Polynucleotides encoding anti-KIT antibodies

Patent metadata

Field	Value
Publication number	US-10189907-B2
Application number	US-201615361936-A
Country	US
Kind code	B2
Filing date	Nov 28, 2016
Priority date	Jan 26, 2011
Publication date	Jan 29, 2019
Grant date	Jan 29, 2019

Abstract

Provided herein, in one aspect, are antibodies that immunospecifically bind to a human KIT antigen comprising the fourth and/or fifth extracellular Ig-like domains (that is, D4 and/or D5 domains), polynucleotides comprising nucleotide sequences encoding such antibodies, and expression vectors and host cells for producing such antibodies. The antibodies can inhibit KIT activity, such as ligand-induced receptor phosphorylation. Also provided herein are kits and pharmaceutical compositions comprising antibodies that specifically bind to a KIT antigen, as well as methods of treating or managing a KIT-mediated disorder or disease and methods of diagnosing a KIT-mediated disorder or disease using the antibodies described herein.

First claim

What is claimed:

1. An polynucleotide comprising nucleotide sequences encoding a VH chain region, a VL chain region, or both a VL chain region and a VH chain region, of an antibody or an antigen-binding fragment thereof, which immunospecifically binds to human KIT (SEQ ID NO: 15) and comprises:
(i) a variable light (“VL”) chain region comprising a VL CDR1, VL CDR2, and VL CDR3 comprising the amino acid sequences of SEQ ID NO: 20, SEQ ID NO: 21, and SEQ ID NO: 22, respectively; and
(ii) a variable heavy (“VH”) chain region comprising a VH CDR1, VH CDR2, and VH CDR3 comprising the amino acid sequences of SEQ ID NO: 23, SEQ ID NO: 24, and SEQ ID NO: 25, respectively.

2. The polynucleotide of claim 1 , wherein the polynucleotide comprises a nucleotide sequence encoding a VH chain region, a VL chain region, or both a VL chain region and a VH chain region, of an antibody or an antigen-binding fragment thereof comprising:
(i) a VL chain region comprising the amino acid sequence of SEQ ID NO: 2; and
(ii) a VH chain region comprising the amino acid sequence of SEQ ID NO: 3 or 5.

3. The polynucleotide of claim 1 , wherein the polynucleotide comprises a nucleotide sequence encoding a VH chain region, a VL chain region, or both a VL chain region and a VH chain region, of an antibody or an antigen-binding fragment thereof which immunospecifically binds to human KIT (SEQ ID NO: 15), wherein said polynucleotide comprises the nucleotide sequence of SEQ ID NO: 8 or 9, or the nucleotide sequences of SEQ ID NOs: 8 and 9.

4. The polynucleotide of claim 1 , wherein the polynucleotide comprises a nucleotide sequence encoding a heavy chain, a light chain, or both a light chain and a heavy chain, of an antibody or an antigen-binding fragment thereof which immunospecifically binds to human KIT (SEQ ID NO: 15), wherein said polynucleotide comprises the nucleotide sequence of SEQ ID NO: 10 or 11, or the nucleotide sequences of SEQ ID NOs: 10 and 11.

5. An expression vector comprising the polynucleotide of any one of claims 1 and 2 - 4 .

6. The expression vector of claim 5 , which is a mammalian expression vector.

7. A host cell comprising the expression vector of claim 5 .

8. A hybridoma cell producing an antibody or an antigen-binding fragment thereof, which immunospecifically binds to human KIT (SEQ ID NO: 15) and comprises:
(i) a VL chain region comprising a VL CDR1, VL CDR2, and VL CDR3 comprising the amino acid sequences of SEQ ID NO: 20, SEQ ID NO: 21, and SEQ ID NO: 22, respectively; and
(ii) a VH chain region comprising a VH CDR1, VH CDR2, and VH CDR3 comprising the amino acid sequences of SEQ ID NO: 23, SEQ ID NO: 24, and SEQ ID NO: 25, respectively.

9. A method of making an antibody or an antigen-binding fragment thereof which immunospecifically binds to human KIT (SEQ ID NO: 15) comprising culturing the host cell of claim 7 .

