Nucleic acids encoding 7C10 and 16C10 CD80-specific antibodies
View Patent ↗The present invention relates to the identification of antibodies which are specific to human B7.1 antigen (CD80) and which are capable of inhibiting the binding of B7.1 to a CD28 receptor and which are not capable of inhibiting the binding of B7.1 to a CTLA-4 receptor. Two of these antibodies, 16C10 and 7C10, significantly inhibit the production of IL-2, in spite of the existence of a second activating ligand B7.2 (CD86). Blocking of the primary activation signal between CD28 and B7.1 (CD80) with these antibodies while allowing the unimpaired or coincident interaction of CTLA-4 and B7.1 and/or B7.2 represents a combined antagonistic effect on positive co-stimulation with an agonistic effect on negative signaling. These antibodies may be used as specific immunosuppressants, e.g., for the treatment of autoimmune diseases and to prevent organ transplant rejection.
1. A nucleic acid encoding a monoclonal antibody or fragment thereof that binds specifically to human CD80 antigen, wherein the antibody comprises variable regions of a 7C10 antibody, produced by a hybridoma assigned ATCC Accession No. HB-12117, or variable regions of a 16C10 antibody, produced by a hybridoma assigned ATCC Accession No. HB-12119.
2. The nucleic acid of claim 1 , wherein the antibody comprises a human constant region selected from the group consisting of a human gamma 1 constant region, a human gamma 4 constant region, and a human gamma 4PE constant region.
3. The nucleic acid of claim 1 , wherein the antibody comprises variable regions of a 16C10 antibody, produced by a hybridoma assigned ATCC Accession No. HB-12119 and a human gamma 1 constant region.
4. The nucleic acid of claim 1 , wherein the antibody fragment is selected from the group consisting of Fab, F(ab′) 2 and Fv.
5. A nucleic acid encoding a primatized monoclonal antibody which specifically binds to human CD80 antigen, wherein the antibody comprises the light chain and heavy chain variable regions of SEQ ID NO: 2 and SEQ ID NO: 4, respectively, and human light chain and heavy chain constant regions.
6. The nucleic acid of claim 5 , wherein the human heavy chain constant region is a human gamma 1 constant region, human gamma 4 constant region, or human gamma 4 PE constant region.
7. A nucleic acid encoding a primatized monoclonal antibody which specifically binds to human CD80 antigen, wherein the antibody comprises the variable light and heavy regions contained in SEQ ID NO: 10 and SEQ ID NO: 12, respectively, and human light chain and heavy chain constant regions.
8. The nucleic acid of claim 7 , wherein the human heavy chain constant region is a human gamma 1 constant region, human gamma 4 constant region, or human gamma 4 PE constant region.
9. A nucleic acid encoding a monoclonal antibody, wherein the antibody specifically binds to human CD80 antigen and comprises a light chain and heavy chain variable region derived from the light and heavy chain variable region of an antibody produced by a hybridoma assigned ATCC Accession No. HB-12117 and constant regions derived from human constant regions.
10. The nucleic acid of claim 9 , wherein the constant regions are a human heavy chain constant region and a human light chain constant region.
11. The nucleic acid of claim 10 , wherein the human heavy chain constant region is a human gamma 1 constant region, human gamma 4 constant region, or human gamma 4 PE constant region.
12. The nucleic acid of claim 9 , wherein the antibody comprises variable regions of an antibody produced by the hybridoma assigned ATCC Accession No. HB-12117.
13. A nucleic acid encoding a monoclonal antibody, wherein the antibody specifically binds to human CD80 antigen and comprises a light and heavy chain variable region derived from the light and heavy chain variable region of an antibody produced by a hybridoma assigned ATCC Accession No. HB-12119 and constant regions derived from human constant regions.
14. The nucleic acid of claim 13 , wherein the constant regions are a human heavy chain constant region and a human light chain constant region.
15. The nucleic acid of claim 14 , wherein the human heavy chain constant region is a human gamma 1 constant region, human gamma 4 constant region, or human gamma 4 PE constant region.
16. The nucleic acid of claim 13 , wherein the antibody comprises variable regions of an antibody produced by the hybridoma assigned ATCC Accession No. HB-12119.