ANTIGEN BINDING CONSTRUCTS TO CD3

• US 20150118252A1
• Filed: 06/13/2013
• Published: 04/30/2015
• Est. Priority Date: 06/15/2012
• Status: Active Grant

• Current Assignee: ImaginAb, Inc.
• Original Assignee: ImaginAb, Inc.
• Inventors: Ho, David T., Olafsen, Tove, Behrenbruch, Christian P., Romero, Jason
• Granted Patent: US 10,301,389 B2
• Time in Patent Office: Days
• US Class Current: 424/173.1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 47/6849 the antibody targeting a receptor, a cell surface antigen or a cell surface determinant
• CPC Class Codes: A61K 51/1027 against receptors, cell-surface antigens or cell-surface determinants
• CPC Class Codes: C07K 16/2809 against the T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/526 CH3 domain
• CPC Class Codes: C07K 2317/53 Hinge
• CPC Class Codes: C07K 2317/565 Complementarity determining region [CDR]
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/626 Diabody or triabody
• CPC Class Codes: C07K 2317/64 comprising a combination of variable region and constant region components
• CPC Class Codes: G01N 2333/7051 T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: G01N 33/56966 Animal cells

Abstract

Antigen binding constructs that bind to CD3, for example antibodies, including antibody fragments (such as minibodies and cys-diabodies) that bind to CD3, are described herein. Methods of use are described herein.

Claims

1. An antigen binding construct that comprises:

a HCDR1 of the HCDR1 in SEQ ID NO;

6 or 86;

a HCDR2 of the HCDR2 in SEQ ID NO;

6 or 86;

a HCDR3 of the HCDR3 in SEQ ID NO;

6 or 86;

a LCDR1 of the LCDR1 in SEQ ID NO;

3;

a LCDR2 of the LCDR2 in SEQ ID NO;

3; and

a LCDR3 of the LCDR3 in SEQ ID NO;

3.

2. The antigen binding construct thereof of claim 1, further comprising at least one of:

a LFR3 of the LFR3 in SEQ ID NO;

3;

or

a HFR3 of the HFR3 in SEQ ID NO;

6 or 86.

3. The antigen binding construct of claim 1, wherein the antigen binding construct binds specifically to CD3.

4. The antigen binding construct of claim 1, further comprising a detectable marker selected from the group consisting of at least one of a radioactive substance, a dye, a contrast agent, a fluorescent compound, a bioluminescent compound, an enzyme, an enhancing agent, or a nanoparticle.

16. A nucleic acid encoding an antibody of claim 1.

19. A method of detecting the presence or absence of a CD3, the method comprising:

applying an antigen binding construct thereof of claim 1 to a sample; and

detecting a binding or an absence of binding of the antigen binding construct thereof to CD3.

22. The method of claim 19, wherein detecting binding or absence of binding of the antigen binding construct thereof to CD3 comprises positron emission tomography.

23. The method of claim 19, the method further comprising applying a secondary antibody or fragment thereof to the sample, wherein the secondary antibody or fragment thereof binds specifically to the antigen binding construct.

24. The method of claim 19, wherein the antibody or fragment thereof is incubated with the sample for no more than 1 hour.

25. A method of targeting a therapeutic agent to a CD3, the method comprising administering to a subject an antigen binding construct of claim 1, wherein the antigen binding construct is conjugated to a therapeutic agent.

26. A method of neutralizing a T cell in a subject in need thereof, the method comprising administering to the subject an antigen binding construct of claim 1.

27. The method of claim 26, wherein the subject has one of rheumatoid arthritis, multiple sclerosis, type 1 diabetes, lupus erythematosus.

5. (canceled)

6. (canceled)

7. (canceled)

8. A humanized cys-diabody that binds to CD3, the humanized cys-diabody comprising a polypeptide that comprises:

a single-chain variable fragment (scFv) comprising a variable heavy (V_H) domain linked to a variable light (V_L); and

a C-terminal Cysteine.

9. The humanized cys-diabody of claim 8, wherein the order of the variable domains, from N terminus to C terminus of the polypeptide is V_L, V_H.

10. The humanized cys-diabody of claim 8, wherein the order of the variable domains, from N terminus to C terminus of the polypeptide is V_H, V_L.

12. The humanized cys-diabody of claim 8, wherein the humanized cys-diabody comprises:

a HCDR1 of the HCDR1 in SEQ ID NO;

6;

a HCDR2 of the HCDR2 in SEQ ID NO;

6;

a HCDR3 of the HCDR3 in SEQ ID NO;

6;

a LCDR1 of the LCDR1 in SEQ ID NO;

3;

a LCDR2 of the LCDR2 in SEQ ID NO;

3; and

a LCDR3 of the LCDR3 in SEQ ID NO;

3.

11. (canceled)

13. A humanized minibody that binds to CD3, the humanized minibody comprising a polypeptide that comprises:

a single-chain variable fragment (scFv) that binds to CD3, the scFv comprising a variable heavy (VH) domain linked a variable light (VL) domain;

a hinge-extension domain comprising a human IgG1 hinge region; and

a human IgG C_H3 sequence.

14. The humanized minibody of claim 13, further comprising a detectable marker selected from the group consisting of a radioactive substance, a dye, a contrast agent, a fluorescent compound, a bioluminescent compound, an enzyme, an enhancing agent, or a nanoparticle.

15. The humanized minibody of claim 13, wherein the humanized minibody comprises:

a HCDR1 of the HCDR1 in SEQ ID NO;

6 or 86;

a HCDR2 of the HCDR2 in SEQ ID NO;

6 or 86;

a HCDR3 of the HCDR3 in SEQ ID NO;

6 or 86;

a LCDR1 of the LCDR1 in SEQ ID NO;

3;

a LCDR2 of the LCDR2 in SEQ ID NO;

3; and

a LCDR3 of the LCDR3 in SEQ ID NO;

3.

17. (canceled)

18. (canceled)

20. (canceled)

21. (canceled)