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Antibody-Developability-Prediction

Creative Biolabs is the leading custom service provider that has extensive experience in various antibody production and engineering fields. Our service portfolio includes mouse and rat monoclonal antibody production using hybridoma technology, human, monkey, rabbit, chicken, dog, llama and camel monoclonal antibody production using various antibody library technologies (including phage display, bacterial display and yeast display). <br><br>https://www.creative-biolabs.com/preciab/

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Antibody-Developability-Prediction

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  1. Antibody Antibody Developability Developability Prediction Prediction -Providing first class antibody developability prediction service- Leverage the expertise of our senior scientists to offer custom antibody developability prediction service to fit your project.

  2. In silico In silico technology platform technology platform Our PreciAbTM Withyearsofexplorationinantibodyengineering,Creative hasbuiltafull-scalein insilico silicotechnologyplatform.Basedonour advancedplatform,weofferhighqualityantibodydevelopability predictionservicesforcustomersallovertheworld,including AntibodyAggregationPredictionandAntibodyImmunogenicity CreativeBiolabs Biolabs prediction. 2 info@creative-biolabs.com www.creative-biolabs.com/preciab/

  3. Table of Contents Table of Contents 4 1. Antibody Developability Prediction…............................….. 5 1.1 Antibody Aggregation Prediction….............................................. 7 1.2 Antibody Immunogenicity Prediction…......................................... 11 2. PreciAbTMPlatform…......................................................….... 13 3. In silico Analysis Approaches…......................................…... 14 3.1 N-Glycosylation Sites and Cysteines in Fv Domains Analysis….…........ 16 3.2 Lysine Glycation Sites Analysis…................................................. 17 3.3 Isoelectric Point and Charge Distribution Analysis…............…......... 3.4 Prediction of Asparagine and Aspartate Degradation Hotspots in Fv Domains Analysis…...................................…....... 18 3.5 Immunogenicity Analysis….............................................…........ 19 20 4. Custom Antibody Developability Services…....….........…... Wholeheartedly Wholeheartedly serve every clients serve every clients To accelerate the development of therapeutic antibodies, a variety of in silico analysis approaches are available in Creative Creative Biolabs Biolabs. Our scientists are confident in proving the first class antibody developability prediction services to contribute to your antibody development process. ✓ Professional ✓ Accurate ✓ Omni-directional 3 info@creative-biolabs.com www.creative-biolabs.com/preciab/

  4. 1. Antibody Developability 1. Antibody Developability Prediction Prediction Overview Overview Developability refers to the possibility for the successful development of a lead candidate into a stable, safe, manufacturable, and efficacious drug, which is enable to be used as an additional selection criterion. By using a class of small-scale, fast, and predictive tests addressing biochemical and biophysical features, as well as in silico analysis, enable to evaluate a clinical candidate molecule with promising properties at an early stage of drug development. Developability Developability workflow workflow 4 info@creative-biolabs.com www.creative-biolabs.com/preciab/

  5. Overview Overview At present, protein aggregation still remains a main area of focus in the production of monoclonal antibodies. Increasing the intrinsic properties of antibodies can promote manufacturability, attrition rates, formulation, safety, titers, immunogenicity, and solubility. On account of the identification of aggregation-prone regions and their contribution to the thermodynamic stability of the protein, predicting and decreasing the aggregation propensity of monoclonal antibodies become available. 1.1 Antibody 1.1 Antibody Aggregation Prediction Aggregation Prediction Just for You Just for You With years of exploration in antibody engineering, Creative Biolabs Creative Biolabs has built a full-scale in silico technology platform. Based on our advanced platform, we offer high quality antibody aggregation prediction services for customers all over the world. 5 info@creative-biolabs.com www.creative-biolabs.com/preciab/

  6. Our Vision Our Vision With our comprehensive antibody aggregation prediction services, designing and engineering novel antibodies with desired therapeutic properties is available. We customize the service according to the specific requirements from the customers. We also provide other structure-based antibody reformatting services. In silico analysis of aggregation propensity in antibody crystal structures Our Approaches Our Approaches ✓ Empirical force field FoldX ✓ Statistical thermodynamic algorithm TANGO 6 info@creative-biolabs.com www.creative-biolabs.com/preciab/

  7. 1.2 Antibody Immunogenicity Prediction 1.2 Antibody Immunogenicity Prediction Overview Overview Nowadays, immune response to foreign proteins is mostly well understood, on account of years of thorough study of parameters influencing vaccine efficacy. A number of factors are related to the protein immunogenicity, including delivery route, delivery vehicle, dose regimen, aggregation, innate immune system activation and the capacity of the protein to interface with the humoral (B cell) and cellular (T cell) immune systems. Based on the well-established in silico technology platform in Creative Creative Biolabs Biolabs, now, it is available to evaluate the T-cell Our Our services services epitope content of a protein relatively accurately, and also to measure the regional and overall immune potential of a protein therapeutic. 7 info@creative-biolabs.com www.creative-biolabs.com/preciab/

