Anti-DPEP3 antibodies and methods of use
View Patent ↗Provided herein are novel anti-DPEP3 antibodies and antibody drug conjugates (ADC), including derivatives thereof, and methods of using the same to treat proliferative disorders.
1. A monoclonal antibody or immunoreactive fragment thereof that specifically binds to an epitope in human dipeptidase 3 (DPEP3) protein, comprising three complementarity-determining regions (CDRs) of a light chain variable region set forth as SEQ ID NO: 205 (CDRL1, CDRL2 and CDRL3), and three CDRs of a heavy chain variable region set forth as SEQ ID NO: 207 (CDRH1, CDRH2 and CDRH3).
2. The monoclonal antibody of claim 1 , comprising residues 24-34 of SEQ ID NO: 205 for CDRL1, residues 50-56 of SEQ ID NO: 205 for CDRL2, residues 89-97 of SEQ ID NO: 205 for CDRL3, residues 31-35 of SEQ ID NO: 207 for CDRH1, residues 50-65 of SEQ ID NO: 207 for CDRH2 and residues 95-102 of SEQ ID NO: 207 for CDRH3, wherein the CDR residues are numbered according to Kabat.
3. The monoclonal antibody of claim 1 , comprising residues 24-34 of SEQ ID NO: 205 for CDRL1, residues 50-56 of SEQ ID NO: 205 for CDRL2, residues 89-97 of SEQ ID NO: 205 for CDRL3, residues 26-32 of SEQ ID NO: 207 for CDRH1, residues 52-56 of SEQ ID NO: 207 for CDRH2 and residues 95-102 of SEQ ID NO: 207 for CDRH3, wherein the CDR residues are numbered according to Chothia.
4. The monoclonal antibody of claim 1 , comprising residues 30-36 of SEQ ID NO: 205 for CDRL1, residues 46-55 of SEQ ID NO: 205 for CDRL2, residues 89-96 of SEQ ID NO: 205 for CDRL3, residues 30-35 of SEQ ID NO: 207 for CDRH1, residues 47-58 of SEQ ID NO: 207 for CDRH2 and residues 93-101 of SEQ ID NO: 207 for CDRH3, wherein the CDR residues are numbered according to MacCallum.
5. The monoclonal antibody of claim 1 , comprising a light chain variable region set forth as SEQ ID NO: 205 and a heavy chain variable region set forth as SEQ ID NO: 207.
6. The monoclonal antibody of claim 1 , comprising one or more unpaired cysteine residues.
7. The monoclonal antibody of claim 6 , comprising two light chains and two heavy chains, wherein each light chain or each heavy chain comprises an unpaired cysteine residue.
8. The monoclonal antibody of claim 7 , wherein the unpaired cysteine residue of each of the light chains is C214.
9. The monoclonal antibody of claim 7 , wherein the heavy chain is IgG1 and the unpaired cysteine residue of each of the heavy chains is C220.
10. The monoclonal antibody of claim 7 , wherein the monoclonal antibody is conjugated or associated with a cytotoxin.
11. The monoclonal antibody of claim 1 , comprising a full length light chain set forth as SEQ ID NO: 224 and a full length heavy chain set forth as SEQ ID NO: 225.
12. The monoclonal antibody of claim 1 , comprising a full length light chain set forth as SEQ ID NO: 224 and a full length heavy chain set forth as SEQ ID NO: 226.
13. The monoclonal antibody of claim 1 , wherein the monoclonal antibody is conjugated or associated with a cytotoxin.
14. The monoclonal antibody of claim 1 , which is selected from the group consisting of a chimeric antibody, CDR-grafted antibody, humanized antibody, primatized antibody, multispecific antibody, bispecific antibody, monovalent antibody, multivalent antibody, diabody, Fab fragment, F(ab′) 2 fragment, Fv fragment, and ScFv fragment.
15. The monoclonal antibody of claim 14 , wherein the monoclonal antibody is conjugated or associated with a cytotoxin.