E. R. Squibb Sons, Inc.

Bristol-Myers Squibb Compnay

Manne, Veeraswamy

Barbacid, Mariano

Mariano Barbacid

Veeraswamy Manne

Eric M Gordon

Scott A Biller

David R Magnin

Chester A Meyers

Fabienne Lamballe

Alexandra Joyner

Rudiger Klein

Ximena Montano

A novel method for preventing, stabilizing or causing regression of cancer is disclosed. The method comprises administering to a patient in need thereof a tyrosine protein kinase inhibitor.

Method for treating cancer using a tyrosine protein kinase inhibitor

A method is provided by blocking or preventing the prenylation of CAAX box containing proteins including ras oncogene products thereby preventing and/or treating ras-related tumors which includes the step of administering a therapeutically effective amount of a protein-prenyl transferase inhibitor.

Method for blocking neoplastic transformation of cells induced by ras

Method for inactivating the function produced by a protein using an intracellularly expressed antibody or fragment thereof.

Method for inactivation of protein function

The present invention provides mice and mouse cell lines having a homozygous or heterozygous deficiency in a gene encoding a neurotrophin receptor. In a preferred embodiment of this invention, mice and cell lines carry a trkB locus specifically targeted within its tyrosine protein kinase sequences. Mice homozygous for this mutation express gp95.sup.trkB receptor of unknown function but not the high affinity functional gp145.sup.trkB tyrosine protein kinase receptors. This mutation results in multiple CNS and PNS neuronal deficiencies and in a postembryonic lethal phenotype. Such genetically modified mice are useful in model systems for studying human diseases involving neuronal degeneration and neuronal cell loss, as well as in screening for genes, proteins, or other compounds that may prevent or impede neuronal cell death or stimulate neuronal regeneration.

Mice deficient in nerve growth factor receptors encoded by trkB

Nucleic acid sequences, particularly DNA sequences, coding for all or part of a trkC protein, expression vectors containing the DNA sequences, host cells containing the expression vectors, and methods utilizing these materials. The invention also concerns polypeptide molecules comprising all or part of a trkC protein and methods for producing these polypeptide molecules.

DNA encoding TRKC protein

Nucleic acid sequences, particularly DNA sequences, coding for all or part of a vav mouse proto-oncogene protein or for a modified vav mouse proto-oncogene protein, expression vectors containing the DNA sequences, host cells containing the expression vectors, and methods utilizing these materials. The invention also concerns polypeptide molecules comprising all or part of a vav mouse proto-oncogene protein or a modified vav mouse proto-oncogene protein, and methods for producing these polypeptide molecules.

Mouse vav proto-oncogene DNA and protein sequences

Assays for farnesyl-protein transferase (FT) which can be used to identify substances that block the farnesylation of ras oncogene products are described. Because farnesylation is required for ras oncogene activity, inhibitory compounds identified in the assays of the invention can block neoplastic transformation mediated by the ras oncogene. The assays of the invention are targeted for a step subsequent to the synthesis of farnesyl pyrophosphate (FPP), the donor of the farnesyl residue, and an intermediate in cholesterol synthesis and other important cellular pathways. Therefore, compounds which inhibit ras mediated transformation, yet do not cause major disruptions of important cell pathways that require FPP as an intermediate may be identified using the assays of the invention.

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Lawrenceville, NJ, United States of America

Mariano Barbacid