Genetics Institute, Inc.

Wyeth

Other

Ono Pharmaceutical Co., Ltd.

Edward R LaVallie

Lisa A Racie

John M McCoy

Kenneth A Jacobs

David Merberg

Maurice Treacy

Vikki A Spaulding

Cheryl Evans

Lisa Anne Collins-Racie

Christopher John Corcoran

Michael J Agostino

John R McCoy

Michael R Bowman

Katy Evangelia Georgiadis

Bethany Annis Freeman

Carl Ralph Flannery

Stephane Olland

Thomas Saltmarsh Rush, Iii

Thomas E McDonagh

Edward M DeRobertis

Elizabeth DiBlasio-Smith

Kathleen Grant

Stewart Andrews Mackie

Ravindra Kumar

Phaik-Eng Sum

Gordon G Wong

Sha Mi

Mark L Stahl

Lidia Mosyak

Gary Hattersley

Hilary Clark

Kathleen N Tomkinson

Jeffrey S Deetz

Xiaotian Zhong

Zhijian Lu

Steven M Vicik

James R Mercer

Neil L Schauer

Tara K Crawford

Maya Arai

Dwight Winters

Lydia Mosyak

Kim Fechtel

Weilan Zeng

Jenifer L Thomas

Catherine A Briasco

Tracy Hebert

Robert J Steininger, Ii

John Mccoy

The present invention is based on the discovery that &#x3b6;PKC expression is increased in the tissues of arthritis patients as compared to normal individuals. Accordingly, the present invention provides methods of diagnosing, prognosing, and monitoring the course of arthritis in a patient based on increased &#x3b6;PKC gene expression in arthritic tissue. The present invention further provides compounds that inhibit the expression of &#x3b6;PKC for use as remedies in the treatment of arthritis, including, but not limited to, inhibitory polynucleotides and polypeptides, small molecules, and peptide inhibitors. In addition, the present invention provides pharmaceutical formulations and routes of administration for such remedies, as well as methods for assessing their efficacy.

Protein kinase C zeta as a drug target for arthritis and other inflammatory diseases

This invention relates to aggrecanase polypeptides and aggrecanase polypeptide/ligand complexes, crystals of aggrecanase and aggrecanase polypeptide/ligand complexes, and related methods and software systems.

Aggrecanase structure

Novel polynucleotides and the proteins encoded thereby are disclosed.

Secreted proteins and polynucleotides encoding them

Truncated aggrecanase proteins and nucleotides sequences encoding them as well as processes for producing them are disclosed. Additionally, aggrecanases with amino acid mutations that lead to increased stability and expression levels in comparison with wild-type or native aggrecanases are also disclosed. Aggrecanases of the invention are especially useful for development of compositions for treatment of diseases such as osteoarthritis. 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.

Truncated aggrecanase molecules

The present invention relates to modified ADAMTS4 proteins having improved stability comparing to the corresponding native, unmodified proteins. The modified ADAMTS4 proteins can be expressed and isolated in large quantities, thus allowing further characterization of the proteins, such as crystallographic and enzyme kinetic studies. The purified, stable proteins would also facilitate the production of anti-ADAMTS antibodies and the development of inhibitors to ADAMTS enzymes.

Modified ADAMTS4 molecules and method of use thereof

Novel aggrecanase proteins and the nucleotide sequences encoding them as well as processes for producing them are disclosed. Methods of identifying and 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

Purified human SDF-5 proteins and processes for producing them are disclosed. DNA molecules encoding the human SDF-5 proteins are also disclosed. The proteins may be used in regulating the binding of Wnt genes to their receptor. In preferred embodiments, the proteins may be used for inducing formation, growth, differentiation, proliferation and/or maintenance of chondrocytes and/or cartilage tissue, and for other tissue repair, such as pancreatic tissue repair.

Human SDF-5 protein and compositions

Provided are nucleic acid sequence sequences encoding enterokinase activity, the expression products thereof, and methods for using same.

Cloning of enterokinase and method of use

Method of inhibiting angiogenesis using secreted proteins

Provided is a fusion molecule comprising a DNA sequence encoding a thioredoxin-like protein fused to a DNA sequence encoding a second peptide or protein. The peptide or protein may be fused to the amino terminus of the thioredoxin-like molecule, the carboxyl terminus of the thioredoxin-like molecule, or within the thioredoxin-like molecule, for example at the active-site loop of the molecule. The fusion molecule may be modified to introduce one or more metal-binding/chelating amino-acid residues to aid in purification. Expression of this fusion molecule under the control of a regulatory sequence capable of directing its expression in a desired host cell, produces high levels of stable and soluble fusion protein. The fusion protein, located in the bacterial cytoplasm, may be selectively released from the cell by osmotic shock or freeze/thaw procedures. It may be optionally cleaved to liberate the soluble, correctly folded heterologous protein from the thioredoxin-like portion.

Peptide and protein fusions to thioredoxin, thioredoxin-like molecules,

Human L105 polypeptides and polynucleotides encoding same

Purified chordin proteins and processes for producing them are disclosed. DNA molecules encoding the chordin proteins are also disclosed. The proteins may be used in the treatment of bone, cartilage, other connective tissue defects and disorders, including tendon, ligament and meniscus, in wound healing and related tissue repair, as well for treatment of disorders and defects to tissue which include epidermis, nerve, muscle, including cardiac muscle, and othe tissues and wounds, and organs such as liver, brain, lung, cardiac, pancreas and kidney tissue. The proteins may also be useful for the induction inhibition of growth and/or differentiation of undifferentiated embryonic and stem cells. The proteins may be complexed with other proteins, particularly members of the transforming growth factor-beta superfamily of proteins.

Chordin compositions

Growing community of inventors

Tewksbury, MA, United States of America

Edward R LaVallie