Custom Services. Further Your Discoveries with Quantitative Near-infrared Technology

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1 Custom Services Further Your Discoveries with Quantitative Near-infrared Technology

2 50+ Worldwide patents for imaging technologies 15+ Registered clinical trials using LI-COR IRDye Infrared Dye products for investigative purposes 10K+ Publications citing Odyssey Imaging Systems for detection and quantitation of protein expression 300+ Publications citing the Pearl Imaging System for in vivo small animal imaging applications 100+ Publications citing IRDye Infrared Dye products in therapeutic and diagnostic imaging applications

3 Delivering Innovative Solutions From bench to translational research For more than 25 years, our team at LI-COR has been dedicated to advancing the use of near-infrared (NIR) fluorescence quantitation technology in biosciences, from molecules to diagnostics. Our IRDye Infrared Dye fluorophores yield high signalto-noise ratios in the NIR spectrum (700 to 800 nm) where background fluorescence and absorption are low on membranes, cells, and tissues. High sensitivity, photo-stable chemistry, and the ability to attach the fluorophores covalently to targeting molecules, make them the choice for detection and quantitation in in vitro assays, in vivo imaging studies, and human clinical applications. Our Odyssey and Pearl Imaging System platforms provide a wide dynamic range to detect and quantitate NIR signals from cells, membranes, arrays, multi-well plates, slides, tissues, whole organs, and small animals. We have an extensive knowledge base from years of experience in synthesizing dyes and derivatives, optimizing conjugation reactions, and developing best practices for quantitative assays and applications. Our technology solutions customized to your research needs From compound synthesis and dye conjugation, to quantitative assay development, and manufacturing under current Good Manufacturing Practices (cgmp), the LI-COR Custom Services team is equipped to expand your capabilities and support your projects through to completion. Let us help further your discoveries with quantitative near-infrared technology. 3

4 Chemistry and Conjugation Services Take your compounds from structures to yield Whether you need starting materials, intermediates, or derivatives, LI-COR Custom Services provides on-demand synthesis of organic compounds, from milligram to multigram amounts. Enlist our team as your trusted partner in optimizing synthesis reactions, performing chemical modifications, or generating dyes and small molecule compounds. Get the labeling chemistry right Our IRDye Infrared Dye products and labeling technologies could be optimized to yield high signal-to-noise ratios in many of your in vitro, in vivo, and ex vivo imaging assays, and clinical imaging applications. We also conjugate other fluorescent and non-fluorescent labels and quenchers to biomolecules, polymers, and nanoparticles. With our state-of-the-art instrumentation and qualified chambers, we can purify your compounds, provide a comprehensive analytical assessment, and perform ICH stability studies. 4

5 Organic synthesis Biomolecule conjugation Dual labeling Quenched probes Reverse phase purification FLASH chromatography HPLC analysis GC/MS NMR analysis UV/Vis FTIR Karl Fischer Quantum yield ICH stability studies Extinction coefficient For a free consultation, go to licor.com/conjugation

6 Biological Assay Services Reproducibly measure the outcome of your experiments Count on our team for all your protein quantitation needs. With LI-COR s industry-leading suite of Odyssey imagers, IRDye infrared dye technology, and expertise in establishing quantitative bioassay protocols, we offer an unparalleled portfolio for measuring protein expression changes on membranes, arrays, multi-well plates, cells, and tissues. We can help you get started by validating reagents and optimizing experimental conditions. You can request comprehensive proteomic assay services including sample prep, detection, imaging, and data analysis using near-infrared fluorescence, chemiluminescence, or colorimetric chemistries. We also perform nucleic acid cloning and amplification, protein expression and purification, microscopy, and advanced image cytometry. 6

7 Quantitative Western blotting In-Cell and On-Cell Western assays Tissue section imaging Cell-based biochemical assays Array scanning Gel-shift assays (EMSA) ELISA Binding assays Specificity studies Enzyme kinetics Antibody validation Probe validation Reagent and protocol optimization Microscopy Immunocytochemistry For a free consultation, go to licor.com/bioassays

