Production and use of red blood cells

• US 10,786,534 B2
• Filed: 07/06/2017
• Issued: 09/29/2020
• Est. Priority Date: 03/11/2013
• Status: Active Grant

• Current Assignee: HTYR Acquisition LLC
• Original Assignee: Taiga Biotechnologies, Inc.
• Inventors: Turner, Brian C., Refaeli, Yosef, Bird, Gregory A.
• Primary Examiner(s): Ton, Thaian N.
• Application Number:
  US15/643,133
• Publication Number:
  US 20180177827A1
• Time in Patent Office: 1,181 Days
• CPC Class Codes: A01K 2207/12 Animals modified by administration of exogenous cells
• CPC Class Codes: A01K 2207/15 Humanized animals
• CPC Class Codes: A01K 2227/105 Murine
• CPC Class Codes: A01K 2267/0331 Animal model for proliferative diseases
• CPC Class Codes: A01K 2267/0381 Animal model for diseases of the hematopoietic system
• CPC Class Codes: A01K 67/0271 Chimeric vertebrates, e.g. comprising exogenous cells
• CPC Class Codes: A61K 35/18 Erythrocytes haemoglobin A61K38/42
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/06 Antianaemics
• CPC Class Codes: C12N 2501/14 Erythropoietin [EPO]
• CPC Class Codes: C12N 2501/2303 Interleukin-3 (IL-3)
• CPC Class Codes: C12N 2501/26 Flt-3 ligand (CD135L, flk-2 ligand)
• CPC Class Codes: C12N 2501/48 Regulators of apoptosis
• CPC Class Codes: C12N 2501/606 c-Myc
• CPC Class Codes: C12N 5/0641 Erythrocytes
• CPC Class Codes: C12N 5/0647 Haematopoietic stem cells; Uncommitted or multipotent progenitors
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

The present disclosure relates to the production of red blood cells from hematopoietic stem cells, by differentiating such cells in the presence of a protein that induces cell survival and proliferation.

Claims

1. A method for increasing the viability of a population of primary mature red blood cells in vitro comprising:

treating the population of primary mature red blood cells in a culture media comprising a TAT-Bcl-2 fusion protein, wherein said treating results in increased viability in the population of primary mature red blood cells when compared to an untreated control.

2. The method of claim 1, wherein the population of primary mature red blood cells is produced by in vitro differentiation of hematopoietic stem cells.

3. The method of claim 1, wherein the population of primary mature red blood cells is obtained from peripheral blood of a subject.

4. The method of claim 1, wherein the population of primary mature red blood cells is an RBC concentrate.

5. The method of claim 1, wherein the population of primary mature red blood cells is a clinical RBC product.

6. The method of claim 1, wherein the culture media is a red blood cell storage media.

7. The method of claim 1, wherein the TAT-Bcl-2 fusion protein is provided in the culture media as a single bolus or provided in the culture media at intervals.

8. The method of claim 1, wherein the TAT-Bcl-2 fusion protein is provided in the culture media every 24 hours, every 48 hours, every 72 hours, or every 96 hours.

9. The method of claim 1, wherein the TAT-Bcl-2 fusion protein is provided in the culture media at a concentration of 0.5 μ

g/ml to 100 μ

g/ml.

10. The method of claim 1, wherein the TAT-Bcl-2 fusion protein is provided in the culture media at a concentration of 1 μ

g/ml, 5 μ

g/ml, 10 μ

g/ml, 25 μ

g/ml, or 50 μ

g/ml.