# US 2014/0154702 A1 · Methods For Treating Cancer Using Combination Therapies

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- Number: US 2014/0154702 A1
- Document ID: US20140154702A1
- Status: Published application
- Kind: A1
- Application number: 13/803,392
- Filed: 2013-03-14
- Published: 2014-06-05
- Earliest claimed: 2012-11-30
- Assignees: Endocyte, Inc.
- Applicants: Endocyte, Inc.
- Inventors: Nikki L. PARKER; Christopher P. LEAMON; Iontcho R. VLAHOV
- Web page: https://patentgrep.com/patent/US20140154702A1

## CPC

- A61K 47/551: {one of the codrug's components being a vitamin, e.g. niacinamide, vitamin B3, cobalamin, vitamin B12, folate, vitamin A or retinoic acid}
- A61K 31/454: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. pimozide, domperidone
- G01N 33/575: for cancer
- G01N 33/6893: {related to diseases not provided for elsewhere}
- G01N 2800/7095: Inflammation
- 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)
- G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q)

## Abstract

Described are methods, uses, and kits for utilizing a targeted ligand conjugate in combination with a thiol inhibitor or a system xc− inhibitor for the treatment of cancer or inflammation. Also described are in vitro assays utilizing a targeted ligand conjugate in combination with a thiol inhibitor or a system xc− inhibitor.

## Claims

### Claim 1

An in vitro assay for identifying a ligand conjugate suitable for co-administration to a patient with a thiol inhibitor, the assay comprising:
a) adding the ligand conjugate to the culture medium of a first sample of cultured cells, wherein the ligand conjugate comprises a disulfide linkage;
b) adding the thiol inhibitor to the culture medium of the first sample of cultured cells to provide a test sample;
c) adding the ligand conjugate to the culture medium of a second sample of cultured cells to provide a control sample;
d) measuring the non-ligand-specific activity of the ligand conjugate or the nonspecific uptake of the drug in the test sample;
e) measuring the non-ligand-specific activity of the ligand conjugate or the nonspecific uptake of the drug in the control sample; and
f) determining that the ligand conjugate is suitable for co-administration to the patient with the thiol inhibitor if the non-ligand-specific activity of the ligand conjugate and/or the nonspecific uptake of the drug are decreased in the test sample relative to the control sample,
wherein the ligand conjugate is of the formula BLDX, wherein B is a cell surface receptor targeting ligand, D is an independently selected drug, x is an integer selected from 1, 2, 3, 4 and 5; and L is a releasable polyvalent linker comprising a thiol reactive linkage; or a pharmaceutically acceptable salt thereof,
wherein B is a PSMA binding ligand, and
wherein the PSMA binding ligand is