Antibody therapeutics that bind CD123
View Patent ↗There is disclosed compositions and methods relating to or derived from anti-CD123 antibodies. More specifically, there is disclosed fully human antibodies that bind CD123, CD123-antibody binding fragments and derivatives of such antibodies, and CD123-binding polypeptides comprising such fragments. Further still, there is disclosed nucleic acids encoding such antibodies, antibody fragments and derivatives and polypeptides, cells comprising such polynucleotides, methods of making such antibodies, antibody fragments and derivatives and polypeptides, and methods of using such antibodies, antibody fragments and derivatives and polypeptides, including methods of treating a disease.
1. A recombinant anti-CD123 antibody, or an antigen-binding fragment thereof, that binds to CD123, comprising heavy chain variable domain and light chain variable domain amino acid sequences comprising all of the complementarity determining regions (CDRs) as set forth in a heavy and light chain variable domain amino acid sequences of either SEQ ID NO. 9 and SEQ ID NO. 10, or SEQ ID NO. 15 and SEQ ID NO. 16, respectively.
2. The recombinant fully human anti-CD123 antibody of claim 1 , wherein the antibody comprises heavy chain and light chain variable domain sequences of either SEQ ID NO. 9 and SEQ ID NO. 10, or SEQ ID NO. 15 and SEQ ID NO. 16, respectively.
3. A method for treating a CD123 positive cancer in a human subject in need thereof, the method comprising the step of administering an effective amount of the recombinant fully human anti-CD123 antibody of claim 2 , such that the cancer is treated.
4. The method of claim 3 , wherein the recombinant fully human anti CD123 antibody comprises heavy chain and light chain variable domain sequences of SEQ ID NO. 9 and SEQ ID NO. 10.
5. The method of claim 3 , wherein the recombinant fully human anti-CD123 antibody comprises heavy chain and light chain variable domain sequences of SEQ ID NO. 15 and SEQ ID NO. 16.
6. The method of claim 3 , wherein the cancer is selected from the group consisting of non-Hodgkin's lymphoma, Burkitt's lymphoma, multiple myeloma, B chronic lymphocytic leukemia, B and T acute lymphocyticleukemia, T cell lymphoma, acute myeloid leukemia, hairy cell leukemia, Hodgkin's Lymphoma, and chronic myeloid leukemia.
7. The recombinant fully human anti-CD123 antibody of claim 2 , wherein the antibody has a dissociation constant (K D ) of at least 1×10 −6 M.
8. The recombinant fully human anti-CD123 antibody of claim 2 , wherein the antibody is classified as an IgG isotype.
9. The recombinant fully human anti-CD123 antibody of claim 8 , wherein the antibody is an IgG1 or an IgG4.
10. The recombinant anti-CD123 antibody, or antigen-binding fragment thereof, of claim 1 , wherein antibody, or antigen-binding fragment is selected from the group consisting of a Fab, a Fab′, a F(ab′)2, an Fv, a single chain antibody, a chimeric antibody, a diabody, a triabody, and a tetrabody.
11. The recombinant anti-CD123 antigen-binding fragment of claim 1 , which is a single chain antibody.
12. The recombinant anti-CD123 antibody, or antigen-binding fragment thereof, of claim 1 , which has a K D of at least 1×10 −6 M.
13. A pharmaceutical composition comprising the recombinant anti-CD123 antibody, or antigen-binding fragment thereof, of claim 1 , and a pharmaceutically acceptable carrier.
14. The recombinant anti-CD123 antibody, or antigen-binding fragment thereof, of claim 1 , wherein the antibody, or antigen-binding fragment thereof, is classified as an IgG isotype.
15. The recombinant anti-CD123 antibody, or antigen-binding fragment thereof, of claim 14 , wherein the antibody, or antigen-binding fragment thereof, is an IgG1 or an IgG4.
