# US 10,441,541 B2 · Methods and compositions for treating osteoarthritis and promoting cartilage formation

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- Number: US 10,441,541 B2
- Document ID: US10441541B2
- Status: Granted
- Kind: B2
- Application number: 15/262,372
- Filed: 2016-09-12
- Published: 2018-02-08
- Granted: 2019-10-15
- Earliest claimed: 2015-09-14
- Assignees: New York University
- Applicants: New York University
- Inventors: Bruce N. Cronstein; Carmen Corciulo
- Web page: https://patentgrep.com/patent/US10441541B2

## CPC

- A61K 9/127: Synthetic bilayered vehicles, e.g. liposomes or liposomes with cholesterol as the only non-phosphatidyl surfactant
- 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 31/517: ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
- A61K 31/519: ortho- or peri-condensed with heterocyclic rings
- A61K 31/52: Purines, e.g. adenine
- A61K 31/522: having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
- A61K 31/53: having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine (melarsoprol A61K31/555 {; with four nitrogen atoms A61K31/495})
- A61K 31/7076: containing purines, e.g. adenosine, adenylic acid
- A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
- A61K 47/02: Inorganic compounds
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- A61K 47/24: containing atoms other than carbon, hydrogen, oxygen, halogen, nitrogen or sulfur, e.g. cyclomethicone or phospholipids
- A61K 47/28: Steroids, e.g. cholesterol, bile acids or glycyrrhetinic acid
- A61K 47/44: Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin (synthetic glycerides, e.g. medium-chain triglycerides, A61K47/14)
- A61P 19/02: for joint disorders, e.g. arthritis, arthrosis
- 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

The invention provides methods and compositions for treating or inhibiting the development of osteoarthritis in a subject having osteoarthritis or at risk for developing osteoarthritis and for stimulating or increasing cartilage production or formation in a subject. The methods feature administering to the subject a therapeutically effective amount of a composition comprising one or more agent from among adenosine, an adenosine receptor agonist, and an agent that upregulates or increases the amount of or the biological activity of adenosine, or an analog or derivative thereof. The adenosine receptor may be an A1, A2A, A2B and A3 adenosine receptor. The agent that upregulates or increases the amount of or the biological activity of adenosine may be dipyridamole or ticagrelor. The composition may be administered via intraarticular injection such as injection into the synovial fluid of a joint. The composition may be effective to reduce or inhibit degeneration or damage to cartilage or to stimulate or increase cartilage production or formation. The composition may be a liposomal composition or contain a liposome.

## Claims

### Claim 1

A method for treating or inhibiting the development of osteoarthritis in a subject having osteoarthritis, comprising administering to the subject via intraarticular injection a therapeutically effective amount of a composition comprising one or more agent selected from the group consisting of adenosine, an adenosine receptor A2A agonist, and ticagrelor, or an analog or derivative thereof, wherein the composition extends the biological activity of the agent.

### Claim 2 (depends on 1)

The method of claim 1 wherein and the adenosine receptor A2A agonist is a selective adenosine receptor A2A agonist.

### Claim 3 (depends on 1)

The method of claim 1 further comprising administering one or more other therapeutically effective compound or agent.

### Claim 4 (depends on 3)

The method of claim 3 wherein the one or more other therapeutically effective compound or agent is selected from the group consisting of an anti-inflammatory compound, a bisphosphonate and a growth factor.

### Claim 5 (depends on 1)

The method of claim 1 wherein the composition is injected into synovial fluid of a joint.

### Claim 6 (depends on 1)

The method of claim 1 wherein the composition is effective to reduce or inhibit degeneration or damage to cartilage.

### Claim 7 (depends on 1)

The method of claim 1 wherein the composition is a liposomal composition or comprises a liposome.

### Claim 8

A method for stimulating or increasing cartilage production or formation in a subject comprising administering to the subject via intraarticular injection a therapeutically effective amount of a composition comprising one or more agent selected from the group consisting of adenosine, an adenosine receptor A2A agonist, and ticagrelor, or an analog or derivative thereof, wherein the composition extends the biological activity of the agent.

### Claim 9 (depends on 8)

The method of claim 8 wherein and the adenosine receptor A2A agonist is a selective adenosine receptor A2A agonist.

### Claim 10 (depends on 8)

The method of claim 8 further comprising administering one or more other therapeutically effective compound or agent.

### Claim 11 (depends on 10)

The method of claim 10 wherein the one or more other therapeutically effective compound or agent is selected from the group consisting of an anti-inflammatory compound, a bisphosphonate and a growth factor.

