Antibody partnership has eggs-cellent potential

Morphotek partners with Synageva BioPharma to develop therapeutic monoclonal antibodies

Lloyd Dunlap
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EXTON, Pa.—Using its Synageva Expression Platform (SEP) technology and related expertise, Synageva BioPharma Corp. will produce and develop a Morphotek therapeutic monoclonal antibody, states Dr. Philip M. Sass, executive vice president and chief operating officer of Morphotek Inc. SEP is an integrated platform of proprietary systems for protein production, processing and purification. Monoclonal antibodies that result from the collaboration may have potential for treatment of various forms of cancer and infectious disease.

Morphotek, a subsidiary of Eisai Corp. of North America, uses its proprietary Morphodoma technology to generate fully human antibodies, including antibodies optimized for affinity and/or titer, targeted against disease-associated antigens. The company leverages its other technology, morphogenics, to improve and enhance the activity of the antibodies that are generated by the Morphodoma technology, Sass explains.

"Unlike other technology, Morphodoma starts with human antibodies, and it does not manipulate the antibodies in vitro or convert mouse antibodies to human antibodies," Sass says. "We have a rich pipeline of antibody products such as MORAb-003, or farletuzumab, for ovarian cancer in Phase III, MORAb-009 for pancreatic cancer in Phase II and MORAb-004 that is pan-cancer specific in Phase I. We are always exploring new ways that may enhance the manufacturing process for our antibody products as a means to fulfill Eisai's human healthcare mission."

Synageva and Morphotek initiated discussions earlier this year, notes Dr. A.J. Joshi, senior vice president of Synageva Medical Operations & Commercial Development.
"Morphotek is one of the leaders in the antibody space with their high affinity antibodies against a variety of targets," he states. "SEP is an ideal platform for antibodies, both neutralizing antibodies and in particular antibodies that work by killing their targets (high ADCC or cytotoxicity) such as antibodies for various cancers. We are looking forward to a fruitful and long-term relationship with Morphotek."

The fundamental strength of the proprietary SEP is its ability to express almost any biopharmaceutical protein, Joshi says.

"Our team begins by sequencing the human protein of interest and designing constructs whereby this sequence is inserted alongside a customized, tissue specific promoter," he says. "The unique combination of the vector and promoter drives expression of the protein of interest in egg white. Synageva's research team continues to make unprecedented scientific advances such that our vectors presently express protein at ~5 g/L and are set to reach ~10 g/L later this year. 

"Since egg white is an extremely stable, protein-friendly environment, it enables development of potential therapeutic proteins that are difficult to effectively express with other technologies," Joshi continues. "In addition, certain proteins expressed through SEP have advantageous glycosylation patterns with respect to their potential activity. For example, Synageva and its partners will be able to develop and commercialize
next generation monoclonal antibodies (mAbs) with glycosylation patterns that increase ADCC activity up to 100-fold—thus increasing potency and potentially efficacy for oncology targets; novel therapeutic proteins for orphan diseases without available therapies; and next generation and follow-on cytokines, with certain compounds possessing significantly superior activity profiles."

Morphotek's Sass notes that the company has extensive collaborations with investigators at leading corporate and academic institutions and a deep portfolio of antibodies for possible development and licensing in several therapeutic categories. The company develops protein and antibody products through the use of novel and proprietary technologies. These technologies have been successfully applied to a variety of molecules that are suitable for pharmaceutical product development in the areas of antibody therapeutics, protein therapeutics, product manufacturing, drug target discovery and improved output traits for commercial applications. The company is currently focusing its platform on the development and manufacturing of therapeutic antibodies for the treatment of cancer, inflammation and infectious disease.

Lloyd Dunlap

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