# US 2014/0154305 A1 · Use of umirolimus and its derivatives for treating cancer

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

- Number: US 2014/0154305 A1
- Document ID: US20140154305A1
- Status: Published application
- Kind: A1
- Application number: 14/093,876
- Filed: 2013-12-02
- Published: 2014-06-05
- Earliest claimed: 2012-12-03
- Assignees: Manli International Ltd.
- Applicants: Manli Internatioal Ltd.
- Inventors: Ting-Bin Yu; Shih-Horng Su
- Web page: https://patentgrep.com/patent/US20140154305A1

## CPC

- A61K 9/1273: Polymersomes; Liposomes with polymerisable or polymerised bilayer-forming substances
- A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)}
- A61K 9/107: Emulsions {; Emulsion preconcentrates; Micelles (composition of emulsions A61K47/00)}
- A61K 9/1075: {Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers (A61K9/0026 takes precedence)}
- A61K 9/1271: Non-conventional liposomes, e.g. PEGylated liposomes or liposomes coated or grafted with polymers (liposomes as conjugates {A61K47/6911})
- A61K 31/436: the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- 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

## Abstract

Novel encapsulated umirolimus and umirolimus polymer conjugate formulations having enhanced permeability and retention at tumor sites. Also provided are methods for treating cancer by administering the umirolimus formulations.

## Claims

### Claim 1

A pharmaceutical formulation comprising umirolimus encapsulated in a liposome or a polymer micelle, and a pharmaceutically acceptable excipient, carrier, or diluent, wherein the liposome or the polymer micelle has a particle size of 10-200 nm.

### Claim 2 (depends on 1)

The formulation of claim 1, wherein the umirolimus is encapsulated in a liposome that includes a polyethylene glycol (PEG) conjugated phospholipid (PEGylated phospholipid) and a phosphatidylcholine (PC), the umirolimus is present at a molar ratio of 0.1-10% based on the amount of the PEGylated phospholipid and the PC, and the PEG has a length of 10-3000 monomeric units.

### Claim 3 (depends on 2)

The formulation of claim 2, wherein the phospholipid is selected from the group consisting of distearoylphosphatidylcholine (DSPC), distearoylphosphatidylethanolamine (DSPE), distearoylphosphatidylglycerol (DSPG), dimyristoylphosphatidylcholine (DMPC), dioleoylphosphatidylcholine (DOPC), dioleoylphosphatidylethanolamine (DOPE), and dipalmitoylphosphatidylglycerol (DPPG).

### Claim 4 (depends on 3)

The formulation of claim 3, wherein the PC is hydrogenated soy PC (HSPC), egg PC, or soy PC.

### Claim 5 (depends on 4)

The formulation of claim 4, wherein the phospholipid is DSPE, the PC is HSPC, and a molar ratio between the umirolimus, the PEGylated phospholipid, and the PC is 10:60:30.

### Claim 6 (depends on 4)

The formulation of claim 4, further comprising cholesterol, wherein the phospholipid is DSPE, the PC is HSPC, the umirolimus is present at the molar ratio of 0.1-2%, and a molar ratio between the PEGylated phospholipid, the PC, and the cholesterol is 55-65:2-10:20-40.

### Claim 7 (depends on 1)

The formulation of claim 1, wherein the umirolimus is encapsulated in a polymer micelle that includes a di-block co-polymer and the umirolimus is present at 5-40% by weight of the polymer micelle.

### Claim 8 (depends on 7)

The formulation of claim 7, wherein the di-block co-polymer is polyethyleneglycol-polylactide (PEG-PLA) or polyethyleneglycol-polycaprolactone (PEG-PCL).

### Claim 9 (depends on 1)

The formulation of claim 1, wherein the umirolimus is encapsulated in a polymer micelle that includes a tri-arm block co-polymer and the umirolimus is present at 5-40% by weight of the polymer micelle.

### Claim 10 (depends on 9)

The formulation of claim 9, wherein the tri-arm block co-polymer is polyethyleneglycol(polylactide)2 [PEG(PLA)2].

### Claim 11 (depends on 1)

The formulation of claim 1, wherein the umirolimus is encapsulated in a polymer micelle that includes a block co-peptide containing a hydrophilic peptide and a hydrophobic peptide, the hydrophilic peptide is 40-300 amino acids in length, the hydrophobic peptide is 10-40 amino acids in length, and the umirolimus is present at 5-40% by weight of the polymer micelle.

### Claim 12 (depends on 11)

The formulation of claim 11, wherein the hydrophilic peptide is poly-Asp, poly-Gln, poly-Asn, or poly-Glu.

### Claim 13 (depends on 12)

The formulation of claim 12, wherein the hydrophobic peptide is poly-Ala, poly-Leu, poly-Ile, poly-Val, poly-Phe, poly-Tyr, or poly-Trp.

### Claim 14 (depends on 13)

The formulation of claim 13, wherein the hydrophilic peptide is poly-rac-Asp and the hydrophobic peptide is poly-rac-Phe.

### Claim 15 (depends on 1)

The formulation of claim 1, wherein the umirolimus is encapsulated in a polymer micelle that includes a hydrophobic peptide conjugated to a hydrophilic polymer, the hydrophobic peptide is 5-40 amino acids in length, and the hydrophilic polymer has a molecular weight of 2000-100000 Dal.

### Claim 16 (depends on 15)

The formulation of claim 15, wherein the hydrophobic peptide is poly-Tyr, poly-Leu, poly-Phe, poly-Ala, poly-Ile, poly-Val, or poly-Phe.

### Claim 17 (depends on 16)

The formulation of claim 16, wherein the hydrophilic polymer is PEG.

### Claim 18 (depends on 1)

A method for treating cancer, comprising administering to a subject in need thereof an effective amount of the pharmaceutical formulation of claim 1.

### Claim 19 (depends on 18)

The method of claim 18, wherein the cancer is selected from the group is consisting of gastric cancer, pancreatic cancer, myeloma, lung cancer, ovarian cancer, liver cancer, chronic myelogenous leukemia, colorectal cancer, and breast cancer.

### Claim 20 (depends on 8)

A method for treating cancer, comprising administering to a subject in need thereof an effective amount of the pharmaceutical formulation of claim 8.

### Claim 21 (depends on 20)

The method of claim 20, wherein the cancer is selected from the group consisting of gastric cancer, pancreatic cancer, myeloma, lung cancer, ovarian cancer, liver cancer, chronic myelogenous leukemia, colorectal cancer, and breast cancer.