# US 8,784,849 B2 · Hydroxyapatite-targeting poly(ethylene glycol) and related polymers

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- Number: US 8,784,849 B2
- Document ID: US8784849B2
- Status: Granted
- Kind: B2
- Application number: 13/764,399
- Filed: 2013-02-11
- Published: 2013-06-13
- Granted: 2014-07-22
- Earliest claimed: 2000-11-14
- Assignees: Nektar Therapeutics
- Applicants: Nektar Therapeutics
- Inventors: Michael J. Roberts; Antoni Kozlowski
- Web page: https://patentgrep.com/patent/US8784849B2

## CPC

- A61K 47/18: Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K 31/715: Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K 47/24: containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
- A61K 47/60: the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
- C08G 65/329: with organic compounds
- C08G 65/3353: {containing oxygen in addition to phosphorus}
- C08L 2203/02: for biomedical use
- 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)
- C08G: MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08L: COMPOSITIONS OF MACROMOLECULAR COMPOUNDS (compositions based on polymerisable monomers C08F, C08G; artificial filaments or fibres D01F; textile treating compositions D06)

## Abstract

Isolatable, hydroxyapatite-targeting polymeric structures, and biologically active conjugates thereof, are provided. The polymeric structure includes a linear or branched water-soluble and non-peptidic polymer backbone, such as a PEG backbone, having at least two termini, a first terminus being covalently bonded to a hydroxyapatite-targeting moiety, such as a bisphosphonate, and a second terminus covalently bonded to a chemically reactive group, wherein said chemically reactive group is protected or unprotected. Methods of preparing and using hydroxyapatite-targeting polymeric structures, and biologically active conjugates thereof, are also provided.

## Claims

### Claim 1

A method of administering a polymeric structure, said method comprising:
a) providing a water-soluble polymer comprising at one terminus, a hydroxyapatite-targeting moiety;
b) binding the water-soluble polymer from step (a) with a hydroxyapatite- or calcium phosphate-coated prosthetic or drug delivery device or surface under conditions effective to promote said binding to form the polymeric structure; and
c) administering the polymeric structure to a mammal.

### Claim 2 (depends on 1)

The method of claim 1, wherein the water-soluble polymer is selected from the group consisting of poly(alkylene glycol), poly(oxyethylated polyol), poly(olefinic alcohol), poly(vinylpyrolidone), poly(hydroxypropylmethacrylamide), poly(α-hydroxy acid), poly(vinyl alcohol), polyphosphazene, polyoxazoline, and copolymers and terpolymers thereof.

### Claim 3 (depends on 2)

The method of claim 2, wherein the water-soluble polymer is a poly(alkylene glycol).

### Claim 4 (depends on 3)

The method of claim 3, wherein the water-soluble polymer is a poly(ethylene glycol).

### Claim 5 (depends on 4)

The method of claim 4, wherein the poly(ethylene glycol) is linear.

### Claim 6 (depends on 4)

The method of claim 4, wherein the poly(ethylene glycol) is branched.

### Claim 7 (depends on 4)

The method of claim 4, wherein the water-soluble polymer has a molecular weight ranging from about 100 daltons to about 100,000 daltons.

### Claim 8 (depends on 7)

The method of claim 7, wherein the water-soluble polymer has a molecular weight ranging from about 6,000 daltons to about 80,000 daltons.

### Claim 9 (depends on 1)

The method of claim 1, wherein the hydroxyapatite-targeting moiety is selected from the group consisting of tetracycline, calcein, bisphosphonates, polyaspartic acid, polyglutamic acid, and aminophosphosugars.

### Claim 10 (depends on 1)

The method of claim 1, wherein the hydroxyapatite-targeting moiety is a bisphosphonate.

### Claim 11 (depends on 10)

The method of claim 10, wherein the bisphosphonate is selected from the group consisting of etidronate, alendronate, and 3-amino-1-hydroxypropane-1-1-diphosphonic acid (AHPDP).

### Claim 12 (depends on 10)

The method of claim 10, wherein the water-soluble polymer is a poly(ethylene glycol).

### Claim 13 (depends on 1)

The method of claim 1, wherein said binding comprises incubating the hydroxyapatite or calcium phosphate coated prosthetic or drug delivery device or surface with a solution comprising the hydroxyapatite-targeting water-soluble polymer under conditions effective to promote binding thereto.