# US 9,434,610 B2 · HPMA—docetaxel conjugates and uses therefore

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

- Number: US 9,434,610 B2
- Document ID: US9434610B2
- Status: Granted
- Kind: B2
- Application number: 12/575,276
- Filed: 2009-10-07
- Published: 2010-04-22
- Granted: 2016-09-06
- Earliest claimed: 2008-10-07
- Assignees: Rexahn Pharmaceuticals, Inc.; University of Maryland, Baltimore
- Applicants: Young B. Lee; Deog J. Kim; Chang H. Ahn; Anjan Nan; Hamidreza Ghandehari; Abhijit Ray
- Inventors: Young B. Lee; Deog J. Kim; Chang H. Ahn; Anjan Nan; Hamidreza Ghandehari; Abhijit Ray
- Web page: https://patentgrep.com/patent/US9434610B2

## CPC

- A61K 47/58: obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
- A61K 47/551: {one of the codrug's components being a vitamin, e.g. niacinamide, vitamin B3, cobalamin, vitamin B12, folate, vitamin A or retinoic acid}
- 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 47/65: Peptidic linkers, binders or spacers, e.g. peptidic enzyme-labile linkers
- A61P 35/00: Antineoplastic agents
- A61P 35/02: specific for leukemia
- B82Y 5/00: Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
- 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
- B82Y: SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES

## Abstract

Disclosed are water-soluble compositions of gemcitabine and docetaxel formed by conjugating the gemcitabine or docetaxel to a water-soluble polymer such as N-2-hydroxypropyl methacrylamide (HPMA). Also disclosed are methods of using the compositions of the invention for the treatment of cancer.

## Claims

### Claim 1

A compound comprising:
a carrier molecule,
a linker molecule covalently attached to the carrier molecule,
a targeting ligand covalently attached to the carrier molecule, optionally through a second linker, and
an anticancer agent covalently attached to the linker molecule, wherein the anticancer agent is docetaxel, and wherein the carrier molecule comprises poly(N-2-hydroxypropylmethacrylamide) (poly-HPMA).

### Claim 2 (depends on 1)

The compound of claim 1, wherein the linker is selected from the group consisting of an amino acid and an oligopeptide.

### Claim 3 (depends on 2)

The compound of claim 2, wherein the amino acid or the oligopeptide is selected from the group consisting of Gly-Phe-Leu-Gly (SEQ ID NO: 1), Gly-Ile-Phe, Gly-Val-Phe, Gly-Gly-Phe, Gly-Gly-Phe-Phe (SEQ ID NO: 2), Gly-Ile-Tyr, Phe, Gly, Gly-Gly, Ala, Ser, Gly-Phe, Gly-Leu-Phe, Gly-Phe-Phe, Gly-D-Phe-Phe, Ala-Gly-Val-Phe (SEQ ID NO: 3), Gly-Gly-Val-Phe (SEQ ID NO: 4), Gly-Phe-Tyr, Gly-B-Ala-Tyr, Gly-Leu, Gly-Phe-Gly, His-Ser-Ser-Lys-Leu-Gln (SEQ ID NO: 5) and glutaryl-4-hydroxyprolyl-Ala-Ser-cyclohexaglycyl-Gln-Ser-Leu (SEQ ID NO: 6).

### Claim 4 (depends on 1)

The compound of claim 1, wherein the carrier molecule comprises poly-HPMA, and the anticancer agent is linked to the carrier molecule through a GFLG (SEQ ID NO: 1) oligopeptide chain.

### Claim 5 (depends on 1)

The compound claim 1, wherein the carrier molecule has a molecular weight of from about 10,000 daltons to about 250,000 daltons.

### Claim 6 (depends on 5)

The compound of claim 5, wherein the carrier molecule has a molecular weight of from about 100,000 daltons to about 170,000 daltons.

### Claim 7 (depends on 1)

The compound of claim 1, wherein the targeting ligand is selected from the group consisting of RGDfK, EPPT1, and folate.

### Claim 8 (depends on 1)

The compound of claim 1, wherein the targeting ligand is covalently attached to the carrier molecule through the second linker, and the second linker comprises an oligopeptide Gly-Gly (GG).

### Claim 9 (depends on 1)

The compound of claim 1, wherein the compound circulates in the bloodstream.

### Claim 10 (depends on 1)

The compound of claim 1, wherein the targeting ligand is folate.

### Claim 11 (depends on 1)

A method of treating cancer comprising administering a therapeutically effective amount of a compound according to claim 1 to a person in need thereof, wherein the cancer is selected from the group consisting of breast cancer, adenocarcinoma, non-small cell lung cancer, prostate cancer, pancreatic cancer, colon cancer, squamous cell carcinoma of head and neck, T-cell lymphoma, small cell lung cancer, gastric cancer, ovarian cancer, melanoma, and esophageal carcinoma.

### Claim 12

A compound comprising:
a carrier molecule,
an anticancer agent covalently attached to the carrier molecule, optionally through a linker molecule, and
a targeting ligand covalently attached to the carrier molecule, optionally through a second linker molecule, wherein the targeting ligand is selected from the group consisting of RGDfK, EPPT1, and folate, wherein the anticancer agent is docetaxel, and wherein the carrier molecule comprises poly(N-2-hydroxypropylmethacrylamide) (poly-HPMA).

### Claim 13 (depends on 12)

The compound of claim 12, wherein the linker is selected from the group consisting of an amino acid and an oligopeptide.

### Claim 14 (depends on 12)

The compound of claim 12, wherein the targeting ligand is covalently attached to the carrier molecule through the second linker, and the second linker comprises an Gly-Gly (GG) oligopeptide.

### Claim 15 (depends on 12)

The compound of claim 12, wherein the anticancer agent is linked to the carrier molecule through a GFLG (SEQ ID NO: 1) oligopeptide linker, and the second linker is a GG oligopeptide linker.

### Claim 16 (depends on 12)

The compound of claim 12, wherein the carrier molecule has a molecular weight of from about 10,000 daltons to about 250,000 daltons.

### Claim 17 (depends on 12)

The compound of claim 12, wherein the carrier molecule has a molecular weight of from about 100,000 daltons to 170,000 daltons.

### Claim 18 (depends on 12)

The compound of claim 12, wherein the targeting ligand is folate.

### Claim 19 (depends on 12)

A method of treating cancer comprising administering a therapeutically effective amount of a compound according to claim 12 to a person in need thereof, wherein the cancer is selected from the group consisting of breast cancer, adenocarcinoma, non-small cell lung cancer, prostate cancer, pancreatic cancer, colon cancer, squamous cell carcinoma of head and neck, T-cell lymphoma, small cell lung cancer, gastric cancer, ovarian cancer, melanoma, and esophageal carcinoma.