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HCAb Plus™

mRNA

 
Idea to IND

Beacon® Single B Cell Screening

Our Beacon® Platforms and Technology

High Throughput Screening
Antibody Discovery by Beacon® Technology
SCB Platform Workflow
hyperSCREEN: AI-Guided Screening

High Throughput Screening

Nona Biosciences has developed cutting-edge high-throughput screening platforms to expedite antibody discovery.

Since early 2019, our scientific team has established a single B cell cloning (SBC) platform using Berkeley Lights Beacon® Optofluidic technology. We have accumulated substantial expertise in Beacon® and SBC through dozens of antibody discovery projects. Leveraging optimized murine plasma cell enrichment methods, robust and reliable in-chip assay development process, highly efficient single cell sequencing technology, and high-throughput recombinant antibody screening techniques, we’ve successfully applied our SBC platform to more than 50 different antibody generation projects with shortened screening timeline and increased sequence diversity.

We’ve also optimized an innovative high-throughput technology for rapid direct cloning and production of fully human HCAbs from B cells of HCAb Harbour Mice®, which was originally developed in 2016 (Drabek, D. et al. Frontiers in Immunology 7, 3–12 (2016)). This technology facilitates the production of fully human HCAbs in 96-well plates and expedites the process of functional screening.

Despite the capacity of these high-throughput technologies to rapidly screen tens of thousands of B cells and provide a wide array of sequences we are highly motivated to embrace new technologies, such as artificial intelligence (AI), to further increase the screening efficiency and sequence diversity. Through the integration of next-generation sequencing and machine learning, we can explore a more extensive sequence space and uncover sequences that cannot be easily identified by other screening methods.

Introduction

Empowering Targeted Biotherapeutics

Antibody-LNP Conjugation for Cargo Delivery

Introduction

Welcome to the forefront of biotherapeutic innovation, where Nona Biosciences leverages advanced antibody-LNP conjugation techniques to revolutionize targeted delivery systems. Our state-of-the-art technology enhances the precision and efficacy of therapeutic cargo delivery, offering groundbreaking solutions for various medical applications.

Welcome to the forefront of biotherapeutic innovation, where Nona Biosciences leverages advanced antibody-LNP conjugation techniques to revolutionize targeted delivery systems. Our state-of-the-art technology enhances the precision and efficacy of therapeutic cargo delivery, offering groundbreaking solutions for various medical applications.

High Throughput Chip

Each 20K OptoSelect chip has 20,000 individual NanoPen chambers and can separate and screen up to 20,000 cells within a single run.

Versatile In-Chip Assays

With real-time fluorescent microscopy technology, different assays could be performed in-chip for plasma cell screening, including:

  • Antigen beads binding assay
  • Cell binding assay
  • Competition assay
  • Reporter cell assay

All these advantages make SBC platform to become highly efficient and robust antibody discovery platform.

Precisely Single Cell Exporting

Opto-electro positioning (OEP) technology precisely manipulates and unloads cells to 96-well plates preloaded with single-cell sequencing reagents.

Precisely Single Cell Exporting

Opto-electro positioning (OEP) technology precisely manipulates and unloads cells to 96-well plates preloaded with single-cell sequencing reagents.

Strategies for Nanoparticle Targeted Delivery

At Nona Biosciences, we explore both passive and active targeting strategies to optimize nanoparticle delivery systems. Our focus is on tissue-specific and cell-specific delivery to achieve unparalleled precision in reprogramming cells in vivo.

  • Passive vs. Active Targeting:

Tailoring delivery strategies to meet diverse therapeutic objectives.

  • Cell Targeting Technology:

Essential for precise in vivo cell reprogramming.

At Nona Biosciences, we explore both passive and active targeting strategies to optimize nanoparticle delivery systems. Our focus is on tissue-specific and cell-specific delivery to achieve unparalleled precision in reprogramming cells in vivo.

  • Passive vs. Active Targeting:

Tailoring delivery strategies to meet diverse therapeutic objectives.

  • Cell Targeting Technology:

Essential for precise in vivo cell reprogramming.

