CD123 binding agents and uses thereof

Patent metadata

Field	Value
Publication number	US-9850310-B2
Application number	US-201514844194-A
Country	US
Kind code	B2
Filing date	Sep 3, 2015
Priority date	Sep 5, 2014
Publication date	Dec 26, 2017
Grant date	Dec 26, 2017

Abstract

Provided herein are antibodies that immunospecifically bind to CD123. Also described are related polynucleotides capable of encoding the provided CD123-specific antibodies or antigen-binding fragments, cells expressing the provided antibodies or antigen-binding fragments, as well as associated vectors and detectably labeled antibodies or antigen-binding fragments. In addition, methods of using the provided antibodies are described. For example, the provided antibodies may be used to diagnose, treat, or monitor CD123-expressing cancer progression, regression, or stability; to determine whether or not a patient should be treated for cancer; or to determine whether or not a subject is afflicted with CD123-expressing cancer and thus may be amenable to treatment with a CD123-specific anti-cancer therapeutic, such as the multispecific antibodies against CD123 and CD3 described herein.

First claim

What is claimed:

1. An isolated antibody, or an antigen-binding fragment thereof, that binds immunospecifically to Interleukin-3 Receptor alpha (IL3-Rα) SP2 and IL3-Rα SP1 comprising a heavy chain and a light chain having:
a. a heavy chain CDR1 having the amino acid sequence of SEQ ID NO: 012, a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 013, a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 014, a light chain CDR1 having the amino acid sequence of SEQ ID NO: 015, a light chain CDR2 having the amino acid sequence of SEQ ID NO: 016, and a light chain CDR3 having the amino acid sequence of SEQ ID NO: 017; or
b. a heavy chain CDR1 having the amino acid sequence of SEQ ID NO: 051, a heavy chain CDR2 having the amino acid sequence of SEQ ID NO: 052, a heavy chain CDR3 having the amino acid sequence of SEQ ID NO: 053, a light chain CDR1 having the amino acid sequence of SEQ ID NO: 024, a light chain CDR2 having the amino acid sequence of SEQ ID NO: 025, and a light chain CDR3 having the amino acid sequence of SEQ ID NO: 054.

2. The antibody or antigen-binding fragment of claim 1 , wherein the heavy chain of the antibody comprises the amino acid sequence of SEQ ID NO: 120, and the light chain of the antibody comprises the amino acid sequence of SEQ ID NO:165.

3. The antibody or antigen-binding fragment of claim 1 , wherein the heavy chain of the antibody comprises the amino acid sequence of SEQ ID NO: 136 and light chain of the antibody comprises the amino acid sequence of SEQ ID NO: 168.

4. The antibody or antigen-binding fragment of any one of claims 1 to 3 , wherein said antibody or antigen-binding fragment is an IgG1 or IgG4 isotype.

5. An isolated cell expressing the antibody or bispecific antigen-binding fragment of any one of claims 1 to 3 .

6. A pharmaceutical composition comprising the antibody or antigen-binding fragment of claim 1 and a pharmaceutically acceptable carrier.

7. An isolated bispecific antibody or antigen-binding fragment comprising a first heavy chain (HC1), a second heavy chain (HC2), first light chain (LC1) and a second light chain (LC2), such that the HC1 and the LC1 pair to form a first antigen-binding site that immunospecifically binds IL3-Rα, and the HC2 and the LC2 pair to form a second antigen-binding site that immunospecifically binds CD3, or an IL3-Rα and CD3-bispecific binding fragment thereof, wherein:
i) HC1 and LC1 comprise either of the following pairs:
a. SEQ ID NO: 203 and SEQ ID NO: 204, or
b. SEQ ID NO: 205 and SEQ ID NO: 206, respectively; and

ii) HC2 and LC2 comprise any one of the following pairs:
a. SEQ ID NO: 193 and SEQ ID NO: 194,
b. SEQ ID NO: 195 and SEQ ID NO: 196,
c. SEQ ID NO: 197 and SEQ ID NO: 198,
d. SEQ ID NO: 199 and SEQ ID NO: 200, or
e. SEQ ID NO: 201 and SEQ ID NO: 202, respectively.

8. The bispecific antibody or antigen-binding fragment of claim 7 wherein HC1 comprises SEQ ID NO: 203 and LC1 comprises SEQ ID NO: 204 and HC2 comprises SEQ ID NO: 193 and LC2 comprises SEQ ID NO: 194.

9. An isolated cell expressing the bispecific antibody or antigen-binding fragment of claim 8 .

10. A pharmaceutical composition comprising the bispecific antibody or antigen-binding fragment of claim 8 and a pharmaceutically acceptable carrier.

11. The bispecific antibody or antigen-binding fragment of claim 7 wherein HC1 comprises SEQ ID NO: 205 and LC1 comprises SEQ ID NO: 206 and HC2 comprises SEQ ID NO: 193 and LC2 comprises SEQ ID NO: 194.

12. An isolated cell expressing the bispecific antibody or antigen-binding fragment of claim 11 .

13. A pharmaceutical composition comprising the bispecific antibody or antigen-binding fragment of claim 11 and a pharmaceutically acceptable carrier.

14. An isolated cell expressing the bispecific antibody or antigen-binding fragment of claim 7 .

15. A pharmaceutical composition comprising the bispecific antibody or antigen-binding fragment of claim 7 and a pharmaceutically acceptable carrier.

16. A bispecific antibody or antigen-binding fragment comprising:
a. a paired heavy and light chain that immunospecifically binds CD3, wherein said heavy chain comprises SEQ ID NO: 184 and said light chain comprises SEQ ID NO: 190, and
b. a paired heavy and light chain that immunospecifically binds IL3-Rα, wherein
i. said heavy chain comprises SEQ ID NO: 120 and said light chain comprises SEQ ID NO: 165, or
ii. said heavy chain comprises SEQ ID NO: 136 and said light chain comprises SEQ ID NO: 168.

17. An isolated cell expressing the bispecific antibody or antigen-binding fragment of claim 16 .

18. A pharmaceutical composition comprising the bispecific antibody or antigen-binding fragment of claim 16 and a pharmaceutically acceptable carrier.

19. A kit comprising the antibody or antigen-binding fragment of any one of claims 1 , 7 , 8 , 11 and 16 and packaging for the same.

20. The bispecific antibody or antigen-binding fragment of any one of claims 7 , 8 , 11 and 16 , wherein said bispecific antibody or antigen-binding fragment binds immunospecifically to IL3-Rα CD123 SP2 and IL3-Rα SP1.

Assignees

• Janssen Pharmaceutica Nv

Inventors

• Gaudet Francois
• Nemeth Jennifer F
• Attar Ricardo
• Harman Benjamin C
• Li Yingzhe
• Luo Jinquan
• Mcdaid Ronan
• Pomerantz Steven C
• Tam Susan H
• Teplyakov Alexey
• Wheeler John
• Wu Sheng-Jiun

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/02

  specific for leukemia · CPC title

• C07K16/3061

  Blood cells · CPC title

• C07K16/2809 Primary

  against the T-cell receptor (TcR)-CD3 complex · CPC title

• C07K2299/00

  Coordinates from 3D structures of peptides, e.g. proteins or enzymes · CPC title