# US 10,869,932 B2 · Compositions and methods for modifying the surface of cells and methods of use

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- Number: US 10,869,932 B2
- Document ID: US10869932B2
- Status: Granted
- Kind: B2
- Application number: 16/378,922
- Filed: 2019-04-09
- Published: 2019-08-01
- Granted: 2020-12-22
- Earliest claimed: 2014-01-20
- Assignees: University of Utah Research Foundation
- Applicants: University of Utah Research Foundation
- Inventors: Young-Wook Won; David A. Bull; Amit N. Patel
- Web page: https://patentgrep.com/patent/US10869932B2

## CPC

- A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
- A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- A61K 47/64: Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent (peptidic linkers A61K47/65)
- A61K 47/6425: {the peptide or protein in the drug conjugate being a receptor, e.g. CD4, a cell surface antigen, i.e. not a peptide ligand targeting the antigen, or a cell surface determinant, i.e. a part of the surface of a cell}
- A61K 47/6911: {the form being a liposome}
- A61K 49/0041: {Xanthene dyes, used in vivo, e.g. administered to a mice, e.g. rhodamines, rose Bengal (in vivo G01N)}
- A61K 49/0047: {Green fluorescent protein [GFP]}
- A61K 49/0084: {liposome, i.e. bilayered vesicular structure}
- C12N 5/0006: {Modification of the membrane of cells, e.g. cell decoration}
- C12N 5/0662: {Stem cells}
- C12N 5/0663: {Bone marrow mesenchymal stem cells (BM-MSC)}
- A61K 2035/124: {the cells being hematopoietic, bone marrow derived or blood 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)
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Described herein are compounds, compositions and methods for modification of the surface of a living cell with a therapeutically relevant targeting moiety. Also described herein are methods for treating disease states, such as acute myocardial ischemia or infarction, with said compositions, in a subject.

## Claims

### Claim 1

A method of localizing a cell to a location having associated therewith a target ligand, the method comprising delivering to the location a composition comprising a cell bound to the compound of formula (I):
L-Y—X-T (I)
wherein
L is a phospholipid selected from the group consisting of 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine, 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine and 1,2-distearoyl-sn-glycero-3-phosphocholine;
Y is a poly(ethylene glycol) having a molecular weight between about 2 kDa and about 10 kDa;
X is a linker derived from a reactive functional group; and
T is a targeting moiety adapted to bind to the target ligand.

### Claim 2 (depends on 1)

The method of claim 1, wherein L is 1,2-dimyristoyl-sn-glycero-3-phosphoethanolamine.

### Claim 3 (depends on 1)

The method of claim 1, wherein the poly(ethylene glycol) has a molecular weight of about 5 kDa.

### Claim 4 (depends on 1)

The method of claim 1, wherein the reactive functional group is selected from the group consisting of maleimide, N-hydroxysuccinimide, hydroxyl, amino, carboxyl, thiol, silane, and azide.

### Claim 5 (depends on 1)

The method of claim 1, wherein the target ligand is SDF-1.

### Claim 6 (depends on 1)

The method of claim 1, wherein the target ligand is CRIP2.

### Claim 7 (depends on 1)

The method of claim 1, wherein T is selected from the group consisting of a protein, a peptide, a glycoprotein, a glycopeptide, a steroid, a polysaccharide, a hormone, a cofactor, a nucleic acid, an antibody, a chimeric antigen receptor, and a drug.

### Claim 8 (depends on 1)

The method of claim 1, wherein T is a protein.

### Claim 9 (depends on 8)

The method of claim 8, wherein T is CXCR4.

### Claim 10 (depends on 8)

The method of claim 8, wherein T is CRPPR.

### Claim 11 (depends on 9)

The method of claim 9, wherein the reactive functional group is maleimide.

### Claim 12 (depends on 1)

The method of claim 1, wherein L interacts hydrophobically with the lipid bilayer wall of the cell.

### Claim 13 (depends on 1)

The method of claim 1, wherein the cell is selected from the group consisting of a white blood cell, an endothelial cell, a hepatocyte, a kuppfer cell, a hepatic stellate cell, an allogeneic stem cell, a NK cell, a T cell, an endothelial progenitor cell, an hematopoietic stem cell, a pluripotent stem cell, an induced pluripotent stem cell, a lymphokine activated killer cell, a dendritic cell, and a mesenchymal stem cell.

### Claim 14 (depends on 1)

The method of claim 1, wherein the cell is a mesenchymal stem cell.