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Methods and compositions using immunomodulatory compounds in combination therapy

A technology of immune regulation and composition, which can be applied in the direction of drug combination, anhydride/acid/halide active ingredients, pharmaceutical formulations, etc., can solve problems such as increasing the activity of hematopoietic stem cell proliferation and self-renewal

Inactive Publication Date: 2009-07-29
CELGENE CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0022] Although valproic acid has been shown to increase the proliferation and self-renewal activity of hematopoietic stem cells, it also shows potent antitumor activity in vitro and in vivo (see Kaiser et al., 2006 Haematologica 91 (2): 248-251; Li et al., 2005 , Mol.Cancer Ther.4(12J:1912-1922), but providing safe and effective therapy for hematopoietic stem cell-related diseases and disorders still needs improvement (Bug et al., 2005, Cancer Res.65(7):2537-2541)

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  • Methods and compositions using immunomodulatory compounds in combination therapy
  • Methods and compositions using immunomodulatory compounds in combination therapy
  • Methods and compositions using immunomodulatory compounds in combination therapy

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Embodiment Construction

[0044] Embodiments of the present invention are based on the discovery that immunomodulatory compounds (e.g., 4-(amino)-2-(2,6-dioxo(3-piperidinyl))-isoindoline-1,3-dihydro ketone or 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione) with valproic acid, hydroxyurea or triclosan Combined use of bacteriostatin A has additive and synergistic effects on CD34+ hematopoietic stem cell expansion, fetal hemoglobin expression, malignant cell apoptosis and anti-malignant cell proliferation.

[0045] Accordingly, in one embodiment, the invention provides a composition (eg, a pharmaceutical composition) comprising an effective amount of an immunomodulatory compound and valproic acid, hydroxyurea, or trichostatin A.

[0046] In another embodiment, the present invention also provides a composition (eg, a pharmaceutical composition) comprising an effective amount of 4-(amino)-2-(2,6-dioxo(3-piperidinyl) )-isoindoline-1,3-dione or 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-pi...

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Abstract

Provided herein are compositions comprising one or more immunomodulatory compounds and valproic acid, hydroxyurea or trichostatin A, methods for their use in CD34+ hematopoietic stem cell expansion in vitro and in vivo for bone marrow reconstitution and bone marrow transplantation, increasing fetal hemoglobin expression, and methods for treating, preventing and / or managing cancer, tumors and hematological diseases and disorders.

Description

[0001] This application claims priority to US Provisional Application No. 60 / 808,602, filed May 26, 2006, the entire contents of which are incorporated herein by reference. 1. Technical field [0002] The present invention provides compositions comprising one or more immunomodulatory compounds and valproic acid, hydroxyurea, or trichostatin A for the in vitro and in vivo expansion of CD34+ hematopoietic stem cells for bone marrow reconstitution and bone marrow transplantation. Methods of increasing fetal hemoglobin expression, and methods of treating, preventing and / or managing cancer, tumors and hematological diseases and disorders. 2. Background technology [0003] 2.1 IMiDs TM [0004] Numerous studies have been conducted with the aim of providing compounds that are safe and effective in the treatment of diseases associated with abnormal TNF-α production, see, eg, Marriott, J.B., et al. Expert Opin. Biol. Ther. 1(4): 1-8 (2001); G.W. Muller, et al. Journal of Medicinal ...

Claims

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Application Information

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IPC IPC(8): A61K31/165A61K31/17A61K31/19A61K31/454A61P7/06A61P35/02A61P35/00C12N5/07C12N5/0789C12N5/095
CPCA61K31/19A61K31/17A61K31/165A61K31/454A61P35/00A61P35/02A61P37/02A61P43/00A61P7/06
Inventor 多米尼克·维希里凯乐·陈劳拉·克拉尔劳瑞·穆塔-德帕塞维尔海伦·布拉迪
Owner CELGENE CORP
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