Genetic Engineering & Biotechnology News

JUL 2017

Genetic Engineering & Biotechnology News (GEN) is the world's most widely read biotech publication. It provides the R&D community with critical information on the tools, technologies, and trends that drive the biotech industry.

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i 30 | JULY 2017 | | Genetic Engineering & Biotechnology News Michael J. Karney In synthetic research, all scientific decision- making ultimately rests on one thing: data. The ability to generate a product and ac- quire data about said product is paramount to making changes to synthetic methods or structural elements. As a result, the genera- tion of product should be as fast as (or close to) the analytical method used to acquire the necessary data for the next rational step in the scientific method. This idea of producing a compound quickly, efficiently, and reliably is central to high-efficiency solid-phase peptide synthesis (HE-SPPS) methodology 1 . The perspective of "single peptides, fast" offers distinct ad- vantages to the synthetic process as well as applied testing of peptides after isolation. Examining the case of a hypothetical 20mer, this peptide is made in almost 20 hours using room temperature chemistry methods. Under HE-SPPS protocols, the same se- quence is complete in only two hours, a rate enhancement of 10-fold (Figure). The chem- ist utilizing HE-SPPS can synthesize, analyze, and plan the next step in a rational optimiza- tion strategy for this sequence (or carry prod- uct on to in vitro or in vivo testing) before the third amino acid is coupled with room tem- perature methods. In addition to providing speed, the micro- wave heating of high-efficiency methods pro- vides simplified optimization, higher peptide purity, and even creation of sequences not accessible by conventional methods. Con- ventional optimization typically consists of a shotgun approach: screen resins, screen dif- ferent reagent excesses, screen activators, etc. This process necessitates tens or hundreds of reactions, but optimization of purity does not necessitate this process. Reaction Kinetics Better reaction kinetics through micro- wave heating during deprotection and cou- pling steps overcomes many of the variables found in these obsolete strategies, and chem- ists can focus on making rational synthetic decisions related to fewer variables and fewer test syntheses. In addition to simplify- ing optimization, microwave HE-SPPS also provides more complete reactions, and cor- respondingly higher purities, due to elevated temperatures (Table). More usable peptide product means more therapeutic testing in the pursuit of a lead candidate. By minimizing synthesis time, optimization time, and repeat syntheses, HE-SPPS method- ology brings a high level of practical value to synthetic chemists. Accessing "single peptides, fast" ultimately means earlier discovery of the next peptide therapeutic opportunity. Reference 1. Collins, J. M.; Porter, K. A.; Singh, S. K.; Vanier, G. S., Org. Lett., 2014, 6, 940. Accelerating Novel Therapeutic Discovery Bioprocessing Perspectives Utilizing High-Efficiency Solid-Phase Peptide Synthesis (HE-SPPS) Methodology Insights Bioprocessing Rentschler Biotechnologie, a CDMO, and Rentschler Fill Solutions, an independent specialist for aseptic fill and finish services, formed a strategic partnership to provide new state-of-the-art fill-and-finish facilities and one-stop solutions for biopharmaceutical products to meet the needs of Rentschler Biotechnologie's clients. Rentschler Fill Solutions will prospectively serve as the exclusive partner for the fill-and-finish services of Rentschler Biotechnologie's manufacturing projects. Rentschler Fill Solutions is owned by the Rentschler family and will begin operations in mid-2018. In addi- tion to servicing Rentschler Biotechnologie's clients, Rentschler Fill Solutions will offer its fill-and-finish ser- vices on a clinical as well as commercial scale to its own client base. "Based on the maturity of the biotech industry and demand for new drugs in growing international mar- kets, we are seeing more and more demand, not only in terms of manufacturing for clinical studies, but for com- mercial-scale manufacturing and market supply," said Frank Mathias, Ph.D., CEO of Rentschler Biotechnologie. "Clients will have one contact person and qualified project manager who is responsible for managing all aspects of the clinical full-service project," explained Rentschler Biotechnologie's spokesperson Marion Schrader, Ph.D. "With the processes all optimally aligned, Rentschler should be able to meet the client's projected timelines (to get on the market)." The new technologies and facilities in Austria will enable both companies to meet the future needs of their clients, added Dr. Schrader, who noted that the area in Rankweil, Austria "easily allows" any further ex- pansions of the facility. Reinhold Elsaesser, general manager of Rentschler Fill Solutions, said that as an independent specialist for the aseptic filling of liquid and lyophilized biopharma- ceuticals, "we aim to manage the specific filling require- ments of a wide range of biopharmaceutical compa- nies from clinical studies through market supply." He pointed out that the Rankweil facility will be able to handle small to medium-sized batches (up to 60,000 vials/240 L per batch) and offer advanced aseptic fill- ing technology with a RABS (restricted access barrier system). Single-use and stainless-steel equipment will be available. "The facility contains a 15 m 2 freeze dryer with a maxi- mum capacity of 60,000 vials based on DIN2R and there is a capping process within RABS," continued Elsaesser. "Analytics will be performed according to EP/USP, and include stability and process validation services as well as terminal stabilization." n Rentschler Companies Partner on New Fill-and-Finish Facilities Michael J. Karney (Michael.karney@ is product manager for the life sciences division of CEM. Website: Figure. Building a 20mer peptide with HE-SPPS Table. Comparative Conventional Room Temperature and HE-SPPS Syntheses Peptide Length Conventional Synthesis Purity HE-SPPS Purity 1 65-74 ACP 10 AA 39 93 2 JR 10mer 10 AA 42 67 3 ABRF 1992 16 AA 56 82 4 ABC 20mer 20 AA 70 73 5 Thymosin 28 AA 37 61 6 1-42 β-Amyloid 42 AA 56 72

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