Amgen Inc.

Biogen Ma Inc.

Alivegen Inc.

Atara Biotherapeutics, Inc.

Hq Han

Xiaolan Zhou

Thomas Charles Boone

Hosung Min

Keith Soo-Nyung Kwak

Jeonghoon Sun

Yue-Sheng Li

Mark Leo Michaels

Lei-Ting Tony Tam

Rohini Deshpande

The present disclosure describes novel hybrid soluble ActRIIB-ECD polypeptides which fully retain binding affinity for myostatin and activin A but demonstrate significantly reduced binding to BMPs, especially BMP-9. The novel compositions described herein can be used to prepare novel hybrid ActRIIB ligand trap proteins, which can be used for modulating the growth of muscle, bone, cartilage, fat, fibroblast, blood and neuronal tissue to counteract muscle wasting, bone loss, anemia, inflammation and fibrosis in a therapeutically meaningful manner. Because these novel next-generation myostatin/activin inhibitors are safer and more effective molecules than the currently available myostatin inhibitors, they are useful in a wide variety of clinical indications.

Methods for treating muscle wasting and bone disease using novel hybrid ActRIIB ligand trap proteins

Hybrid ActRIIB ligand trap proteins for treating muscle wasting diseases

The present invention provides novel activin IIB5 receptor polypeptides capable of binding and inhibiting the activities of activin A, myostatin, or GDF-11. The present invention also provides polynucleotides, vectors and host cells capable of producing the receptor polypeptides. Compositions and methods for treating muscle-wasting, metabolic and other disorders are also provided.

Isolated protein comprising an activin type IIB5 receptor polypeptide and uses thereof

The present invention provides stabilized activin IIB receptor polypeptides and proteins capable of binding and inhibiting the activities of activin A, myostatin, or GDF-11. The present invention also provides polynucleotides, vectors and host cells capable of producing the stabilized polypeptides and proteins. Compositions and methods for treating muscle-wasting diseases and metabolic disorders are also provided.

Stabilized activin IIB receptor polypeptides and uses thereof

The present invention provides binding agents comprising peptides capable of binding myostatin and inhibiting its activity. In one embodiment the binding agent comprises at least one myostatin-binding peptide attached directly or indirectly to at least one vehicle such as a polymer or an Fc domain. The binding agents of the present invention produced increased lean muscle mass when administered to animals and decreased fat to muscle ratios. Therapeutic compositions containing the binding agents of the present invention are useful for treating muscle-wasting disorders and metabolic disorders including diabetes and obesity.

Method of increasing muscle mass by administering a myostatin binding agent

Isolated nucleic acid molecule comprising the amino acid sequence of SEQ ID NO:1

Binding agents which inhibit myostatin

Polynucleotides encoding myostatin binding agents

Myostatin binding agents

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Thousand Oaks, CA, United States of America

Hq Han