检索结果-内蒙古大学图书馆

Inside Front Cover: Chemical process development in the Pharmaceutical Industry in Europe: Insights and Perspectives from Industry Scientists

引用

Angewandte Chemie 2025年

作者： Joachim Krueger André P. dieskau Jorma Hassfeld Joerg Gries Oliver Block Hilmar Weinmann daniel Kaufmann Stefan Hildbrand Volker Kraft robert Moeckel Juan r. dehli Ulrich Scholz Carl Friedrich Nising Pharmaceuticals CMC & Technology Bayer AG D-42096 Wuppertal Germany Global CMC Development Merck Healthcare KGaA D-64293 Darmstadt Germany Chemical Process R&D Johnson & Johnson Innovative Medicine Beerse B-2340 Belgium Chemical & Analytical Development Novartis AG Basel CH-4056 Switzerland Process Chemistry & Catalysis F. Hoffmann-La Roche Ltd Basel CH-4070 Switzerland R&D Global CMC Development Synthetics Sanofi-Aventis Deutschland GmbH D-65926 Frankfurt Germany Chemical Development Boehringer Ingelheim Pharma GmbH & Co. KG D-55216 Ingelheim am Rhein Germany

来源：评论

学校读者我要写书评

暂无评论

Formation of Transient Highly-Charged mAb Clusters Strengthens Interactions with Host Cell Proteins (Hcps) and results in Poor Hcp removal by Protein a Chromatography

SSRN

引用

SSrN 2022年

作者： Luo, Haibin du, Qun Qian, Chen Mlynarczyk, Michelle Pabst, Timothy M. damschroder, Melissa Hunter, Alan K. Wang, William K. Purification Process Sciences AstraZeneca LLC One Medimmune Way GaithersburgMD20878 United States AstraZeneca LLC One Medimmune Way GaithersburgMD20878 United States Analytical Sciences BioPharmaceutical Development Biopharmaceuticals R&D AstraZeneca LLC One Medimmune Way GaithersburgMD20878 United States

Protein A chromatography with a high salt wash usually leads to robust clearance of host cell proteins (HCPs) in most recombinant monoclonal antibodies (mAbs), but a small subset of recalcitrant mAbs show significant HCP copurification. In this study, we carried out systematic studies using 4 different mAbs to explore the HCP copurification mechanism. HCP identification results revealed that the 3 high-HCP mAbs had many common HCPs which do not copurify with the low-HCP mAb, suggesting a similar mechanism is at play. Through wash evaluation, surface patch analysis, chain-swapping, domain evaluation, and structure-guided mutations, several charged residues in each mAb were found which correlated with HCP copurification. Surprisingly, these residues are also critical for self-association propensity. We observed an inverse correlation between diffusion interaction parameter and HCP copurification. Each of the high-HCP mAbs could form dynamic clusters consisting of 3~6 mAb molecules. Therefore, a mAb cluster can exhibit higher net positive charges on the order of 3 to 6, compared with the individual mAb. In Protein A chromatography, high-HCP mAbs had elution tailing which contained high level of HCPs. Addition of Arginine-HCl or point mutations preventing cluster formation effectively reduced HCP copurification and elution tailing. Based on these results, we propose a novel HCP-copurification mechanism that formation of mAb clusters strengthens charge-charge interactions with HCPs and thus compromises HCP removal by Protein A chromatography. Besides arginine, histidine under acidic pH conditions prevented cluster formulation and resulted in effective HCP removal. Finally, structure-guided protein engineering and solution screening by using cluster size as indicator are useful tools for managing mAbs with high-HCP issues. © 2022, The Authors. All rights reserved.

关键词： Monoclonal antibodies

来源：评论

学校读者我要写书评

暂无评论

Inside Front Cover: Chemical process development in the Pharmaceutical Industry in Europe: Insights and Perspectives from Industry Scientists

