Repligen says strategic partnerships are strengthening its proteins business, following a quarter which saw deals inked with Navigo Proteins and Purolite.
During a financial call last week, Repligen said its strength in it proteins business is coming from existing customers including MilliporeSigma, GE Healthcare, and Purolite (which extended its Protein A ligand supply deal until 2022 last year).
But CEO Tony Hunt added the growth of both its ligand and resin portfolio and Protein A sales have been driven by strategic partnerships with companies which Repligen believe have technologies which fit into its platform.
This includes deals struck in the quarter with Navigo Proteins to develop next-generation ligands, and a commercialization deal with Purolite Life Sciences.
"Both collaborations strengthened our long-term Repligen-owned affinity ligand strategy within our proteins franchise," Hunt said. "Navigo and Purolite are examples of the types of partnerships that we can put in place, and our plan would be over the next year to have additional partnerships that would further strengthen the portfolio whether it's in filtration or chromatography."
Navigo and Purolite
"With Navigo Proteins, we signed a long-term agreement to co-develop a series of affinity ligands focused on monoclonal antibody on non-Mab targets," Hunt said. "The agreement secures for Repligen both IP and exclusivity on the ligands that we co-develop with Navigo, using their high-throughput screening platform."
Purolite, meanwhile, will combine Repligen's next-generation Protain A ligand NGL-Impac A with its Praesto agarose jetting base bead technology.
"Purolite's Jetted A50 resin product is now available to the broader bioprocessing customer base, so we expect good traction for ligands in the marketplace based on the initial performance data and customer feedback."
Purolite: In November 2022, With Repligen, a business that provided the bulk of Protein A ligands, Purolite stated that it has increased and extended its ligand supply relationship with them. Praesto Jetted A50 HipH, a new protein A resin that combines Purolite's base beads with Repligen's ligand technology, was created and commercialised as a result of the pre-existing cooperation.
Protein A Chromatography relies on the specific and reversible binding of antibodies to an immobilized protein A ligand. Protein A is a 56 kDa surface protein of Staphylococcus aureus. It is composed of five immunoglobulin-binding domains, each of which are able to bind proteins from many mammalian species, most notably Immunoglobulin G (IgG) through the heavy chain within the Fc region. While the native form of Protein A was used as the ligand for first generation Protein A resins, recombinant forms (rProtein A) produced in E. coli are the most prevalent today. Modifications to the protein structure of the ligand, the advent of ligands composed of single domain multimers, and multipoint attachment have given rise to the caustic stable, high capacity and extremely robust Protein A resins in use today.
TOYOPEARL Protein A Resins
TOYOPEARL Super A is the latest of Tosoh Bioscience's bouquet of Protein A affinity resins, based on alkaline stable, Animal origin free, recombinant ligands coupled to the proven TOYOPEARL polymethacrylate matrix. They are derived from one of the IgG binding domains of protein A. For the ultra-high capacity TOYOPEARL Super A, this domain was further optimized and expressed as a hexamer in order to further increase IgG binding capacity. Multipoint attachment of the ligands to the TOYOPEARL matrix enhances the chemical and thermal stability of the resins.
配基描述：
An enhanced, animal-origin free, recombinant protein A ligand is bound to the polymethacrylate base bead via multipoint attachment resulting in excellent base stability for up to 100 CIP cycles with 0.5 mol/L NaOH and up to 70 CIP cycles with 1 mol/L NaOH while maintaining 90 % of its initial DBC.
产品属性中的配基信息：
Ligand: modified, code-optimized C domain, hexameric ligand with multipoint attachment
Durham, NC, US (ISO 9001)
Peabody, MA, US (ISO 9001)
Jessup, MD, US (ISO 9001)
Tampa, FL, US (ISO 9001)
Riverside, CA, US (ISO 9001)
Dublin, IE (ISO 9001)
CaptureSelect and POROS Purification Products
Purifying next-generation bio-therapeutics 201
CaptureSelect technology 202
POROS technology 203
Quality you can count on 204
Affinity chromatography 205
Purification of antibody-derived therapeutics 205
Purification of recombinant proteins, biosimilars, and vaccines 206
Purification of viral vectors 207
Ion exchange chromatography 208
Hyphobic interaction chromatography 210
Large-scale pre-packed columns 211
Process screening and optimization 213
Analytical tools 214
Custom chromatography services 216
rSPA - Native Recombinant Staphylococcal Protein A Ligand
rSPA –Native Recombinant Staphylococcal Protein A Ligand – is the most advanced non-mutant Protein A ligand available from Repligen. The combination of performance and purity to native Protein A and outstanding economics and supply chain security, makes rSPA the automatic first choice for all new Protein A ligand applications.
