Genetics Institute, Inc.

Wyeth

Elisabeth Ann Morris

Renwen Zhang

Diane Peluso

Neil M Wolfman

Jason Shaoyun Xiang

Phaik-Eng Sum

Vicki A Rosen

Lisa A Racie

Gary Hattersley

Steve Yikkai Tam

Michael J Agostino

Joshua James Sabatini

David Brian How

Matthew Douglas Vera

Yonghan Hu

Thomas Saltmarsh Rush, Iii

Katy Evangelia Georgiadis

Darrin William Hopper

Sonya Glasson

Natalie C Twine

The present invention relates to biaryl sulfonamides and their use as, for example, metalloproteinase inhibitors.

Biaryl sulfonamides and methods for using same

Methods and compositions are provided for the treatment of articular cartilage defects and disease involving the combination of tissue, such as osteochondral grafts, with active growth factor. The active growth factor is preferably a composition containing at least one bone morphogenetic protein and a suitable carrier. The method results in the regeneration and/or functional repair of articular cartilage tissue.

Methods and compositions for healing and repair of articular cartilage

The present invention relates to methods of treating ADAMTS-5-associated diseases and particularly osteoarthritis comprising administering an agent capable of modulating ADMATS-5 activity to a subject afflicted with the disease. The agent is preferably a biaryl sulfonamide compound. The invention is based, in part, on the discovery that transgenic animals that do not express functional ADAMTS-5 show a reduction in the degree of osteoarthritis after the induction of osteoarthritis as compared to WT animals. Furthermore, the ADAMTS-5 transgenic animals have reduced aggrecanase activity in articular tissue as compared to WT animals. These animals are good models for ADAMTS-5-associated diseases, and for screening of drugs useful in the treatment and/or prevention of these diseases. There are no other animal models in which the deletion of the activity of a single gene is capable of abrogating the course of osteoarthritis. Accordingly, these animals also show that osteoarthritis can be prevented and/or treated by administering to a subject an ADAMTS-5 inhibitory agent and particularly an agent capable of inhibiting the aggrecanase activity of ADAMTS-5.

Method for treating ADAMTS-5-associated disease

Methods and compositions are provided for the treatment of articular cartilage defects and disease involving the combination of tissue, such as osteochondral grafts, with active growth factor. The active growth factor is preferably a composition containing at least one bone morphogenetic protein and a suitable carrier. The method results in the regeneration of functional repair of articular cartilage tissue.

Aggrecanase proteins and the nucleotides sequences encoding them as well as processes for producing them are disclosed. Methods for developing inhibitors of the aggrecanase enzymes and antibodies to the enzymes for treatment of conditions characterized by the degradation of aggrecan are also disclosed.

Aggrecanase molecules

Compositions of proteins with cartilaginous tissue inducing and maintenance activity are disclosed. The compositions are useful in the treatment of osteoarthritis, cartilage defects and in related tissue repair.

Cartilage induction by bone morphogenetic proteins

Growing community of inventors

Sherborn, MA, United States of America

Elisabeth Ann Morris