Abstract: In certain aspects, the present invention provides compositions and methods for modulating (promoting or inhibiting) growth of a tissue, such as bone, cartilage, muscle, fat, and/or neuronal tissue. The present invention also provides methods of screening compounds that modulate activity of an ActRIIB protein and/or an ActRIIB ligand. The compositions and methods provided herein are useful in treating diseases associated with abnormal activity of an ActRIIB protein and/or an ActRIIB ligand.
Type:
Grant
Filed:
July 1, 2016
Date of Patent:
April 16, 2019
Assignee:
ACCELERON PHARMA INC.
Inventors:
John Knopf, Jasbir Seehra, Ravindra Kumar
Abstract: In certain aspects, the disclosure provides soluble heteromeric polypeptide complexes comprising an extracellular domain of a type I serine/threonine kinase receptor of the TGF-beta family and an extracellular domain of a type II serine/threonine kinase receptor of the TGF-beta family. In some embodiments, the disclosure provides soluble polypeptide complexes comprising an extracellular domain of a type II receptor selected from: ActRIIA, ActRIIB, TGFBRII, BMPRII, and MISRII. In some embodiments, the disclosure provides soluble polypeptide complexes comprising an extracellular domain of a type I receptor selected from: ALK1, ALK2, ALK3, ALK4, ALK5, ALK6, and ALK7. Optionally the soluble complex is a heterodimer. In certain aspects, such soluble polypeptide complexes may be used to regulate (promote or inhibit) growth of tissues or cells including, for example, muscle, bone, cartilage, fat, neural tissue, tumors, cancerous cells, and/or cells of hematopoietic lineages, including red blood cells.
Type:
Grant
Filed:
April 6, 2016
Date of Patent:
March 12, 2019
Assignee:
ACCELERON PHARMA INC.
Inventors:
Ravindra Kumar, Asya Grinberg, Dianne Sako, Robert Scott Pearsall, Roselyne Castonguay
Abstract: In certain aspects, the disclosure provides soluble heteromeric polypeptide complexes comprising an extracellular domain of an ALK7 receptor and an extracellular domain of ActRIIB. In certain aspects, these ALK7:ActRIIB heteromultimers are can be used to improve metabolic parameters in a patient in need thereof. In certain aspects, these ALK7:ActRIIB heteromultimers are can be used to treat or prevent one or more kidney-associated disease or condition in a patient in need thereof.
Type:
Grant
Filed:
April 6, 2016
Date of Patent:
March 12, 2019
Assignee:
ACCELERON PHARMA INC.
Inventors:
Ravindra Kumar, Asya Grinberg, Dianne Sako, Robert Scott Pearsall, Roselyne Castonguay, Gang Li, Yossi Dagon, John Knopf
Abstract: In certain aspects, the present disclosure relates to the insight that a polypeptide comprising a ligand-binding portion of the extracellular domain of activin-like kinase I (ALK1) polypeptide may be used to inhibit angiogenesis in vivo, particularly in mammals suffering angiogenesis-related disorders. Additionally, the disclosure demonstrates that inhibitors of ALK1 may be used to increase pericyte coverage in vascularized tissues, including tumors and the retina. The disclosure also identifies ligands for ALK1 and demonstrates that such ligands have pro-angiogenic activity, and describes antibodies that inhibit receptor-ligand interaction.
Type:
Application
Filed:
July 30, 2018
Publication date:
February 14, 2019
Applicants:
Acceleron Pharma Inc., Ludwig Institute for Cancer Research Ltd.
Inventors:
Asya Grinberg, John Knopf, Robert S. Pearsall, Ravindra Kumar, Jasbir Seehra, Kristian Pietras
Abstract: In certain aspects, the disclosure provides soluble heteromeric polypeptide complexes comprising an extracellular domain of an ALK4 receptor and an extracellular domain of ActRIIB. In certain aspects, such soluble ALK4:ActRIIB complexes may be used to regulate (promote or inhibit) growth of tissues or cells including, for example, muscle, bone, cartilage, fat, neural tissue, tumors, and/or cancerous cells. In certain aspects, such ALK4:ActRIIB complexes are can be used to improve muscle formation, bone formation, metabolic parameters, and disorders associated with these tissues, cellular networks, kidney, and endocrine systems.
Type:
Grant
Filed:
April 6, 2016
Date of Patent:
February 5, 2019
Assignee:
ACCELERON PHARMA INC.
Inventors:
Ravindra Kumar, Asya Grinberg, Dianne Sako, Robert Scott Pearsall, Roselyne Castonguay
Abstract: In certain aspects, the present disclosure provides compositions and methods for increasing red blood cell and/or hemoglobin levels in vertebrates, including rodents and primates, and particularly in humans. In some embodiments, the compositions of the disclosure may be used to treat or prevent sideroblastic anemias and myelodysplastic syndromes or one or more complications associated sideroblastic anemias and myelodysplastic syndromes.
Type:
Grant
Filed:
December 3, 2015
Date of Patent:
January 29, 2019
Assignee:
ACCELERON PHARMA INC.
Inventors:
Kenneth M. Attie, Christopher Robert Rovaldi
Abstract: In certain aspects, the present invention provides compositions and methods for increasing red blood cell and/or hemoglobin levels in vertebrates, including rodents and primates, and particularly in humans.
Type:
Grant
Filed:
October 23, 2017
Date of Patent:
November 20, 2018
Assignee:
ACCELERON PHARMA INC.