High Throughput Chip

Each 20K OptoSelect chip has 20,000 individual NanoPen chambers and can separate and screen up to 20,000 cells within a single run.

Versatile In-Chip Assays

With real-time fluorescent microscopy technology, different assays could be performed in-chip for plasma cell screening, including:

  • Antigen beads binding assay
  • Cell binding assay
  • Competition assay
  • Reporter cell assay

All these advantages make SBC platform to become highly efficient and robust antibody discovery platform.

Precisely Single Cell Exporting

Opto-electro positioning (OEP) technology precisely manipulates and unloads cells to 96-well plates preloaded with single-cell sequencing reagents.

Precisely Single Cell Exporting

Opto-electro positioning (OEP) technology precisely manipulates and unloads cells to 96-well plates preloaded with single-cell sequencing reagents.

Enhanced Endocytosis with Antibody-LNP Conjugation

Nona’s innovative LNP conjugation with specific antibodies significantly improves endocytosis in targeted cells. The advancement underscores our commitment to enhancing therapeutic delivery and efficacy.

IgG-LNP conjugation

HCAb-LNP conjugation

VHH-LNP conjugation

Fig.  Various antibody formats for Antibody-LNP conjugate

Key Highlights

1. Anti-CD3/CD5 Conjugation

  • Enhances uptake in CD3/CD5-expressing cells.
  • Demonstrated improved transfection with EGFP mRNA encapsulated in LNPs.
1. Anti-CD3/CD5 Conjugation

  • Enhances uptake in CD3/CD5-expressing cells.
  • Demonstrated improved transfection with EGFP mRNA encapsulated in LNPs.
2. Targeting Different T Cell Subsets

  • Anti-CD3 LNPs improve endocytosis in CD4+ and CD8+ T cells.
  • Anti-CD5 and anti-CD8 LNPs provide targeted uptake with varying efficacy.
2. Targeting Different T Cell Subsets

  • Anti-CD3 LNPs improve endocytosis in CD4+ and CD8+ T cells.
  • Anti-CD5 and anti-CD8 LNPs provide targeted uptake with varying efficacy.
3. Tumor-Specific Targeting

  • Anti-TAA HCAb-LNP conjugates enhance endocytosis in TAA+ tumor cells.
  • Site-specific conjugation of VH antibodies to LNPs shows superior targeting efficiency.
3. Tumor-Specific Targeting

  • Anti-TAA HCAb-LNP conjugates enhance endocytosis in TAA+ tumor cells.
  • Site-specific conjugation of VH antibodies to LNPs shows superior targeting efficiency.

HCAb-LNP conjugation

Fig. The LNP conjugated with anti-TAA HCAb improves the delivery to TAA+ tumors   and increases Fluc expression in tumors

VHH-LNP conjugation

Fig. Anti-TAA VH site-specific conjugation to LNP can improve endocytosis on TAA+ tumor cells

Establishing Cutting-Edge Technology Platforms

Nona Biosciences is dedicated to advancing biotherapeutic innovation through robust technology platforms:

Beacon® Plasma Cell Workflow
mRNA-LNP Encoding Biologics

Efficiently deliver genetic material to target cells.

Antibody Conjugated Nanoparticles

Precisely target and deliver therapeutic agents.

HCAb-based CAR Library Screening (HCAb CARFx)

Accelerate the development of highly specific CAR-T therapies.

Step one

Antibody Discovery

Leveraging Harbour Mice® platforms and expertise, Nona provides a complete solution for fully human H2L2, HCAb, and bi/multi-specific antibody discovery, including antigen preparations, immunization, antibody screening, engineering, and functional evaluation.

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H2L2
HCAb
HBICE

Introduction

Fully Human HCAb-based mRNA-LNP

mRNA-Encoding Biologics:

A Breakthrough in Medicine

Introduction

mRNA-encoding biologics are revolutionizing the field of medicine by harnessing the power of mRNA technology. Our innovative approach leverages the Harbour HCAb Mice® platform to develop HCAbs encoded by mRNA and delivered via LNP. This cutting-edge technology provides a versatile and powerful method for creating therapeutic agents with enhanced efficacy and specificity.

