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Santa Clara, CA, United States

Patent
Crown Bioscience | Date: 2013-08-01

Disclosed are novel nitrogen-containing, heterocyclic, c-Met inhibitor compounds, processes for their preparation and formulations thereof. The compounds are useful as therapeutical agents for the inhibition, regulation, and control of c-Met kinase signal pathway, and useful for treating in a subject a cell proliferative disorder or disorders mediated by c-Met.


The present invention provides an immuno-deficient animal useful as an animal model for a human disease associated with a first mutation of a target gene, wherein the animal comprises (a) a first human xenograft comprising the target gene comprising the first mutation; (b) a second human xenograft comprising the target gene but lacking the first mutation, wherein the first human xenograft and second human xenograft are isogenic. Also provided here are methods of producing the animal model and methods of using such animal model.


The present teachings relate to methods of screening for a therapeutic agent, selecting a treatment and monitoring a treatment for a human disease or infection and methods for producing a mouse model for human disease or infection wherein the mouse has a functioning human immune system. The method includes administering a test substance to an immunocompromised NOD/SCID mouse with a reconstituted human immune system and is also engrafted with a substance containing a diseased or infectious cell derived from a human diseased or infected patient and a step of assessing improvement in the disease or infection of the mouse and/or to monitor a side effect of the test substance.


The present teachings relate to methods of screening for a therapeutic agent for human acute myelogenous leukemia (AML) and methods for treating AML. The method includes administering a test substance to an immunocompromised NOD/SCID mouse engrafted with a substance containing a leukemic cell derived from a human AML patient and a step of assessing improvement in leukemia in the mouse and/or to monitor a side effect of the test substance. The method can further include monitoring a side effect of the test substance in the mouse.


The present invention provides a method for using non-human animals to mimick human clinical trial comprising: (a) obtaining cells or tissues from n human subjects suffered from a disease, wherein n>1; (b) establishing a control group and a treatment group, wherein i) the control group comprises i control non-human animals, wherein in, wherein cells or tissue from each human subject are grafted to at least one control non-human animal; ii) the treatment group comprises j treatment non-human animals, wherein jn, wherein cells or tissue from each human subject are grafted to at least one treatment non-human animal; and iii) each control non-human animal or treatment non-human animal is grafted with cells or tissues from one human subject; (c) administering a first agent to the control group and administering a second agent to the treatment group, wherein the first agent is different from the second agent; (d) obtaining the end point of the control group and the treatment group; and (e) comparing the end point of the control group to the end point of the treatment group.

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