Next Generation Site-Specific Conjugation and Linker Technologies for ADCs

AJICAP®’s VALUE

Therapeutic Window Enhancement

  • ADCs with higher efficacy and lower toxicity achieved by site-specific conjugation and stable & hydrophilic linker

Straightforward Site-Specific Conjugation Method

  • Direct modification on native antibody by chemical method
  • No genetic engineering and no enzyme required
  • Simple and high yield manufacturing process
  • Precisely controlled DAR2 and higher

Applicable for Versatile ADCs

  • Site-specific conjugation applicable for any IgG molecule and a variety of payloads
  • Stable & hydrophilic linker compatible with various payloads

Technology

AJICAP® Site-Specific Conjugation

AJICAP® site-specific conjugation is an innovative direct chemical site-specific conjugation method for intact native antibodies, offering significant advantages for next generation ADCs.

AJICAP® Site-Specific Conjugation consists of:
  1. Introduction of bio-orthogonal functionalities (thiol, azide etc) onto specific Lys residue in Fc region*

  2. Conjugation with
    linker-payload

* Site-specificity is derived from peptide in AJICAP® reagent binding to specific moiety in Fc region.

Advantage of AJICAP® Site-Specific Conjugation
  1. Higher efficacy and lower toxicity achieved due to site-specificity

  2. Simple manufacturing and purification process providing CMC advantage

  3. Precisely controlled DAR2 or higher DAR on specific sites

  4. Applicable for a wide variety of antibodies i.e. IgG1, IgG2 and IgG4

  5. Compatible with various payload-linkers i.e. small molecule to large molecule


Application of AJICAP® Site-Specific Conjugation:
  • ADC platform with various payloads (toxin and others)

  • In-vivo radio imaging/therapy platform with radioisotopes

  • Long-acting biopharmaceutical platform for peptides and oligonucleotides

  • Bispecific platform with proteins


AJICAP® Stable and and Hydrophilic Linker

AJICAP® linker is a novel stable and hydrophilic linker, applicable to various payloads, offering significant advantages for versatile ADCs.

Characteristics of AJICAP® stable and hydrophilic linker
  1. Higher serum stability and controlled release in cancer tissues

  2. Hydrophilic masking of payload


Advantage of AJICAP® Stable and Hydrophilic Linker
  1. Higher efficacy and lower toxicity achieved due to higher serum stability and controlled release in cancer tissues

  2. Dramatically lower aggregation of ADCs by hydrophilic masking of payloads

  3. Applicable for a variety of conjugation technologies including AJICAP® conjugation


Application of AJICAP® Stable and Hydrophilic Linker Technology:

Compatible with a variety of conjugation technologies including:

AJICAP® Site-Specific Conjugation Technology

Native Cys conjugation
DAR4-DAR8

Other genetic engineering and
enzymatic method


Biological Activity of AJICAP®-ADCs

ADCs generated by AJICAP® site-specific conjugation and stable & hydrophilic linker has higher efficacy and lower toxicity.


Global Service Offering

Ajinomoto Bio-Pharma Services provides a Global service in Japan and United States.


Service Flow

Service flow of AJICAP® is simple and easy. The following steps outline the process:

  • Research plan discussion

  • Client ships antibody (and payload) to Ajinomoto Bio-Pharma Services

  • Ajinomoto Bio-Pharma Services generates ADCs or other conjugates

  • Client evaluates ADCs or conjugates in vitro and in vivo

  • Technology license Go/No Go decision

  • GxP production discussion


Resources

Resources related to AJICAP® can be found here.

Research Publications

1. Scale-Up Synthesis of Site-Specific Antibody–Drug Conjugates Using AJICAP Second-Generation Technology

Org. Process Res. Dev. 2023, 27, 6, 1136–1143

The paper described that the AJICAP® second-generation process is a robust and practical approach for the manufacture of ADCs.

2. AJICAP Second Generation: Improved Chemical Site-Specific Conjugation Technology for Antibody–Drug Conjugate Production

Bioconjugate Chemistry, Articles ASAP

The report of AJICAP® second generation, affinity peptide mediated site-specific functionalization that enables the synthesis of next-generation antibody conjugates.