8 Imaging probe labeling Nanoparticle labeling Imaging probe characterization Biodistribution studies Clearance studies Uptake Localization Bone density Ex vivo characterization Whole organ imaging Tissue micro-analysis Tissue macro-analysis For a free consultation, go to licor.com/probes

9 Translational Services Further your research to translation and beyond As you prepare to take your fluorophore-conjugated agent to in vivo testing in small animals, place your confidence in LI-COR. Our team has developed a number of IRDye fluorophore-conjugated probes1-7 for imaging molecular targets implicated in cancer. We have a thorough understanding of probe characterization, testing, and process optimization.8 Rely on our extensive knowledge of IRDye infrared dyes pharmacokinetic and pharmacodynamic properties. Our fluorophores are not only exceptional for monitoring bio-distribution and localization in small animals, but they are also powering imaging and therapeutic agents in Phase I and II clinical trials. We provide in vivo imaging solutions for all types of fluorophores. The award-winning Pearl platform for dualmode small animal optical imaging provides excellent sensitivity for characterizing in vivo performance of your fluorophore-conjugated agent. When used in tandem with the Odyssey Imaging System for probe validation assays and tissue section imaging, it allows seamless integration of in vitro, in vivo, and ex vivo data from one platform to another. 9

10 Clinical Trials Using IRDye infrared dye-conjugated imaging agents IRDye 800CW and 700DX labeled imaging agents are being used in more than 15 clinical trials. For further details, go to licor.com/trials Esophageal cancer VEGF-targeted Fluorescence Near-Infrared (NIR) Endoscopy in (Pre)Malignant Esophageal Lesions (VICE) UMCG, Netherlands Breast cancer Fluorescence Guided Surgery in Breast Cancer UMCG, Netherlands VEGF-targeted Fluorescent Tracer Imaging in Breast Cancer UMCG, Netherlands Pancreatic cancer Cetuximab-IRDye 800CW and Intraoperative Imaging in Finding Pancreatic Cancer in Patients Undergoing Surgery Stanford University, USA Near-infrared Image Guided Surgery in Pancreatic Adenocarcinoma (PENGUIN) UMCG, Netherlands Colorectal cancer Molecular Fluorescence Endoscopy in Patients With Familial Adenomatous Polyposis, using Bevacizumab-IRDye 800CW (FLUOFAP) UMCG, Netherlands Visualization of Rectal Cancer During Endoscopy, using a Fluorescent Tracer (RAPIDO-TRACT) UMCG, Netherlands 10

11 IRDye 800CW IRDye 700DX Head and neck cancer Cetuximab IRDye 800 Study as an Optical Imaging Agent to Detect Cancer During Surgical Procedures University of Alabama, Birmingham, USA Phase I Panitumumab IRDye 800 Optical Imaging Study Stanford University, USA A Microdose Evaluation Study of ABY-029 in Recurrent Glioma (ABY-029) Dartmouth-Hitchcock Medical Center, USA IRDye 800CW-BBN PET-NIRF Imaging Guiding Surgery in Patients With Glioblastoma Beijing Tiantan Hospital, China Cetuximab-IRDye 800CW in Detecting Tumors in Patients With Malignant Glioma Undergoing Surgery Stanford University, USA Study of RM-1929 and Photoimmunotherapy in Patients With Recurrent Head and Neck Cancer Aspyrian Therapeutics, Inc., USA Light-activated AU-011 for the Treatment of Ocular Melanoma Aura Biosciences, USA Kidney cancer Intraoperative Dual-modality Imaging in Renal Cell Carcinoma Radboud University, Netherlands Endometriosis Feasibility Study of Using Molecular Fluorescence Guided Surgery in Endometriosis (Endo-light) UMCG, Netherlands 11

12 ISO and cgmp quality systems Active Pharmaceutical Ingredients (API) IRDye technology for clinical application Early phase clinical Custom molecule design New reagent formulations Lyophilization services Bulk reagents For a free consultation, go to licor.com/manufacturing

