Omeros Corporation

University of Washington

Munehisa Yabuki

W Jason Cummings

Larry W Tjoelker

Christi L Wood

Nancy Maizels

Daniel S Allison

Thomas Dudler

John Benjamin Leppard

Gregory A Demopulos

Patrick W Gray

Peter Kurt Nollert Von Specht

Sadam Yaseen

William Jason Cummings

Yi Li

Kathleen A Shaffer

Jeremy A Freeman

Disclosed herein are monoclonal antibodies that specifically bind to human mature Factor D and that do not bind to human Pro-Factor D, monoclonal antibodies that specifically bind to human Pro-Factor D and do not bind to human mature Factor D, and monoclonal antibodies that bind to both human mature Factor D and human Pro-Factor D. Also disclosed are methods of using the monoclonal antibodies, and compositions comprising the same, for detection of the mature and/or the pro-form of Factor D in biological samples, to determine the status of the Alternative Pathway of Complement (APC) in a mammalian subject, or to determine the status of Factor D after treatment with a MASP-3 inhibitory agent which inhibits the conversion of Pro-Factor D to mature Factor D.

Monoclonal antibodies, compositions and methods for detecting complement factor D

Isolated monoclonal antibodies and antigen-binding fragments thereof are provided that specifically bind to an epitope within the serine protease domain of human MASP-2. In some embodiments, the antibodies or antigen-binding fragments thereof inhibit lectin pathway complement activation. Also provided are polynucleotides encoding the disclosed monoclonal antibodies or antigen-binding fragments thereof, and cloning vectors or expression cassettes comprising such polynucleotides. Further provided are methods of inhibiting lectin pathway complement activation and methods of treating lectin pathway diseases and disorders.

Therapeutic antibodies that bind to the serine protease domain of MASP-2 and uses thereof

The present invention relates to MASP-3 inhibitory antibodies and compositions comprising such antibodies for use in inhibiting the adverse effects of MASP-3 dependent complement activation.

Antibodies specifically binding to MASP-3 for the treatment of various diseases and disorders

In one aspect, the invention provides a method of making a bioactive peptide-bearing antibody, or fragment thereof, comprising (a) engrafting the amino acid sequence of at least one bioactive peptide of interest into (i) at least one of CDR-H1, CDR-H2 or CDR-H3 of a heavy chain variable region comprising one or more chicken framework regions and/or (ii) at least one of CDR-L1, CDR-L2 or CDR-L3 of the light chain variable region comprising one or more chicken framework regions, and (b) determining whether the antibody has substantially the same biological activity as the bioactive peptide.

Methods of generating bioactive peptide-bearing antibodies and compositions comprising the same

Nucleic acids encoding antibodies specifically binding to MASP-3

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

Munehisa Yabuki