Contains the same amino acid sequence and molecular mass as the native Protein A sourced from S. aureus
Manufactured with animal-free materials
Native Protein A Ligand
Native Protein A is a purification ligand used to isolate IgG from crude protein mixtures. It binds with high affinity to the Fc region of IgG's. When immobilized on a matrix, e.g; Sepharose, Protein A (native) can be used to isolate IgG from crude protein mixtures.
Native Protein A meets the strictest demands of drug manufacturers in terms of purity, reproducibility, binding capacity, specificity and other key measures critical to the quality of downstream processes.
Reliable performance: Fc specific binding to IgG
Guaranteed purity: > 95% purity by SEC
Activity: > 95% IgG-binding activity
Not purified by hIgG affinity
Produced according to cGMP
Customer First.
Support is part of the Repligen DNA. Our goal is to provide exceptional customer experience, and to support the efficient and successful adoption and implementation of all Repligen products and services.
Thermo Fisher Scientific has entered into a strategic partnership with a biotechnology firm to co-develop innovative protein A resin products. This collaboration is poised to drive innovation and meet the growing demand for efficient purification processes in biomanufacturing.
第227条："In-house manufactured Protein A ligand" - 内部制造的Protein A配基
第228条："In-house manufactured Protein A ligand, expressed in yeast" - 内部制造的Protein A配基，在酵母中表达
第229条："The in-house manufactured Protein A ligand is produced in yeast to ensure a non-animal derived production process" - 内部制造的Protein A配基在酵母中生产，以确保非动物来源的生产工艺
第230条："on a Protein A ligand manufactured in-house" - 基于内部制造的Protein A配基
第231条："Second-site sourcing for the CaptureSelect affinity ligands is assured by manufacturing capabilities at the Thermo Fisher... An in-house manufactured Protein A" - Thermo Fisher的制造能力确保了CaptureSelect亲和配基的第二来源...一个内部制造的Protein A
第233条："A cost-effective, high performance protein A resin developed from in-house sourced protein A" - 由内部采购的Protein A开发的具有成本效益、高性能的protein A树脂
结论：Thermo Fisher的Protein A配基是自主生产（内部制造）的，在酵母中表达
Bio-Rad的配基来源（部分确认）：
第288条："UNOsphere SUPrA Affinity Resin combines UNOsphere bead technology with a recombinant Protein A ligand" - UNOsphere SUPrA亲和树脂结合了UNOsphere珠技术与重组Protein A配基
Thermo Scientific MabCaptureC Protein A Resin supports stable binding capacity and alkaline resistance for dependable purification performance.
Benefits of MabCaptureC Protein A chromatography resin
Integrating Protein A chromatography into antibody capture workflows helps maintain reproducibility and process control from development through scale-up. This approach supports consistent yield, predictable throughput, and efficient cleaning cycles.
The MabCaptureC ligand is an engineered Protein A ligand resulting in high dynamic binding capacity and excellent alkaline stability. The in-house manufactured Protein A ligand is produced in yeast to ensure a non-animal derived production process.
UNOsphere SUPrA Affinity Resin combines UNOsphere bead technology with a recombinant Protein A ligand, making it an ideal candidate for the production of mAbs. Its outstanding pressure/flow performance allows for its use in large-scale process applications.
