Methods of increasing platelet and hematopoietic stem cell production

• US 8,067,367 B2
• Filed: 09/18/2003
• Issued: 11/29/2011
• Est. Priority Date: 09/18/2002
• Status: Expired due to Fees

• Current Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Original Assignee: Janssen Pharmaceutica NV (Johnson & Johnson)
• Inventors: MacDonald, Brian R., Kaushansky, Kenneth
• Primary Examiner(s): Bunner; Bridget E
• Application Number:
  US10/667,096
• Publication Number:
  US 20050282277A1
• Time in Patent Office: 2,994 Days
• Field of Search: None
• US Class Current: 514/7.8
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• 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 38/196 Thrombopoietin
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 7/00 Drugs for disorders of the blood or the extracellular fluid
• CPC Class Codes: A61P 7/04 Antihaemorrhagics; Procoagulants; Haemostatic agents; Antifibrinolytic agents
• CPC Class Codes: A61P 7/06 Antianaemics

Abstract

A method of increasing hematopoietic stem cell production is disclosed. The method includes administering a TPO mimetic compound to a subject. Pharmaceutical compositions including a TPO mimetic compound and a pharmaceutically acceptable carrier are also disclosed.

Claims

1. A method of providing hematopoietic stem cells to a subject comprising the steps of:

administering a thrombopoietin (TPO) mimetic compound to a subject to increase stem cells in said subject;

harvesting one or more of the stem cells;

treating said subject with a bone marrow ablative treatment; and

transplanting the harvested stem cells into the subject,

wherein the TPO mimetic compound has the following sequence;

2. The method of claim 1, wherein the subject is a human.

3. The method of claim 1, wherein the one or more stem cells are cryopreserved after harvesting.

4. The method of claim 3, wherein the one or more cryopreserved stem cells are thawed and determined to be viable prior to transplanting the stem cells into the subject.

5. The method of claim 3, wherein the one or more stem cells are transplanted into the subject when the subject is in need of such transplantation.

6. The method of claim 1, wherein the TPO mimetic compound has reduced immunogenicity relative to one or more of rhTPO and rhIL-11.

7. The method of claim 1, wherein the TPO mimetic compound has an improved pharmacokinetic profile relative to one or more of rhTPO and rhIL-11.

8. The method of claim 1, wherein said TPO mimetic compound is covalently attached to a hydrophilic polymer.

9. The method of claim 8, wherein said hydrophilic polymer has an average molecular weight of between about 500 to about 40,000 daltons.

10. The method of claim 9, wherein said hydrophilic polymer has an average molecular weight of between about 5,000 to about 20,000 daltons.

11. The method of claim 10, wherein said hydrophilic polymer has an average molecular weight of about 20,000 daltons.

12. The method of claim 8, wherein said polymer is polyethylene glycol.

13. The method of claim 1, wherein each of the dimeric subunits of said TPO mimetic compound is covalently attached to a hydrophilic polymer.

14. The method of claim 13, wherein said hydrophilic polymer has an average molecular weight of between about 500 to about 40,000 daltons.

15. The method of claim 14, wherein said hydrophilic polymer has an average molecular weight of between about 5,000 to about 20,000 daltons.

16. The method of claim 15, wherein said hydrophilic polymer has an average molecular weight of about 20,000 daltons.

17. The method of claim 13, wherein said polymer is polyethylene glycol.

18. The method of claim 1, wherein said stem cells are within said subject'"'"'s bone marrow.

19. The method of claim 1, wherein said stem cells are within said subject'"'"'s peripheral circulation.

20. The method of claim 1, wherein said subject is treated with chemotherapy.

21. The method of claim 1, wherein said subject is treated with radiation therapy.

22. A method of reducing a time to engraftment following reinfusion of stem cells in a subject comprising the steps of:

administering a thrombopoietin (TPO) mimetic compound to the subject;

increasing stem cells in said subject;

harvesting one or more of the stem cells;

treating said subject with a bone marrow ablative treatment; and

transplanting the one or more harvested stem cells into the subject, thereby reducing the time to engraftment of stem cells,

wherein the TPO mimetic compound has the following sequence;

23. A method of reducing the incidence of delayed primary engraftment comprising the steps of:

administering a thrombopoietin (TPO) mimetic compound to the subject;

increasing stem cells in said subject;

harvesting one or more of the stem cells;

treating said subject with a bone marrow ablative treatment; and

transplanting the one or more harvested stem cells into the subject, thereby reducing the incidence of delayed primary engraftment,

wherein the TPO mimetic compound has the following sequence;

24. A method of reducing the incidence of secondary failure of platelet production comprising the steps of:

administering a thrombopoietin (TPO) mimetic compound to the subject;

increasing stem cells in said subject;

harvesting one or more the stem cells;

treating the subject with a bone marrow ablative treatment; and

transplanting the one or more harvested stem cells into the subject, thereby reducing the incidence of secondary failure of platelet production,

wherein the TPO mimetic compound has the following sequence;

25. A method of reducing the time of platelet and/or neutrophil engraftment following reinfusion of stem cells in a subject comprising the steps of:

administering a thrombopoietin (TPO) mimetic compound to the subject;

increasing stem cells in said subject;

harvesting one or more of the stem cells;

treating the subject with a bone marrow ablative treatment; and

transplanting the one or more harvested stem cells into the subject, thereby reducing the time of platelet and/or neutrophil engraftment following reinfusion of stem cells,

wherein the TPO mimetic compound has the following sequence;