Innovative and Life-Changing Activin Receptor Therapy for Healing

Introduction

This stabilized activin IIB receptor polypeptide technology offers a groundbreaking approach to enhancing muscle growth, repair, and regeneration, presenting new possibilities for treating muscular disorders and supporting tissue recovery. Designed to remain stable and active in various biological conditions, this polypeptide therapy provides a targeted method to promote muscle strength, mass, and repair, making it invaluable for patients facing muscle-wasting diseases, recovery challenges, or other regenerative health needs. For companies in pharmaceuticals and regenerative medicine, this activin receptor technology represents a unique opportunity to develop treatments that transform patient care and elevate therapeutic outcomes.

The Challenge: Managing Muscle-Wasting and Regenerative Needs

Muscle-wasting diseases, such as muscular dystrophy and sarcopenia, pose a significant health challenge, affecting millions and often leaving patients with limited options for effective treatment. These conditions result in muscle degeneration, weakness, and a diminished quality of life, with few existing therapies targeting the underlying biological factors that govern muscle regeneration and strength. Healthcare providers and patients are in urgent need of solutions that can address these needs and support better recovery and muscle preservation, particularly as demand grows for regenerative and muscle-supportive therapies.

Stabilized Activin IIB for Enhanced Muscle Health

This activin receptor therapy technology leverages stabilized polypeptides to activate critical pathways involved in muscle growth and repair. By enhancing the activin IIB receptor’s stability, this technology ensures consistent therapeutic effects, even in challenging biological environments, leading to more effective treatment outcomes. Patients benefit from targeted muscle recovery, improved strength, and long-term muscle preservation, making this therapy ideal for those with muscular degenerative diseases, post-surgical recovery needs, or regenerative therapy requirements. This unique mechanism addresses the core biological processes in muscle health, offering a tailored approach to healing and recovery.

Key Benefits for Pharmaceuticals and Regenerative Medicine

For pharmaceutical companies, this technology presents a distinct advantage in creating a line of therapeutic products that specifically target muscle growth, repair, and preservation. Healthcare providers in regenerative medicine can integrate this therapy to support patients experiencing muscle degradation, offering a reliable, scientifically advanced solution for long-term muscle health. Its targeted action on activin IIB receptors allows for applications across diverse therapeutic areas, including recovery from injury, degenerative disease support, and enhanced quality of life for aging populations.

Invest in Transformative Muscle Recovery Solutions

Licensing this activin receptor therapy positions your company as a leader in regenerative medicine and muscle health. By offering an effective, stabilized solution for muscle and tissue repair, your business can address the growing demand for advanced therapeutic solutions that improve patient outcomes and quality of life. This technology is a valuable investment for companies committed to developing innovative treatments in muscle health, recovery, and regenerative care.

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Abstract
Claims

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.

What is claimed is:

1. An isolated protein comprising a stabilized activin IIB receptor polypeptide (svActRIIB) wherein said polypeptide is selected from the group consisting of:

(a) a polypeptide consisting of the sequence set forth in SEQ ID NO: 2, except for a single amino acid substitution at position 28, and a single amino acid substitution at position 44, wherein the substitution at position 28 is selected from the group consisting of W and Y, and the substitution at position 44 is T;

(b) a polypeptide consisting of the sequence set forth in amino acids 19 through 134 of SEQ ID NO: 2, except for a single amino acid substitution at position 28, and a single amino acid substitution at position 44, wherein the substitution at position 28 is selected from the group consisting of W and Y, and the substitution at position 44 is T;

(c) a polypeptide consisting of the sequence set forth in amino acids 23 through 134 of SEQ ID NO: 2, except for a single amino acid substitution at position 28, and a single amino acid substitution at position 44, wherein the substitution at position 28 is selected from the group consisting of W and Y, and the substitution at position 44 is T;

(d) a polypeptide consisting of the sequence set forth in amino acids 25 through 134 of SEQ ID NO: 2, except for a single amino acid substitution at position 28, and a single amino acid substitution at position 44, wherein the substitution at position 28 is selected from the group consisting of W and Y, and the substitution at position 44 is T;

(e) a polypeptide of any one of (a) through (d), except for a single amino acid substitution at position 28, and a single amino acid substitution at position 44, wherein the substitution at position 28 is selected from the group consisting of W and Y, and the substitution at position 44 is T, wherein the polypeptide is capable of binding myostatin, activin A, or GDF-11.

2. An isolated protein comprising a stabilized activin IIB receptor polypeptide, wherein said polypeptide is selected from a polypeptide consisting of the sequence set forth in the group consisting of SEQ ID NO: 4, 6, 12 and 14.

3. The protein of claim 2, wherein the polypeptide is connected to at least one heterologous protein.

4. The protein of claim 3, wherein the heterologous polypeptide is an IgG Fc domain.

5. The protein of claim 3, wherein the heterologous polypeptide is connected to the polypeptide by a linker sequence.

6. The protein of claim 5, wherein the linker is selected from the group consisting of: SEQ ID NO: 25, SEQ ID NO: 27, SEQ ID NO: 38, SEQ ID NO: 40, SEQ ID NO: 42, SEQ ID NO: 44, SEQ ID NO: 45, SEQ ID NO: 46, SEQ ID NO: 48, SEQ ID NO: 49 and SEQ ID NO: 50.

7. The protein of claim 2, wherein the amino acid residue at position 64 is alanine.

8. A pharmaceutical composition comprising an effective amount of the protein of claim 1 or 2 in admixture with a pharmaceutically acceptable carrier.

9. A method of inhibiting myostatin activity or activin activity in a subject in need of such treatment comprising administering a therapeutically effective amount of the composition of claim 8 to the subject.

10. A method of increasing lean muscle mass or increasing the ratio of lean muscle mass to fat mass in a subject in need of such treatment comprising administering a therapeutically effective amount of the composition of claim 8 to the subject.

11. A method of treating a muscle-wasting disease or metabolic disorder in a subject in need of such treatment comprising administering a therapeutically effective amount of the composition of claim 8 to the subject.

12. The method of claim 11, wherein the muscle-wasting disease is selected from muscular dystrophy, amyotrophic lateral sclerosis, congestive obstructive pulmonary disease, chronic heart failure, cancer cachexia, AIDS, renal failure, uremia, rheumatoid arthritis, age-related sarcopenia, organ atrophy, carpal tunnel syndrome, androgen deprivation, burn injury, diabetes, and muscle-wasting due to prolonged bed rest, spinal chord injury, stroke, bone fracture, aging or exposure to micro-gravity.

13. The method of claim 11, wherein the metabolic disorder is selected from diabetes, obesity, hyperglycemia, and bone loss.

14. A method of treating a disease in which activin is overexpressed in a subject in need of such treatment comprising administering a therapeutically effective amount of the composition of claim 8 to said subject.

15. The method of claim 14, wherein the disease is cancer.

Title

Stabilized activin IIB receptor polypeptides and uses thereof

Inventor(s)

Jeonghoon Sun, Lei-Ting Tony Tam, Mark Leo Michaels, Thomas C. Boone, Rohini Deshpande, Yue-Sheng LiHq Han

Assignee(s)

Amgen Inc, Atara Biotherapeutics Inc

Patent #

8410043

Patent Date

April 2, 2013