# US 10,245,321 B2 · Combination therapy for inducing immune response to disease

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- Number: US 10,245,321 B2
- Document ID: US10245321B2
- Status: Granted
- Kind: B2
- Application number: 15/623,890
- Filed: 2017-06-15
- Published: 2017-10-05
- Granted: 2019-04-02
- Earliest claimed: 2012-08-14
- Assignees: IBC Pharmaceuticals, Inc.
- Applicants: IBC Pharmaceuticals, Inc.
- Inventors: Chien-Hsing Chang; David M. Goldenberg; Edmund A. Rossi; Diane Rossi; Hans J. Hansen
- Web page: https://patentgrep.com/patent/US10245321B2

## CPC

- A61K 39/39558: {against tumor tissues, cells, antigens}
- A61K 38/21: Interferons {[IFN]}
- A61K 38/212: {IFN-alpha}
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/68037: {the drug being a camptothecin [CPT] or derivatives}
- A61K 47/6851: {the antibody targeting a determinant of a tumour cell}
- A61K 47/6879: {the immunoglobulin having two or more different antigen-binding sites, e.g. bispecific or multispecific immunoglobulin}
- C07K 16/2803: {against the immunoglobulin superfamily}
- C07K 16/2809: {against the T-cell receptor (TcR)-CD3 complex}
- C07K 16/2833: {against MHC-molecules, e.g. HLA-molecules}
- C07K 16/2863: {against receptors for growth factors, growth regulators}
- C07K 16/2887: {against CD20}
- C07K 16/30: from tumour cells
- C07K 16/3007: {Carcino-embryonic Antigens}
- C07K 16/32: against translation products of oncogenes
- C07K 16/44: against material not provided for elsewhere {, e.g. haptens, metals, DNA, RNA, amino acids}
- A61K 2039/505: {comprising antibodies}
- C07K 2317/31: multispecific
- C07K 2317/54: F(ab')2
- C07K 2317/55: Fab or Fab'
- C07K 2317/622: Single chain antibody (scFv)
- C07K 2317/73: Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
- C07K 2317/76: Antagonist effect on antigen, e.g. neutralization or inhibition of binding
- A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D)
- C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00)

## Abstract

The present invention concerns compositions and methods of use of bispecific antibodies comprising at least one binding site for Trop-2 (EGP-1) and at least one binding site for CD3. The bispecific antibodies are of use for inducing an immune response against a Trop-2 expressing tumor, such as carcinoma of the esophagus, pancreas, lung, stomach, colon, rectum, urinary bladder, breast, ovary, uterus, kidney or prostate. The methods may comprising administering the bispecific antibody alone, or with one or more therapeutic agents such as antibody-drug conjugates, interferons (preferably interferon-α), and/or checkpoint inhibitor antibodies. The bispecific antibody is capable of targeting effector T cells, NK cells, monocytes or neutrophils to induce leukocyte-mediated cytotoxicity of Trop-2+ cancer cells. The cytotoxic immune response is enhanced by co-administration of interferon, checkpoint inhibitor antibody and/or ADC.

## Claims

### Claim 1

A composition comprising bispecific antibody that comprises
a) a first antibody moiety that binds to human CD3, conjugated to an AD (anchoring domain) moiety from an AKAP protein; and
b) a second antibody moiety that binds to human Trop-2, 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 bispecific antibody.

### Claim 2 (depends on 1)

The composition of claim 1, wherein the bispecific antibody comprises at least one antibody fragment selected from the group consisting of a scFv, a Fab and a dAb.

### Claim 3 (depends on 1)

The composition of claim 1, wherein the second antibody moiety comprises a humanized RS7 (anti-Trop-2) antibody or antigen-binding fragment thereof.

### Claim 4 (depends on 1)

The composition of claim 1, wherein the first antibody comprises an Okt3 (anti-CD3) antibody or antigen-binding fragment thereof.

### Claim 5

A bispecific antibody comprising
a) a first antibody moiety that binds to human CD3, conjugated to an AD (anchoring domain) moiety from an AKAP protein; and
b) a second antibody moiety that binds to human Trop-2, 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 bispecific antibody.

### Claim 6 (depends on 5)

The bispecific antibody of claim 5, wherein the second antibody moiety comprises a humanized RS7 (anti-Trop-2) antibody or antigen-binding fragment thereof.

### Claim 7 (depends on 5)

The bispecific antibody of claim 5, wherein the first antibody moiety comprises an Okt3 (anti-CD3) antibody or antigen-binding fragment thereof.

### Claim 8 (depends on 5)

The bispecific antibody of claim 5, wherein the bispecific antibody comprises at least one antibody fragment selected from the group consisting of an scFv, a Fab and a dAb.