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From Russia with love
BOSTON, Mass.—To underscore its untapped potential, MSM Protein Technologies (MSM) notes that of 4,000 multi-spanning proteins, less than 1 percent have been targeted with antibodies, whereas virtually every soluble protein found in man has been. Perhaps eyeing that potential, Merck Serono, a division of Merck KGaA in Darmstadt, Germany, has entered into collaboration with MSM to create antibody based products targeted to G-protein coupled receptors (GPCRs) and other possible targets in the cell membrane.
MSM will provide its proprietary technology and expertise to display selected targets in their native form and work with Merck Serono's scientists to apply these in various drug discovery platforms. Dr. Tajib Mirzabekov, MSM president and chief scientific officer, says that "Merck Serono has excellent scientists in this space and we will be working shoulder to shoulder with them to identify monoclonal antibodies against very difficult and very valuable targets."
Under the terms of the agreement, MSM—a privately held company that eschews interest from outside investors—will receive an upfront payment and is eligible to receive further payments on achievement of development and commercial milestones, as well as royalties on sales of potential products resulting from the collaboration. Financial details of this agreement were not disclosed.
A membrane spanning protein connects the internal to the external surface of the biological membrane, or lipid bilayer, in which it is embedded. These proteins are expressed on a number of cell types, including on the surface of bacteria and viruses.
Multi-spanning membrane proteins, as the name implies, span a membrane a number of times. They are the most important class of cell-surface targets for therapeutic intervention and represent the majority of the targets for drugs sold today. Many well-validated multi-spanning membrane proteins have not yet been successfully targeted with drugs. Still others may be best targeted with an antibody scaffold with superior results to small molecule drugs.
Davis Farmer, MSM's chairman, points out that the company's other three founders were all educated in Russia—Mirzabekov, Dr. David Kriemer, COO, and Dr. Eldar Kim, director of research. MSM was formed in 2005 on the basis of technology originally developed at the Dana Farber Cancer Institute by Mirzabekov and subsequently licensed to MSM.
Since then, the company has developed its proprietary SIMPL platform and magnetic proteoliposome particles (MPLs) to display multi-spanners such as GPCRs in highly concentrated and purified form while retaining their native conformation and orientation to maximize the probability of raising functional antibodies.
SIMPL is a third-generation display technology, Farmer explains, developed to provide a more sensitive, powerful tool for "going after" ion channels and transporters. The platform has been very successful with GPCRs, Farmer says, raising functional human antibodies against about a dozen GPCRs and other membrane proteins.
"And this is a very substantial proportion of all that have been done," he notes.
Among the advantages of antibodies in Farmer's view are that they are safer and more specific for indications such as cancer where they kills cells and block metastasis and "bind where you want them to, not to the ovaries, testes or liver." Antibodies are also better for antivirals, he says, because they are less likely to fail due to mutations, and due to their mass, they can cover the target completely.