The Picower Institute for Medical Research

Yale University

The Rockefeller University

Cytokine Pharmasciences, Inc.

Baxalta Gmbh

Alteon Incorporated

Other

Baxter International Inc.

Baxter Healthcare Sa

The United States Government As Represented by the Department of Veterans Affairs

Glaxosmithkline Biologicals Sa

The Picower Institute of Medical Research

Richard J Bucala

Anthony Cerami

Helen Vlassara

Robert A Mitchell

Yousef Al-Abed

Kevin J Tracey

Peter C Ulrich

Christine N Metz

Jurgen Bernhagen

Thierry F Calandra

William L Jorgensen

Henry W Founds

Lin Leng

Jason A Chesney

Peter Gregersen

Xini Zhang

John A Baugh

Smita Chitnis

Lawrence H Young

Seamus C Donnelly

Joanita Monteiro

Carla J Cerami

Andrew John Geall

Peter Senter

Michael Peter Vitek

Michael A Yamin

Katherine Meyer Siegler

Pedro L Vera

Svetlana Ivanova

Yousef Al Abed

Kenneth Iczkowski

Iain D Nicholl

Jason Chesney

Glenn C Rice

Xini Xhang

Seamas Donnelly

Peter K Gregersen

Klaus Bendrat

Robert Mitchell

The invention provides novel heterocyclic compounds, pharmaceutical compositions and methods of treatment that modulate levels of MIF expression and treat disorders associated with high or low levels of MIF expression.

MIF modulators

This invention relates to compositions (e.g. vaccine compositions) which can be used to provide a subject with protective immunity against a parasite infection. The compositions comprise: (i) an immunologically effective amount of a nucleic acid (e.g. a nucleic acid-based vaccine) comprising a sequence which encodes a parasite macrophage migration inhibitory factor (MIF) antigen; (ii) a parasite MIF antigen; or (iii) an antibody which specifically binds to a parasite MIF antigen. The compositions may be used to treat infections and diseases caused by parasitic protozoans, such as aparasite, or parasitic helminths.

Uses of parasite macrophage migration inhibitory factors

The present invention relates to novel methods and compositions for increasing AMPK activity and glucose uptake comprising administering a macrophage migration inhibitory factor (MIF) pathway agonist in a subject in need thereof. The invention also relates to methods for selecting a subject for treatment with an agonist of MIF, identifying a subject at risk for developing a condition in which increased AMPK activity is desirable, and for predicting whether a subject is susceptible to a condition in which increased AMPK activity is desirable.

Use of MIF and MIF pathway agonists

The present invention relates to the discovery that reduced levels of D-dopachrome tautomerase (D-DT) (also known as MIF-2) are associated with ischemia-reperfusion injury. Thus, the present invention relates to methods of administering D-DT and recombinant D-DT for the treatment of ischemia-reperfusion injury.

Methods of administering D-dopachrome tautomerase (D-DT) to treat ischemia-reperfusion injury

Methods and compositions for using the MHC class II invariant chain polypeptide, Ii (also known as CD74), as a receptor for macrophage migration inhibitory factor (MIF), are disclosed. These include methods and compositions for using this receptor, as well as agonists and antagonists of MIF which bind to this receptor, or which otherwise modulate the interaction of MIF with CD74 or the consequences of such interaction, in treatment of conditions characterized by locally or systemically altered MIF levels, particularly inflammatory conditions and cancer.

Method of inhibiting binding or activity of MIF by administering a MIF antagonist

Describe herein is a novel CATT-tetranucleotide repeat polymorphism at position &#x2212;817 of the human Mif that functionally affects the activity of the Macrophage Inhibitory Factor (MIF) promoter in gene reporter assays. Four genotypes are described which comprise 5, 6, 7, or 8-CATT repeat units. Of these, the 5-CATT allele has the lowest level of basal and stimulated MIF promoter activity in vitro. The presence of the low expressing, 5-CATT repeat allele correlated with low disease severity in a cohort of rheumatoid arthritis patients. Methods, compositions and apparatus for detecting this CATT-tetranucleotide repeat polymorphism at position &#x2212;817 of the human Mif gene, and for using same for assessing predisposition to severe inflammatory disease, are also disclosed.

Macrophage migration inhibitory factor (MIF) promoter polymorphism in inflammatory disease

MIF antagonists

The present invention relates to the risk assessment, detection, diagnosis, or prognosis of prostate cancer. More specifically, this invention relates to the detection of certain polymorphism in the promoter region of the MIF gene to determine the risk, detect, diagnose, or prognosticate prostate cancer. Applicants have discovered that the presence of a &#x2212;173C and/or &#x2212;749 (CATT)repeat predispose an individual to prostate cancer.

Polymorphism in the macrophage migration inhibitory factor (MIF) gene as marker for prostate cancer

Method for screening for compounds using MHC class II invariant chain polypeptide and macrophage migration inhibitory factor

The present invention relates to compositions and methods for inhibiting the release and/or biological activity of migration inhibitory factor (MIF). In particular, the invention relates to the uses of such compositions and methods for the treatment of various conditions involving cytokine-mediated toxicity, which include, but are not limited to shock, inflammation, graft versus host disease, and/or autoimmune diseases.

Anti-MIF antibodies

Describe herein is a CATT-tetranucleotide repeat polymorphism at position &#x2212;817 of the human Mif gene that functionally affects the activity of the Macrophage Inhibitory Factor (MIF) promoter in gene reporter assays. Four genotypes are described which comprise 5, 6, 7, or 8-CATT repeat units. Of these, the 5-CATT allele has the lowest level of basal and stimulated MIF promoter activity in vitro. The presence of the low expressing, 5-CATT repeat allele correlated with low disease severity in a cohort of rheumatoid arthritis patients. Methods, compositions and apparatus for detecting this CATT-tetranucleotide repeat polymorphism at position &#x2212;817 of the human Mif gene, and for using same for assessing predisposition to severe inflammatory disease, are also disclosed.

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Cos Cob, CT, United States of America

Richard J Bucala