University of Florida Research Foundation Inc

University System of Maryland

Dovetail Technologies, Inc.

Carol H Pontzer

Howard Marcellus Johnson

Fuller Warren Bazer

Gino Van Heeke

Nathan D Griggs

Troy Lee Ott

Floyd E Taub

Lorelie H Villarete

Jackeline Campos

Prem S Subramaniam

Christina Dancz Clark

Lynnette H Shorts

Prem Shankar Subramaniam

The present invention is directed to the field of animal and human health, and more particularly to pharmacological uses of analogs or mutants of interferon-tau (IFN-&tgr;) that differ from native IFN-&tgr; because of substitutions of amino acids near the amino terminus of the IFN-&tgr; molecule that impart improved biological activity. The IFN-&tgr; mutants described in this disclosure have low toxicity, retain the same or slightly reduced antiviral activity compared with highly effective IFN-alpha, and have enhanced antiproliferative activity compared to native IFN-tau, making them useful in treating viral infections, cancer, and immune system diseases including autoimmune diseases. The present invention is also directed to a method for making novel recombinant proteins, especially interferons, interleukins, and cytokines, polypeptide hormones and other biopharmaceuticals that have improved biological activity over known proteins and/or lower toxicity and/or increased stability.

Interferon tau mutants and methods for making them

The present invention relates to methods of using peptide-like compounds, e.g., aminocarboxylic acid amide derivatives, to bias the immune system toward producing, enhancing, or maintaining a polarized Th1 response, and to methods for treating diseases that improve by creating a Th1 response. The invention also relates to a method of treating diseases associated with elevated soluble TNF alpha levels by administering beta-alethine together with NAC to reduce soluble TNF alpha, and to a pharmaceutical composition comprising same. The present compounds can be used to modulate cytokines including IFN-gamma and IL-10.

Small molecules that elicit a polarized Th1 response and for modulation of cellular immunity

The invention describes a method of reducing the cytotoxicity of interferon-alpha by making defined amino acid substitutions in the N-terminal portion of the polypeptide sequence. Also described are human interferon-alpha analogs with low cytotoxicity, and therapeutic applications of the low toxicity interferon-alpha analogs.

Low-toxicity human interferon-alpha analogs

The invention provides fusion proteins comprising an N-terminal region derived from an interferon-tau (IFN-&tgr;) polypeptide and a C-terminal region derived from another type I interferon polypeptide, such as IFN-&agr; or IFN-&bgr;. The fusion proteins exhibit reduced cytotoxicity as compared to the corresponding unmodified type I interferons.

Hybrid interferon &tgr;/type I interferon polypeptides

The invention provides antitumor therapeutic methods employing bovine or ovine interferon-tau (IFN-.tau.) proteins and polypeptides. The IFN-.tau. proteins exhibit the antiviral and antiproliferative properties characteristic of type I interferons. An advantage of the invention is that IFN-.tau. has essentially no cytotoxic effects on treated cells as does, for example, IFN-.alpha..

Antitumor therapy using ovine or bovine interferon-tau

The invention provides antiviral therapeutic methods employing bovine or ovine interferon-tau (IFN-.tau.) proteins and polypeptides. The IFN-.tau. proteins exhibit the antiviral and antiproliferative properties characteristic of type I interferons. An advantage of the invention is that IFN-.tau. has essentially no cytotoxic effects on treated cells as does, for example, IFN-.alpha..

Antiviral therapy using ovine or bovine interferon-tau

The present invention describes hybrid interferon fusion polypeptides formed of a first segment that contains the N-terminal amino acid sequence of an interferon-tau polypeptide, and a second segment that contains the C-terminal amino acid sequence of a non-tau interferon type I polypeptide. The two segments are joined in the region of a mature interferon polypeptide between about residues 8 and 37. Also described are nucleic acid sequences encoding such interferon fusion polypeptides, expression vectors containing such sequences, and therapeutic applications of the interferon fusion polypeptides. The therapeutic applications include antiviral and anticellular proliferation applications. One advantage of the interferon fusion polypeptides of the present invention is that they do not have cytotoxic side-effects when used to treat cells.

Hybrid interferon tau/alpha polypeptides, their recombinant production,

The subject invention concerns novel peptide agonists and antagonists of staphylococcal enterotoxin A. Specifically exemplified are peptide agonists which stimulate T cell proliferation.

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Silver Spring, MD, United States of America

Carol H Pontzer