Antigen binding constructs to CD3

• US 10,882,909 B2
• Filed: 04/25/2019
• Issued: 01/05/2021
• Est. Priority Date: 06/15/2012
• Status: Active Grant

• Current Assignee: ImaginAb, Inc.
• Original Assignee: ImaginAb, Inc.
• Inventors: Ho, David T., Olafsen, Tove, Romero, Jason, Behrenbruch, Christian P.
• Primary Examiner(s): Skelding, Zachary S
• Application Number:
  US16/394,957
• Publication Number:
  US 20190309068A1
• Time in Patent Office: 621 Days
• Field of Search: None
• 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. A nucleic acid comprising a nucleotide sequence encoding a polypeptide comprising:

a variable light (VL) domain comprising an amino acid sequence of SEQ ID NO;

3;

a variable heavy (VH) domain comprising an amino acid sequence of SEQ ID NO;

6 or 86;

a linker comprising an amino acid sequence of SEQ ID NO;

98, wherein the linker links the VL and the VH domains;

a C_H3; and

a hinge region linking the VH domain to the C_H3.

2. A nucleic acid comprising a nucleotide sequence encoding a humanized antigen binding construct, wherein the humanized antigen binding construct 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,

wherein the humanized antigen binding construct binds specifically to CD3,

wherein the humanized antigen binding construct comprises a humanized minibody or a humanized cys-diabody, and

wherein the human antigen binding construct further comprises 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 nucleic acid of claim 2, wherein the antigen binding construct comprises the humanized minibody.

4. The nucleic acid of claim 2, wherein the antigen binding construct comprises a heavy chain variable domain that is a heavy chain variable domain in SEQ ID NO:

86, and a light chain variable domain that is a light chain variable domain in SEQ ID NO;

3.

5. The nucleic acid of claim 4, wherein the nucleic acid comprises a sequence at least about 80% identical to SEQ ID NO:

85.

6. The nucleic acid of claim 2, wherein the antigen binding construct comprises a heavy chain variable domain that is a heavy chain variable domain in SEQ ID NO:

6, and a light chain variable domain that is a light chain variable domain in SEQ ID NO;

3.

7. The nucleic acid of claim 6, wherein the nucleic acid comprises a sequence at least about 80% identical to SEQ ID NO:

83.

8. A vector comprising a nucleic acid of claim 2.

9. A nucleic acid comprising a nucleotide sequence encoding a humanized OKT3 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 to a variable light (VL) domain,

wherein the scFv comprises a LFR3 of the LFR3 in SEQ ID NO;

3, or a HFR3 of the HFR3 in SEQ ID NO;

6 or 86, or both;

a hinge;

a human IgG C_H3 sequence;

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.

10. A nucleic acid comprising a nucleotide sequence encoding a humanized minibody that binds to CD3, wherein the humanized minibody comprises:

a polypeptide that comprises;

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

wherein the scFv comprises a LFR3 of the LFR3 in SEQ ID NO;

3, or a HFR3 of the HFR3 in SEQ ID NO;

6 or 86, or both;

a hinge;

a human IgG C_H3 sequence;

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.