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Veterinary Therapeutic Antibody Development

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Antibody Discovery Therapeutic Antibody Development Therapeutic Bispecific Antibody Development Effectiveness and Safety Assessments Therapeutic Antibody Manufacturing Antibody Targets Why Choose Us?

Therapeutic antibodies have become an indispensable part of the medical market in recent decades. Companion animals such as canines and felines also suffer from a range of diseases, including cancer, allergic diseases, autoimmune diseases, inflammatory diseases, and pain. Antibody therapy may provide companion animals with huge benefits. The wealth of experience and transferable skills allows researchers to shift their focus to veterinary therapeutic antibody development. BioVenic offers comprehensive veterinary therapeutic antibody development services, tailored to species-specific therapeutic antibodies, enabling clients to efficiently achieve development goals from an animal-oriented perspective.

Fig.1 A brief view of the veterinary therapeutic antibody development platform and development process. (BioVenic Original)

Antibody Discovery

  • Target Screening

In veterinary therapeutic antibody development, target screening plays a foundational role, and its success directly impacts the therapeutic efficacy of antibodies in later stages. BioVenic has established a target screening platform that offers plenty of high-throughput screening techniques, including library screening and cell sequencing to assist in identifying suitable therapeutic targets.

Services Description
CRISPR Library Screening Induced mutations for loss-of-function type screening, and gain-of-function type screening through activation of transcription, with relatively low off-target efficiency and a wider range of sites of action, including both coding and non-coding regions of genes.
siRNA Library Screening Specific inhibition or reduction of the expression of specific genes is performed by siRNA-mediated gene silencing.
NGS Single-Cell Sequencing Examine the genomes or transcriptomes of individual cells to identify genes that are associated with specific diseases or physiological processes under different conditions, including overexpressed genes or mutations that are associated with disease.
  • Antibody Preparation

BioVenic has established diverse veterinary therapeutic antibody preparation platforms tailored to specific needs. These platforms include the hybridoma platform, single B cell platform, and phage display platform. Each of these platforms is equipped with novel technologies, ensuring the preparation of high-quality veterinary therapeutic antibodies.

Platforms Description
Hybridoma Platform Fusion of mouse B lymphocytes and myeloma cells to generate monoclonal antibody cell lines.
Single B Cell Platform A single B-cell sorting technique is used to screen for highly specific antibodies that bind to the target antigen from immunized animals of different species.
Phage Display Platform Utilizing phage display technology, exogenous genes are inserted into phages for antibody screening to rapidly obtain high-affinity antibodies, which can be applied to therapeutic antibody development for a wide range of species.

BioVenic provides veterinary therapeutic antibody characterization services for preliminary screened veterinary therapeutic antibodies. These services encompass various aspects of analysis, from the multi-level structure of proteins to the interaction between antigens and antibodies, through structural and functional characterization.

Structural Characterization Functional Characterization
Primary Structure
Secondary and Higher-Order Structures
Post-Translational Modification
Antigen-antibody Interaction
Cellular Function

BioVenic offers antibody engineering services to address the high immunogenicity of veterinary therapeutic antibodies in heterologous animals. Through our antibody caninization and felinization services, veterinary therapeutic antibodies are more acceptable to the immune system of companion animals. And BioVenic offers antigen affinity maturation services to avoid the possible loss of antigen affinity during antibody caninization and felinization. For antibody half-life, BioVenic provides Fc engineering modification services to prolong the half-life of veterinary therapeutic antibodies, improving the efficacy.

Species-Specific Therapeutic Antibody Development

Compared to small-molecule drugs, therapeutic antibodies are generally characterized by species specificity. Antigen structures vary across species, and the use of heterologous antibodies leads to immune system activation in the treated animals, causing adverse reactions due to the recognition of the antibodies as foreign proteins. BioVenic offers species-specific therapeutic antibody development services to enhance therapeutic efficacy while maintaining safety in therapeutic antibody development for different animal species. Whether it involves modifying heterologous antibodies or directly developing therapeutic antibodies from canine or feline sources, we are dedicated to serving specific needs.

Fig.2 Process for species-specific therapeutic antibody preparation. (Beirão, 2016)Fig.1 Process for species-specific therapeutic antibody preparation. 1

  • Antibody Caninization and Felinization

BioVenic provides antibody caninization and felinization services, utilizing chimeric antibody technology to replace the constant region of the antibody. CDR transplantation technology is also used to transplant the CDR of the original antibody onto the antibody framework region of the canine or feline to realize the caninization and felinization of therapeutic antibodies.

  • Fully Canine and Feline Antibody Development

The residual heterologous portions of hybrid antibodies may still be recognized as foreign, leading to reduced antibody efficacy. BioVenic offers services for the development of full canine and feline therapeutic antibodies. This approach ensures that the antibodies are fully compatible with the immune systems of canines and felines, minimizing the risk of immunogenic reactions.

Phage Display

Phage display libraries from full canine or feline sources encompass billions of natural antibody types, and you can select the appropriate target antibodies based on your target antigens without the need for animal immunization, prioritizing animal welfare.

