GVHD Models

• Graft-versus-host disease model in B-NDG

PK parameters

Pharmacodynamics (PD) and Exploratory Toxicology 

Drug safety is an important step in therapeutic antibody development. We have experts with years of experience in this field and provide high quality solutions and service for antibody safety assessment. Early stage PD and toxicological tests combined with toxicokinetic studies give more information for non-clinical studies, phase I dose selection, toxic reactions and severity analysis, etc. In some cases, short-term subacute toxicity tests (1-3 months) convey safety issues, and help determine whether the innovative candidate can progress towards IND filing and early clinical trials.

ADA Analysis 

In preclinical models and clinical trials, antibodies often elicit Anti-Drug Antibodies (ADA), which can then interfere with antibody efficacy evaluation. Thus, ADA detection and evaluation facilitates understanding of potential immune responses to biologic drugs as well as potential risks. We provide solutions to determine ADA production at discovery and preclinical stage and our services include:

• Generation of detection antibodies and solutions
• Detection of ADA against conjugated drugs
• Detection of anti-drug neutralizing antibody
• Production and detection of anti-idiotype antibody

Receptor Occupancy (RO) Assay

Receptor Occupancy (RO) on the corresponding target is quantified with fluorescent- labeled antibody to detect the percentage of unoccupied receptors from in vivo samples or cell lines.

Cytokine Assays

Cytokines are biomarkers for efficacy and potential side effects, such as Cytokine Release Syndrome (CRS). CRS is a systemic inflammatory response caused by disease complications, infections or antibody administration or other adverse effects of biological therapies. Therefore, studies to evaluate CRS resulting from drug candidates is a critical part of PCC screening. We routinely run assays for Th1, Th2, Th17 and CRS cytokine detections with high-speed and accuracy.

CRS detection assays available

• Customized cytokine detection
• MSD multiplex Assay
• FACS CBA multiplex Assay
• ELISA Assay

Clinical Chemistry (CHEM) 

The results from Clinical Chemistry (CHEM) studies are important indicators reflecting the metabolism or content of carbohydrates, lipids, and proteins in urine/kidney, liver, gallbladder, cardiovascular, pancreatic and gastrointestinal tract samples. The indicators provide us data on the toxicological and biological significance of the PCCs. We have accumulated extensive experience in CHEM testing, and provided comprehensive services that meet our customer’s needs.

Chemistry testing with BS-240VET Analyzer

• Liver function: ALT, AST, ALP, T-Bil-D II, TP II, ALB, γ-GT, etc.
• Kidney function: UREA, CREA, MALB, etc.
• Myocardial enzyme spectrum: CK
• Glucose metabolism: Glu, β-HB, etc.
• Fat: TC, TG, etc.
• Pancreas: α-AMY
• Complement proteins: C3, C4 (under development)
• Rheumatism: CRP, ASOII (under development)
• Anemia: Fe, FER (under development)

Hematology (HEM) 

Hematology (HEM) tests are used as an auxiliary means for disease diagnosis and drug safety evaluation. The assays mainly include red blood cell count, white blood cell count, platelet count and hemoglobin content. By analysis of blood test data, we provide preliminary safety evaluation and offer conclusions on the use of the therapeutics being evaluated.  

Detection technology

• Auto Hematology Analyzer (BC-5000Vet)

Types of HEM testing

• White blood cell counts: WBC, Neutrophils, Lymphocytes, Monocytes, Eosinophils Basophils and NK cells
• Red blood cells: RBC, HGB, HCT, MCV, MCH, MCHC, RDW-CV, RDW-SD
• Platelets: PLT, MPV, PDW, PCT

Coagulation Analysis for Mematological Diseases 

Coagulation function tests evaluate clot formation after activating  the coagulation cascade. The coagulation function system used at WuXi Biologics offers pre-analytic sample checks and four methods simultaneously on a single platform including coagulation end-point, chromogenic kinetic analysis, turbidity immunoassay and automated platelet aggregation.

Detection technology

• Automatic hemostasis analyzer Sysmex CS-2400 analyzer

Types of testing

• Operation: automatic
• Analysis mode: chromogenic, immunologic
• Sample type: whole blood
• Coagulation: PT, APTT, Fbg, TT, PS, PC, LA1, LA2
• Exogenous coagulation factors: II, V, VII, X
• Endogenous coagulation factors: VIII, IX, XI, XII
• Chromogenic kinetic analysis: AT III, αTPI, Plg, PC, FXIII, Hep, C1
• Turbidity immunoassay: D dimer, FDP, ADP, Col and Epi

MSD-ECL Detection System

Electrochemiluminescence immunoassay (ECLIA) is a specific chemiluminescent reaction initiated by electrochemistry on the electrode surface.

The MSD-ECL platform uses an electrochemiluminescent-labeled antibody conjugate for detection purposes. The label usually uses a SULFO-TAG marker. After the electrode surfaces of MULTI-ARRAY and MULTI-SPORT microplates are electrified, the electrochemical action excites the SULFO-TAG marker to emit a strong light. Utilizing the MSD S600MM system with Methodical Mind Software, we significantly facilitate the bioanalyses of our  PK, ADA, and Cytokine platforms.

Advantages

• High Sensitivity: low limits of detection and broad dynamic ranges
• High Stability: consistent results from single-factor and multi-factor detection
• Small sample volume: ≤50ul
• Broad Dynamic Range: 4-5 log
• Multiplexed: high throughput, cost-effective for two or more analytes

Key Applications

• Biomarker detection
• Biological drug metabolism
• Immunogenicity
• High-throughput antibody affinity assay
• Signal pathway phosphorylation detection
• High throughput with 384 well plates

Immunization Platform

Hybridoma technology is a classic technology in monoclonal antibody development. We have state-of-art facilities and experts to provide timely and high quality services to our clients.

Advantages:

• Certified facilities (e.g., AALAC)
• Highly effective and high quality immunization strategies and protocols (utilizing our own internally developed intellectual property)
• Immunization strategies for DNA, polypeptide / protein, cells, liposome, nanoparticle or combinations of these various antigens
• Ligand’s OmniAb® and Alloy Therapeutics’ ATX-Gx™ platforms to provide humanized monoclonal antibody development services.

DNA-encoded antibody delivery 

Monoclonal antibodies have been widely used in the treatment for tumor, inflammatory and autoimmune disorders. However, high costs, and dose frequency limit patients’ accessibility to these therapeutic modalities. DNA delivery presents a labor- and cost-effective alternative to antibody therapeutics, with less frequent delivery and simpler formulation. Nanoparticle delivery systems overcome the biological barriers in vivo, and prolong circulation and improve antibody expression and sustainability. Thus, DNA delivery provides a viable, long-term treatment option.  At WuXi Biologics, we have an experienced team to perform in vivo and ex vivo studies to identify lead candidate in this new area for biologics.