Acceleron Pharma Inc.

Genetics Institute, Inc.

Other

The Brigham and Women's Hospital, Inc.

Wyeth

Adimab, LLC

University of Michigan

Ludwig Institute for Cancer Research Limited

Dyax Corporation

Accleron Pharma Inc.

Accerelon Pharma Inc.

Ravindra Kumar

Asya Grinberg

Jasbir S Seehra

Dianne S Sako

John L Knopf

Roselyne Castonguay

Robert Scott Pearsall

Gray D Shaw

Jonathan Belk

Yossi Dagon

Geertruida Machteld Veldman

Glenn R Larsen

Dale Anthony Cumming

Xiao-Jia Chang

Rita M Steeves

Francis Sullivan

Naga Venkata Sai Rajasekhar Suragani

Nathan J Sharkey

Rajasekhar Naga Venkata Sai Suragani

Gang Li

Ronald Kriz

Eric Werner

Erik M Vogan

Jennifer Lachey

Rachel B Kent

Paul B Yu

Monique V Davies

David Buckler

Janja Cosic

Tzu-Hsing Kuo

Ray Camphausen

Alan Koncarevic

Tom McDonagh

Diana Martik

Kristian Pietras

Rita Steeves

Naga Venkata Suragani

Phaik-Eng Sum

Edward R LaVallie

Lisa Anne Collins-Racie

Lidia Mosyak

Christopher John Corcoran

Xiaotian Zhong

Stephane Olland

Thomas Saltmarsh Rush, Iii

Katy Evangelia Georgiadis

Thomas E McDonagh

Benjamin Levi

Shailesh Agarwal

Vandana Verma

Stewart Andrews Mackie

Tracy Hebert

Jin Xu

Jia Li

Pedro Martinez

Dianne Sako

Rajasekhar Naga Suragani

This disclosure provides ALK7-binding proteins such as anti-ALK7 antibodies, and compositions and methods for making the ALK7-binding proteins. In certain embodiments, the ALK7-binding proteins inhibit or antagonize ALK7 activity. In addition, the disclosure provides compositions and methods for diagnosing and treating overweight, obesity, diabetes, overweight, obesity, type 2 diabetes, and their associated conditions; metabolic disorders, and other diseases or conditions that can be treated, prevented or ameliorated by targeting ALK7.

ALK7 binding proteins and uses thereof

In part, the present disclosure relates methods for treating heterotopic ossification or one or more complications of heterotopic ossification. In particular, the disclosure provided methods for treating heterotopic ossification by administering to a patient in need thereof one or more TGFβ antagonists, optionally in combination with one or more additional active agents or supportive therapies for treating heterotopic ossification. For example, in some embodiments, the disclosure provided methods for treating heterotopic ossifications by administering to a patient in need thereof an effective amount of a TβRII polypeptide.

Methods for treating heterotopic ossification

In some aspects, the disclosure relates to GDF/BMP antagonists and methods of using GDF3/BMP antagonists to treat, prevent, or reduce the progression rate and/or severity of pulmonary hypertension (PH), particularly treating, preventing or reducing the progression rate and/or severity of one or more PH-associated complications. The disclosure also provides methods of using a GDF/BMP antagonist to treat, prevent, or reduce the progression rate and/or severity of a variety of conditions including, but not limited to, pulmonary vascular remodeling, pulmonary fibrosis, and right ventricular hypertrophy. The disclosure further provides methods of using a GDF/BMP antagonist to reduce right ventricular systolic pressure in a subject in need thereof.

Compositions and methods for treating pulmonary hypertension

In certain aspects, the disclosure provides soluble single-arm heteromeric polypeptide complexes comprising an extracellular domain of a type I serine/threonine kinase receptor of the TGF-beta family or an extracellular domain of a type II serine/threonine kinase receptor of the TGF-beta family. In some embodiments, the disclosure provides soluble single-arm 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 single-arm 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 for the treatment or prevention of various TGF-beta associated conditions, including without limitation diseases and disorders associated with, for example, cancer, muscle, bone, fat, red blood cells, metabolism, fibrosis and other tissues that are affected by one or more ligands of the TGF-beta superfamily.

