LIGHT CHAIN-BRIDGED BISPECIFIC ANTIBODY

• US 20130165638A1
• Filed: 12/27/2012
• Published: 06/27/2013
• Est. Priority Date: 12/27/2011
• Status: Abandoned Application

• Current Assignee: DCB-USA LLC, Development Center for Biotechnology
• Original Assignee: Development Center for Biotechnology
• Inventors: Hsu, Yu-Shen, Sheu, Show-Shan, Chang, Ming-I, Lo, Cheng-Kai
• Application Number:
  US13/728,839
• Publication Number:
  US 20130165638A1
• Time in Patent Office: Days
• US Class Current: 530/387.3
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 16/00 Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies antibodies with enzymatic activity, e.g. abzymes C12N9/0002
• CPC Class Codes: C07K 16/2809 against the T-cell receptor (TcR)-CD3 complex
• CPC Class Codes: C07K 16/2887 against CD20
• CPC Class Codes: C07K 16/30 from tumour cells
• 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 2317/52 Constant or Fc region; Isotype
• CPC Class Codes: C07K 2317/522 CH1 domain
• CPC Class Codes: C07K 2317/53 Hinge
• CPC Class Codes: C07K 2317/622 Single chain antibody (scFv)
• CPC Class Codes: C07K 2317/64 comprising a combination of variable region and constant region components
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
• 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
• CPC Class Codes: C07K 2319/00 Fusion polypeptide

Abstract

This invention describes a novel format of monomeric bispecific fusion protein with immune activating property for clinical therapies. A bispecific fusion protein includes a first targeting domain with a specificity for a first target of interest; a bridging domain derived from a constant region of a light chain or heavy chain of an immunoglobulin, which may be a human immunoglobulin; and a second targeting domain with a specificity for a second target of interest. The bispecific fusion protein may further include a linker fused to the N-terminus or the C-terminus of the bridging domain. The first targeting domain is fused to the bridging domain and the second targeting domain is fused to the bridging domain or the linker. The linker may include a GGGGS sequence. The first target of interest may be CD20, Her2/neu, or EpCAM, and the second targeting domain is a T-lymphocyte activating domain.

Claims

1. A bispecific fusion protein, comprising:

a first targeting domain with a specificity for a first target of interest;

a bridging domain derived from a constant region of a light chain or heavy chain of an immunoglobulin; and

a second targeting domain with a specificity for a second target of interest.

2. The bispecific fusion protein of claim 1, further comprising a linker fused to the N-terminus or the C-terminus of the bridging domain.

3. The bispecific fusion protein of claim 1, wherein the first targeting domain is fused to the bridging domain or the linker and the second targeting domain is fused to the bridging domain or the linker.

4. The bispecific fusion protein of claims 1, wherein the immunoglobulin is a human immunoglobulin.

5. The bispecific fusion protein of claim 4, wherein the bridging domain is a kappa chain, a Lambda chain, a Lambda-5 surrogate light chain, or a mutant of the kappa chain, the Lambda chain, or the Lambda-5 surrogate light chain that mimics the light chain constant region, or a derivative of the kappa chain, the Lambda chain, or the Lambda-5 surrogate light chain.

6. The bispecific fusion protein of claim 2, wherein the linker comprises a GGGGS sequence.

7. The bispecific fusion protein of claim 1, wherein the second targeting domain is a T-lymphocyte activating domain.

8. The bispecific fusion protein of claim 1, wherein the first target of interest is CD20, Her2/neu, or EpCAM.

9. The bispecific fusion protein of claim 1, wherein the first targeting domain comprises a first ScFv with a specificity for the first target of interest, and the second targeting domain comprises a second ScFv with a specificity for the second target of interest.

10. The bispecific fusion protein of claim 9, wherein each of the first ScFv and the second ScFv comprises a human sequence.

11. The bispecific fusion protein of claim 9, wherein the first ScFv comprises VH-linker-VL or VL-linker-VH having a binding specificity for a first antigen and the second ScFv comprises VH-linker-VL or VL-linker-VH having a binding specificity for a second antigen.

12. The bispecific fusion protein of claim 11, wherein each of the first ScFv and the second ScFv comprises a human sequence.

13. The bispecific fusion protein of a claim 11, wherein the linker comprises a GGGGS sequence.