Transgenic Mice

Utilizing genetic engineering techniques, canine or feline antibody DNA is introduced into the genome of mouse progenitor cells, enabling mice to produce full canine or feline therapeutic antibodies in vivo.

Single B Cell

Single B cell technology isolates, cultures, and screens individual B cells directly after animal immunization, effectively identifies and selects the B cells that produce the desired antibody and performs single-cell antibody sequencing to obtain the target antibody sequence.

Veterinary Therapeutic Bispecific Antibody Development

The bispecific antibodies are composed of two distinct binding domains (variable regions or complementarity-determining regions) capable of binding to two different antigens or two different epitopes of the same antigen, enhancing therapeutic efficacy and safety. Additionally, they possess unique advantages in redirecting cytotoxic effector cell activity. BioVenic has established a platform for the development of veterinary therapeutic bispecific antibodies, assisting in utilizing these novel technologies for therapeutic applications in animals.

Platforms Description
Chemical Conjugation Chemically modifying two different monoclonal antibody molecules and then coupling them together through chemical reactions to form a bispecific antibody.
Hybrid-Hybridoma (Quadroma) Technology Fusing hybridoma cells from two different monoclonal antibodies. This results in hybrid cells that express both antibody fragments, creating a bispecific antibody.
Genetic Engineering Using recombinant DNA technology, the genetic information for the variable domains of each antibody is harnessed to construct a unified genetic entity, giving rise to bispecific formats such as single-chain variable fragments (scFv), diabodies, or Fab fragments.

Veterinary Therapeutic Antibody Effectiveness and Safety Assessments

BioVenic provides a comprehensive service for the effectiveness and safety assessment of veterinary therapeutic antibodies. Through a series of in vitro and in vivo assays, we have the ability to evaluate factors such as pharmacodynamics, pharmacokinetics, safety, and immunogenicity of veterinary therapeutic antibodies. This service is designed to offer valuable insights into the efficacy and safety of veterinary therapeutic antibodies, supporting their development.

  • Disease Modeling

BioVenic has established animal models for a wide range of disease types to meet the needs of veterinary therapeutic antibody development programs, including model animals such as mice and rats, also target animals such as canines and felines.

Subcutaneous Tumor Transplantation Animal Model

Melanoma
Mammary Tumor
Liver Cancer
Skin Cancer
Squamous Cell Carcinoma
Brain Tumor
Osteosarcoma

In Situ Tumor Transplantation Animal Model

Liver Cancer
Brain Tumor
Mammary Tumor

Metastatic Tumor Animal Model

Melanoma
Lymphoma
Liver Cancer
Brain Tumor
Osteosarcoma
Mammary Tumor

Allergic Disease Animal Model

Atopic Dermatitis
Asthma
Allergic Rhinitis

Autoimmune Disease Animal Model

Rheumatoid Arthritis
Systemic Lupus Erythematosus
Experimental Sjögren's Syndrome
Delayed Type Hypersensitivity

  • In Vitro Assays

BioVenic provides comprehensive in vitro assays to support the development of veterinary therapeutic antibodies. By leveraging advanced technologies, BioVenic ensures that each therapeutic antibody is thoroughly evaluated for its therapeutic potential, providing valuable insights that guide the optimization and selection of promising candidates for further development in veterinary medicine.

In Vitro Assays
Bioactivity
  • Cell-based or antigen-antibody binding activity assays. (ELISA, SPR, FACS, ECL)
  • Fab/Fc function assays. (ADCC, CDC, FcγR/ FcRn)
Pharmacodynamics
  • Biophysical Testing. (SPR, DLS, DSC)
  • Biochemical Testing. (CL, FP, ELISA)
  • Cytologic assays. (Cell viability, apoptosis, proliferation, death, and cell cycle assays, Cell migration assay, Signaling pathway assay, HTRF protein expression level detection)
Pharmacokinetics
  • Physical and chemical property testing. (Solubility, oil-water partition coefficient, protein binding, whole blood plasma partitioning, chemical stability testing)
  • Drug absorption and transporters assays. (Permeability assessments, transporter protein assays)
  • Drug Metabolism assays. (Hepatic, Plasma/whole blood stability testing, metabolite identification)
  • Drug-drug interaction assays. (CYP/UGT phenotyping, Inhibition, CYP Induction)
Safety
  • Genotoxicity studies. (Ames test, micronucleus test)
  • Hepatotoxicity studies. (Hepatocyte activity test, lipoatrophy/phospholipid deposition test)
  • Mitochondrial Toxicity studies. (Fluorescence oxygen depletion assay, mitochondrial membrane potential assay)
  • Cytotoxicity studies. (MTT assay, LDH assay)
Immunogenicity
  • Cytokine Detection. (IL-2、IL-6、IL-10、IFN-γ, TNF-α, etc.)
  • In Vivo Assays

BioVenic offers an extensive range of in vivo assays to support veterinary therapeutic antibody development. By utilizing advanced in vivo models, BioVenic assesses how these therapeutic antibodies interact within a living organism, providing valuable insights into their therapeutic potential, optimal dosing regimens, and potential side effects.