引用

Angewandte Chemie International Edition 2025年

来源：评论

学校读者我要写书评

暂无评论

In Support of Early-Career researchers

引用

OrGANIC LETTErS 2023年第5期25卷 715-719页

作者： Bandichhor, rakeshwar Borovik, A. S. de Bettencourt-dias, Ana Eastgate, Martin d. radu, Nora S. Shi, Feng McElwee-White, Lisa API R&D IPDO Dr. Reddy’s Laboratories Ltd. Bachupally Hyderabad Telangana 500090 India Department of Chemistry University of California 1102 Natural Science II Irvine California 92797 United States Department of Chemistry University of Nevada Reno Nevada 89557 United States Chemical Process Development Bristol Myers Squibb 1 Squibb Drive New Brunswick New Jersey 08903 United States DuPont Co. Experimental Station E336 200 Powder Mill Road Wilmington Delaware 19803 United States Research Center of Chiral Functional Heterocycles School of Chemistry and Materials Science Jiangsu Normal University Xuzhou 221116 China School of Petrochemical Engineering Changzhou University Changzhou 213164 China Department of Chemistry University of Florida Gainesville Florida 32611-7200 United States

来源：评论

学校读者我要写书评

暂无评论

Green Chemistry Articles of Interest to the Pharmaceutical Industry

引用

OrGANIC process rESEArCH & development 2024年第3期28卷 652-660页

作者： Ashley, Melissa A. Aukland, Miles H. Bryan, Marian C. Cismesia, Megan A. dutschei, Theresa Engl, Oliver d. Engl, Pascal S. Garcia, Aprimelvaro Enriquez Molina, Alejandro Gimenez Harawa, Vanessa Kelly, Christopher B. Leclair, Alexandre Lei, Zhen Li, Wei Pawlas, Jan Scott, Samuel C. Steven, Alan Takale, Balaram S. Treitler, daniel S. Wu, Hao Zeng, Mingshuo Zhang, Yongda Genentech Inc. 1 DNA Way South San Francisco California 94080 United States Chemical Development Pharmaceutical Technology & Development Operations AstraZeneca Macclesfield SK10 2NA U.K. Janssen R&D 1400 McKean Road Spring House Pennsylvania 19002 United States Corteva Agriscience 9330 Zionsville Road Indianapolis Indiana 46268 United States Synthetic Biochemistry GSK Gunnels Wood Road Stevenage SG1 2NY U.K. Biogen 115 Broadway Cambridge Massachusetts 02142 United States Department of Process Chemistry & Catalysis F. Hoffmann-La Roche Ltd 4070 Basel Switzerland Discovery Chemistry Research and Technology Eli Lilly and Company Avenida de la Industria S/N 28100 Alcobendas Madrid Spain Novo Nordisk A/S Smørmosevej 17-19 2880 Bagsværd Denmark Chemical and Analytical Development Novartis AG 4056 Basel Switzerland Boehringer Ingelheim Pharmaceuticals 900 Ridgebury Road Ridgefield Connecticut 06877 United States 18-1 Tonglian Road Bixi Subdistrict Changshu Jiangsu 215537 China PolyPeptide Limhamnsvägen 108 P.O. Box 30089 20061 Limhamn Sweden CatSci Ltd CBTC2 Capital Business Park Cardiff South Glamorgan CF3 2PX U.K. Chemical Development Neurocrine Biosciences San Diego California 92130 United States Bristol Myers Squibb 556 Morris Avenue Summit New Jersey 07901 United States

来源：评论

学校读者我要写书评

暂无评论

Physicochemical and functional assessment of messenger rNA 5′Cap-end impurities under forced degradation conditions

引用

Molecular Therapy Nucleic Acids 2025年第2期36卷

作者： J. Hutchinson F. Schweikart r. Shannon A. Murthy S.M. Bates S. Leone T. Nissan d. Sideris C. Lal J. Button r. rani G. Thom N. Bond E. Örnskov S. Trabulo Process and Analytical Sciences BioPharmaceuticals Development BioPharmaceuticals R&D AstraZeneca Cambridge CB2 0AA UK Advanced Drug Delivery Pharmaceutical Sciences BioPharmaceuticals R&D AstraZeneca 431 83 Gothenburg Sweden Immune Safety Clinical Pharmacology and Safety Sciences BioPharmaceuticals R&D AstraZeneca Cambridge CB2 0AA UK Cell Therapy Safety Clinical Pharmacology and Safety Sciences BioPharmaceuticals R&D AstraZeneca Cambridge CB2 0AA UK Nucleic Acid Therapeutics Discovery Sciences BioPharmaceuticals R&D AstraZeneca Cambridge CB2 0AA UK