Inventors:
Jasbir Seehra, Robert Scott Pearsall, Ravindra Kumar
Abstract: In certain aspects, the present invention provides compositions and methods for promoting bone growth and increasing bone density and strength. In certain embodiments, the present invention provides ALK3 polypeptides, including ALK3-Fc fusion proteins.
Abstract: In certain aspects, the present invention provides compositions and methods for increasing red blood cell and/or hemoglobin levels in vertebrates, including rodents and primates, and particularly in humans.
Type:
Grant
Filed:
November 20, 2014
Date of Patent:
October 9, 2018
Assignee:
ACCELERON PHARMA INC.
Inventors:
Matthew L. Sherman, Jasbir Seehra, Niels Borgstein
Abstract: In certain aspects, the present disclosure relates to the insight that a polypeptide comprising a truncated, ligand-binding portion of the extracellular domain of endoglin (ENG) polypeptide may be used to inhibit angiogenesis in vivo, particularly in mammals suffering angiogenesis-related disorders.
Type:
Application
Filed:
February 28, 2018
Publication date:
September 13, 2018
Applicant:
Acceleron Pharma, Inc.
Inventors:
Asya Grinberg, Roselyne Castonguay, Eric Werner, Ravindra Kumar
Abstract: In certain aspects, the present disclosure relates to the insight that a polypeptide comprising a ligand-binding portion of the extracellular domain of activin-like kinase I (ALK1) polypeptide may be used to inhibit angiogenesis in vivo, particularly in mammals suffering angiogenesis-related disorders. Additionally, the disclosure demonstrates that inhibitors of ALK1 may be used to increase pericyte coverage in vascularized tissues, including tumors and the retina. The disclosure also identifies ligands for ALK1 and demonstrates that such ligands have pro-angiogenic activity, and describes antibodies that inhibit receptor-ligand interaction.
Type:
Grant
Filed:
April 13, 2012
Date of Patent:
August 28, 2018
Assignee:
Acceleron Pharma Inc.
Inventors:
Asya Grinberg, John Knopf, Robert S. Pearsall, Ravindra Kumar, Jasbir Seehra, Kristian Pietras
Abstract: In certain aspects, the present disclosure relates to the insight that a polypeptide comprising a ligand-binding portion of the extracellular domain of activin-like kinase I (ALK1) polypeptide may be used to inhibit angiogenesis in vivo, particularly in mammals suffering angiogenesis-related disorders. Additionally, the disclosure demonstrates that inhibitors of ALK1 may be used to increase pericyte coverage in vascularized tissues, including tumors and the retina. The disclosure also identifies ligands for ALK1 and demonstrates that such ligands have pro-angiogenic activity, and describes antibodies that inhibit receptor-ligand interaction.
Type:
Application
Filed:
February 13, 2018
Publication date:
June 28, 2018
Applicants:
Ludwig Institute for Cancer Research Ltd., Acceleron Pharma, Inc.
Inventors:
Asya Grinberg, John Knopf, Robert S. Pearsall, Ravindra Kumar, Jasbir Seehra, Kristian Pietras
Abstract: In certain aspects, the present invention provides compositions and methods for increasing thermogenic adipocytes (e.g., brown adipocytes or other UCP-1 expressing adipocytes) by administering an antagonist of an ActRIIB signaling pathway. Examples of such antagonists include ActRIIB polypeptides, anti-ActRIIB antibodies, anti-myostatin antibodies, anti-GDF3 antibodies, anti-Nodal, anti-activin, and anti-GDF11 antibodies. A variety of metabolic and other disorders may be treated by causing an increase in thermogenic adipocytes.
Type:
Application
Filed:
September 13, 2017
Publication date:
June 14, 2018
Applicant:
Acceleron Pharma Inc.
Inventors:
John Knopf, Jasbir Seehra, Ravindra Kumar
Abstract: In certain aspects, the present disclosure provides compositions and methods for inhibiting activity of TGF? superfamily ligands, particularly ligands such as GDF8, GDF11, activin A, activin B, activin C and activin E, in vertebrates, including rodents and primates, and particularly in humans. In some embodiments, the compositions of the disclosure may be used to treat or prevent diseases or disorders that are associated with abnormal activity of a follistatin-related polypeptide and/or a follistatin ligand.
Type:
Grant
Filed:
March 25, 2016
Date of Patent:
May 22, 2018
Assignee:
ACCELERON PHARMA INC.
Inventors:
Ravindra Kumar, Asya Grinberg, Dianne S. Sako
Abstract: Provided herein are methods of treating beta-thalassemia by subcutaneous administration of about 0.8 mg/kg of an ActRII signaling inhibitor. Also provided herein are methods of adjusting the dose of the ActRII signaling inhibitor administered to the subject.
Type:
Application
Filed:
May 12, 2016
Publication date:
May 10, 2018
Applicants:
CELGENE CORPORATION, ACCELERON PHARMA INC.
Inventors:
Kenneth M. Attie, Abderrahmane Laadem, Rajesh Chopra, Jay Backstrom
Abstract: In certain aspects, the present disclosure relates to the insight that a polypeptide comprising a truncated, ligand-binding portion of the extracellular domain of endoglin (ENG) polypeptide may be used to inhibit angiogenesis in vivo, particularly in mammals suffering angiogenesis-related disorders.
Type:
Grant
Filed:
April 19, 2012
Date of Patent:
April 3, 2018
Assignee:
Acceleron Pharma, Inc.
Inventors:
Asya Grinberg, Roselyne Castonguay, Eric Werner, Ravindra Kumar