Compositions for biological systems and methods for preparing and using the same

• US 10,213,463 B2
• Filed: 08/11/2017
• Issued: 02/26/2019
• Est. Priority Date: 06/13/2016
• Status: Expired due to Fees

• Current Assignee: Smart Surgical, Inc.
• Original Assignee: Smart Surgical, Inc.
• Inventors: Jones, Christopher D., Quintanar, Nathan
• Primary Examiner(s): Hobbs, Lisa J
• Application Number:
  US15/675,542
• Publication Number:
  US 20170354684A1
• Time in Patent Office: 564 Days
• CPC Class Codes: A61K 2035/124 the cells being hematopoietic, bone marrow derived or blood cells
• CPC Class Codes: A61K 35/15 Cells of the myeloid line, e.g. granulocytes, basophils, eosinophils, neutrophils, leucocytes, monocytes, macrophages or mast cells; Myeloid precursor cells; Antigen-presenting cells, e.g. dendritic cells presenting a specific antigen A61K39/00; therapeutic combinations of antibodies, or fragments thereof, and blood-derived cells A61K39/00
• CPC Class Codes: A61K 35/17 Lymphocytes; B-cells; T-cells; Natural killer cells; Interferon-activated or cytokine-activated lymphocytes when activated by a specific antigen A61K39/00
• CPC Class Codes: A61K 35/28 Bone marrow; Haematopoietic stem cells; Mesenchymal stem cells of any origin, e.g. adipose-derived stem cells
• CPC Class Codes: A61K 35/51 Umbilical cord; Umbilical cord blood; Umbilical stem cells
• CPC Class Codes: A61K 38/18 Growth factors; Growth regulators
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 47/20 containing sulfur, e.g. dimethyl sulfoxide [DMSO], docusate, sodium lauryl sulfate or aminosulfonic acids
• CPC Class Codes: 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
• CPC Class Codes: 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
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: C12N 2500/34 Sugars
• CPC Class Codes: C12N 2500/90 Serum-free medium, which may still contain naturally-sourced components
• CPC Class Codes: C12N 5/0037 Serum-free medium, which may still contain naturally-sourced components
• CPC Class Codes: C12N 5/0665 Blood-borne mesenchymal stem cells, e.g. from umbilical cord blood

Abstract

A method for performing a therapy in a subject includes providing a composition including a solution having a first volume and including a low pH fluid base including dextrose, and albumin, wherein the concentration of albumin in the solution is between about 10 mg/ml and about 150 mg/ml, and implanting within, near, or adjacent tissue of the subject an effective amount of the composition.

Claims

1. A method for performing a medical therapy in a human subject comprising:

providing a composition comprising;

a low pH fluid base, wherein the low pH fluid base comprises dextrose;

mononuclear cells obtained from human umbilical cord blood; and

albumin, wherein the concentration of albumin is between about 10 mg/ml and about 150 mg/ml; and

implanting within, near, or adjacent to tissue of the subject an effective amount of the composition.

2. The method of claim 1, wherein the step of implanting comprises implanting the composition between adjacent vertebrae to be fused.

3. The method of claim 2, wherein the composition is implanted in combination with a load-bearing device.

4. The method of claim 3, wherein the load-bearing device comprises a fusion cage.

5. The method of claim 3, wherein the load-bearing device comprises at least two pedicle screws and at least one rod.

6. The method of claim 2, wherein the subject is skeletally mature.

7. The method of claim 1, wherein the step of implanting comprises implanting the composition between adjacent portions of bone to be fused.

8. The method of claim 7, wherein the adjacent portions of bone comprise a first portion of bone and a second portion of bone.

9. The method of claim 8, wherein the first portion of bone is from a different bone in the skeletal system of the subject than the second portion of bone.

10. The method of claim 8, wherein the first portion of bone is from the same bone in the skeletal system of the subject as the second portion of bone.

11. The method of claim 7, wherein the composition is implanted in combination with a load-bearing device.

12. The method of claim 11, wherein the load-bearing device is selected from the list consisting of a plate, a rod, a nail, a screw, a hook, and a pin.

13. The method of claim 7, wherein the subject is skeletally mature.

14. The method of claim 1, wherein the step of implanting comprises implanting the composition within, near, or adjacent soft tissue.

15. The method of claim 1, wherein the pH of the composition is between 4.1 and 7.4.

16. The method of claim 1, wherein the composition further comprises a base configured to modify the pH of the composition.

17. The method of claim 1, wherein the low pH fluid base further comprises dimethyl sulfoxide (DMSO).

18. The method of claim 1, wherein the low pH fluid base comprises a cryopreservative.

19. The method of claim 1, wherein the low pH fluid base further comprises dextran.

20. The method of claim 1, wherein the composition further comprises stem cells.

21. The method of claim 1, wherein the composition comprises between about 100,000 and about 75 million live mononuclear cells per ml.

22. The method of claim 1, wherein the composition further comprises one or more bioactive agents.

23. The method of claim 22, wherein the one or more bioactive agents comprise one or more cytokines.

24. The method of claim 22, wherein the one or more bioactive agents comprise one or more growth factors.

25. The method of claim 22, wherein the one or more bioactive agents are selected from the group consisting of macrophage inflammatory protein alpha (MIP-1α

), macrophage inflammatory protein beta (MIP-1β

), interferon gamma-induced protein 10 (IP-10), interleukin 1 Beta (IL-1β

), interleukin 2 (IL-2), interleukin 4 (IL-4), interleukin 5 (IL-5), interleukin 6 (IL-6), interleukin 7 (IL-7), interleukin 8 (IL-8), interleukin 9 (IL-9), interleukin 10 (IL-10), interleukin 12 (IL-12), interleukin 13 (IL-13), interleukin 15 (IL-15), interleukin 17 (IL-17), interleukin 18 (IL-18), interleukin 21 (IL-21), interleukin 22 (IL-22), interleukin 23 (IL-23), interleukin 27 (IL-27), interleukin 31 (IL-31), interferon alpha (INFα

), a lymphokine, granulocyte macrophage colony stimulating factor (GM-CSF), stem cell factor (KL), tumor necrosis factor alpha (TNF-α

), vascular endothelial growth factor (VEGF), nerve growth factor, platelet-derived growth factor (PDGF), fibroblast growth factor 2 (FGF-2), epidermal growth factor (EGF), keratinocyte growth factor, transforming growth factor (TGF), insulin-like growth factor, des(1-3)-IGF-I (brain IGF-I), neurotrophin-3 (NT-3), brain-derived neurotrophic factor (BDNF), eotaxin, CXC ligand 1 (GROa), interleukin 1 receptor antagonist (IL-1RA), interleukin 1 alpha (IL-1α

), leukemia inhibitory factor (LIF), placental growth factor (PLGF), chemokine ligand 5 (RANTES), stem cell factor (SCF), stromal cell derived factor (SDF1α

), and tumor necrosis factor (TNF β

).