MPS ANTIBODY DISCOVERY

The industry leader in discovering monoclonal antibodies against multipass membrane proteins

We deliver lead therapeutic candidates with a >95% success rate for:

✓ GPCRs
✓ Transporters
✓ Ion Channels

MAbs against membrane proteins are notoriously difficult to isolate

Our platform is specifically tailored to work with membrane proteins

Integral Molecular is uniquely capable of isolating MAbs against multipass membrane proteins

Traditional discovery platforms produce small panels of non-functional MAbs

Our MPS Antibody Discovery platform delivers large panels of functional MAbs

MPS Antibody Discovery

The MPS Discovery Engine® is the only MAb discovery platform specifically built for multipass membrane protein targets. Our technologies enable robust immune responses against conserved proteins and deep screening, resulting in a >95% success rate.

“Access to Integral Molecular’s capabilities complements our ability to advance our therapeutic pipeline, which is dedicated to delivering novel antibody therapeutics to patients.”

- CECILE GEUIJEN, PhD, VP OF ONCOLOGY RESEARCH, MERUS

Delivering Antibodies for Difficult Targets

Optimized Antigen Expression

We engineer target proteins for increased expression, stability, and enhanced surface trafficking, using proprietary techniques

Native Epitope Targeting

Protein (Lipoparticle) and DNA immunization with proprietary adjuvants are used to ensure maximal immune responses against a protein’s native conformation

Access to Diverse Epitopes

We target even conserved epitopes by using chickens for immunization, enabling maximal epitope coverage and MAb developability and dual specificity for human and rodent orthologs

Large Panels of Diverse Antibodies

 Picomolar affinity
 Isoform-selective
 Agonists
 Antagonists
 State-specific

High-Throughput, Deep Screening Technologies

We use Lipoparticle-phage display strategies with protocols specifically tailored to the challenges of membrane proteins to isolate rare and diverse MAbs against native epitopes

Our proprietary microfluidic B cell cloning platform allows high-throughput screening of millions of B cells isolated directly from immunized animals

Antibody Selection and Optimization

Lead Selection

Leads are selected based on functional testing, binding affinity, epitope location (Shotgun Mutagenesis), and specificity profiling (Membrane Proteome Array)

Lead Optimization

Leads are optimized for developability and preclinical testing, including:

  • Fc reformatting
  • Minimized immunogenicity
  • Affinity maturation

“We have been impressed by Integral Molecular’s membrane protein expertise and their proven record in discovering antibodies against them.”

- HIDEAKI TADA, EXECUTIVE DIRECTOR, CENTER OF ONCOLOGY RESEARCH, ONO PHARMACEUTICAL CO., LTD.

Featured Case Studies

Case-Study-Transporter-SLC2A4

State-specific SLC2A4 (GLUT4) transporter MAbs for diabetes

Case-Study-GPCR-CB1

Antagonist MAbs against the GPCR CB1 for NASH liver disease

Case-Study-P2X7

Agonist and antagonist MAbs targeting the P2X7 ion channel for autoimmune disorders

Case-Study-Tight-Junction-CLDN6

Highly specific MAbs against the tight junction protein Claudin-6 for solid tumors

Frequently Asked Questions

MPS Antibody Discovery is Integral Molecular’s proven platform for delivering lead panels of MAbs against complex membrane protein targets. Harnessing our full array of proprietary technologies, the MPS platform overcomes the challenges of working with membrane proteins to isolate, optimize, and characterize antibodies against otherwise intractable targets.

The MPS Antibody Discovery platform has been successfully applied to every type of membrane protein, including GPCRs, ion channels, and transporters, as well as multi-subunit proteins and immuno-oncology targets. Our platform is specifically designed to overcome the challenges of targeting multipass membrane proteins that are highly conserved, toxic, or poorly expressed.

The MPS Antibody Discovery platform is specifically designed to overcome the many challenges of discovering antibodies against membrane protein targets. To overcome the poor expression and high toxicity of membrane proteins, we use proprietary vectors and targeted mutagenesis strategies to engineer targets for enhanced surface expression, trafficking, and stability. To deal with issues of limited immunogenicity and antibody diversity, we immunize divergent species using DNA and Lipoparticles. Our proven immunization strategy yields a robust, high-titer immune response, even against highly conserved proteins, and results in panels of antibodies that bind diverse epitopes. Finally, our optimized phage display and B-cell cloning techniques enable the isolation of rare agonist, antagonist, and state-dependent antibodies.

Yes! Functional antibodies against membrane protein targets are often very rare and challenging antibodies to isolate, but are also of critical value for therapeutic development. Using our platform, we have isolated agonist, antagonist, and state-specific antibodies against complex membrane protein targets.

Many membrane proteins are notoriously difficult to work with due to their low surface expression and high toxicity. We use proprietary vectors and targeted mutagenesis methods to engineer membrane proteins for enhanced surface expression, trafficking, and stability. Using these methods, we typically achieve expression levels of engineered targets in Lipoparticles that are 10- to 100-fold higher than wild-type levels. Importantly, our engineering strategies maintain the native extracellular structure of each membrane protein, ensuring that the antibody response to the engineered protein will recapitulate the wild-type immune response.

The final deliverable of an MPS Antibody Discovery project is usually a panel of highly specific, diverse, and functional MAbs that meet the customer’s specifications. Using our MPS Antibody Discovery platform, we have a very high success rate (>95%) in delivering such MAb panels. In addition to the final deliverable, customers receive 4 progress reports during their MPS project:

  1. Target Expression Report – Summarizes target expression after engineering and the proposed immunization strategy

  2. Serum Reactivity Report – Summarizes the immune response of each animal to the target protein

  3. Clone Screen Report – Summarizes MAb selection results and the diversity of discovered MAbs

  4. Clone Reactivity Report – Summarizes target reactivity and the full sequence of each validated MAb. This report is provided simultaneously with 100 μg of purified, ready-to-use IgG of each validated MAb for customer testing

Our MPS Antibody Discovery platform typically results in the discovery of antibodies having low nM to high pM affinities. Integral Molecular offers additional services for antibody maturation (affinity/specificity) and humanization.

Our MPS Antibody Discovery platform involves a number of proprietary components that are only available within partnerships, including our high-expressing engineered membrane proteins, proprietary adjuvants, optimized DNA immunization vectors, divergent animal (e.g. chicken) immunization protocols, phage display and B-cell cloning technologies specifically designed for membrane proteins, and antibody affinity maturation and humanization platforms. Our standard Lipoparticles are available to all customers, but Lipoparticles with engineered receptors are available only for partner projects.

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