Methods of obtaining a specific binding member that binds eotaxin
View Patent ↗Specific binding members directed to eotaxin-1, in particular human antibodies and antibody fragments against human eotaxin-1 and especially those which neutralize eotaxin-1 activity. The antibodies VH and/or VL domain of the scFv fragment herein termed CAT-212 and of the IgG4 antibody herein termed CAT 213. One or more complementary determining regions (CDRs) of the CAT-212/-213 VH and/or VL domains, especially VH CRD3 in other antibody framework regions. Compositions containing specific binding members, and their use in methods of inhibiting or neutralizing eotaxin, including methods of treatment of the human or animal body by therapy.
1. A method of producing an antibody heavy chain variable region (VH) domain, the method comprising culturing host cells under conditions for production of said VH domain, wherein said host cells are transformed with a nucleic acid which comprises a nucleotide sequence encoding a polypeptide comprising a VH domain, wherein said VH domain comprises VH CDRs 1-3 with the amino acid sequences of SEQ ID NO:5, SEQ ID NO:6 and SEQ ID NO:7, respectively, and wherein when the VH domain is paired with an antibody light chain variable region (VL) domain comprising VL CDRs 1-3 with the amino acid sequences of SEQ ID NO:8, SEQ ID NO:9 and SEQ ID NO:10, respectively, an antibody antigen binding site that binds eotaxin is provided.
2. The method according to claim 1 , wherein said VH domain comprises the CAT-212 VH domain (SEQ ID NO:2).
3. The method according to claim 1 , further comprising isolating and/or purifying said VH domain.
4. The method according to claim 1 , further comprising formulating the VH domain into a composition including at least one additional component.
5. The method of claim 1 , wherein the polypeptide further comprises an antibody heavy chain constant region.
6. The method of claim 5 , wherein the antibody heavy chain constant region is an IgG4 constant region.
7. A method of producing an antibody light chain variable region (VL) domain, the method comprising culturing host cells under conditions for production of said VL domain, wherein said host cells are transformed with a nucleic acid which comprises a nucleotide sequence encoding a polypeptide comprising a VL domain, wherein said VL domain comprises VL CDRs 1-3 with the amino acid sequences of SEQ ID NO:8, SEQ ID NO:9 and SEQ ID NO:10, respectively, and wherein when the VL domain is paired with an antibody heavy chain variable region (VH) domain comprising VH CDRs 1-3 with the amino acid sequences of SEQ ID NO:5, SEQ ID NO:6 and SEQ ID NO:7, respectively, an antibody antigen binding site that binds eotaxin is provided.
8. The method according to claim 7 , wherein said VL domain comprises the CAT-212 VL domain (SEQ ID NO:4).
9. The method according to claim 7 , further comprising isolating and/or purifying said VL domain.
10. The method according to claim 7 , further comprising formulating the VL domain into a composition including at least one additional component.
11. The method of claim 7 , wherein the polypeptide further comprises an antibody light chain constant region.
12. The method of claim 11 , wherein the antibody light chain constant region is a Cλ constant region.