IP Library Granted Patent US 8,088,813
Granted Patent B2
US 8,088,813 · App. 12/873,565 · Granted Jan 3, 2012

3′-[(2Z)-[1-(3,4-dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4H-pyrazol-4-ylidene]hydrazino]-2′-hydroxy-[1,1′-biphenyl]-3-carboxylic acid bis-(monoethanolamine)

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Quick Facts
Patent No.
US 8,088,813
App. No.
12/873,565
Granted
Jan 3, 2012
Kind
B2
Abstract

An improved thrombopoietin mimetic, the bis-(monoethanolamine) salt of 3′-[(2Z)-[1-(3,4-dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4H-pyrazol-4-ylidene]hydrazino]-2′-hydroxy-[1,1′-biphenyl]-3-carboxylic acid.

Claims (10)

1. A method for enhancing platelet production obtained from a human donor which comprises administering to such donor an effective amount of the compound 3′-[(2Z)-[1-(3,4-dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4H-pyrazol-4-ylidene]hydrazino]-2′-hydroxy-[1,1′-biphenyl]-3-carboxylic acid bis-(monoethanolamine) prior to platelet pheresis, blood donation or platelet donation.

2. A method for enhancing the number of peripheral blood stem cells obtained from a human donor which comprises administering to such donor an effective amount of the compound 3′-[(2Z)-[1-(3,4-dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4H-pyrazol-4-ylidene]hydrazino]-2′-hydroxy-[1,1′-biphenyl]-3-carboxylic acid bis-(monoethanolamine) prior to leukapheresis.

3. A method of claim 2 further comprising co-administering a therapeutically effective amount of a hematopoietic-cell mobilizing agent selected from the group consisting of: a colony stimulating factor, cytokine, chemokine, interleukin or cytokine receptor agonist, adhesion molecule antagonists or antibodies.

4. The method of claim 3 wherein the mobilizing agent is selected from the group consisting of: G-CSF, GM-CSF, TPO, EPO, Gro-beta, IL-8, cytoxan, VLA-4 inhibitors, SCF, FLT3 ligand or a biologically active derivative of G-CSF, GM-CSF, TPO, EPO, Gro-beta or IL-8.

5. An in vitro or ex vivo method for enhancing stimulation of megakaryocyte maturation and/or platelet production which comprises adding an effective amount of the compound 3′-[(2Z)-[1-(3,4-dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4H-pyrazol-4-ylidene]hydrazino]-2′-hydroxy-[1,1′-biphenyl]-3-carboxylic acid bis-(monoethanolamine) to a culture medium of cells that express the TPO receptor.

6. An in vitro or ex vivo method for enhancing stimulation of megakaryocyte maturation and/or platelet production which comprises adding an effective amount of the compound 3′-[(2Z)-[1-(3,4-dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4H-pyrazol-4-ylidene]hydrazino]-2′-hydroxy-[1,1′-biphenyl]-3-carboxylic acid bis-(monoethanolamine) to a culture medium of stem cells, bone marrow cells, cord-blood cells or peripheral blood cells followed by optional administration the megakaryocytes and/or platelets to a subject following chemotherapy or radiation therapy.

7. An in vitro or ex vivo method for enhancing the survival and/or proliferation of stem cells, bone marrow cells, cord-blood cells, peripheral blood cells or other types of cells expressing the TPO receptor in culture which comprises culturing said cell in a medium containing an effective amount of the compound 3′-[(2Z)-[1-(3,4-dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4H-pyrazol-4-ylidene]hydrazino]-2′-hydroxy-[1,1′-biphenyl]-3-carboxylic acid bis-(monoethanolamine) followed by optional administration the stem cells to a subject following chemotherapy or radiation therapy.

8. A method of claim 7 further comprising co-administration of a therapeutically effective amount of a colony stimulating factor, cytokine, chemokine, interleukin or cytokine receptor agonist.

9. A method of treating of neutropenia in a mammal, including a human, in need thereof which comprises administering to such mammal a therapeutically effective amount of the compound 3′-[(2Z)-[1-(3,4-dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4H-pyrazol-4-ylidene]hydrazino]-2′-hydroxy-[1,1′-biphenyl]-3-carboxylic acid bis-(monoethanolamine).

10. An in vitro or ex vivo method for enhancing stimulation of neutrophil production which comprises adding an effective amount of the compound 3′-[(2Z)-[1-(3,4-dimethylphenyl)-1,5-dihydro-3-methyl-5-oxo-4H-pyrazol-4-ylidene]hydrazino]-2′-hydroxy-[1,1′-biphenyl]-3-carboxylic acid bis-(monoethanolamine) to a culture medium of stem cells, bone marrow cells, cord-blood cells, peripheral blood cells or other types of cells expressing the TPO receptor followed by optional administration the neutrophils to a subject following chemotherapy or radiation therapy.

Assignments (3)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 3, 2015
From: NOVARTIS PHARMA AG
To: NOVARTIS AG
Reel/Frame 035812/0424 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 2, 2015
From: GLAXOSMITHKLINE LLC
To: GLAXO GROUP LIMITED
Reel/Frame 035806/0320 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jun 2, 2015
From: GLAXO GROUP LIMITED
To: NOVARTIS PHARMA AG
Reel/Frame 035806/0563 →