In Vivo Assays
Pharmacodynamics
  • Biomarker detection and analysis. (HE staining, qPCR, ELISA, western blot)
  • Optical in vivo Imaging. (Bioluminescence, fluorescence)
Pharmacokinetics
  • Pharmacogenetic/toxicogenic sample analysis. (ELISA, LC-MS, MS)
  • Calculation of pharmacokinetic parameters. (F, T1/2, Cmax, Tmax, CL, Css, AUC)
Safety
  • General toxicology studies. (Maximum tolerated dose, dose range finding)
  • Carcinogenicity studies.
  • Reproductive and developmental toxicology studies.
  • Genetic toxicology studies.
  • Safety pharmacology studies.
  • Drug dependence studies.
  • Toxicokinetic studies.
Immunogenicity
  • ADA screening and confirmatory assays. (Bridging ELISA, ELISA, RIA, ECL, SPR)
  • NAb detection. (Cell-based Assay, non-cell competitive ligand-binding assay)

Veterinary Therapeutic Antibody Manufacturing

BioVenic provides laboratory-scale manufacturing services for the development and preliminary evaluation of candidate veterinary therapeutic antibodies.

  • Design and Preparation of Antigens

BioVenic offers services for the design and production of antigens to ensure the generation of high-quality, specific antibodies.

Proteins Peptides DNA mRNA VLP
  • Antibody Production

Utilizing efficient expression systems, BioVenic provides services for producing therapeutic antibodies on a laboratory scale, ensuring high purity and excellent biological activity.

Bacterial Expression System Yeast Expression System Mammalian Cell Expression System
  • Quality Control

BioVenic implements rigorous quality control measures to ensure that the provided antibodies meet high quality.

Cell Identification
  • Cell morphology identification.
  • Biochemical assays. (isoenzyme assays)
  • Immunological assays.
  • Genetic assays. (Chromosomal karyotyping, marker chromosome assays)
  • Genetic marker assays. (DNA fingerprinting, STR mapping)
Pathogenic Microorganism Detection
  • Sterility checks on cell culture supernatants. (Direct inoculation, membrane filtration methods)
  • Internal and external virus detection. (qPCR, NGS, cell culture)
Impurity Analysis
  • Purity analysis. (CE-SDS, SDS-PAGE, SEC, RP, LC, LC/MS, GC, GC/MS, SFC)
  • Charge heterogeneity analysis. (IEF, CEX, CIEF, iCIEF)
Stability Testing
  • Appearance, pH value.
  • Potency assay. (ELISA)
  • Thermal stability testing. (DSC)
  • Solubility testing. (CIC, AC-SINS, CSI-BLI)

Hot Veterinary Therapeutic Antibody Targets

A therapeutic target refers to a specific molecule or a group of crucial molecules participating in one or more disease-related processes. These targets enable the recognition and precise treatment of these diseases. Targeted therapy offers an optimal disease-specific characteristic while reducing harm to healthy tissues, thereby mitigating potential side effects. BioVenic offers groundbreaking therapeutic antibody development services to meet animal healthcare needs, involving various key targets in veterinary treatment. These hotspots encompass a range of diseases, from cancer, allergic diseases, autoimmune diseases, inflammatory diseases, and pain, to common infectious diseases. The table below lists common target types for which BioVenic provides development services, covering various diseases affecting animal species such as companion animals like canine, feline, equine, and more.

Veterinary Cancer Targets
Veterinary Allergic Disease Targets
Veterinary Autoimmune Disease Targets
Veterinary Inflammatory Disease Targets
Veterinary Pain Targets
Veterinary Infectious Disease Targets

Why Choose Us?

Our one-stop-shop covers the entire veterinary therapeutic antibody development process, from antibody discovery, species-specific antibody development to in vitro and in vivo assays.

Not only monoclonal antibodies, but the introduction of emerging technologies also allows us to provide development services for veterinary therapeutic bispecific antibodies and nanobodies.

Tailored to target species, our services leverage extensive experience in species-specific therapeutic antibody development, assisting in the minimization of antibody heterologous components.

Based on several hot veterinary therapeutic antibody targets, we provide veterinary therapeutic antibody development services for many types of animal diseases.

Therapeutic antibody development for animals is gaining increasing popularity among researchers. If you are looking to enter this promising field, BioVenic offers a full range of services for veterinary therapeutic monoclonal antibodies, bispecific antibodies, and nanobodies. With a focus on practical effectiveness, we also offer species-specific therapeutic antibody development services and cover specific therapeutic targets for various animal diseases, ensuring that you can have more effective results. If you are interested in this service, please do not hesitate to contact us!

References

  1. Beirão, Breno CB, et al. "Challenges and opportunities for monoclonal antibody therapy in veterinary oncology." The Veterinary Journal 218 (2016): 40-50.
  2. Salvador, J-Pablo, et al. "Nanobody: outstanding features for diagnostic and therapeutic applications." Analytical and bioanalytical chemistry 411 (2019): 1703-1713.
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