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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 engraftment
Implant failure or delayed implant failure is associated with increased mortality, increased healthcare costs, and decreased quality of life for subjects

Method used

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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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PUM

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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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