# US 12,178,850 B2 · Injectable bone morphogenetic protein

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- Number: US 12,178,850 B2
- Document ID: US12178850B2
- Status: Granted
- Kind: B2
- Application number: 16/863,630
- Filed: 2020-04-30
- Published: 2020-08-13
- Granted: 2024-12-31
- Earliest claimed: 2018-03-21
- Assignees: Warsaw Orthopedic, Inc.
- Applicants: Warsaw Orthopedic, Inc.
- Inventors: Ping Li
- Web page: https://patentgrep.com/patent/US12178850B2

## CPC

- A61K 38/1875: {Bone morphogenic factor; Osteogenins; Osteogenic factor; Bone-inducing factor}
- 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 9/08: Solutions {(composition of solutions A61K47/00)}
- A61K 9/19: lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)}
- A61K 47/02: Inorganic compounds
- A61K 47/10: Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
- A61K 47/12: Carboxylic acids; Salts or anhydrides thereof
- A61K 47/183: {Amino acids, e.g. glycine, EDTA or aspartame}
- A61K 47/20: containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
- A61K 47/26: Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
- A61K 47/46: Ingredients of undetermined constitution or reaction products thereof, e.g. skin, bone, milk, cotton fibre, eggshell, oxgall or plant extracts
- A61P 19/00: Drugs for skeletal disorders
- A61P 19/08: for bone diseases, e.g. rachitism, Paget's disease
- 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

A method of treating a bone defect is provided. The method comprises administering to the bone defect an injectable solution comprising about 20 μg to about 5000 μg of bone morphogenetic protein-2 (BMP-2) in an aqueous carrier. Kits and methods of making are also provided.

## Claims

### Claim 1

A method of making an injectable bone morphogenetic protein-2 (BMP-2) solution for administering directly into a bone defect, the method comprising providing 28 μg of BMP-2 in lyophilized form; providing an aqueous carrier; and mixing the BMP-2 with the aqueous carrier to form the injectable BMP-2 solution in a volume of 100 μL, wherein the injectable solution has a pH of about 6.0, and wherein the BMP-2 is recombinant human BMP-2 (rhBMP-2).

### Claim 2 (depends on 1)

The method of claim 1, wherein the aqueous carrier comprises a buffering agent comprising tris (hydroxymethyl) aminomethane (Tris), ethylenediaminetetraacetic acid (EDTA), (2-[4-(2-hydroxyethyl)-1l-piperazinylJethanesulfonic acid) (HEPES), 2-(N-morpholino) ethanesulfonic acid (MES), sodium acetate, sodium citrate, sodium phosphate, potassium phosphate, phosphate buffered saline (PBS), sodium chloride, potassium chloride, calcium chloride, glycerol, sucrose, glycine, L-glutamic acid, polysorbate 80, or a combination thereof.

### Claim 3 (depends on 2)

The method of claim 2, wherein (i) the buffering agent comprises sucrose, glycine, L-glutamic acid, sodium chloride, polysorbate 80, or a combination thereof; or (ii) the buffering agent is at a concentration from about 1 mM to 100 mM.

### Claim 4 (depends on 1)

The method of claim 1, wherein the injectable solution further comprises a clotting factor in an amount of about 0.0001% to about 5% of the injectable solution.

### Claim 5 (depends on 1)

The method of claim 1, wherein the aqueous carrier is not osteoinductive or osteoconductive.

### Claim 6 (depends on 1)

The method of claim 1, wherein (i) the injectable solution is for administering percutaneously to a long bone fracture; or (ii) the injectable solution is for administering directly into a fracture site that has a hematoma.

### Claim 7 (depends on 1)

The method of claim 1, wherein the injectable solution is for administering a single dose injection to the bone defect.

### Claim 8 (depends on 1)

The method of claim 1, wherein the injectable solution is for administering multiple intermittent bolus injections at different stages of healing of a bone fracture.

### Claim 9 (depends on 8)

The method of claim 8, wherein the multiple intermittent bolus injections comprise a first intermittent bolus injection administered at a time of injury during a hematoma formation, a second intermittent bolus injection administered between one to about two weeks at an onset of a bone reparative phase, and a third intermittent bolus injection administered at an onset of a bone remodeling phase.

### Claim 10 (depends on 1)

The method of claim 1, wherein the administering is via a pump.