Omeros Corporation

University of Washington

Nancy Maizels

Munehisa Yabuki

W Jason Cummings

Daniel S Allison

Larry W Tjoelker

Christi L Wood

John Benjamin Leppard

The present invention relates generally to mutagenesis of target genes that takes advantage of the natural mutagenic capabilities of B cells, and enhances those capabilities by bringing the process of diversification under control. The invention provides a method for rapidly and inducibly generating point mutations and other types of diversification in expressed genes, such as antibody genes. This method can be coupled with selection to identify B cell clones that produce, for example, antibodies of high affinity or specificity. The diversification process can be modulated, accelerated, halted, switched between methods of mutagenesis and the like. The modulation of diversification in accordance with the invention is both inducible and reversible. The invention provides a means of rapid and feasible development of a repertoire of variant immunoglobulins and other polypeptides.

Inducible mutagenesis of target genes

The present invention relates generally to anti-FZD10 antibodies and to methods of using anti-FZD10 antibodies. In particular, the anti-FZD10 antibodies described herein are useful for altering one or more of survival, replication, differentiation and epithelial-to-mesenchymal cell transition of embryonic stem cells and/or for the treatment of diseases, such as a variety of cancers, associated with expression of FZD10, including as stand-alone therapies and in combination therapies with other agents.

Anti-FZD10 monoclonal antibodies and methods for their use

The disclosure relates generally to the targeting of genes to, and their integration into, an immunoglobulin (antibody) heavy chain locus. In particular, the methods described herein contemplate replacing the single rearranged heavy chain V, D, and J genes of a B cell lymphoma such as DT40 with independently rearranged V-D-Jgenes of chicken, in a system for generating immunoglobulin diversity. Also contemplated is replacement of the chicken V-D-Jwith rearranged V-D-Jgenes of other vertebrates including human in a system for generating immunoglobulin diversity, with the exception of any substitution disclosed and claimed in PCT application WO 2009/029315 A2. Also described is construction of a diverse chicken immunoglobulin heavy chain VDJ library in DT40 by homologous gene replacement of the single endogenous rearranged VDJ gene with a chicken VDJ repertoire using the described targeting vectors.

Composition and method for diversification of target sequences

The present invention relates generally to anti-FN14 antibodies. In particular, the anti-FN14 antibodies described herein are useful for the treatment of diseases, such as a variety of cancers, associated with expression of FN14.

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Seattle, WA, United States of America

Nancy Maizels