High Throughput Chip

Each 20K OptoSelect chip has 20,000 individual NanoPen chambers and can separate and screen up to 20,000 cells within a single run.

Versatile In-Chip Assays

With real-time fluorescent microscopy technology, different assays could be performed in-chip for plasma cell screening, including:

  • Antigen beads binding assay
  • Cell binding assay
  • Competition assay
  • Reporter cell assay

All these advantages make SBC platform to become highly efficient and robust antibody discovery platform.

Precisely Single Cell Exporting

Opto-electro positioning (OEP) technology precisely manipulates and unloads cells to 96-well plates preloaded with single-cell sequencing reagents.

Precisely Single Cell Exporting

Opto-electro positioning (OEP) technology precisely manipulates and unloads cells to 96-well plates preloaded with single-cell sequencing reagents.

Key Features

1. Exceptional Cytotoxicity

The HCAb TAA x CD3 mRNA-LNP demonstrates significant cytotoxic effects on TAA-expressing target cells.

1. Exceptional Cytotoxicity

The HCAb TAA x CD3 mRNA-LNP demonstrates significant cytotoxic effects on TAA-expressing target cells.

2.Specific Killing Effect

The TAA x CD3 mRNA-LNP targets TAA-positive cells specifically, minimizing off-target effects and underscoring the precision of the mRNA-LNP therapy.

2.Specific Killing Effect

The TAA x CD3 mRNA-LNP targets TAA-positive cells specifically, minimizing off-target effects and underscoring the precision of the mRNA-LNP therapy.

3. Distinct Killing Pattern

The TAA x CD3 mRNA-LNP displays a unique killing pattern compared to traditional recombinant proteins.

3. Distinct Killing Pattern

The TAA x CD3 mRNA-LNP displays a unique killing pattern compared to traditional recombinant proteins.

4. Potent Anti-Tumor Efficacy

The TAA x CD3 mRNA-LNP significantly reduces tumor volume in vivo in a dose-dependent manner.

The fully human HCAb-based mRNA-LNP platform, developed using Harbour HCAb Mice®, offers a promising approach for designing highly specific and potent biologics. With precise targeting and effective killing patterns, Nona Biosciences’ mRNA-LNP platform demonstrates potent anti-tumor efficacy, positioning it at the forefront of next-gen therapies.

 
4. Potent Anti-Tumor Efficacy

The TAA x CD3 mRNA-LNP significantly reduces tumor volume in vivo in a dose-dependent manner.

The fully human HCAb-based mRNA-LNP platform, developed using Harbour HCAb Mice®, offers a promising approach for designing highly specific and potent biologics. With precise targeting and effective killing patterns, Nona Biosciences’ mRNA-LNP platform demonstrates potent anti-tumor efficacy, positioning it at the forefront of next-gen therapies.

Step two

ADC Bioconjugation

Nona offers a variety of bioconjugation technologies such as lysine/cysteine-based conjugation with optimized DAR value and optimization of reaction conditions. Our proprietary DAR2 site-specific conjugation and linker-payload library include the majority of classical linker-payloads, like cleavable and non-cleavable linkers.

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step Three

ADC Biophysical Characterizations

Based on Nona’s deep understanding of ADC molecules, we perform a comprehensive assessment of molecules for lead identification and characterization, including DAR determination, conjugation stability, plasma stability and drug-releasing efficiency.

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In Vitro
In Vivo
Step four

ADC In Vitro and In Vivo Characterization

A full range of in vitro bioactivity studies for both monoclonal antibodies and ADCs is available, including antigen binding, internalization, soluble antigen interference, cytotoxicity, and bystander killing. Nona also encompasses integral capabilities for in vivo studies, including various pharmacological models for ADC efficacy assessment, such as CDX, PDX, and heterogeneous tumor models. Additionally, pre-toxicity evaluation and small animal PK studies complete the integrated ADC R&D services.

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Start your Harbour Mice HCAb PLUS™ Project

Having questions? Contact us at BD@nonabio.com

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