# US 10,105,399 B2 · Methods and compositions for treatment of bone defects with placental cell populations

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- Number: US 10,105,399 B2
- Document ID: US10105399B2
- Status: Granted
- Kind: B2
- Application number: 15/093,185
- Filed: 2016-04-07
- Published: 2017-03-02
- Granted: 2018-10-23
- Earliest claimed: 2006-10-23
- Assignees: Celularity Inc.
- Applicants: Celularity, Inc.
- Inventors: James W. Edinger; Robert J. Hariri; Jia-Lun Wang; Qian Ye; Kristen S. Labazzo; Marian Pereira; Sascha Dawn Abramson
- Web page: https://patentgrep.com/patent/US10105399B2

## CPC

- A61K 35/50: Placenta; Placental stem cells; Amniotic fluid; Amnion; Amniotic stem cells
- 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 47/36: Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K 47/42: Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein (oligopeptides having up to five amino acids {A61K47/183}; polyamino acids A61K47/34)
- 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}
- A61P 19/00: Drugs for skeletal disorders
- A61P 19/08: for bone diseases, e.g. rachitism, Paget's disease
- A61P 35/00: Antineoplastic agents
- C12N 5/0605: {Cells from extra-embryonic tissues, e.g. placenta, amnion, yolk sac, Wharton's jelly}
- C12N 5/0654: {Osteocytes, Osteoblasts, Odontocytes; Bones, Teeth}
- C12N 5/0668: {Mesenchymal stem cells from other natural sources}
- A61K 35/12: Materials from mammals; Compositions comprising non-specified tissues or cells; Compositions comprising non-embryonic stem cells; Genetically modified cells (vaccines or medicinal preparations containing antigens or antibodies A61K39/00)
- C12N 2500/38: Vitamins
- C12N 2500/42: Organic phosphate, e.g. beta glycerophosphate
- C12N 2501/39: Steroid hormones
- C12N 2506/025: from extra-embryonic cells, e.g. trophoblast, placenta
- C12N 2506/03: from non-embryonic pluripotent stem cells
- C12N 2533/18: Calcium salts, e.g. apatite, Mineral components from bones, teeth, shells
- C12N 2533/54: Collagen; Gelatin
- 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)
- 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)
- A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- C12N: MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA (microbiological testing media C12Q1/00)

## Abstract

Provided herein are methods of using adherent placental stem cells and placental stem cell populations, and methods of culturing, proliferating and expanding the same. Also provided herein are methods of differentiating the placental stem cells. Further provided herein are methods of using the placental stem cells to formulate implantable or injectable compositions suitable for administration to a subject. Still further provided herein are provides methods for treating bone defects with stem cells and compositions comprising stem cells.

## Claims

### Claim 1

A method for treating a bone defect in a subject, wherein said bone defect is an osteolytic lesion associated with multiple myeloma, bone cancer, or metastatic cancer characterized by bone metastases, comprising administering to a subject in need thereof an implantable or injectable composition comprising a population of placental stem cells,
wherein said population is predominantly CD34−, CD10+, CD105+, and CD200+;
wherein said stem cells express genes at a detectably higher level than an equivalent number of bone marrow-derived mesenchymal stem cells (BM-MSCs);
and wherein said genes comprise CPA4, TCF21, VTN, B4GALT6, FLJ10781, or NUAK1; thereby treating the bone defect in the subject.

### Claim 2 (depends on 1)

The method of claim 1, wherein said placental stem cells have been passaged at least six times.

### Claim 3 (depends on 1)

The method of claim 1, wherein said population is predominantly CD34−, CD45−, CD10+, CD90+, CD105+, and CD200+.

### Claim 4 (depends on 1)

The method of claim 1, wherein said placental stem cells comprise at least 70% of cells in said composition.

### Claim 5 (depends on 1)

The method of claim 1, wherein said placental stem cells comprise at least 90% of cells in said composition.

### Claim 6 (depends on 1)

The method of claim 1, wherein said osteolytic lesion is an osteolytic lesion associated with multiple myeloma.

### Claim 7 (depends on 1)

The method of claim 1, wherein said osteolytic lesion is an osteolytic lesion associated with bone cancer.

### Claim 8 (depends on 1)

The method of claim 1, wherein said osteolytic lesion is an osteolytic lesion associated with metastatic cancer.

### Claim 9 (depends on 1)

The method of claim 1, wherein said placental stem cells are cells from a placental stem cell bank.

### Claim 10 (depends on 1)

The method of claim 1, wherein said composition is formulated as a suspension or liquid that can be administered intravenously.

### Claim 11 (depends on 1)

The method of claim 1, wherein said composition comprises 5×106 said placental stem cells per milliliter.

### Claim 12 (depends on 1)

The method of claim 1, wherein said composition comprises an implantable substrate or matrix.

### Claim 13 (depends on 1)

The method of claim 1, wherein said composition comprises human serum albumin (HSA) and dextran-40.

### Claim 14 (depends on 1)

The method of claim 1, wherein said placental stem cells are autologous to said subject.

### Claim 15 (depends on 1)

The method of claim 1, wherein said placental stem cells have been cryopreserved.

### Claim 16 (depends on 1)

The method of claim 1, wherein said population is predominantly CD73+.

### Claim 17 (depends on 16)

The method of claim 16, wherein at least 80% of the placental stem cells in said population are CD73+, CD105+, and CD200+.

### Claim 18 (depends on 16)

The method of claim 16, wherein at least 90% of the placental stem cells in said population are CD73+, CD105+, and CD200+.

### Claim 19 (depends on 1)

The method of claim 1, wherein said population has been passaged at least three times.

### Claim 20 (depends on 19)

The method of claim 19, wherein said population has been passaged no more than ten times.