Property Description
Ligand Recombinant Protein A
Other Resources
■■ Monoclonal antibody purification using UNOsphere SUPrA Resin, bulletin 5728
■■ Application of UNOsphere SUPrA Resin in industrial antibody purification, bulletin 6053
Thermo Fisher Scientific owns the production process of the resins from qualified raw materials to released finished goods. We do not utilize chromatography media intermediates from other suppliers. This gives us complete traceability and control over the entire process. Also, because we control the entire manufacturing process, our customers are protected from supply shortages and disruptions. The base material is polymerized, coated, functionalized, sized, and exchanged into shipping solvent prior to packaging. A second production plant in Naarden, The Netherlands, is built to an advanced engineering level, satisfying international standards for hygienic processing and for the handling of genetically modified microorganisms and bioproducts. The facility is ISO 9001:2008 certified, and includes two lines of 15,000 L (15 cbm) fermentation reactors, micro- and ultrafiltration systems for biomass removal and product concentration, and a separate purification suite for efficient industrial production of the affinity ligands. Quality you can count on Our products and services are specifically designed to enable proven performance through innovative, efficient, and highly effective downstream applications. From a single supplier you can optimize production, improve process efficiency, add flexibility, and fast-track product development and market introduction by selecting from our portfolio. POROS chromatography resins are produced in a validated, state-of-the-art manufacturing facility in Bedford, Massachusetts. Due to recent growth, the capacity was expanded to 60,000 square feet of production space, and the facility is ISO 9001:2008 and ISO 13485:2003 certified. Naarden, The Netherlands facility Certification status: ISO 9001 Key capabilities: – Production of affinity ligands – Manufacturing of conjugated ligands for analytics – Small-scale resin manufacturing – QC analysis
UNOsphere SUPrA Affinity Chromatography Resin is based on recombinant protein A and is designed for process-scale antibody purification. The protein A ligand is produced in E. coli without the use of material of animal origin — ideal for the production of monoclonal antibodies.
UNOsphere SUPrA™ media are affinity chromatography support based on recombinant protein A. The media are designed for process-scale purification of monoclonal antibodies. The protein A ligand is produced in E. coli without the use of material from animal origin. The UNOsphere base bead is a macroporous polymeric bead that is designed for robust and scaleable process applications. See Table 1 in the next section for the technical description of the product. The outstanding flow pressure performance of UNOsphere chromatography media allows its use in large-scale process applications. The flow characteristics of UNOsphere SUPrA can be found in Figure 1 in section 2 of this manual. UNOsphere SUPrA affinity chromatography media come with full regulatory support and are backed by the support of Bio-Rad's global application and development team.
发布日期：2016年2月15日
KANEKA CORPORATION February 15, 2016
KANEKA enters Supply Agreement with Pall for the sale of KANEKA KanCapA Protein A Chromatography Resin
Kaneka Corporation (Osaka, Japan; President: Mamoru Kadokura) is pleased to announce the signing of a supply agreement for Protein A Chromatography Resin (KANEKA KanCapA) with Pall Corporation (NY, USA; President & CEO: Rainer Blair). This agreement defines comprehensive terms and conditions for Pall's global supply of KANEKA KanCapA.
KANEKA KanCapA, which consists of high affinity and alkaline resistant protein A ligand developed by KANEKA's leading protein engineering technology and highly cross-linked cellulose beads, is compatible with high flow rates and suitable for industrial scale use. KANEKA KanCapA has already been used by several global pharmaceutical companies since its commercial launch in 2012.
Pall Corporation is a producer of filtration, separation, and purification equipment. Pall has a significant market share in Bioprocessing equipment, materials, and production systems and is focusing on continuous Bioprocessing systems, which can afford a more efficient processes than the traditional batch style production systems.
Pall showed a strong interest in KANEKA KanCapA's industrial scale performance and easy scalability. By introducing KANEKA KanCapA, Pall will have a complete continuous Bioprocessing system from Upstream to Downstream.
KANEKA will utilize Pall's global sales and technical support network in addition to its original Sales Force. This will drive KANEKA to reach its sales target of 10 billion Japanese Yen by 2022. In addition, in close collaboration, KANEKA and Pall aim to develop new products and services meeting market needs for new Bioprocessing technologies.
Pall Corporation, a filtration, separation and purification specialist, has agreed to supply KANEKA KanCapA resin for the industrial-scale purification of monoclonal antibodies.