The 5′Cap is a modified nucleotide structure added to the 5′end of mrNA, which plays a critical role in stability and translation of the molecule. Accurate characterization of 5′Cap impurities is crucial during development of mrNA therapeutics. Here, we utilized orthogonal liquid chromatography-mass spectrometry (LC-MS) workflows to characterize Cap-1-modified mrNA. A complex mixture of uncapped and, notably, 5′Cap chemical degradation variants, was detected. We subjected Cap-1 analogs to process-related forced degradation conditions and characterized multiple degradation routes of the 5′Cap structure, including hydrolysis and depurination. 5′Cap hydrolysis was observed in a representative in vitro transcription (IVT) reaction buffer and was driven by factors including pH, temperature, and the presence of spermidine and MgCl 2 . Method-induced artifactual degradation occurred during LC-MS data acquisition, emphasizing the importance of using reference standards and optimizing methods to reduce such artifacts. We investigated the effect of 5′Cap degradation on expression and reactogenicity in vitro using model mrNAs with elevated impurity levels. mrNA 5′Cap degradation impurities significantly impacted protein expression but did not trigger innate immune response pathways. 5′Cap degradation impurities should be considered as a critical quality attribute of mrNA therapeutics and should be monitored during production, purification, formulation, and storage.

关键词： MT: oligonucleotides: therapies and applications rNA 5′Cap liquid chromatography-mass spectrometry critical quality attributes forced degradation

来源：评论

学校读者我要写书评

暂无评论

High-Performance Flip Chip Bonding Mechanism Study with Laser Assisted Bonding

High-Performance Flip Chip Bonding Mechanism Study with Lase...

引用

Electronic Components and Technology Conference (ECTC)

作者： MinHo Gim ChoongHoe Kim SeokHo Na dongSu ryu Kyungrok Park JinYoung Kim Adv. Process & Material Development Group R&D center Amkor Technology Korea Inc. Incheon Republic of Korea

ISBN: (数字)9781728161808

ISBN: (纸本)9781728161815

recent advanced flip chip ball grid array (FCBGA) packages require high input/output (I/O) counts, fine-pitch bumps and large/thin package substrates. One of the key hurdles to accommodate these requirements is the flip chip bonding process. Therefore, advanced flip chip bonding technologies are continuously being developed and one of the promising solutions is laser assisted bonding (LAB) technology. The key advantage of LAB is its extremely short bonding time (less than 1 sec) with a localized heating area which provides low thermal and mechanical *** this study, two bonding profiles of "time fixed" and "power fixed" are tested using 15.2 x 15-mm 2 FCBGA test vehicles with three difference die thicknesses. Wetting sequences of the solder joints are inspected with time interval of 100 ms. Solder bump interconnections are analyzed by cross section and reliability tests are performed. LAB is also compared with thermocompression bonding (TCB) for process and solder joint characteristics.

关键词： Bonding Flip-chip devices Silicon Soldering Power lasers Heating systems Laser modes

来源：评论

学校读者我要写书评

暂无评论

Thermal performance enhancement of novel integrated vapor compression and organic rankine cycle for electricity production: a full-condensing vs. desuperheating approach comparison in ultra-low-grade waste heat recovery

引用

e-Prime - Advances in Electrical Engineering, Electronics and Energy 2024年 7卷

作者： Asim, Muhammad Khan, Sheheryar Zia, Abdul Wasy Siddiqui, Farooq riaz Leung, Michael K.H. School of Professional Education & Executive Development The Hong Kong Polytechnic University Kowloon Hong Kong Institute of Mechanical Process and Energy Engineering (IMPEE) School of Engineering and Physical Sciences Heriot-Watt University Edinburgh EH14 4AS United Kingdom Department of Mechanical and Aerospace Engineering The Hong Kong University of Science and Technology Hong Kong 100077 Hong Kong Ability R&D Energy Research Centre School of Energy and Environment City University of Hong Kong Hong Kong Hong Kong

