From Russia with love

Merck Serono joins Russian-led team at MSM Protein Technologies to raise antibodies to complex cell surface receptors

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BOSTON, Mass.—To underscore its untapped potential, MSMProtein Technologies (MSM) notes that of 4,000 multi-spanning proteins, lessthan 1 percent have been targeted with antibodies, whereas virtually everysoluble protein found in man has been. Perhaps eyeing that potential, MerckSerono, a division of Merck KGaA in Darmstadt, Germany, has entered intocollaboration with MSM to create antibody based products targeted to G-proteincoupled receptors (GPCRs) and other possible targets in the cell membrane.
MSM will provide its proprietary technology and expertise todisplay selected targets in their native form and work with Merck Serono'sscientists to apply these in various drug discovery platforms. Dr. TajibMirzabekov, MSM president and chief scientific officer, says that "Merck Seronohas excellent scientists in this space and we will be working shoulder toshoulder with them to identify monoclonal antibodies against very difficult andvery valuable targets."
Under the terms of the agreement, MSM—a privately heldcompany that eschews interest from outside investors—will receive an upfrontpayment and is eligible to receive further payments on achievement ofdevelopment and commercial milestones, as well as royalties on sales ofpotential products resulting from the collaboration. Financial details of thisagreement were not disclosed.
A membrane spanning protein connects the internal to theexternal surface of the biological membrane, or lipid bilayer, in which it isembedded. These proteins are expressed on a number of cell types, including onthe surface of bacteria and viruses.
Multi-spanning membrane proteins, as the name implies, spana membrane a number of times. They are the most important class of cell-surfacetargets for therapeutic intervention and represent the majority of the targetsfor drugs sold today. Many well-validated multi-spanning membrane proteins havenot yet been successfully targeted with drugs. Still others may be besttargeted with an antibody scaffold with superior results to small moleculedrugs.
Davis Farmer, MSM's chairman, points out that the company'sother 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 thebasis of technology originally developed at the Dana Farber Cancer Institute byMirzabekov and subsequently licensed to MSM.
Since then, the company has developed its proprietary SIMPLplatform and magnetic proteoliposome particles (MPLs) to display multi-spannerssuch as GPCRs in highly concentrated and purified form while retaining theirnative conformation and orientation to maximize the probability of raisingfunctional antibodies.
SIMPL is a third-generation display technology, Farmerexplains, developed to provide a more sensitive, powerful tool for "goingafter" ion channels and transporters. The platform has been very successfulwith GPCRs, Farmer says, raising functional human antibodies against about adozen GPCRs and other membrane proteins.
"And this is a very substantial proportion of all that havebeen done," he notes.
Among the advantages of antibodies in Farmer's view are thatthey are safer and more specific for indications such as cancer where theykills cells and block metastasis and "bind where you want them to, not to theovaries, 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.

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