Advanced AOCs Solutions for Biotechnology Innovation
Antibody-Oligonucleotide Conjugates (AOCs) Discovery Platform
Overview
Achieve targeted gene modulation with the precision and power of AOCs
Antibody-Oligonucleotide Conjugates (AOCs) are a next-generation therapeutic modality combining the targeting antibodies with the gene-silencing power of oligonucleotides (such as siRNA or ASO).
By leveraging precise molecular design, AOCs can selectively deliver siRNA, ASO, or other therapeutic oligonucleotides to disease-relevant tissues, addressing challenges like cell uptake and delivery efficiency.
Our AOC Strategy
RNAi Platform:
Our RNAi discovery platform supports the synthesis and development of AOCs, leveraging advanced chemical modifications and delivery technologies. It is highlighted as:
- Mononucleotide synthesis: Synthesis of over 80 unique monomers supporting diverse oligonucleotide designs
- Custom nucleobase analogs for improved hybridization and nuclease resistance
- Backbone modifications for increased half-life
- Sugar modifications to fine-tune binding affinity
Mononucleotide Synthesis
Synthesis of over 80 unique monomers supporting diverse oligonucleotide designs
- Custom nucleobase analogs for improved hybridization and nuclease resistance
- Backbone modifications for increased half-life
- Sugar modifications to fine-tune binding affinity
Medicilon Optimal Design (MOD)
Targeted sequence design leveraging the Medicilon Optimal Design (MOD) platform with focused-range prediction to enhance silencing efficacy
GalNAc Synthesis and Optimization
- Broad-class GalNAc library creation (>2000 ionizable lipids synthesized)
- Custom GalNAc linker designs for enhanced stability and targeting
- Integration into siRNA and ASO payloads
Ionizable Lipid Synthesis for tailored delivery
- Large-scale synthesis of proprietary ionizable lipids
- Analytical characterization to confirm lipid identity and purity
- Compatibility assessment with different oligonucleotide modalities
Novel carrier design and optimization
REsearch and Application
Conjugation Chemistry Expertise
Medicilon has successfully developed multiple conjugation chemistries to create AOCs
Multiple Conjugation Methods
Click Chemistry (DBCO-Azide)
Maleimide-Thiol Conjugation (MTC)
Amino-Oligo-Antibody Conjugation (AOAC)
Site-Specific Conjugation (SSC) via microbial transglutaminase (mTG nase)
Antibody-C16-siRNA Conjugation (Before Annealing) demonstrated precise conjugation techniques
Antibody-siRNA Conjugation (After Annealing) exhibited optimized post-annealing processes for enhanced stability
Scalability to produce high-purity AOCs
*15 mg target compound was obtained with a purity of 93 % by SEC
- AOCs Characterization and DAR control:
- Advanced purification (AEX, SEC, LC-MS)
- Rigorous DAR (Drug-to-Antibody Ratio) control and verification
Characterization of DAR 2 AOC
- The peak at 5.77 min corresponds to the AOC
- The peak at 7.59 min corresponds to the free ASO
- The AOC peak at 5.77 min is mainly composed of the DAR 2 species, with minimal amounts of other DAR variants present
Bioanalysis and Preclinical Evaluation
Medicilon’s bioanalytical services provide comprehensive support for AOC development, with advanced tools for large molecule analysis.
We ensure accurate and reliable data to support AOC development and regulatory submissions.
LC-MS/MS Analysis
Quantification of antisense (AS) and sense (SS) strands in plasma and liver tissues, as demonstrated in our Cyno Monkey PK study of siRNA
ELISA and Flow Cytometry
Tools like CTL ELISOPT Reader, CytofLEX S Flow Cytometer, and Beckman VI-CELL Cell Analyzer for precise bioanalysis
Metabolite Quantification
Identification and quantification of major metabolites in plasma and liver, ensuring thorough pharmacokinetic profiling
Global Clinical Support
In vitro and in vivo screening, preclinical GLP PK assays, and support for generic bioequivalence (BE) trials
Capabilities
Preclinical Evaluation Capabilities
Medicilon offers extensive preclinical capabilities for AOC and ADC development, supporting IND and NDA approvals. Key features include:
- GLP & Non-GLP Toxicology StudiesSingle/multiple dose toxicity, reproductive toxicity, genotoxicity, carcinogenicity, and immunogenicity studies
- Pharmacokinetic (PK) and Toxicokinetic (TK) Studies
- Cyno Monkey ADC PK StudySingle-dose IV at 1 MPK, with serum and plasma collection up to 336 hours, analyzed via ELISA and LC-MS/MS
- Balb/c Nude Mouse ADC PK StudySingle-dose IV at 10 MPK, with serum, plasma, and tumor tissue analysis using ELISA and LC-MS/MS
- Monkey Plasma and Liver PK Study of siRNADose-dependent exposure analysis with no gender differences, supporting dose range studies (1-10 mg/kg)
Animal Model Capacity:
Species
Rooms
Maximum Number
- NHP
65
2,260
- Dog
71
1,800
- Rabbit
13
570
- Rodent
94
24,100
- Mini-pig
10
200
IND Approvals: Supported 27 ADC preclinical packages for IND/NDA, including PK, PD, and GLP toxicology studies for anticancer indications.
Let Medicilon help you to advance your AOC development
Contact Medicilon to leverage our expertise in RNAi discovery, conjugation chemistry, bioanalysis, and preclinical evaluation.
