Washington University

Human Genome Sciences, Inc.

Ludwig Institute for Cancer Research Limited

Robert D Schreiber

Andrew C Greenlund

Michael A Farrar

Lloyd J Old

David V Goeddel

Holger Wesche

David M Hilbert

Daniel P Bednarik

David M Parmelee

Steven Teitelbaum

Marianne Murphy

Bernadetta Nardelli

Ann Gronowski

The present invention provides transgenic non-human mammals and cells having one or more structurally and functionally disrupted NIK alleles. In addition, the present invention provides methods for making such transgenic mammals and cells, and methods for determining the effect of a compound on an animal or cell that lacks NIK function. The present invention also provides methods for identifying compounds useful in the inhibition of osteoclastogenesis in a mammal, for example to treat osteoporosis or other conditions. Also provided are methods of modulating the extent of osteoclastogenesis in a cell or a mammal using NIK modulators.

NIK-knockout mice

A method for screening substances for oncogenic activity is disclosed. The method involves administering the substance to an animal lacking responsiveness to interferon&ggr; and detecting a higher frequency or earlier time of tumor formation in the test animal compared to control animals. In addition, a method is provided for predicting the aggressiveness of a tumor in a patient.

Method for determining oncogenic activity of a substance

A method for screening substances for oncogenic activity is disclosed. The method involves administering the substance to an animal lacking responsiveness to interferon.gamma. and detecting a higher frequency or earlier time of tumor formation in the test animal compared to control animals. In addition, a method is provided for predicting the aggressiveness of a tumor in a patient.

This invention relates to the use of the baculovirus glycoprotein, Interferon Stimulating Protein (ISP) (also known as gp67, gp64 EFP, or gp64), or the gene sequence encoding ISP, to stimulate production of interferon, such as for immunotherapy, anti-viral, anti-cancer, anti-bacterial, or anti-parasitic therapy. This invention also relates to novel mutant forms of ISP that show enhanced biological (i.e., anti-viral) activity, increased stability, higher yield or better solubility.

Interferon stimulating protein and uses thereof

Compositions for inhibition of intracellular transcription factors and

Novel compositions and methods that result in the inactivation of IFN.gamma. inducible transcription factors by binding to the transcription factor in the cell and inhibiting the transcriptional activity of the factors are disclosed. The composition comprises an isolated peptide that contains the amino acid sequence Xaa.sub.1 -Asp-Xaa.sub.2 -Xaa.sub.3 -His SEQ ID No. 1 where Xaa.sub.1 is phosphorylated tyrosine and Xaa.sub.2 and Xaa.sub.3 are any amino acid, or derivatives and functional equivalents thereof, that is capable of specifically binding to the p91 family of IFN.gamma. inducible transcription factors in a cell. A method for inhibiting the intracellular activation of a transcription factor by introducing into a cell an effective amount of a peptide that contains the 5 amino acid sequence described or a derivative thereof, which specifically binds to a transcription factor in the cell is also provided.

Methods for inhibition of intracellular transcription factor

Novel compositions and methods that result in the inactivation of IFN.gamma. inducible transcription factors by binding to the transcription factor in the cell and inhibiting the transcriptional activity of the factors are disclosed. The composition comprises an isolated peptide that contains the amino acid sequence Xaa.sub.1 -Asp-Xaa.sub.2 -Xaa.sub.3 -His where Xaa.sub.1 is phosphorylated tyrosine and Xaa.sub.2 and Xaa.sub.3 are any amino acid, or derivatives and functional equivalents thereof, that is capable of specifically binding to the p91 family of IFN.gamma. inducible transcription factors in a cell. A method for inhibiting the intracellular activation of a transcription factor by introducing into a cell an effective amount of a peptide that contains the 5 amino acid sequence described or a derivative thereof, which specifically binds to a transcription factor in the cell is also provided.

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St. Louis, MO, United States of America

Robert D Schreiber