3. Chemical Site-Specific Conjugation Platform to Improve the Pharmacokinetics and Therapeutic Index of Antibody–Drug Conjugates

Mol. Pharmaceutics 2021, 18, 4058-4066.

The report of the compatibility and robustness of AJICAP® technology, which enabled the synthesis of a wide variety of ADCs. This is the first report of the therapeutic index estimation of site-specific ADCs produced by utilizing Fc affinity reagent conjugation.

4. AJICAP: Affinity Peptide Mediated Regiodivergent Functionalization of Native Antibodies

Angew. Chem., Int. Ed. 2019, 58, 5592–5597.

The report of AJICAP® first generation, a novel strategy with affinity peptide mediated site-specific functionalization that enables the synthesis of next-generation antibody conjugates.

5. Comparison of Analytical Methods for Antibody–Drug Conjugates Produced by Chemical Site-Specific Conjugation: First-Generation AJICAP

Anal. Chem. 2019, 91, 12724−12732.

The report of further investigation focusing on comparison of several different analytical methods for drug–antibody ratio (DAR) determination of first-generation AJICAP®-ADC (Angew. Chem., Int. Ed.2019, 58, 5592–5597). The analytical strategy reported here can be applied to the DAR determination of site-specific ADCs.

6. Gram-Scale Antibody–Drug Conjugate Synthesis by Site-Specific Chemical Conjugation: AJICAP First Generation

Org. Process Res. Dev. 2019, 23, 2647−2654.

The report of the first gram-scale ADC synthesis using AJICAP® first generation technology (Angew. Chem., Int. Ed.2019, 58, 5592–5597) employing a scale-down manufacturing approach using tangential flow filtration. The results reported herein for the gram-scale optimization indicate that AJICAP® technology is amenable to relevant manufacturing production scales.

7. Good Manufacturing Practice Strategy for Antibody–Drug Conjugate Synthesis Using Site-Specific Chemical Conjugation: First-Generation AJICAP

ACS Omega 2019, 4, 20564−20570.

The report of the preparation of site-specific ADCs based on first-generation AJICAP® technology for the utilization in good laboratory practice studies.

8. Proof of site-specificity of antibody-drug conjugates produced by chemical conjugation technology: AJICAP first generation

Journal of Chromatography B 2020, 1140, 121981.

The report of further investigation focusing on peptide mapping of the AJICAP®-ADC to confirm the exact conjugation position of the first generation AJICAP®-ADC. The analytical strategy described herein demonstrated a robust analytical methodology for revealing the conjugation site of ADCs.

9. Biological Evaluation of Maytansinoid-Based Site-Specific Antibody-Drug Conjugate Produced by Fully Chemical Conjugation Approach: AJICAP®

Front. Biosci. (Landmark Ed) 2022, 27, 234.

The report of comparing site-specific maytansinoid-based ADCs synthesized by AJICAP® and T-DM1 in rat safety studies.

10. Application of Native Ion Exchange Mass Spectrometry to Intact and Subunit Analysis of Site-Specific Antibody–Drug Conjugates Produced by AJICAP First Generation Technology

J. Am. Soc. Mass. Spectrom. 2020, 31, 1706−1712.

The report of site specific conjugated AJICAP®-ADC Native ion exchange mass spectrometry (SCX-UV-MS) .

11. Chromatographic analysis of site-specific antibody-drug conjugates produced by AJICAP first-generation technology using a recombinant FcγIIIa receptor-ligand affinity column

Journal of Chromatography B 2021, 1177, 122753.

The report of the chromatographic separation of site-specific ADCs produced by AJICAP® technology using an analytical affinity chromatography HPLC column containing a recombinant FcγIIIa receptor-ligand immobilized on a non-porous polymer resin (NPR).


Contact Us

For further information, please contact us using the link below and an Ajinomoto Bio-Pharma Services representative will contact you.


Story of AJICAP®