The Picower Institute for Medical Research

Cytokine Pharmasciences, Inc.

Robert A Mitchell

Richard J Bucala

Anthony Cerami

Jurgen Bernhagen

Thierry F Calandra

Jason A Chesney

Peter Senter

Yousef Al-Abed

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

A diagnostic method for determining MIF protein content in a sample using a direct or an indirect detection technique and wherein MIF is a human MIF protein having a molecular weight of approximately 12.5 kDa.

Method for determining MIF content

Composition containing anti-MIF antibody

There is disclosed a cancer malignancy diagnostic assay comprising obtaining a sample of a body fluid or tissue, performing a sequence identity assay to look for the presence of iPFK-2 specific sequences; an anticancer pharmaceutical composition comprising a specific antisense oligonucleotide to the inventive isolated iPFK-2 sequence and a pharmaceutically acceptable oligonucleotide carrier; and a method for finding therapeutically active anti-cancer compounds comprising screening compounds for activity to inhibit iPFK-2, preferably kinase activity.

Inducible phosphofructokinase and the Warburg effect

There are disclosed methods of use and pharmaceutical compositions for two related genera of low molecular weight compounds comprising optionally substituted iminoquinone or orthoquinone ring systems. The compounds have MIF (macrophage migration inhibitory factor) antagonist activity and find utility as such. For example, the compounds are useful for treating a variety of diseases involving inflammatory activity or pro-inflammatory cytokine responses, such as autoimmune diseases (including rheumatiod arthritis, insulin-dependent diabetes, multiple sclerosis, graft versus host disease, lupus syndromes), asthma, arthritis, EAE, ARDS, psoriasis, interleukin-2 toxicity, proliferative vascular disease, and various forms of sepsis and septic shock, and other conditions characterized by underlying MIF responses including, for instance, tumor growth and neovascularization (angiogenesis).

Compounds having MIF antagonist activity

There is disclosed a cancer malignancy diagnostic assay comprising obtaining a sample of a body fluid or tissue, performing a sequence identity assay to look for the presence of PFK-2 specific sequences; an anticancer pharmaceutical composition comprising a specific antisense oligonucleotide to the inventive isolated PFK-2 sequence and a pharmaceutically acceptable oligonucleotide carrier; and a method for finding therapeutically active anti-cancer compounds comprising screening compounds for activity to inhibit PFK-2 but not PFK.

Inducible phosphofructokinase and the warburg effect

Diagnostic assays for MIF

There is disclosed a method for treating an individual having a disease caused by cytokine-mediated toxicity comprising administering to the individual an effective amount of (a) an antibody that binds to an MIF polypeptide, wherein the MIF polypeptide has a molecular weight of about 12.5 kDa in combination with (b) anti-TNF.alpha., anti-IL1, anti-IFN-.gamma., IL-1RA, a steroid, a glucocorticoid, or IL-10.

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New York, NY, United States of America

Robert A Mitchell