Single-arm type I and type II receptor fusion proteins and uses thereof

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.

ALK4:actriib heteromultimers and uses thereof

In certain aspects, the present invention provides compositions and methods for modulating (promoting or inhibiting) growth of red blood cells or 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.

Variant ActRIIB proteins and uses thereof

In part, the present disclosure relates methods for treating, preventing, or reducing the progression rate and/or severity of myelofibrosis or one or more complications of myelofibrosis (extramedullary hematopoiesis, splenomegaly, anemia, and fibrosis). In certain aspects, the disclosure provides ActRIIB antagonists for use in treating, preventing, or reducing the progression rate and/or severity of one or more complications associated with Janus kinase inhibitor therapy in a patient (e.g., anemia).

Methods and compositions for treating myelofibrosis

In certain aspects, the present disclosure relates to TβRII fusion polypeptides comprising a heterologous portion and a truncated, ligand-binding portion of the extracellular domain of TβRII polypeptide useful to selectively antagonize a TβRII ligand. The disclosure further provides compositions and methods for use in treating or preventing TGFβ associated disorders.

Transforming growth factor-beta (TGF-beta) receptor type II fusion polypeptides

In certain aspects, the disclosure provides multispecific binders (e.g., ActRIIB:TβRII heteromultimers comprising an ActRIIB polypeptide and a TβRII polypeptide). In some embodiments, the disclosure provides for novel binders comprising a TβRII polypeptide and a heterologous portion. The disclosure further provides that such multispecific binders (e.g., ActRIIB:TβRII heteromultimer) may be used to treat various disorders or conditions.

Binders of TGFβ-superfamily ligands and uses thereof

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. The disclosure also identifies ligands for ALK1 and demonstrates that such ligands have pro-angiogenic activity, and antibodies that inhibit receptor-ligand interaction.

ALK1 receptor and ligand antagonists and uses thereof

In certain aspects, the disclosure provides multispecific binders (e.g., ActRIIA:TβRII heteromultimers comprising an ActRIIA polypeptide and a TβRII polypeptide). The disclosure further provides that such multispecific binders (e.g., ActRIIA:TβRII heteromultimer) may be used to treat various disorders or conditions.

Multispecific binders of TGFBeta-superfamily ligands and uses thereof

Methods of treatment of muscular dystrophy with ALK4:ActRIIB heteromultimers

This disclosure provides ActRII-binding proteins such as anti-ActRIIA and anti-ActRIIB antibodies, and compositions and methods for making the ActRII-binding proteins. In certain aspects the ActRII-binding proteins inhibit, or antagonize ActRII activity. In addition, the disclosure provides compositions and methods for diagnosing and treating diseases and conditions associated musle wasting; a fibrotic condition; an inflammatory, cardiovascular, pulmonary, musculoskeletal, neurologic, ocular, skeletal, autoimmune, or metabolic disease or condition; wound healing; and cancer, and other ActRII-mediated diseases and conditions.

Activin type 2 receptor binding proteins methods of making them

In certain aspects, the disclosure provides ALK7 antagonists. In certain aspects, these ALK7 antagonists are can be used to improve metabolic parameters in a patient in need thereof. In certain aspects, these ALK7 antagonists can be used to treat or prevent one or more kidney-associated disease or condition in a patient in need thereof. In certain aspects, these ALK7 antagonists can be used to treat or prevent cancer.

ALK7 antagonists and uses thereof

The disclosure provides ALK7-binding proteins such as anti-ALK7 antibodies, and compositions and methods for making the ALK7-binding proteins. In certain embodiments, the ALK7-binding proteins inhibit, or antagonize ALK7 activity. In addition, the disclosure provides compositions and methods for diagnosing and treating overweight, obesity, diabetes, obesity, type 2 diabetes, and their associated conditions, metabolic disorders, and other diseases or conditions that can be treated by targeting ALK7.

Growing community of inventors

Acton, MA, United States of America

Ravindra Kumar