# US 9,517,247 B2 · Encapsulated liver cell composition

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- Number: US 9,517,247 B2
- Document ID: US9517247B2
- Status: Granted
- Kind: B2
- Application number: 14/027,932
- Filed: 2013-09-16
- Published: 2014-01-16
- Granted: 2016-12-13
- Earliest claimed: 2009-04-27
- Assignees: Cytonet GmbH & Co. KG
- Applicants: Cytonet GmbH & Co. KG
- Inventors: Krasimira Aleksandrova; Peter Pediaditakis; Jo Salisbury; Wolfgang Rüdinger
- Web page: https://patentgrep.com/patent/US9517247B2

## CPC

- A61K 35/407: Liver; Hepatocytes
- A61K 9/48: Preparations in capsules, e.g. of gelatin, of chocolate {(A61K9/0004 takes precedence; bite capsules A61K9/0056)}
- A61K 9/5031: {obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poly(lactide-co-glycolide)}
- A61K 9/5036: {Polysaccharides, e.g. gums, alginate; Cyclodextrin}
- A61K 38/1816: {Erythropoietin [EPO]}
- A61K 47/42: Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein (oligopeptides having up to five amino acids {A61K47/183}; polyamino acids A61K47/34)
- A61P 1/16: for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
- A61P 3/00: Drugs for disorders of the metabolism (of the blood or the extracellular fluid A61P7/00)
- A61P 5/00: Drugs for disorders of the endocrine system
- A61P 31/00: Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P 31/14: for RNA viruses
- A61P 31/20: for DNA viruses
- A61P 35/04: specific for metastasis
- A61P 43/00: Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- Y02A 50/30: Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
- 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
- Y02A: TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE

## Abstract

Microcapsules including a capsule shell encapsulating a suspension of a therapeutically effective amount of liver cells in physical contact with a liver cell stimulating amount of erythropoietin.

## Claims

### Claim 1

A method for introducing liver cells into a subject in need thereof comprising: administering microcapsules comprising a capsule shell encapsulating a suspension of liver cells embedded in a biocompatible matrix with erythropoietin into a subject in need thereof, wherein the concentration of liver cells in the suspension is 104 to 108 liver cells/ml and the concentration of erythropoietin in the suspension is 10−7 to 10−2 U/ml, wherein the administering step occurs by parenteral administration of said microcapsules under the liver capsule, into the liver, into the liver pulp, into the splenic artery, or into the portal vein of the subject, and wherein the erythropoietin maintains ATP/ADP ratios at an increased rate in said liver cells as compared to liver cells identically capsulated except without said erythropoietin.

### Claim 2 (depends on 1)

The method according to claim 1, wherein the liver cells are selected from the group consisting of hepatic precursor cells, hepatic stem cells, hepatoblasts, endothelial cells and hepatocytes.

### Claim 3 (depends on 1)

The method according to claim 1, wherein the liver cells are obtained from adult liver, fetal liver, neonatal liver or liver cell cultures.

### Claim 4 (depends on 1)

The method according to claim 1, wherein the liver cells are human liver cells, non-human primate liver cells, pig liver cells, dog liver cells, cat liver cells, rabbit liver cells, mouse liver cells or rat liver cells.

### Claim 5 (depends on 1)

The method according to claim 1, wherein the microcapsules have an average diameter from 100 to 700 μm.

### Claim 6 (depends on 1)

The method according to claim 1, wherein the liver cells have an average diameter of 8 to 14 μm.

### Claim 7 (depends on 1)

The method according to claim 1, wherein the concentration of erythropoietin in the suspension is 10−7 to 10−3 U/ml.

### Claim 8 (depends on 1)

The method according to claim 1, wherein erythropoietin is wild type erythropoietin or recombinant erythropoietin.

### Claim 9 (depends on 1)

The method according to claim 1, wherein the capsule shell is made from a biocompatible material selected from the group consisting of alginate, alginate-chitosan (AC), alginate-poly-L-lysine (APA), thermogelation-polymer and PEG-hydrogel.

### Claim 10 (depends on 1)

The method according to claim 1, wherein in addition to the liver cells at least one further cell type is present in the microcapsule.

### Claim 11 (depends on 1)

The method according to claim 1, wherein the microcapsules are coated.