This paper presents the thermodynamic analysis, performance assessment and working fluid selection for a novel integrated vapor compression cycle and the organic rankine cycle system, which recovers ultra-low-temperature waste heat (50 °C) rejected by the condenser of a vapor compression cycle (VCC). The study is conducted on a vapor compression system of a 35 kW cooling capacity, followed by the component sizing of the organic rankine cycle (OrC) based on the available waste heat in the condenser of the refrigeration system. The effect of the operational parameters of the vapor compression cycle on the overall system performance are investigated. The system performance of the integrated system is estimated in terms of coefficient of performance, cycle thermal efficiency and exergy efficiency. The novel integrated systems has been analyzed thermodynamically for 36 pairs of pure refrigerants. results show that the working fluid pair r600a/r141b with combined coefficient of performance (3.54), OrC thermal efficiency (3.05 %), electricity saving ratio (13.34 %) and total exergy destruction (6.94 kW) is the most suitable VCC/OrC working fluid pair in full condensing method. r407c-r141b is found to be the best working fluid pair in desuperheating method for the same integrated system. The performance analysis for full condensation and desuperheating methods are also investigated. The results indicate a 12.5 % improvement in the coefficient of performance of the integrated system using the full condensation method and a 2.5 % improvement using the desuperheating method compared to the standalone air conditioning system. Additionally, the sensitivity analysis results show that there exists optimum operating condition that maximize the system performance of the integrated system. © 2024 The Author(s)

关键词： Compatible working fluids de-superheating Exergy efficiency Full-condensing Organic rankine cycle Performance assessment Vapor compression cycle Waste heat recovery

来源：评论

学校读者我要写书评

暂无评论

Lessons Learned in developing a Manufacturing Facility for Flow Chemistry

引用

Organic process research and development 2025年

作者： Usutani, Hirotsugu Technology Research & Development Division Process Research & Development Laboratories Formerly of Sumitomo Pharma Co. Ltd. Kasugade-naka 3-1-98 Konohana-ku Osaka554-0022 Japan CMC & Production Department Chemical Process R&D Ono Pharmaceutical Co. Ltd. Sakurai 3-1-1 Shimamoto-cho Mishima-gun Osaka618-8585 Japan

Specific designs are necessary when installing manufacturing facilities for active pharmaceutical ingredient (API) plants, especially for scaling up manufacturing using flow chemistry. Each flow reactor is a device focused on an intended reaction. However, due to the required heat exchange (heating or cooling), the parts responsible for carrying out the reactions (the flow reactor itself) are often enclosed in a jacket or setup in a way that makes it difficult to verify the internal structure from the external view. In this paper, we present a case where a piping error made during the installation of a flow system, designed for oxidation reactions with heating, led to a subsequent manufacturing failure, as the error went undetected before operation was started. In retrospect, it would have been possible to identify the piping error ahead of starting manufacture, based on data, such as the internal pressures, obtained during the premanufacturing test. Specifically, the mistake highlighted the importance of identifying the flow lines with ″synchronized internal pressures″ and prediction of the flow lines where the internal pressure is expected to be at its highest or lowest. It is thought that our observations regarding the failure offer an example for OPr&d’s special issue on ‘Lessons Learned in Organic process Chemistry’ and the details will be disclosed. © 2025 American Chemical Society.

关键词： Oxidation

来源：评论

学校读者我要写书评

暂无评论

15P Enhancement Platform for immune Cells (EPiC): invIOs’s innovative cell-therapy platform for creating personalized cancer treatments

引用

ESMO Open 2023年第1期8卷 100981-100981页

作者： Kuttke, M. Gugenberger, r. Thell, K. Bischof, S. Peball, B. Muehleisen, H. Urban, M. Gapp, B. Bugajska-Schretter, A. Halfmann, A. Morley, P. dohnal, A. R&D invIOs GmbH Vienna Austria invIOs GmbH Vienna Austria Clinical Development invIOs GmbH Vienna Austria Clinical Operations invIOs GmbH Vienna Austria Process Development invIOs GmbH Vienna Austria Corporate Development invIOs GmbH Vienna Austria Communications invIOs GmbH Vienna Austria

来源：评论

学校读者我要写书评

暂无评论

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案：

请选择收藏分类：

通借通还

建议与咨询 留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

时间限定

文献类型

馆藏选择

核心期刊

语言

文献类型

帮助

文字说明：

检索规则说明：

检索范例：

分类表

所选分类

限定检索结果

文献类型

馆藏范围

日期分布

学科分类号

主题

机构

作者

语言

请选择保存的检索档案： 新增检索档案 确定 取消

请选择收藏分类： 新增自定义分类 确定 取消

通借通还

建议与咨询留下您的常用邮箱和电话号码，以便我们向您反馈解决方案和替代方法

请选择保存的检索档案：

请选择收藏分类：