# US 11,027,021 B2 · Combinations of PBD-based antibody drug conjugates with Bcl-2 inhibitors

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- Number: US 11,027,021 B2
- Document ID: US11027021B2
- Status: Granted
- Kind: B2
- Application number: 16/085,460
- Filed: 2017-03-15
- Published: 2019-03-14
- Granted: 2021-06-08
- Earliest claimed: 2016-03-15
- Assignees: Seagen Inc.
- Applicants: Seagen Inc.
- Inventors: William Arthur; Robert Thurman; Travis Biechele; Rory Rohm
- Web page: https://patentgrep.com/patent/US11027021B2

## CPC

- A61K 39/39558: {against tumor tissues, cells, antigens}
- A61K 47/68035: {the drug being a pyrrolobenzodiazepine}
- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61K 47/6867: {the tumour determinant being from a cell of a blood cancer}
- A61P 35/02: specific for leukemia
- C07K 16/2803: {against the immunoglobulin superfamily}
- C07K 16/2875: {against the NGF/TNF superfamily, e.g. CD70, CD95L, CD153, CD154 (against NGF C07K16/22, against TNF C07K16/241)}
- C07K 16/2884: {against CD44}
- C07K 16/32: against translation products of oncogenes
- C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- 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

This invention relates to treatment of cancer using antibody drug conjugates that comprise PBD molecules in combination with Bcl-2 inhibitors.

## Claims

### Claim 1

A method of treating cancer in a subject in need of such treatment, the method comprising administering an antibody drug conjugate (ADC) and a Bcl-2 inhibitor, wherein the ADC comprises an antibody conjugated to a PBD cytotoxic agent, wherein the Bcl-2 inhibitor is selected from the group consisting of ABT-199 and ABT-263, and wherein the antibody is selected from the group consisting of:
a) an anti-CD33 antibody comprising the light chain variable region of SEQ ID NO: 1 and the heavy chain variable region of SEQ ID NO: 2; and
b) and anti-CD19 antibody comprising the light chain variable region of SEQ ID NO: 10 and the heavy chain variable region of SEQ ID NO: 11.

### Claim 2 (depends on 1)

The method of claim 1, wherein the PBD cytotoxic agent has the formula

### Claim 3 (depends on 1)

The method of claim 1, wherein the Bcl-2 inhibitor is ABT-199.

### Claim 4 (depends on 1)

The method of claim 1, wherein the Bcl-2 inhibitor is ABT-263.

### Claim 5 (depends on 2)

The method of claim 2, wherein the antibody is an anti-CD33 antibody comprising the light chain variable region of SEQ ID NO: 1 and the heavy chain variable region of SEQ ID NO: 2.

### Claim 6 (depends on 5)

The method of claim 5, wherein the antibody is h2H12.

### Claim 7 (depends on 6)

The method of claim 6, wherein the Bcl-2 inhibitor is ABT-199.

### Claim 8 (depends on 1)

The method of claim 1, wherein the antibody is an anti-CD33 antibody comprising the light chain variable region of SEQ ID NO: 1 and the heavy chain variable region of SEQ ID NO: 2.

### Claim 9 (depends on 8)

The method of claim 8, wherein the cancer is acute myeloid leukemia or myelodysplastic syndrome.

### Claim 10 (depends on 1)

The method of claim 1, wherein the antibody is an anti-CD19 antibody comprising the light chain variable region of SEQ ID NO: 10 and the heavy chain variable region of SEQ ID NO: 11.

### Claim 11 (depends on 10)

The method of claim 10, wherein the cancer is selected from the group consisting of non-hodgkins lymphoma, diffuse large B-cell lymphoma, acute lymphocytic leukemia, and chronic lymphocytic lymphoma.