13 Manufacturing Services Get your compounds manufactured to order Let LI-COR be your trusted partner in the clinical development of your compound. With more than 15 registered clinical trials employing IRDye fluorophore-conjugated probes in imaging and therapeutic applications, we are at the forefront, helping scientists take their research from bench to bedside. You can rely upon our comprehensive understanding of IRDye fluorophore synthesis and scale-up, characterization data, and presence in the pre-clinical and clinical space. At our facility, we provide manufacturing of IRDye fluorophores, fluorophore-conjugated agents, and active pharmaceutical ingredients (API) under current Good Manufacturing Practices (cgmp) for early phase clinical and research use. We also provide small-scale manufacturing services for customized reagent formulations, and bulk quantities of our reagent portfolio. Products manufactured under cgmp for investigational use only. 13

14 References 1. Gong H, Kovar J, Little G, Chen H, Olive DM. (2010). In vivo imaging of xenograft tumors using an epidermal growth factor receptor-specific affibody molecule labeled with a near-infrared fluorophore. Neoplasia. 12(2): Huang R, Vider J, Kovar JL, Olive DM, Mellinghoff IK, Mayer-Kuckuk P, Kircher MF, and Blasberg RG. (2012). Integrin αvβ3- Targeted IRDye 800CW Near-Infrared Imaging of Glioblastoma. Clin Cancer Res. 18(20): Kovar JL, Curtis E, Othman SF, Simpson MA, Olive DM. (2013). Characterization of IRDye 800CW chlorotoxin as a targeting agent for brain tumors. Anal Biochem. 440(2): Kovar JL, Johnson MA, Volcheck WM, Chen J, and Simpson MA. (2006). Hyaluronidase Expression Induces Prostate Tumor Metastasis in an Orthotopic Mouse Model. Am J Pathol. 169(4): Kovar JL, Volcheck WM, Chen J, Simpson MA. (2007). Purification method directly influences effectiveness of an epidermal growth factor-coupled targeting agent for noninvasive tumor detection in mice. Anal Biochem. 361(1): Kovar JL, Volcheck W, Sevick-Muraca E, Simpson MA, Olive DM. (2009). Characterization and performance of a nearinfrared 2-deoxyglucose optical imaging agent for mouse cancer models. Anal Biochem. 384(2): Kovar JL, Xu X, Draney D, Cupp A, Simpson MA, Olive DM. (2011). Near-infrared-labeled tetracycline derivative is an effective marker of bone deposition in mice. Anal Biochem. 416(2): Kovar JL, Simpson MA, Schutz-Geschwender A, Olive DM. (2007). A systematic approach to the development of fluorescent contrast agents for optical imaging of mouse cancer models. Anal Biochem. 367(1):

15 Notes 15

16 Are you ready to empower your research with near-infrared detection? Contact LI-COR Custom Services for a consultation. licor.com/customservices Global Headquarters Serving the United States and Canada 4647 Superior Street Lincoln, NE Phone: Toll free: Fax: biosales@licor.com LI-COR Distributor Network: Regional Offices LI-COR GmbH, Germany Serving Europe, Africa, and the Middle East. LI-COR Biosciences GmbH Siemensstraße 25A Bad Homburg Germany Phone: +49 (0) Fax: +49 (0) bio-eu@licor.com LI-COR Ltd., United Kingdom Serving Denmark, Finland, Iceland, Ireland, Norway, Sweden, and UK. LI-COR Biosciences UK Ltd. St. John s Innovation Centre Cowley Road Cambridge CB4 0WS United Kingdom Phone: +44 (0) Fax: +44 (0) bio-eu@licor.com LI-COR, Odyssey, Pearl, IRDye, and In-Cell Western are trademarks or registered trademarks of LI-COR, Inc. in the United States and other countries. All other trademarks belong to their respective owners. For patent information, visit LI-COR, Inc. 03/ The LI-COR board of directors would like to take this opportunity to return thanks to God for His merciful providence in allowing LI-COR to develop and commercialize products, through the collective effort of dedicated employees, that enable the examination of the wonders of His works. Trust in the LORD with all your heart and do not lean on your own understanding. In all your ways acknowledge Him, and He will make your paths straight. Proverbs 3:5,6

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