Construction and application of bispecific antibody HER2xCD3

• US 9,611,325 B2
• Filed: 07/20/2015
• Issued: 04/04/2017
• Est. Priority Date: 07/21/2014
• Status: Active Grant

• Current Assignee: Wuhan YZY Biopharma Co., Ltd.
• Original Assignee: Wuhan YZY Biopharma Co., Ltd.
• Inventors: Zhou, Pengfei, Zhang, Jing, Hu, Lingli, Wang, Rui, Zhou, Xiang, Fan, Kesu
• Primary Examiner(s): ROARK, JESSICA HOPE
• Application Number:
  US14/803,278
• Publication Number:
  US 20160145339A1
• Time in Patent Office: 624 Days
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: C07K 16/2809 against the T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 16/2878 against the NGF-receptor/TNF-receptor superfamily, e.g. CD27, CD30, CD40, CD95
• CPC Class Codes: C07K 16/2887 against CD20
• CPC Class Codes: C07K 16/2896 against molecules with a "CD"-designation, not provided for elsewhere
• CPC Class Codes: C07K 16/32 against translation products of oncogenes
• CPC Class Codes: C07K 16/468 Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies
• CPC Class Codes: C07K 2317/31 multispecific
• CPC Class Codes: C07K 2317/51 Complete heavy chain or Fd fragment, i.e. VH + CH1
• CPC Class Codes: C07K 2317/515 Complete light chain, i.e. VL + CL
• CPC Class Codes: C07K 2317/60 characterized by non-natural combinations of immunoglobulin fragments
• 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

The present invention provides a bispecific antibody. The bispecific antibody provided by the present invention comprises a single-chain unit and a monovalent unit, wherein the single-chain unit has a specific binding capability against a surface antigen CD3 of an immune cell; the monovalent unit has a specific binding capability against a surface antigen HER2 of a tumor cell; the single-chain unit comprises a single-chain variable fragment ScFv fused with an Fc fragment; and the monovalent unit comprises a light chain and heavy chain pair. The present invention also provides a preparation method of the bispecific antibody and pharmaceutical use of these antibodies.

Claims

1. A bispecific antibody comprising:

(a) a monovalent unit comprising a light chain-heavy chain pair having specificity to a tumor antigen selected from the group consisting of HER2, CD20, CD30 and CD133; and

(b) a single-chain unit comprising the amino acid sequence of SEQ ID NO;

5, wherein the single-chain unit has specificity to CD3.

2. The bispecific antibody of claim 1, wherein the light chain binds to the heavy chain through a disulfide bond;

and the heavy chain binds to the single-chain unit through one or more disulfide bonds.

3. The bispecific antibody of claim 1, wherein the heavy chain comprises the amino acid sequence of SEQ ID NO. 1, and the light chain comprises the amino acid sequence of SEQ ID NO. 3 and the monovalent unit has specificity to HER2.

4. A method of treating a patient having a tumor cell that expresses HER2, comprising administering to the patient an effective amount of the bispecific antibody of claim 3.