Amgen Inc.

Pamela Hunt

Robert A Bosselman

Olaf B Kinstler

Timothy D Bartley

Babru B Samal

Jakob M Bogenberger

Murray O Robinson

Esther S Choi

Janet L Nichol

Martha M Hokom

Disclosed are novel proteins, referred to as megakaryocyte growth and development factors (MGDFs; also generally referred to as Mpl ligands or thrombopoietin, that have a biological activity of stimulating the growth of megakaryocytes and augmenting the differentiation or maturation of megakaryocytes, ultimately to result in the production of platelets. MGDF derivatives comprising MGDF molecules attached to water soluble polymers, such as polyethylene glycol, are also disclosed, along with methods for their preparation. Also disclosed are processes for obtaining the MGDFs in homogeneous form from natural sources and producing them by recombinant genetic engineering techniques from mammals, including humans.

Mono-pegylated proteins that stimulate megakaryocyte growth and

Disclosed are novel proteins, referred to as megakaryocyte growth and development factors (MGDFs; also generally referred to as Mpl ligands), that have a biological activity of stimulating the growth of megakaryocytes and augmenting the differentiation or maturation of megakaryocytes, ultimately to result in the production of platelets. MGDF derivatives comprising MGDF molecules attached to water soluble polymers, such as polyethylene glycol, are also disclosed, along with methods for their preparation. The MGDF proteins and derivatives are useful in methods for treating mammals to increase platelets and/or megakaryocytes. Also disclosed are processes for obtaining the MGDFs in homogeneous form from natural sources and producing them by recombinant genetic engineering techniques from mammals, including humans.

Method for treating mammals with monopegylated proteins that stimulates

Disclosed is a method for increasing the number of platelets in a mammal, which comprises administering to the mammal a platelet number increasing effective amount of an unbound, preferably a soluble, MPL receptor.

Methods for stimulating platelet production

Transgenic mice and methods of preparing such mice are disclosed. The mice exhibit decreased platelet counts and/or megakaryocyte leukemia.

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Thousand Oaks, CA, United States of America

Pamela Hunt