10. The method claim 9 further comprising purifying the antibody obtained from said host cell.

11. A host cell comprising the expression vector of claim 6 .

12. A host cell comprising (i) the polynucleotide of any one of claims 1 and 2 - 6 that comprises nucleotide sequences encoding a VL chain region and a VH chain region of an antibody or an antigen-binding fragment thereof; or (ii) a first polynucleotide of any one of claims 1 and 2 - 6 that comprises a nucleotide sequence encoding a VH chain region of an antibody or an antigen-binding fragment thereof, and a second polynucleotide of any one of claims 1 and 2 - 6 that comprises a nucleotide sequence encoding a VL chain region of said antibody or antigen-binding fragment thereof.

13. The hybridoma cell of claim 8 , wherein:
(i) the VL chain region comprises the amino acid sequence of SEQ ID NO: 2; and
(ii) the VH chain region comprises the amino acid sequence of SEQ ID NO: 3 or 5.

14. A method of making an antibody or an antigen-binding fragment thereof which immunospecifically binds to human KIT (SEQ ID NO: 15) comprising culturing the host cell of claim 11 .

15. The method claim 14 further comprising purifying the antibody obtained from said host cell.

16. A method of making an antibody or an antigen-binding fragment thereof which immunospecifically binds to human KIT (SEQ ID NO: 15) comprising culturing the host cell of claim 12 .

17. The method claim 16 further comprising purifying the antibody obtained from said host cell.

18. A method of making an antibody or an antigen-binding fragment thereof which immunospecifically binds to human KIT (SEQ ID NO: 15) comprising culturing the hybridoma cell of claim 8 .

19. The method claim 18 further comprising purifying the antibody obtained from said hybridoma cell.

20. A method of making an antibody or an antigen-binding fragment thereof which immunospecifically binds to human KIT (SEQ ID NO: 15) comprising culturing the hybridoma cell of claim 13 .

21. The method claim 20 further comprising purifying the antibody obtained from said hybridoma cell.

22. The polynucleotide of any one of claims 1 and 2 - 6 , wherein the antibody is a humanized monoclonal antibody.

23. The polynucleotide of any one of claims 1 and 2 - 6 , wherein the antibody is a monoclonal antibody.

24. The polynucleotide of any one of claims 1 and 2 - 6 , wherein the antibody comprises an Fc region of a human IgG1 or IgG4 antibody.

25. The polynucleotide of any one of claims 1 and 2 - 6 , wherein the antibody is a humanized antibody.

26. The polynucleotide of any one of claims 1 and 2 - 6 , wherein the antibody further comprises a human heavy chain constant region.

27. The polynucleotide of claim 26 , wherein the human heavy chain constant region is a human gamma heavy chain constant region.

28. The polynucleotide of claim 26 , wherein the human heavy chain constant region is an IgG1 or IgG4 human heavy chain constant region.

29. The polynucleotide of any one of claims 1 and 2 - 6 , wherein the antibody further comprises a human light chain constant region.

30. The polynucleotide of claim 29 , wherein the human light chain constant region is a human kappa light chain constant region.

31. The polynucleotide of any one of claims 1 and 2 - 6 , wherein the antibody further comprises a human light chain constant region and a human heavy chain constant region.

32. The polynucleotide of claim 31 , wherein the human light chain constant region comprises the amino acid sequence of SEQ ID NO: 12 and the human heavy chain constant region comprises the amino acid sequence of SEQ ID NO: 13.

33. The polynucleotide of claim 31 , wherein the human light chain constant region is a human kappa light chain constant region and the human heavy chain constant region is a human gamma heavy chain constant region.

34. The polynucleotide of claim 31 , wherein the human light chain constant region is a human kappa light chain constant region and the human heavy chain constant region is an IgG1 or IgG4 human heavy chain constant region.

Assignees

• Celldex Therapeutics Inc

Inventors

• Hadari Yaron
• Radke Susanne
• Schlessinger Joseph
• Suzuki Yoshihisa

Classifications

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07K2317/92

  Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value · CPC title

• C07K2317/77

  Internalization into the cell · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title