Superagonistic anti-CD28 antibodies
The present invention relates to one or more nucleic acid(s) encoding a binding molecule specifically binding to a human CD28 molecule, comprising (a) a nucleic acid sequence encoding a VH region and a nucleic acid sequence encoding a VL region comprising CDRs in a human immunoglobulin framework, wherein (i) the CDRs of the VH region (CDR-H) comprise the amino acid sequences of SEQ ID NOS: 2 or 18 (CDR-H3), 4 or 20 (CDR-H2) and 6 or 22 (CDR-H1) or are encoded by the nucleic acid sequences of SEQ ID NOS: 1 or 17 (CDR-H3), 3 or 19 (CDR-H2) and 5 or 21 (CDR-H1); and (ii) the CDRs of the VL region (CDR-L) comprise the amino acid sequences of SEQ ID NOS: 8 or 24 (CDR-L3), 10 or 26 (CDR-L2) and 12 or 28 (CDR-L1) or are encoded by the nucleic acid sequences of SEQ ID NOS: 7 or 23 (CDR-L3), 9 or 25 (CDR-L2) and 11 or 27 (CDR-L1); and (b) a nucleic acid sequence encoding the constant region of a human IgG1 or IgG4 antibody.
1. A binding molecule encoded by a nucleic acid sequence comprising:
(a) a nucleic acid sequence encoding a V H region and a nucleic acid sequence encoding a V L region comprising CDRs in a human immunoglobulin framework, wherein
(i) the CDRs of the V H region (CDR-H) comprise the amino acid sequences of SEQ ID NOS: 2 or 18 (CDR-H3), 4 or 20 (CDR-H2) and 6 or 22 (CDR-H1) or are encoded by the nucleic acid sequences of SEQ ID NOS: 1 or 17 (CDR-H3), 3 or 19 (CDR-H2) and 5 or 21 (CDR-H1); and
(ii) the CDRs of the V L region (CDR-L) comprise the amino acid sequences of SEQ ID NOS: 8 or 24 (CDR-L3), 10 or 26 (CDR-L2) and 12 or 28 (CDR-L1) or are encoded by the nucleic acid sequences of SEQ ID NOS: 7 or 23 (CDR-L3), 9 or 25 (CDR-L2) and 11 or 27 (CDR-L1); and
(b) a nucleic acid sequence encoding the constant region of a human IgG1 or IgG4 antibody.
2. The binding molecule of claim 1 , wherein
(i) the nucleic acid sequence of the V H region comprises SEQ ID NO: 33 or 37 and/or encodes a (poly)peptide comprising the amino acid sequence SEQ ID NO: 34 or 38; and
(ii) the nucleic acid sequence of the V L region comprises SEQ ID NO: 35 or 39 and/or encodes a (poly)peptide comprising the amino acid sequence SEQ ID NO: 36 or 40.
3. The binding molecule of claim 1 , wherein the nucleic acid sequence
(i) is selected from the group consisting of SEQ ID NO: 13, 29, 41 and 45; or
(ii) encodes a (poly)peptide having the amino acid sequence selected from the group consisting of SEQ ID NO: 14, 30, 42 and 46.
4. The binding molecule of claim 1 , wherein the nucleic acid sequence
(i) is selected from the group consisting of SEQ ID NO: 15, 31, 43 and 47; or
(ii) encodes a (poly)peptide having the amino acid sequence selected from the group consisting of SEQ ID NO: 16, 32, 44 and 48.
5. The binding molecule of claim 1 , wherein the nucleic acid sequence further comprises a nucleic acid sequence encoding a marker element or tag.
6. An antibody or fragment or derivative of an antibody comprising the binding molecule according to claim 1 .
7. The antibody according to claim 6 , which is a monoclonal antibody.
8. The binding molecule of claim 1 , wherein the binding molecule is prepared by
(a) culturing a host cell in suitable conditions, wherein the host cell is transformed or transfected with a vector comprising the nucleic acid sequence encoding the binding molecule; and
(b) isolating the binding molecule from the culture.