# US 2014/0193436 A1 · Extracellular targeted drug conjugates

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- Number: US 2014/0193436 A1
- Document ID: US20140193436A1
- Status: Published application
- Kind: A1
- Application number: 14/128,429
- Filed: 2012-06-25
- Published: 2014-07-10
- Earliest claimed: 2011-06-24
- Assignees: Centrose, LLC
- Inventors: James R. Prudent
- Web page: https://patentgrep.com/patent/US20140193436A1

## CPC

- A61K 47/6803: {Drugs conjugated to an antibody or immunoglobulin, e.g. cisplatin-antibody conjugates}
- A61K 31/7048: having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin {, digitoxin or digoxin}
- A61K 47/6849: {the antibody targeting a receptor, a cell surface antigen or a cell surface determinant}
- A61P 3/10: for hyperglycaemia, e.g. antidiabetics
- A61P 7/06: Antianaemics
- A61P 9/00: Drugs for disorders of the cardiovascular system
- A61P 9/10: for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- A61P 9/14: Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
- A61P 29/00: Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 31/04: Antibacterial agents
- A61P 31/10: Antimycotics
- A61P 31/12: Antivirals
- A61P 35/00: Antineoplastic agents
- A61P 35/04: specific for metastasis
- A61P 37/00: Drugs for immunological or allergic disorders
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- G01N 33/56966: {Animal cells}
- 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
- 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

Extracellular-targeted drug conjugates (EDC) in which a targeting moiety targeting a protein associated with the Na,K-ATPase is linked to a drug that interacts with the Na,K-ATPase through a linker a stable linker are useful in the treatment of disease and as tools for the evaluation of biological systems.

## Claims

### Claim at position 1

1-26. (canceled)

### Claim 27

An extracellular-targeted drug conjugate (EDC) comprising a targeting moiety linked by a non-cleavable linker to a therapeutic agent, wherein the targeting moiety is selected from the group consisting of an antibody, epitope binding peptide, and aptamer and binds to an extracellular target that is not a Na,K-ATPase, and wherein the therapeutic agent acts on the Na,K-ATPase.

### Claim 28 (depends on 27)

The EDC of claim 27, wherein the targeting moiety is an antibody.

### Claim 29 (depends on 28)

The EDC of claim 28, wherein the extracelluar target is selected from the group consisting of: CD147, LAT1, ASCT2, CD98, PrP, EpCAM, MCT1, Integrin, CD166, CD44 (HCELL), CD71, CD56, CD87, TfR1, Sel-1, IGFR, c-MET, FGFR, PDGFR, GluR2, Serotonin transporter, 5-HT1A Receptor, GABAA receptor, EAAT, TLR4, T-cell receptor, mTNF alpha (transmembrane), PLA2, RANKL, Insulin Receptor, PE-NMT, angiotensin II receptor, ATP-sensitive K channel, PE-NMT, angiotensin receptor, TNF-alpha, InsP3R, RS1, and α-klotho.

### Claim 30 (depends on 29)

The EDC of claim 29, in which the antibody specifically binds CD147.

### Claim 31 (depends on 29)

The EDC of claim 29, in which the antibody specifically binds CD56.

### Claim 32 (depends on 29)

The EDC of claim 29, in which the antibody specifically binds CD44.

### Claim 33 (depends on 29)

The EDC of claim 29, in which the antibody specifically binds CD87.

### Claim 34 (depends on 29)

The EDC of claim 29, in which the antibody specifically binds CD98.

### Claim 35 (depends on 29)

The EDC of claim 29, in which the antibody specifically binds CD230.

### Claim 36 (depends on 27)

The EDC of claim 27, in which the therapeutic agent is selected from the group consisting of a steroid and scillarenin

### Claim 37 (depends on 29)

The EDC of claim 29, wherein, on average, therapeutic agent loading per antibody is about 1 to about 6.

### Claim 38 (depends on 27)

A pharmaceutical composition comprising a pharmaceutically acceptable vehicle, vector, diluent, and/or excipient and a therapeutically effective amount of an EDC of claim 27.

### Claim 39 (depends on 27)

A method for treating a disease, comprising administering to a subject in need of treatment for said disease a therapeutically effective amount of an EDC of claim 27.

### Claim 40 (depends on 39)

The method of claim 39, wherein the disease is selected from the group of viral infections, cancers, metastases, cellular apoptosis disorders, degenerative diseases, tissue ischemia, infectious diseases or a viral, bacterial or fungal nature, immune-mediated diseases, inflammation disorders and pathological neo-angiogenesis.

### Claim 41 (depends on 27)

A method for determining if a protein is associated with a Na,K-ATPase on a cell surface, said method comprising: contacting a cell with an EDC of claim 27; and determining if the EDC has an effect on the cell that is different from an effect of contacting the cell with the targeting moiety or the therapeutic agent, wherein the protein is complexed with Na,K-ATPase where the EDC has an effect on the cell that is different from the effect of the targeting moiety or the therapeutic agent.