Transgenic mice expressing human cd20

Abstract

The present invention generally relates to non-human transgenic animals expressing human cellular markers, including CD20 and methods for using the animals to identify agents that are effective to deplete cells bearing human CD20. The transgenic animals are also useful to test safety and efficacy of anti-CD20 therapies.

Description

[0001] This application is being filed as a PCT International Patent Application in the name of Genentech, Inc., a U.S. national corporation and resident, (Applicant for all countries except US); Andrew Chee-Yuen Chan, a U.S. citizen and resident (Applicant for US only); Qian Gong, a Chinese citizen and U.S. resident (Applicant for US only); and Flavius Martin, a Romanian citizen and U.S. resident (Applicant for US only), on 11 Dec. 2003, designating all countries and claiming priority to U.S. provisional application Ser. No. 60 / 434,115, filed Dec. 16, 2002, and U.S. provisional application Ser. No. 60 / 476,481, filed Jun. 5, 2003 which are hereby incorporated by reference.BACKGROUND OF THE INVENTION [0002] T and B cells both comprise cell surface proteins that can be utilized as markers for differentiation and identification. One such human B cell marker is the human B lymphocyte-restricted differentiation antigen Bp35, also known as “CD20”. CD20 is expressed during early pre-B cell...

AI Technical Summary

Benefits of technology

[0012] A non-human transgenic animal of the present invention can further provide an indication of the safety of a particular agent for administration to a human. For example, a humanized antibody or other agent can be administered to the transgenic animal and any toxic or adverse effects as a result of the administration of the agent to the animal can be monitored or identified as an indication of the safety and tolerability of the humanized antibody or agent for in vivo human use. Adverse events that may occur on a short term basis include headache, infection, fever, chills, pain, nausea, asthenia, pharyngitis, diarrhea, rhinitis, infusion reactions, and myalgia. Short term adverse events are measured in days post treatment. Long term adverse effects include cytoxicity of certain cell types, bleeding events due to thrombocytopenia, release of mediators due to inflammatory and / or allergic reactions, inhibition of the immune system and / or development of an anti-therapeutic agent antibody, end organ toxicity, and increased incidence of infection or malignancy. Long term adverse events are measured in months post treatment.

Problems solved by technology

These anti-CD20 antibodies specifically bind to the CD20 cell surface antigen of both normal and malignant B cells, leading to the destruction and depletion of B cells.

In spite of the significant roles of CD20 in human lymphoma and other disorders, animal models are lacking which express the human marker.

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