BUSINESS THE VENERABLE BEAD Ambersynth resin is pitched as high quality and available by the ton.
B I O P H A R M A C E U T I C A L S
ROHM AND HAAS TAKES ON PEPTIDES Ion-exchange resin leader attempts a power play in solid-phase synthesis RICK MULLIN, C&EN NORTHEAST NEWS BUREAU
W
HEN ROHM AND HAAS RE-
structured its ion-exchange resins business in 2000, it formed a new unit specifically for biopharmaceutical applications. The unit includes the Amberchrom and Amberlite resins that it has sold for decades for purification and other adsorption-based downstream processes. But in the catbird seat is a new product line targeting what Rohm and Haas hopes will be on a fast track for growth in biotech drugs—peptide synthesis. Rohm and Haas says that its new 2chlorotrityl chloride (CTC) Ambersynth resin, introduced in May, was designed to address deficiencies inherent in most resins used as anchors in large-scale, solid-phase peptide synthesis. Key among these is homogeneity and overall quality of the polymer resin bead, which can affect the speed of reactions and defray costs by eliminating the need for recoupling steps in the synthesis of long or complicated peptide chains in large batch reactions. The company, a leader in the supply of
ion-exchange resins for water treatment and other applications, is also touting its ability to supply Ambersynth in large quantities. Peptide manufacturers agree that the market for synthesis resins is extremely fragmented with many small suppliers, making it difficult to ensure a consistent supply of highquality resins. Rohm and Haas hopes to parlay its large production capacity and its track record in supplying purification resins into a dominant position in supplying media for the synthesis of peptides. It is also hoping to establish a brand name in Ambersynth. There are two early successes. Senn Chemical and Bachem California have Eicher agreed to use the resin and market it to researchers and drug companies as Ambersynth C T C resins. Both firms have ceased manufacturing their own C T C resins.
Rohm and Haas's ion-exchange division has been selling adsorbent resins in the pharmaceutical market for 4 0 years, according to Jean-Francois Ferraro, general manager of the new advanced biosciences group, which is part of Rohm and Haas's process chemicals division. Most applications were in fermentation processes for antibiotics, primarily cephalosporin, he says. Amberchrom and Amberhte resins were also used in reverse-phase chromatography support and as excipients. Peptide synthesis is seen as a promising and fundamentally new application for Rohm and Haas's resin technology, Ferraro says. Peptide drugs have made a comeback on the strength of new delivery systems that take amino-acid-based therapeutics out of the injection-only category. Currently, more than 30 peptide-based drugs are on the market, and the recent approval of Roche and Trimeris' Fuzeon (enfuvirtide), an H I V treatment featuring a 36amino-acid polymer that Roche will produce in tons-per-year quantities, indicates there will be a trend toward more largescale manufacturing. THE MOVE into major commercial-scale peptide drug production presented an opportunity, Ferraro says. "We recognized that the biopharmaceutical industry was struggling to get enough resin supply to scale up large processes." Although many resin suppliers offer CTC functional groups, Ferraro says Rohm and Haas's clout is in the consistent quality and relatively huge supply—more than 50,000 tons per year from plants in France, England, and Japan—of its basic styrene/divinylbenzene polymer bead. Rohm and Haas does not view the CTC product as a commodity resin, according to Mark Vander Hoff, marketing manager of advanced biosciences. "We see it as the second generation of resins for peptide synthesis," Vander Hoff says.
"The biopharmaceutical industry was struggling to get enough resin supply to scale up large processes." 12
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The Ambersynth resin ranges in price from $4,000 per kg for small quantities to $1,000 per kg for multiton quantities. Vander Hoffsays this represents about a 30% premium over the price ofother functional supports such as Wang and Merrifield resins in small quantities. Carol Eicher, vice president of the process chemicals division at Rohm and Haas, says the company, which does not break out sales by division, sees the advanced biosciences group as a fast-growth venture spurred by the new resin. Eicher says the group will be following up with an enhanced enzyme-immobilizing resin, Amberzyme, which will be introduced at the CPhI conference in Frankfurt in October. Channa Basava, a U.S. marketing manager for Serin in California, says Senn has agreed to purchase Ambersynth resin as a base polymer to which it will add an amino acid as a starting material for synthesis and production. Basava says Senn sees Rohm and Haas as a reliable source ofconsistently high quality resin. Senn is also interested in using the Ambersynth brand name. He says Senn and Rohm and Haas could work on joint proposals to supply peptides or resins to biopharmaceutical companies. Philip Ottiger, president of Bachem California, says his company's decision to buy resin from Rohm and Haas was one of convenience. "It was there, and we are busy with other things," he says. "It's simple." He says, however, that the company may resume producing its own resin at any time. Ottiger says that even though cross-linking ability has improved with new resin systems such as Rohm and Haas's, there is still room for improvement in media for solidphase synthesis. "I'm a little disappointed in how little functional advantage has been added to resins over the pastfiveyears," he says. Most of Bachem's decisions on which resins to use in synthesis and purification are made on the basis ofprice rather than quality concerns, according to Ottiger. PEPTIDE SYNTHESIS has, however, been an area of active development among resin suppliers that serve the pharmaceutical sector. Advanced ChemTech, for example, recently introduced several new resins designed for improved peptide synthesis, according to William D. Bennett, technical marketing specialist. Among Advanced Chemlech's newproducts are polyethylene glycol cross-linked resins that have improved swelling properties and produce long peptides in higher yield and purity than those made with other support resins. The company has also developed resins with a styreneHTTP://WWW.CEN-ONLINE.ORG
2-vinylpyridine copolymer backbone, which Bennett says enhances purity in the synthesis of complex peptide sequences. Other companies, such as Diosynth, are working to develop new processes for peptide synthesis that combine solid-phase and solution-phase processes. Vander Hoff notes that the peptide in Fuzeon is manufactured in two steps: a solid-phase synthesis step followed by a solution phase. Still, the solid-phase component is an enormous brass ring for resin manufacturers, according to Vander Hoff
and Senn's Basava. Roche would not comment on its resin supply Rohm and Haas has its eye on Roche primarily because it is one of very few companies producing tons of peptide material. Peptide producers are hoping that will change. "Solid-phase synthesis is not aproblemforus because we are only producing one or two kilos at a time and can use various resins," says Jeanick Pascal, CEO of Multiple Peptide Systems, a San Diego-based division ofSNPE. "But I hope that in ayear or two resin becomes really important to us." •
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