T-cell redirecting bispecific antibodies for treatment of disease

Patent metadata

Field	Value
Publication number	US-9315567-B2
Application number	US-201313966450-A
Country	US
Kind code	B2
Filing date	Aug 14, 2013
Priority date	Aug 14, 2012
Publication date	Apr 19, 2016
Grant date	Apr 19, 2016

Abstract

The present invention concerns compositions and methods of use of T-cell redirecting complexes, with at least one binding site for a T-cell antigen and at least one binding site for an antigen on a diseased cell or pathogen. Preferably, the complex is a DNL™ complex. More preferably, the complex comprises a bispecific antibody (bsAb). Most preferably, the bsAb is an anti-CD3×anti-CD19 bispecific antibody, although antibodies against other T-cell antigens and/or disease-associated antigens may be used. The complex is capable of targeting effector T cells to induce T-cell-mediated cytotoxicity of cells associated with a disease, such as cancer, autoimmune disease or infectious disease. The cytotoxic immune response is enhanced by co-administration of interferon-based agents that comprise interferon-α, interferon-β, interferon-λ1, interferon-λ2 or interferon-λ3.

First claim

What is claimed is:

1. A method of inducing a T-cell mediated cytotoxic immune response against a Trop-2 positive human cancer cell comprising:
a) administering a T-cell redirecting complex, comprising at least one binding site for human CD3 and at least one binding site for human Trop-2, to a subject to induce a T-cell mediated immune response against the Trop-2 positive human cancer cell and wherein the T-cell redirecting complex comprises: (i) a first antibody moiety conjugated to an AD (anchoring domain) moiety from an AKAP protein; and (ii) a second antibody moiety conjugated to a DDD (dimerization and docking domain) moiety, wherein the amino acid sequence of said DDD moiety is residues 1-44 of human protein kinase A (PKA) RIIα wherein two copies of the DDD moiety form a dimer that binds to one copy of the AD moiety to form the complex after “human cancer cell”.

2. The method of claim 1 , further comprising administering interferon-α to the subject.

3. The method of claim 2 , wherein the combination of interferon and T-cell redirecting complex is more effective than interferon alone and T-cell redirecting complex alone.

4. The method of claim 2 , wherein the interferon is administered before, simultaneously with, or after the T-cell redirecting complex.

5. The method of claim 2 , wherein the interferon is administered as free interferon, PEGylated interferon, an interferon fusion protein or interferon conjugated to an antibody.

6. The method of claim 1 , wherein the T-cell redirecting complex is a bispecific antibody comprising a first antibody moiety that binds to CD3 and a second antibody moiety that binds to Trop-2.

7. The method of claim 6 , wherein the first and second antibody moieties are selected from the group consisting of an scFv, a Fab and a dAb.

8. The method of claim 6 , wherein the second antibody moiety is hRS7.

9. The method of claim 1 , wherein the T-cell redirecting complex is administered intravenously.

10. The method of claim 1 , wherein the T-cell redirecting complex is administered subcutaneously.

Assignees

• Ibc Pharmaceuticals Inc

Inventors

• Chang Chien-Hsing
• Goldenberg David M
• Rossi Edmund A
• Rossi Diane

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61K47/42

  Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein (oligopeptides having up to five amino acids {A61K47/183}; polyamino acids A61K47/34) · CPC title

• C07K16/2851

  against the lectin superfamily, e.g. CD23, CD72 · CPC title

• C07K16/3007

  Carcino-embryonic Antigens · CPC title

• C07K2317/73

  Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation · CPC title