Humanized and chimeric monoclonal antibodies to CD47
Humanized or chimeric anti-CD47 monoclonal antibodies are provided. The antibodies bind to and neutralize human CD47, and find use in various therapeutic methods. Preferred are non-activating antibodies. Embodiments of the invention include isolated antibodies and derivatives and fragments thereof, pharmaceutical formulations comprising one or more of the humanized or chimeric anti-CD47 monoclonal antibodies; and cell lines that produce these monoclonal antibodies. Also provided are amino acid sequences of the antibodies.
1. One or more polynucleotides encoding i) an antibody that binds to human CD47 or ii) an antigen-binding fragment of said antibody, wherein i) the antibody that binds to human CD47 or ii) the antigen-binding fragment of said antibody comprises:
a variable heavy (VH) region comprising CDR1 amino acid sequence of SEQ ID NO: 20, CDR2 amino acid sequence of SEQ ID NO: 21, and CDR3 amino acid sequence of SEQ ID NO: 22, and a variable light (VL) region comprising CDR1 amino acid sequence of SEQ ID NO: 23, CDR2 amino acid sequence of SEQ ID NO: 24, and CDR3 amino acid sequence of SEQ ID NO: 25.
2. The polynucleotide of claim 1 , wherein the variable light (VL) region comprises the amino acid sequence selected from the group consisting of the SEQ ID NO:41, SEQ ID NO: 42 and SEQ ID NO: 43.
3. The polynucleotide of claim 1 , wherein said variable heavy (VH) region comprises the amino acid sequence selected from the group consisting of the SEQ ID NO:36, SEQ ID NO: 37 and SEQ ID NO: 38.
4. The polynucleotide of claim 1 , wherein the antibody is a humanized antibody.
5. The polynucleotide of claim 1 , wherein the antibody is a chimeric antibody.
6. The polynucleotide of claim 1 , wherein the antibody is a single chain antibody.
7. The polynucleotide of claim 1 , further comprising a sequence encoding an immunoglobulin constant region of an isotype selected from IgG1, IgG2a, IgG2b, IgG3, IgG4, and IgA.
8. The polynucleotide of claim 7 , wherein the isotype is IgG4.
9. The polynucleotide of claim 1 , wherein the fragment is an Fab fragment.
10. A polynucleotide vector comprising one or more polynucleotides encoding i) an antibody that binds to human CD47 or ii) an antigen-binding fragment of said antibody, wherein i) the antibody that binds to human CD47 or ii) the antigen-binding fragment of said antibody comprises:
a variable heavy (VH) region comprising CDR1 amino acid sequence of SEQ ID NO: 20, CDR2 amino acid sequence of SEQ ID NO: 21, and CDR3 amino acid sequence of SEQ ID NO: 22, and a variable light (VL) region comprising CDR1 amino acid sequence of SEQ ID NO: 23, CDR2 amino acid sequence of SEQ ID NO: 24, and CDR3 amino acid sequence of SEQ ID NO: 25.
11. The polynucleotide vector of claim 10 , wherein the variable light (VL) region comprises the amino acid sequence selected from the group consisting of the SEQ ID NO:41, SEQ ID NO: 42 and SEQ ID NO: 43.
12. The polynucleotide vector of claim 10 , wherein said variable heavy (VH) region comprises the amino acid sequence selected from the group consisting of the SEQ ID NO:36, SEQ ID NO: 37 and SEQ ID NO: 38.
13. The polynucleotide vector of claim 10 , wherein the antibody is a humanized antibody.
14. The polynucleotide vector of claim 10 , wherein the antibody is a chimeric antibody.
15. The polynucleotide vector of claim 10 , wherein the antibody is a bispecific antibody.
16. The polynucleotide vector of claim 10 , wherein the antibody is a single chain antibody.
17. The polynucleotide vector of claim 10 , further comprising a sequence encoding an immunoglobulin constant region of an isotype selected from IgG1, IgG2a, IgG2b, IgG3, IgG4, and IgA.
18. The polynucleotide vector of claim 10 , wherein the isotype is IgG4.
19. The polynucleotide vector of claim 10 , wherein the fragment is an Fab fragment.
20. Polynucleotides encoding i) an antibody that binds to human CD47 or ii) an antigen-binding fragment of said antibody, wherein the polynucleotides comprise:
a first polynucleotide encoding a variable heavy (VH) region comprising CDR1 amino acid sequence of SEQ ID NO: 20, CDR2 amino acid sequence of SEQ ID NO: 21, and CDR3 amino acid sequence of SEQ ID NO: 22;
and second polynucleotide encoding a variable light (VL) region comprising CDR1 amino acid sequence of SEQ ID NO: 23, CDR2 amino acid sequence of SEQ ID NO: 24, and CDR3 amino acid sequence of SEQ ID NO: 25.
21. The polynucleotides of claim 20 , wherein the variable light (VL) region comprises the amino acid sequence selected from the group consisting of the SEQ ID NO:41, SEQ ID NO: 42 and SEQ ID NO: 43.
22. The polynucleotides of claim 20 , wherein said variable heavy (VH) region comprises the amino acid sequence selected from the group consisting of the SEQ ID NO:36, SEQ ID NO: 37 and SEQ ID NO: 38.
23. The polynucleotides of claim 20 , wherein the antibody is a humanized antibody.
24. The polynucleotides of claim 20 , wherein the antibody is a chimeric antibody.
25. The polynucleotides of claim 20 , further comprising a sequence encoding an immunoglobulin constant region of an isotype selected from IgG1, IgG2a, IgG2b, IgG3, IgG4, and IgA.
26. The polynucleotides of claim 25 , wherein the isotype is IgG4.
27. The polynucleotides of claim 20 , wherein the fragment is an Fab fragment.
28. A cell comprising one or more polynucleotides encoding i) an antibody that binds to human CD47 or ii) an antigen-binding fragment of said antibody, wherein i) the antibody that binds to human CD47 or ii) the antigen-binding fragment of said antibody comprises:
a variable heavy (VH) region comprising CDR1 amino acid sequence of SEQ ID NO: 20, CDR2 amino acid sequence of SEQ ID NO: 21, and CDR3 amino acid sequence of SEQ ID NO: 22, and a variable light (VL) region comprising CDR1 amino acid sequence of SEQ ID NO: 23, CDR2 amino acid sequence of SEQ ID NO: 24, and CDR3 amino acid sequence of SEQ ID NO: 25.
29. The cell of claim 28 , wherein the variable light (VL) region comprises the amino acid sequence selected from the group consisting of the SEQ ID NO:41, SEQ ID NO: 42 and SEQ ID NO: 43.
30. The cell of claim 28 , wherein said variable heavy (VH) region comprises the amino acid sequence selected from the group consisting of the SEQ ID NO:36, SEQ ID NO: 37 and SEQ ID NO: 38.
31. The cell of claim 28 , wherein the antibody is a humanized antibody.
32. The cell of claim 28 , wherein the antibody is a chimeric antibody.
33. The cell of claim 28 , wherein the antibody is a single chain antibody.
34. The cell of claim 28 , further comprising a sequence encoding an immunoglobulin constant region of an isotype selected from IgG1, IgG2a, IgG2b, IgG3, IgG4, and IgA.
35. The cell of claim 28 , wherein the isotype is IgG4.
36. The cell of claim 28 , wherein the fragment is an Fab fragment.