  8. The Ideal Partner for Your Antibody The Ideal Partner for Your Antibody Production Production With our comprehensive antibody immunogenicity prediction services, designing and engineering novel antibodies with desired therapeutic properties is available. We customize the service according to the specific requirements from the customers. Antibody Immunogenicity Antibody Immunogenicity Prediction Services Prediction Services a. T-cell Epitope Prediction A cluster map for domain C2 charts the location and potential immunogenicity of each cluster 8 info@creative-biolabs.com www.creative-biolabs.com/preciab/

  9. Antibody Immunogenicity Prediction Service Antibody Immunogenicity Prediction Service b. B-cell Epitope Prediction DiscoTope B-cell epitope prediction of Sal1 DBP-II and DEKnull Creative Creative Biolabs Biolabs offers high quality B-cell epitope prediction services by using in silico techniques to contribute to the antibody immunogenicity prediction. 3DEX and CEP, B-cell epitope prediction tools, are able to be used to predict B-cell epitopes on a high-throughput basis - We Committed to help you get what you need!- 9 info@creative-biolabs.com www.creative-biolabs.com/preciab/

  10. Antibody Immunogenicity Antibody Immunogenicity Prediction Service Prediction Service c. De-immunization The idea of rational epitope modification is based on the natural process which occurs when tumor cells and pathogens evolve to escape immune pressure by accumulating mutations, in order to decrease the binding of their constituent epitopes to host HLA, rendering the host cell unable to ‘signal’ to T cells the presence of the tumor or pathogen. Schematic presentation of immune evasion mechanisms (HCMV) On account of the disruption of HLA binding, an underlying demand for T-cell stimulation, the de-immunization method by epitope modification has been developed. Creative Creative Biolabs Biolabs offers high-quality de-immunization services by using in silico techniques to customers to promote your project success. 10 info@creative-biolabs.com www.creative-biolabs.com/preciab/

  11. 2. 2. PreciAb PreciAbTM TMPlatform Platform More than 10 years of exploration and expansion More than 10 years of exploration and expansion -The whole new drug discovery and development pipeline- In our PreciAb™ platform, key steps of antibody development are described as follow: Antibody structure construction through combining structure- and ✓ homology-based modeling methods Structure optimization by dynamics simulation, rotamer library, loop ✓ modeling, and etc. Complementarity-determining region identification on the basis of ✓ tertiary structure of the antibody Antibody-antigen complex modeling and interaction analysis ✓ Paratope and epitope identification and key residues analysis ✓ Computer-aided antibody affinity maturation and function ✓ modification Global analysis and optimization of antibody bio-physical properties ✓ (thermodynamic stability, aggregation propensity, immunogenicity) 11 info@creative-biolabs.com www.creative-biolabs.com/preciab/

  12. 2. 2. PreciAb PreciAbTM TMPlatform Platform Our Workflow: Our Workflow: Amino Acid 3D Model Sequence Construction CDR Loop Identification Modification Antibody-antigen Interaction complex analysis simulation Antibody optimization 12 info@creative-biolabs.com www.creative-biolabs.com/preciab/

  13. 3. 3. In Silico In Silico Approaches Approaches N-Glycosylation Sites and ✓ Cysteines in Fv Domains Lysine Glycation Sites ✓ Immunogenicity Analysis ✓ Isoelectric Point & Charge ✓ Distribution Prediction of Asparagine and ✓ Aspartate Degradation Hotspots in Fv Domains Our Features Our Features Skillful technicians and ✓ extensive experience Custom service and ✓ timely feedback Low cost and highly ✓ efficient Best after-sale service ✓ 13 info@creative-biolabs.com www.creative-biolabs.com/preciab/

  14. 3.1 N 3.1 N- -Glycosylation Sites and Glycosylation Sites and Cysteines in in Fv Fv Domains Analysis Domains Analysis Cysteines Typically, Fv glycosylation can influence target binding, and it may also play a crucial role in biodistribution or Overview Overview pharmacokinetics. An additional N-glycosylation site in the Fv domain means another source of product heterogeneity, and the production of such therapeutic antibodies with a consistent human-like glycoform profile remains a big challenge. Fortunately, potential N-glycosylation sites in the Fv domains enable to be determined in the amino acid sequence via their consensus motif NXS or NXT (X may be any amino acid except proline). Alpha backbone structure of human IgG showing functional regions 14 info@creative-biolabs.com www.creative-biolabs.com/preciab/