16. A method of treating a CD123 positive cancer in a human subject in need thereof, said method comprising the step of administering an effective amount of the recombinant anti-CD123 antibody, or antigen-binding fragment thereof, of claim 1 to the subject, such that the cancer is treated.
17. The method of claim 16 , wherein the cancer is selected from the group consisting of non-Hodgkin's lymphoma, Burkitt's lymphoma, multiple myeloma, B chronic lymphocytic leukemia, B and T acute lymphocytic leukemia, T cell lymphoma, acute myeloid leukemia, hairy cell leukemia, Hodgkin's Lymphoma, and chronic myeloid leukemia.
18. A recombinant fully human anti-CD123 antibody fragment that binds to CD123, wherein the fragment comprises heavy chain and light chain variable domain amino acid sequences of either SEQ ID NO. 9 and SEQ ID NO. 10, or SEQ ID NO. 15 and SEQ ID NO. 16, respectively.
19. The recombinant fully human anti-CD123 antibody fragment of claim 18 , wherein the antibody has a K D of at least 1×10 −6 M.
20. A method for treating a CD123 positive cancer in a human subject in need thereof, the method comprising the step of administering an effective amount of the recombinant fully human anti-CD123 antibody fragment of claim 18 , such that the cancer is treated.
21. The method of claim 20 , wherein the recombinant fully human anti-CD123 antibody fragment comprises heavy chain and light chain variable domain sequences of SEQ ID NO. 9 and SEQ ID NO. 10.
22. The method of claim 20 , wherein the recombinant fully human anti-CD123 antibody fragment comprises heavy chain and light chain variable domain sequences of SEQ ID NO. 15 and SEQ ID NO. 16.
23. The method of claim 20 , wherein the cancer is selected from the group consisting of non-Hodgkin's lymphoma, Burkitt's lymphoma, multiple myeloma, B chronic lymphocytic leukemia, B and T acute lymphocytic leukemia, T cell lymphoma, acute myeloid leukemia, hairy cell leukemia, Hodgkin's Lymphoma, and chronic myeloid leukemia.
24. The recombinant fully human anti-CD123 antibody fragment of claim 18 , wherein the fragment is classified as an IgG.
25. The recombinant fully human anti-CD123 antibody fragment of claim 24 , wherein the fragment is an IgG1 or an IgG4.
26. The recombinant anti-CD123 antibody fragment of claim 18 , wherein the fragment is selected from the group consisting of a Fab, a Fab′, a F(ab′)2, an Fv, and a single-chain antibody.
27. A single chain anti-CD123 antibody that binds to CD123, comprising heavy chain and light chain variable domain amino acid sequences of either SEQ ID NO. 9 and SEQ ID NO. 10, or SEQ ID NO. 15 and SEQ ID NO. 16, respectively, and wherein the heavy chain variable domain and the light chain variable domain are connected by a peptide linker.
28. The single chain anti-CD123 antibody of claim 27 , wherein the antibody has a K D of at least 1×10 −6 M.
29. A method for treating a CD123 positive cancer in a human subject in need thereof, the method comprising the step of administering an effective amount of the single chain anti-CD123 antigen-binding fragment of claim 27 , such that the cancer is treated.
30. The method of claim 29 , wherein the anti-CD123 single chain antibody comprises heavy chain and light chain variable domain sequences of SEQ ID NO. 9 and SEQ ID NO. 10.
31. The method of claim 29 , wherein the anti-CD123 single chain antibody comprises heavy chain and light chain variable domain sequences of SEQ ID NO. 15 and SEQ ID NO. 16.
32. The method of claim 29 , wherein the cancer is selected from the group consisting of non-Hodgkin's lymphoma, Burkitt's lymphoma, multiple myeloma, B chronic lymphocytic leukemia, B and T acute lymphocytic leukemia, T cell lymphoma, acute myeloid leukemia, hairy cell leukemia, Hodgkin's Lymphoma, and chronic myeloid leukemia.