# US 11,433,163 B2 · Bone repair compositions

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- Number: US 11,433,163 B2
- Document ID: US11433163B2
- Status: Granted
- Kind: B2
- Application number: 15/303,011
- Filed: 2015-04-09
- Published: 2017-02-02
- Granted: 2022-09-06
- Earliest claimed: 2014-04-10
- Assignees: Bonus Therapeutics Ltd.
- Applicants: Bonus Therapeutics Ltd.
- Inventors: Shai Meretzki
- Web page: https://patentgrep.com/patent/US11433163B2

## CPC

- A61L 27/3891: {as distinct cell layers}
- A61K 31/728: Hyaluronic acid
- A61K 35/28: Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
- A61K 35/44: Vessels; Vascular smooth muscle cells; Endothelial cells; Endothelial progenitor cells
- A61L 27/12: Phosphorus-containing materials, e.g. apatite
- A61L 27/20: Polysaccharides
- A61L 27/3604: {characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel}
- A61L 27/3608: {Bone, e.g. demineralised bone matrix [DBM], bone powder}
- A61L 27/3808: {Endothelial cells}
- A61L 27/3834: {Cells able to produce different cell types, e.g. hematopoietic stem cells, mesenchymal stem cells, marrow stromal cells, embryonic stem cells}
- A61L 27/3847: {Bones}
- A61L 27/46: with phosphorus-containing inorganic fillers
- A61L 27/58: Materials at least partially resorbable by the body
- A61L 2400/06: Flowable or injectable implant compositions
- A61L 2430/02: for reconstruction of bones; weight-bearing implants
- A61L: METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES (preservation of bodies or disinfecting characterised by the agents employed A01N; preserving, e.g. sterilising, food or foodstuffs A23; preparations for medical, dental or toiletry purposes A61K)
- 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)

## Abstract

A composition including, (a) a mineral particle, (b) endothelial cells and mesenchymal cells, and (3) hyaluronic acid, is provided. Moreover, a kit which includes: a syringe, a mineral particle covered with endothelial cells and mesenchymal cells organized in 2 or more cell layers attached to the mineral particle, and hyaluronic acid, is also provided. Last, a method for filling a gap in a bone of a subject in need thereof, including contacting the gap with a composition of: (a) a mineral particle, (b) endothelial cells and mesenchymal cells, and (3) hyaluronic acid is provided.

## Claims

### Claim 1

A composition comprising (a) a mineral particle having a diameter in the range of 50 microns to 2,000 microns and endothelial cells and mesenchymal cells organized in 2 or more cell layers, wherein said 2 or more cell layers are attached to said mineral particle, wherein at least 1×103 endothelial and mesenchymal cells occupy 1 mg of said mineral particle, and (b) an injectable medium comprising hyaluronic acid and liquid solution, wherein said hyaluronic acid is present in an amount of 0.05% to 5% by weight of said injectable medium, said liquid solution comprises a physiological salt buffer, wherein said (a) is dispersed in said (b).

### Claim 2 (depends on 1)

The composition of claim 1, further comprising a biocompatible binder.

### Claim 3 (depends on 2)

The composition of claim 2, wherein said biocompatible binder is albumin.

### Claim 4 (depends on 1)

The composition of claim 1, wherein said endothelial cells and said mesenchymal cells attached to said mineral particle comprise extracellular matrix nanoscale fibers.

### Claim 5 (depends on 1)

The composition of claim 1, comprising adipose tissue derived cells.

### Claim 6 (depends on 5)

The composition of claim 5, comprising 20% to 60% v/v said endothelial cells and mesenchymal cells, said adipose tissue derived cells, or both.

### Claim 7 (depends on 1)

The composition of claim 1, wherein said mineral particle is bone mineral particle.

### Claim 8 (depends on 1)

The composition of claim 1, wherein said mesenchymal cells comprise mesenchymal stem cells.

### Claim 9 (depends on 1)

The composition of claim 1, wherein said mineral particle comprises: a calcium phosphate derivative, a calcium sulfate derivative, calcium hydroxyapatite, a silicate mineral hydroxyapatite, beta-3 calcium phosphate, or any combination thereof.

### Claim 10 (depends on 1)

The composition of claim 1, wherein said particle has a diameter in the range of 100 microns to 1,000 microns.

### Claim 11 (depends on 1)

The composition of claim 1, maintained in-vitro for 2 to 16 days.

### Claim 12 (depends on 1)

A kit comprising: a syringe and the composition of claim 1.

### Claim 13 (depends on 12)

The kit of claim 12, further comprising a mixing means.

### Claim 14 (depends on 1)

A method for filling a gap in a bone of a subject in need thereof, comprising the step of contacting said gap with the composition of claim 1, thereby filling a gap in a bone of a subject in need thereof.

### Claim 15 (depends on 1)

The composition of claim 1, wherein said hyaluronic acid has a molecular weight of 200,000 to 850,000 daltons.
