Methods of increasing platelet and hematopoietic stem cell production

A technology of hematopoietic stem cells and stem cells, which is applied in the direction of pharmaceutical formulas, medical preparations containing active ingredients, peptide/protein components, etc., which can solve problems such as increasing mortality, increasing health care costs, and reducing the quality of life of subjects

Inactive Publication Date: 2006-01-18
ORTHO MCNEIL PHARM INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

Fewer groups (5-10% in autologous transplants, but >20% in allografts) developed secondary thrombocytopenia, sometimes requiring prolonged infusion despite initial

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  • Methods of increasing platelet and hematopoietic stem cell production
  • Methods of increasing platelet and hematopoietic stem cell production
  • Methods of increasing platelet and hematopoietic stem cell production

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Embodiment Construction

[0020] The patent publications and documents cited herein are, in relevant parts, incorporated by reference.

[0021] In one embodiment, the object of the present invention is to increase HSC production by administering to a subject a TPO peptide, a TPO mimetic compound, including but not limited to figure 1 compounds listed in and figure 1 PEGylated forms of the listed compounds. used to figure 1 Methods for PEGylation of compounds shown in are described in US Patent No. 5,869,451.

[0022] In one embodiment, the object of the present invention is to increase the production of HSCs by administering a TPO peptide to a subject, as described in corresponding U.S. Application No. _______ (Attorney Docket No. 038073-5005 PR), filed August 2003 28, the entire contents of which are incorporated herein by reference.

[0023] According to this embodiment, the TPO peptide is a compound having (1) a molecular weight of less than about 5000 Daltons, and (2) 50 Expressed binding affi...

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Abstract

The invention discloses a method for increasing the production of hematopoietic stem cells. The method includes administering a TPO mimetic compound to a subject. The invention also discloses a pharmaceutical composition comprising a TPO mimetic compound and a pharmaceutically acceptable carrier.

Description

[0001] This application claims priority to Serial Nos. 60 / 411,779 and 60 / 411,700, filed September 18,2002. Background of the invention [0002] Thrombopoietin (TPO), originally cloned as a master regulator of platelet production, has a pivotal role in hematopoietic stem cell (HSC) biology. Kaushansky et al., Nature, 369:568-571 (1994). Virtually all primitive HSCs with repopulation activity expressed the receptor for c-Mpl-TPO. Solar et al., Blood, 92:4-10 (1998). TPO alone or in combination with other early acting cytokines such as stem cell factor (SCF), interleukin 3 (IL-3) or Flt-3 ligand enhances the in vitro proliferation of naive HSCs. Ku et al., Blood, 87:4544-4551 (1996); Sitnicka et al., Blood, 87:4998-5005 (1996). In vivo experiments confirmed these conclusions. Kimura et al., Proc. Natl. Acad. Sci. U.S.A., 95: 1195-1200 (1998). The importance of TPO self-renewal and expansion in stem cells is also supported by clinical observations of c-Mpl gene mutations in c...

Claims

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Application Information

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IPC IPC(8): A61K38/18
Inventor K·考尚斯基B·R·麦唐纳
Owner ORTHO MCNEIL PHARM INC
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