IDEC researchers are developing products for the management of immune system cancers and autoimmune and inflammatory diseases. Our antibody products bind to specific subsets of human immune system cells, or to soluble mediators of immune cell activity, and act to deplete or to alter the activity of these cells. The products are administered intravenously and target cells or soluble mediators located in easily accessible compartments of the body, specifically the blood, lymphatic fluid and synovial fluid.

Due to their specificity and affinity for cell surface receptors, monoclonal antibodies are an attractive means by which to treat autoimmune diseases. Attachment of monoclonal antibodies to specific cell surface receptors can be used to suppress aberrant and unwanted immune activity. Historically, however, the use of monoclonal antibodies as an ongoing therapy has been limited by the body’s rejection of the murine components of the antibodies. Murine monoclonal antibodies, which are structurally different from human antibodies, tend to trigger adverse immune reactions when used as therapies. These reactions include a HAMA (human anti-murine antibody) response in which the patient’s immune system produces antibodies against the therapeutic antibody, thus limiting its effectiveness.

IDEC researchers have developed the following proprietary technology for use with and in the development of its products:

PRIMATIZED® Antibody – IDEC researchers have developed a proprietary PRIMATIZED antibody technology designed to avoid HAMA responses and other immunogenicity problems by developing monoclonal antibodies from primate rather than mouse B cells. These antibodies are characterized by their strong similarity to human antibodies and by the absence of mouse components. In 1998, IDEC received an issued U.S. patent covering its PRIMATIZED antibodies. Underlying this proprietary technology is IDEC’s discovery that macaque monkeys produce antibodies that are structurally indistinguishable from human antibodies in their variable (antigen-binding) regions.

Further, IDEC researchers found that the macaque monkey can be immunized to make antibodies that react with human, but not with macaque, antigens. Genetic engineering techniques are then used to isolate the portions of the macaque antibody gene that encode the variable region from a macaque B cell. This genetic material is combined with constant region genetic material from a human B cell and inserted into a host cell line which then expresses the desired antibody specific to the given antigen. The result is a part-human, part-macaque PRIMATIZED antibody which appears structurally to be so similar to human antibodies that it may be accepted by the patient’s immune system as “self.”

This development allows the possibility of therapeutic intervention in chronic diseases or other conditions that are not amenable to treatment with antibodies containing mouse components. IDEC researchers are currently using its PRIMATIZED technology for the development of its IDEC-151, IDEC-152 and IDEC-114 product candidates.

Anti-MIF Antibodies— IDEC researchers have identified high affinity monoclonal antibodies with potent macrophage migration inhibitory factor (MIF) blocking activity. MIF is a pro-inflammatory mediator, which can override the anti-inflammatory activities of corticosteroids. Thus, blocking of MIF function may provide direct anti-inflammatory activity and enhance the effectiveness of corticosteroid therapies. Anti-MIF antibodies were shown to be effective in preclinical animal models of asthma, glomerulonephritis and rheumatoid arthritis.

IDEC signed a collaborative research and development agreement with Taisho Pharmaceuticals Co. Ltd. to develop and commercialize antibody therapeutics against MIF for the treatment of inflammatory and autoimmune diseases. Anti-MIF antibodies are being developed by IDEC under an exclusive license agreement from Cytokine PharmaSciences, Inc. of West Conshohocken, PA. The original research on MIF was done at the Picower Institute for Medical Research.

PAGE-4 Plasmid DNA & PAGE-4 Protein for Prostate Cancer– IDEC researchers are capitalizing on recent advances in genomics and bioinformatics while leveraging IDEC’s core expertise and experience in oncology, monoclonal antibody and radioimmunotherapy technologies.

In April 2000 IDEC signed exclusive patent and technology license agreements with the National Cancer Institute (NCI) and the University of Iowa Research Foundation (UIRF), strengthening the Company’s oncology pipeline by developing new investigational immunotherapies for prostate cancer.

Under the terms of the NCI license agreement, which was preceded by a Cooperative Research and Development greement (CRADA), IDEC has been granted an exclusive worldwide license for the use of PAGE-4 plasmid DNA and PAGE-4 protein for the development and commercialization of a therapeutic vaccine to treat human prostate cancer. Under the terms of the UIRF license agreement, IDEC has been granted an exclusive, worldwide license for the use of a prostate-specific, surface-reactive monoclonal antibody, named 5E10, for evaluation as a potential therapy of prostate carcinoma.

PROVAX™ Antigen Formulation– IDEC has also discovered a proprietary antigen formulation, PROVAX, which has shown the ability to induce cellular immunity, manifested by cytotoxic T lymphocytes, in animals immunized with protein antibodies. Cellular immunity is a counterpart to antibody-based immunity and is responsible for the direct destruction of virally infected and malignant cells. PROVAX is a combination of defined chemical entities and may provide a practical means for the development of effective immunotherapies that act through the induction of both antibody and cell-mediated immunity.

IDEC believes such immunotherapies may be useful for the treatment of certain cancers and viral diseases. Preliminary studies also indicate that PROVAX can be safely administered by injection to human subjects. IDEC intends to make PROVAX available through licenses and collaborations to interested partners for development of immunotherapeutic vaccines.

Proprietary Vector Technologies – IDEC has developed methods of engineering mammalian cell cultures using proprietary gene expression technologies (“vector technologies”) that rapidly and reproducibly select for stable cells, producing high levels of desired proteins. These technologies allow the efficient production of proteins at yields that may be significantly higher, and costs that may be significantly lower, than current, competing cell culture manufacturing methods. IDEC has successfully applied one of these technologies to the commercial scale production of Rituxan. In addition, this technology has been licensed to Genentech, Chugai, Eisai and Boehringer Ingelheim for use in the production of other products.