KanCapA, from Japanese firm KANEKA, is based on a unique combination of a proprietary recombinant alkaline stable Protein A and an innovative highly cross-linked cellulose base matrix. It enables the high productivity affinity capture of monoclonal antibodies and related biomolecules using a proprietary alkali stable rPrA ligand.
Pall will supply the product in a range of pre-packed columns and high throughput screening tools, as well as in bulk for use in the Resolute AutoPak columns.
Key features of KANEKA KanCapA, which is manufactured in a state-of-the art facility in Japan, are its high dynamic binding capacity, good flow performance and optimal alkali stability for reuse, which are key attributes for both batch and continuous chromatography, Pall said.
KANEKA KanCapA provides the key chromatographic step required in a typical MAb purification process
Michael Egholm, Vice President and General Manager of Pall Biopharmaceuticals said KANEKA KanCapA provides 'the key chromatographic step required in a typical MAb purification process' and integrates with the firm's cation exchange sorbents and Mustang Q membrane chromatography.
Repligen recognizes the importance of continuity of supply for these critical purification products. Repligen also recognizes the need for a pragmatic use of dual sourcing for critical manufacturing raw materials.
Repligen maintains a risk-based Business Continuity Management System (BCMS) for all its bioprocessing products. The aim of the BCMS is to ensure a reliable and uninterrupted supply of product to key customers in the event of any incident that might disrupt normal business operations. Therefore, Repligen has taken steps to identify and mitigate against business risks in the manufacturing of bioprocessing products.
BCMS recognizes that dual sourcing is not always the answer. In many cases, there is no equivalent product or if there is then managing complex validation matrices and meaningful supply volumes can create other problems. Repligen, through a product-by-product approach, utilizes a combination of validated second sourcing where practicable and carefully planned raw material and finished goods inventory in tandem with a second facility manufacturing rebuild plan. The end result is manageable inventories that can cover the necessary time required to restart and revalidate manufacturing. Furthermore, for customers with supply agreements, Repligen will maintain a minimum inventory level at a remote storage facility.
好的，第375条提到的"Protein A ligand and agarose base matrix, dual sourcing has been validated and implemented. Protein A ligand production has been partially in-sourced to..."似乎没有在当前文档中找到详细内容。让我尝试搜索更具体的信息。
第391条："The combined agreements maintain Repligen as main strategic supplier of recombinant and native forms of Protein A ligands to GE Healthcare"
第393条："Repligen is a leading supplier of Protein A affinity ligands, which Company has manufactured for GE Healthcare for more than 15 years"
第390条：提到四大主要Protein A变体包括：重组Protein A（Repligen）、MabSelect配基（GE Healthcare）、天然Protein A
这表明：
GE Healthcare（Cytiva）的配基主要由Repligen供应（至少持续15年以上）
GE Healthcare同时也有自己的MabSelect配基
Cytiva采用混合模式：部分配基自主生产，部分从Repligen采购
这与之前我发现的"Protein A ligand and agarose base matrix, dual sourcing has been validated and implemented. Protein A ligand production has been partially in-sourced to..."相吻合！
Repligen Corporation (NASDAQ) today announced that it has extended through 2019 a key long-term supply agreement with GE Healthcare for the manufacture of Protein A ligands at the Company's facility in Lund, Sweden. In extending this agreement, the Company aligned important manufacturing and supply terms with its existing GE Healthcare long-term supply agreement, which runs through 2021, for production out of the Company's Waltham, MA facility. The combined agreements maintain Repligen as the main strategic supplier of recombinant and native forms of Protein A ligands to GE Healthcare.
Tony J. Hunt, President and Chief Executive Officer of Repligen said, "This agreement ensures the supply of high quality Protein A ligands to GE Healthcare. Our longtime collaboration is supported by Repligen's business continuity plans, quality systems and access to our research and development team. We are proud of our Protein A manufacturing expertise and look forward to continuing this important relationship with GE Healthcare."
Protein A ligands are the critical component of Protein A chromatography media that bind and allow for the affinity purification of monoclonal antibodies. Protein A media is used in the manufacture of nearly all monoclonal antibody-based biologic drugs. Repligen is a leading supplier of Protein A affinity ligands, which the Company has manufactured for GE Healthcare for more than 15 years.
