CD123 binding agents and uses thereof

• US 9,850,310 B2
• Filed: 09/03/2015
• Issued: 12/26/2017
• Est. Priority Date: 09/05/2014
• Status: Active Grant

• Current Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Original Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• 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
• Primary Examiner(s): Bunner, Bridget E
• Assistant Examiner(s): HAMUD, FOZIA M
• Application Number:
  US14/844,194
• Publication Number:
  US 20160068605A1
• Time in Patent Office: 845 Days
• Field of Search: None
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/2803 against the immunoglobulin superfamily
• CPC Class Codes: C07K 16/2809 against the T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 16/2866 against receptors for cytokines, lymphokines, interferons
• CPC Class Codes: C07K 16/2896 against molecules with a "CD"-designation, not provided for elsewhere
• CPC Class Codes: C07K 16/3061 Blood cells
• CPC Class Codes: C07K 2299/00 Coordinates from 3D structures of peptides, e.g. proteins or enzymes
• CPC Class Codes: C07K 2317/21 from primates, e.g. man
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/31 multispecific
• CPC Class Codes: C07K 2317/33 Crossreactivity, e.g. for species or epitope, or lack of said crossreactivity
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C07K 2317/94 Stability, e.g. half-life, pH, temperature or enzyme-resistance

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.

Claims

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.

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.

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.

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.

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.