  15. Semi-quantitative results for characterization of Fc N-glycosylation site Asn292 after recovery of Mab from plasma at 48 h relative to starting material. Impaired stability of an example IgG1 mAb containing a free Cys in CDR H2 15 info@creative-biolabs.com www.creative-biolabs.com/preciab/

  16. 3.2 Lysine 3.2 Lysine Glycation Glycation Sites Analysis Sites Analysis Generally, glycation is distributed over many lysines in antibodies, however, a number of researchers describe Overview Overview glycation hotspots, which considers that certain structural features govern the rate of glycation. Apart from solvent accessibility, a contribution of a neighboring acidic residue acting catalytically in the conversion of the initial glucose adduct, a Schiff base, into a more stable Amadori product was proposed taking advantaged of structural and mutational data. Our Capacity Our Capacity Via Via a structural model, we can search for exposed lysine residues in the vicinity of suitable acidic residues, so as to forecast glycation hotspots. Glycation in recombinant monoclonal antibody (mAb1) 16 info@creative-biolabs.com www.creative-biolabs.com/preciab/

  17. 3.3 Isoelectric Point and Charge 3.3 Isoelectric Point and Charge Distribution Analysis Distribution Analysis An isoelectric point high enough (e.g., >7) is regarded as a prerequisite for binding and nonbinding to cation and anion Overview Overview exchange chromatography media, providing two common purification methods. Aggregation and solubility property of a protein is usually favorable at pH values far away from the protein’s isoelectric point, albeit specific interactions of the protein with anions or cations present in the solution enables to modulate solubility to a great extent. What can we offer? What can we offer? A sequence-based prediction of the protein’s net charge as a function of pH, and its isoelectric point, helps to estimate whether or not the values are in the desired range. Besides, a structure-based method to measure net charge and isoelectric point using 3D homology can offer a more accurate result. Calculated isoelectric points of monoclonal antibodies 17 info@creative-biolabs.com www.creative-biolabs.com/preciab/

  18. 3.4 Prediction of Asparagine and 3.4 Prediction of Asparagine and Aspartate Degradation Hotspots Aspartate Degradation Hotspots in in Fv Fv Domains Analysis Domains Analysis Overview: usually, during therapeutic proteins production, storage, or in vivo after administration, deamidation of asparagine residues, isomerization of aspartate residues, and formation of the general cyclic succinimide intermediate are frequent degradation reactions. Our Approaches Our Approaches Our scientists had established a hotspot prediction method which displays greatly increased rates of correct predictions, depending on a large set of antibodies with experimentally determined data. This method, implemented in an automatic homology modeling and hotspot prediction workflow, provides a facile way to assess many candidates. Asparagine and Aspartate degradation pathways 18 info@creative-biolabs.com www.creative-biolabs.com/preciab/

  19. 3.5 Immunogenicity Analysis 3.5 Immunogenicity Analysis Although a variety of factors are related to immunogenicity, including sequence, structure, modifications, route of administration, patient population, others are still only poorly understood. Many attempts have been done to predict the potential immunogenicity of drug candidates during the lead Our Our selection process by in silico, in vitro, or in vivo models. platform platform Essentially, in silico models address potential T-cell epitopes, which are essential (but not sufficient) for T-cell-mediated immunogenicity. These algorithms enable to offer value as a ranking tool for otherwise equivalent drug candidates. Main applications and limitations of current predictive tools for protein immunogenicity 19 info@creative-biolabs.com www.creative-biolabs.com/preciab/

  20. 4. Custom 4. Custom antibody developability developability prediction services prediction services antibody Accelerated & Innovative the development of therapeutic antibodies via custom antibody developability prediction services -Maximize Your Efficiency and Value with Consistent Performance- Aggregation and immunogenicity are two common problems for antibody during all stages of their production and application. Creative Biolabs now provides in silico developability prediction service. The most appropriate project plan will be proposed to best tailor your demands. PreciAb PreciAbTM TMPlatform Platform Highlight Features Highlight Features In silico analysis approaches Experienced staffs ✓ N-Glycosylation Sites and Cysteines in Fv ✓ Domains Analysis Superior quality ✓ Lysine Glycation Sites Analysis ✓ Isoelectric Point and Charge Distribution ✓ Analysis Time- and labor-saving ✓ Prediction of Asparagine and Aspartate ✓ Degradation Hotspots in Fv Domains Analysis Abundant successful cases ✓ Immunogenicity Analysis ✓ 20 info@creative-biolabs.com www.creative-biolabs.com/preciab/

  21. Contact Us Contact Us Please contact us for more information and a detailed quote Please visit www.creative- biolabs.com/preciab/ to find out more 1-631-357-2254 info@creative-biolabs.com 1-631-207-8356 45-1 Ramsey Road, Shirley, NY 11967, USA

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