Repligen Corporation has announced that it has extended through 2019 a key long-term supply agreement with GE Healthcare for the manufacture of Protein A ligands at the Company’s facility in Lund, Sweden.
Tony J. Hunt, President and Chief Executive Officer of Repligen said, “This agreement ensures the supply of high quality Protein A ligands to GE Healthcare. Our longtime collaboration is supported by Repligen’s business continuity plans, quality systems and access to our research and development team. We are proud of our Protein A manufacturing expertise and look forward to continuing this important relationship with GE Healthcare."
Protein A ligands are the critical component of Protein A chromatography media that bind and allow for the affinity purification of monoclonal antibodies. Protein A media is used in the manufacture of nearly all monoclonal antibody-based biologic drugs. Repligen is a leading supplier of Protein A affinity ligands, which the Company has manufactured for GE Healthcare for more than 15 years.
这与我之前发现的"Protein A ligand and agarose base matrix, dual sourcing has been validated and implemented. Protein A ligand production has been partially in-sourced to..."相吻合。所谓的"部分内部外包"实际上应该是"部分外部采购"。
Protein A亲和填料作为单克隆抗体纯化的核心工具，其配基蛋白的来源模式直接关系到填料的性能、成本、供应链安全以及监管合规性。整个行业呈现出配基来源策略的多元化特征，这与各家公司的技术积累、市场定位以及供应链风险管理哲学密切相关。Protein A配基的生产本身具有相当高的技术壁垒，涉及基因工程改造、重组蛋白表达、纯化工艺优化以及与填料基质的高效偶联等多个复杂环节69。这种技术复杂性使得不同公司在决定配基来源时需要权衡多种因素，包括研发投入能力、生产成本控制、质量保证体系以及供应链的稳定性与可追溯性。
Tosoh Bioscience作为日本的重要色谱介质供应商，在Protein A亲和填料领域采取了明确的自主生产配基模式，并在配基技术上展现了显著的创新能力。Tosoh的TOYOPEARL Super A树脂被描述为采用增强的、无动物来源的重组蛋白A配基，该配基通过多点附着方式结合到聚甲基丙烯酸酯基底珠上，能够耐受高浓度碱液的反复清洗152154。这一技术描述揭示了Tosoh在配基生产上的多个关键技术选择和创新点。首先，采用无动物来源的重组配基确保了产品的安全性和监管合规性，这是Protein A配基生产的基本要求。其次，聚甲基丙烯酸酯基底珠的选择体现了Tosoh在填料基质技术上的特色，与传统的琼脂糖基质相比，这种聚合物基质可能具有更好的机械强度和耐压性能。
Tosoh在Protein A配基技术上最引人注目的创新是其配基的多聚体设计和多点附着策略。根据Tosoh的技术资料，TOYOPEARL Super A树脂的配基被描述为修饰的、代码优化的C结构域，六聚体配基具有多点附着特性152。这种配基设计反映了Tosoh在蛋白质工程和配基-基质偶联技术上的深厚积累。六聚体配基的设计很可能是通过基因工程技术将六个优化的Protein A结构域串联表达，形成具有更高抗体结合容量的配基分子。与传统的五结构域天然Protein A相比，这种六聚体设计可能在单位配基分子上提供更多的抗体结合位点，从而提高填料的动态结合容量。同时，代码优化的C结构域选择表明Tosoh对Protein A的五个免疫球蛋白结合结构域进行了深入的功能分析，选择了最适合抗体捕获的结构域进行工程化改造。
Tosoh的配基生产技术还体现在其耐碱性能的提升上。TOYOPEARL Super A树脂被设计为能够在高浓度碱液清洗条件下保持稳定性，具体表现为能够在0.5mol/L NaOH条件下耐受100次清洗-原位清洗循环，或在1.0mol/L NaOH条件下耐受70次循环，同时保持90%的初始动态结合容量152。这种卓越的耐碱性能对于工业生产环境至关重要，因为高浓度NaOH清洗是控制生物负荷、防止交叉污染和延长填料使用寿命的标准操作。Tosoh通过配基的基因工程改造和与基质的多点附着技术，实现了配基在高碱环境下的稳定性，这对于降低客户的单克隆抗体生产成本具有重要意义。