Methods of treating by administering anti-kit antibodies

Patent metadata

Field	Value
Publication number	US-10793639-B2
Application number	US-201816214980-A
Country	US
Kind code	B2
Filing date	Dec 10, 2018
Priority date	Jan 26, 2011
Publication date	Oct 6, 2020
Grant date	Oct 6, 2020

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. A method for treating or managing a KIT-mediated disorder, wherein the KIT-mediated disorder is associated with KIT expression and/or activity, the method comprising administering to a subject in need thereof a therapeutically effective amount of an antibody or an antigen-binding fragment thereof, which immunospecifically binds to human KIT 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. A method for treating or managing a KIT-mediated disorder, wherein the KIT-mediated disorder is associated with KIT expression and/or activity, the method comprising administering to a subject in need thereof a therapeutically effective amount of a conjugate comprising an antibody or an antigen-binding fragment thereof, which immunospecifically binds to human KIT 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,
which antibody or antigen-binding fragment thereof is linked to a therapeutic agent.

3. The method of claim 1 , wherein the KIT-mediated disorder is cancer, an inflammatory condition, or fibrosis.

4. A method for inhibiting KIT activity in a cell expressing KIT comprising contacting the cell with an effective amount of an antibody or an antigen-binding fragment thereof, which immunospecifically binds to human KIT 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.

5. A method for inducing or enhancing apoptosis in a cell expressing KIT comprising contacting the cell with an effective amount of an antibody or an antigen-binding fragment thereof, which immunospecifically binds to human KIT 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.

6. A method for inducing cell differentiation comprising contacting a cell expressing KIT with an effective amount of an antibody or an antigen-binding fragment thereof, which immunospecifically binds to human KIT 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.

7. The method of claim 2 , wherein the KIT-mediated disorder is cancer, an inflammatory condition, or fibrosis.

8. The method of claim 3 , wherein the cancer is leukemia, chronic myelogenous leukemia, lung cancer, small cell lung cancer, or gastrointestinal stromal tumors.

9. The method of claim 7 , wherein the cancer is leukemia, chronic myelogenous leukemia, lung cancer, small cell lung cancer, or gastrointestinal stromal tumors.

10. The method of claim 3 , wherein the cancer is refractory to treatment by a tyrosine kinase inhibitor.

11. The method of claim 7 , wherein the cancer is refractory to treatment by a tyrosine kinase inhibitor.

12. The method of claim 10 , wherein the tyrosine kinase inhibitor is imatinib mesylate or SU11248.

13. The method of claim 11 , wherein the tyrosine kinase inhibitor is imatinib mesylate or SU11248.

14. The method of claim 1 , wherein the method further comprises administering a second therapeutic agent.

15. The method of claim 2 , wherein the method further comprises administering a second therapeutic agent.

16. The method of claim 14 , wherein the second therapeutic agent is a chemotherapeutic agent, tyrosine kinase inhibitor, an antibody, or a cytokine.

17. The method of claim 15 , wherein the second therapeutic agent is a chemotherapeutic agent, tyrosine kinase inhibitor, an antibody, or a cytokine.

18. The method of claim 16 , wherein the tyrosine kinase inhibitor is imatinib mesylate or SU11248.

19. The method of claim 17 , wherein the tyrosine kinase inhibitor is imatinib mesylate or SU11248.

20. The method of claim 6 , wherein the cell is a stem cell.

21. The method of claim 1 , wherein the KIT-mediated disorder is systemic mast cell disorder.

22. The method of claim 2 , wherein the KIT-mediated disorder is systemic mast cell disorder.

Assignees

• Celldex Therapeutics Inc

Inventors

• Hadari Yaron
• Mandel-Bausch Elizabeth M
• Radke Susanne
• Schlessinger Joseph
• Suzuki Yoshihisa

Classifications

• C07K16/2803 Primary

  against the immunoglobulin superfamily · CPC title

• C07K16/2896 Primary

  against molecules with a "CD"-designation, not provided for elsewhere · CPC title

• C07K2317/77

  Internalization into the cell · CPC title

• C07K2317/30

  characterized by aspects of specificity or valency · CPC title

• G01N33/573

  for enzymes or isoenzymes · CPC title