### Claim 12 (depends on 8)

The method of claim 8 wherein the composition is injected into synovial fluid of a joint.

### Claim 13 (depends on 8)

The method of claim 8 wherein the composition is effective to reduce or inhibit degeneration or damage to cartilage.

### Claim 14 (depends on 8)

The method of claim 8 wherein the composition is a liposomal composition or comprises a liposome.

### Claim 15 (depends on 1)

The method for treating or inhibiting the development of osteoarthritis in a subject having osteoarthritis according to claim 1 wherein the composition contains a liposome or liposomal composition, a hyaluronate suspension, a microsphere, a nanofiber, a protein conjugate, or a nanoparticle.

### Claim 16 (depends on 8)

The method for stimulating or increasing cartilage production or formation in a subject according to claim 8 wherein the composition contains a liposome or liposomal composition, a hyaluronate suspension, a microsphere, a nanofiber, a protein conjugate, or a nanoparticle.

### Claim 17

A method for treating or inhibiting the development of osteoarthritis in a subject having osteoarthritis, comprising administering to the subject via intraarticular injection a therapeutically effective amount of a composition comprising one or more agent selected from the group consisting of adenosine and ticagrelor, or an analog or derivative thereof, wherein the composition extends the biological activity of the agent.

### Claim 18 (depends on 17)

A method for treating or inhibiting the development of osteoarthritis in a subject having osteoarthritis according to claim 17, comprising administering to the subject via intraarticular injection a therapeutically effective amount of a composition comprising adenosine or an analog or derivative thereof, wherein the composition extends the biological activity of the adenosine.

### Claim 19 (depends on 17)

A method for treating or inhibiting the development of osteoarthritis in a subject having osteoarthritis according to claim 17, comprising administering to the subject via intraarticular injection a therapeutically effective amount of a composition comprising ticagrelor or an analog or derivative thereof, wherein the composition extends the biological activity of the ticagrelor.

### Claim 20

A method for stimulating or increasing cartilage production or formation in a subject comprising administering to the subject via intraarticular injection a therapeutically effective amount of a composition comprising one or more agent selected from the group consisting of adenosine and ticagrelor, or an analog or derivative thereof, wherein the composition extends the biological activity of the agent.

### Claim 21 (depends on 20)

A method for stimulating or increasing cartilage production or formation in a subject according to claim 20 comprising administering to the subject via intraarticular injection a therapeutically effective amount of a composition comprising adenosine, or an analog or derivative thereof, wherein the composition extends the biological activity of the adenosine.

### Claim 22 (depends on 20)

A method for stimulating or increasing cartilage production or formation in a subject according to claim 20 comprising administering to the subject via intraarticular injection a therapeutically effective amount of a composition comprising ticagrelor, or an analog or derivative thereof, wherein the composition extends the biological activity of the ticagrelor.

### Claim 23 (depends on 17)

The method of claim 17 further comprising administering one or more other therapeutically effective compound or agent.

### Claim 24 (depends on 23)

The method of claim 23 wherein the one or more other therapeutically effective compound or agent is selected from the group consisting of an anti-inflammatory compound, a bisphosphonate and a growth factor.

### Claim 25 (depends on 17)

The method of claim 17 wherein the composition is injected into synovial fluid of a joint.

### Claim 26 (depends on 17)

The method of claim 17 wherein the composition is effective to reduce or inhibit degeneration or damage to cartilage.

### Claim 27 (depends on 17)

The method of claim 17 wherein the composition contains a liposome or liposomal composition, a hyaluronate suspension, a microsphere, a nanofiber, a protein conjugate, or a nanoparticle.

### Claim 28 (depends on 20)

The method of claim 20 further comprising administering one or more other therapeutically effective compound or agent.

### Claim 29 (depends on 28)

The method of claim 28 wherein the one or more other therapeutically effective compound or agent is selected from the group consisting of an anti-inflammatory compound, a bisphosphonate and a growth factor.

### Claim 30 (depends on 20)

The method of claim 20 wherein the composition is injected into synovial fluid of a joint.

### Claim 31 (depends on 20)

The method of claim 20 wherein the composition is effective to reduce or inhibit degeneration or damage to cartilage.

### Claim 32 (depends on 20)

The method of claim 20 wherein the composition contains a liposome or liposomal composition, a hyaluronate suspension, a microsphere, a nanofiber, a protein conjugate, or a nanoparticle.