NO:254.
9. An isolated antibody that binds human Regulated upon Activation, Normal T-cell Expressed, and Secreted (RANTES) when human RANTES is bound to a glycosaminoglycan (GAG), wherein said antibody comprises:
(a) a V H CDR1 region comprising the amino acid sequence of SEQ ID NO: 8;
(b) a V H CDR2 region comprising the amino acid sequence of SEQ ID NO: 9;
(c) a V H CDR3 region comprising the amino acid sequence of SEQ ID NO: 20;
(d) a V L CDR1 region comprising the amino acid sequence of SEQ ID NO: 14;
(e) a V L CDR2 region comprising the amino acid sequence of SEQ ID NO: 15; and
(f) a V L CDR3 region comprising the amino acid sequence of SEQ ID NO: 16.
10. The antibody of claim 9 , wherein said antibody is a monoclonal antibody or an antigen-binding fragment thereof.
11. The antibody of claim 9 , wherein said antibody is a fully human monoclonal antibody or an antigen-binding fragment thereof.
12. The antibody of claim 9 , wherein said antibody is an IgG isotype.
13. The antibody of claim 9 , wherein said antibody is an IgG1 isotype.