# US 11,439,620 B2 · Synergistic effect of anti-trop-2 antibody-drug conjugate in combination therapy for triple-negative breast cancer when used with microtubule inhibitors or PARP inhibitors

> Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt

- Number: US 11,439,620 B2
- Document ID: US11439620B2
- Status: Granted
- Kind: B2
- Application number: 16/204,297
- Filed: 2018-11-29
- Published: 2019-03-21
- Granted: 2022-09-13
- Earliest claimed: 2015-06-25
- Assignees: Immunomedics, Inc.
- Applicants: Immunomedics, Inc.
- Inventors: David M. Goldenberg; Thomas M. Cardillo
- Web page: https://patentgrep.com/patent/US11439620B2

## CPC

- A61K 33/243: Platinum; Compounds thereof
- A61K 31/337: having four-membered rings, e.g. taxol
- A61K 31/35: having six-membered rings with one oxygen as the only ring hetero atom
- A61K 31/357: having two or more oxygen atoms in the same ring, e.g. crown ethers, guanadrel
- A61K 31/4184: condensed with carbocyclic rings, e.g. benzimidazoles
- A61K 31/4375: the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
- A61K 31/454: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
- A61K 31/4745: condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines (yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48)
- A61K 31/502: ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine
- A61K 31/513: having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 31/52: Purines, e.g. adenine
- A61K 31/661: Phosphorus acids or esters thereof not having P—C bonds, e.g. fosfosal, dichlorvos, malathion {or mevinphos}
- A61K 31/675: having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
- A61K 31/7088: Compounds having three or more nucleosides or nucleotides
- A61K 31/713: Double-stranded nucleic acids or oligonucleotides
- A61K 39/39558: {against tumor tissues, cells, antigens}
- 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 47/6853: {Carcino-embryonic antigens}
- C07K 16/2803: {against the immunoglobulin superfamily}
- C07K 16/2833: {against MHC-molecules, e.g. HLA-molecules}
- C07K 16/2887: {against CD20}
- C07K 16/30: from tumour cells
- C07K 16/3007: {Carcino-embryonic Antigens}
- C07K 2317/92: Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
- C07K 2317/94: Stability, e.g. half-life, pH, temperature or enzyme-resistance
- 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 relates to combination therapy with ADCs against a tumor-associated antigen, such as Trop-2, and drugs, such as microtubule inhibitors and/or PARP inhibitors. Where ADCs are used, they preferably incorporate SN-38 or another drug that induces DNA strand breaks. Preferably, the combination of ADC and PARPi or microtubule inhibitor exhibits synergistic effects against the cancer. The combination therapy can reduce solid tumors in size, reduce or eliminate metastases and is effective to treat cancers resistant to standard therapies, such as radiation therapy, chemotherapy or immunotherapy.

## Claims

### Claim 1

A method of treating cancer, consisting of: a) administering to a human subject with a cancer that expresses Trop-2 an antibody-drug conjugate (ADC), wherein the ADC is sacituzumab govitecan; and b) administering to the human subject at least one checkpoint inhibitor selected from the group consisting of tremelimumab, atezolizumab, durvalumab, avelumab, pidilizumab, and BMS936559.

### Claim 2 (depends on 1)

The method of claim 1, wherein the cancer is selected from the group consisting of colon cancer, stomach cancer, esophageal cancer, medullary thyroid cancer, kidney cancer, breast cancer, lung cancer, pancreatic cancer, urinary bladder cancer, ovarian cancer, uterine cancer, cervical cancer, testicular cancer, prostate cancer, liver cancer, skin cancer, bone cancer, brain cancer, rectal cancer, and melanoma.

### Claim 3 (depends on 1)

The method of claim 1, wherein the cancer is selected from the group consisting of triple-negative breast cancer, ovarian cancer, endometrial cancer, urothelial cancer, non-small-cell lung cancer, small-cell lung cancer and metastatic colorectal cancer.

### Claim 4 (depends on 1)

The method of claim 1, wherein the cancer is triple negative breast cancer or urothelial cancer.

### Claim 5 (depends on 1)

The method of claim 1, wherein the checkpoint inhibitor is durvalumab.

### Claim 6 (depends on 1)

The method of claim 1, wherein the patient has not previously been treated with an anti-cancer therapy.

### Claim 7 (depends on 1)

The method of claim 1, wherein the patient has relapsed from or been resistant to at least one anti-cancer therapy.

### Claim 8 (depends on 1)

The method of claim 1, wherein the ADC is administered at a dosage of between 4 mg/kg and 16 mg/kg.

### Claim 9 (depends on 1)

The method of claim 1, wherein the ADC is administered at a dosage of between 8 mg/kg and 10 mg/kg.

### Claim 10 (depends on 8)

The method of claim 8, wherein the dosage is selected from the group consisting of 6 mg/kg, 8 mg/kg, 9 mg/kg, 10 mg/kg, and 12 mg/kg.

### Claim 11 (depends on 1)

The method of claim 1, wherein the cancer is a solid tumor and the treatment results in a reduction in tumor size of at least 15%, at least 20%, at least 30%, or at least 40%.

### Claim 12 (depends on 1)

The method of claim 1, wherein the cancer is metastatic.

### Claim 13 (depends on 12)

The method of claim 12, further comprising reducing in size or eliminating the metastases.