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Integral Molecular

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Philadelphia, Pennsylvania, US

About Integral Molecular

Integral Molecular is a research-driven biotechnology company enabling antibody discovery against complex membrane proteins. The company provides characterization services, reagents, and a full antibody discovery platform optimized to work with membrane protein targets, including GPCRs, ion channels, and transporters.

Founded in 2001, Integral has worked with over 300 different partners and customers, including all top 10 pharmaceutical companies.

Our Services (5)


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Reporter Virus Particles

Price on request

Integral Molecular offers pseudotyped Reporter Virus Particles to test infectivity and neutralization for:

• SARS-CoV-2

• SARS-CoV-2 D614G

• SARS-CoV-1

• MERS-CoV

• Dengue serotypes 1-4

• Zika

Reporter Virus Particles (RVPs) are replication-incompetent pseudotyped virus particles that enable safe (BSL-2), easy, and high-throughput viral infectivity and neutralization assays using standard detection instrumentation. RVPs display antigenically correct envelope/spike protein and carry a modified genome that expresses a convenient

optical reporter gene (GFP or luciferase) within 24 hours of cellular infection. RVPs are available as a ready-to-use reagent that provides a safe and efficient alternative to plaque assays, and are produced under quality-controlled conditions as a critical reagent to enable regulatory submissions.

Applications of RVPs

• Antibody neutralization

• Serum screening

• High-throughput assays

Advantages of SARS-CoV-2 RVPs 

• Safe in a BSL-2 environment

• Quantitative (luciferase) or fluorescent (GFP) read-out

• Compatible with high-throughput plate-based assays

• Quality-controlled production for use as a critical reagent

Click here for additional information on coronavirus RVPS

Click here for additional information on dengue and Zika RVPs

Publications 

Whitbeck ET AL. 2020. Antigenicity, Stability and Reproducibility of Zika Reporter Virus Particles for Long-term Applications. PLoS Negl Trop Dis. 14(11):e0008730. doi: 10.1371/journal.pntd.0008730

Mattia ET AL. 2011. Dengue Reporter Virus Particles for Measuring Neutralizing Antibodies Against Each of the Four Dengue Serotypes. PLOS ONE 6(11):e27252. doi: 10.1371/journal.pone.0027252.


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Membrane Proteome Array

Price on request

Approximately 25% of antibodies are polyspecific and off-target drug binding can lead to serious adverse events. De-risk your program by choosing the right lead molecule using Integral Molecular’s Membrane Proteome Array. MPA is the largest array of membrane proteins for specificity profiling of biotherapeutics including antibodies and CAR-T cell therapy.

Advantages of the Membrane Proteome Array:

• 6,000 human membrane proteins (~95% of the membrane proteome)

• Sensitive detection of physiologically relevant targets using high throughput flow cytometry

• Screening on live, unfixed cells preserves native epitopes

• Fully validated, IND-ready interaction report in 4 weeks

Applications of the Membrane Proteome Array:

Specificity Profiling: Your antibody or CAR-T therapeutic is screened to identify potential off-target interactions

Antibody Deorphaning: Your antibody is screened to identify binding partner(s)

Membrane Proteome Array Case Studies

Click here to see how FairJourney established that their antibodies do not demonstrate off-target binding

Click here to understand how a MAb can cross-react with a completely unrelated protein

Click here to learn how the Membrane Proteome Array was used to deorphan panels of antibodies with unknown targets


Toxicology Biopharmaceutical Characterization Profiling Target Identification Antibodies membrane protein GPCR Ion Channel flow cytometry specificity profiling high throughput monoclonal antibody Show 12 more tags Show less

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Epitope Mapping

Price on request

Integral Molecular’s proprietary Shotgun Mutagenesis technology is used to reliably map conformational epitopes at single amino acid resolution with a >95% success rate. We have mapped 1,000+ epitopes to date, including:

• Epitopes on GPCRs, transporters, and viral envelope proteins

• Conformational epitopes

• Epitopes on multi-subunit proteins

• State-dependent epitopes

How Does Shotgun Mutagenesis Work?

1. Automated point mutation of every residue in the target protein to alanine

2. Native expression of individual mutants in human cells, enabling mapping of conformational epitopes

3. High-throughput expression, antibody reactivity, and functional testing

4. 3D structural visualization of the epitope

Applications of High-Resolution Epitope Mapping:

• Lead candidate selection by uncovering mechanisms of action

• MAb protection by strengthening IP

Epitope Mapping Project Deliverables:

Assay Setup Report: Summary of optimized conditions for screening

Final Report: Amino acid resolution epitopes and publication-ready figures

Shotgun Mutagenesis Epitope Mapping Case Studies

Click here to see how Novartis characterized the mechanism of action for CXCR2 antibodies

Click here to see how Covagen distinguished HER2 antibodies from existing therapeutics

Click here to learn how epitope mapping enhances antibody protection 

Select Publications Featuring Shotgun Mutagenesis Epitope Mapping

Dussupt et al., 2020. Potent Zika and dengue cross-neutralizing antibodies induced by Zika vaccination in a dengue-experienced donor. NATURE MED 26, 228-235.

Zhang et al., 2018. Mxra8 is a receptor for multiple arthritogenic alphaviruses. NATURE 557, 570-574.

Zhao et al., 2017. Immunization-elicited broadly protective antibody reveals Ebolavirus fusion loop as a site of vulnerability. CELL 169, 891-904.

Davidson and Doranz. 2014. A high-throughput shotgun mutagenesis approach to mapping B-cell antibody epitopes. IMMUNOLOGY 143(1), 13-20.

Fong et al., 2014. Exposure of epitope residues on the outer face of the Chikungunya virus envelope trimer determines antibody neutralizing efficacy. J VIROL 88(24), 14364-14379.

Paes et al., 2009. Atomic-level mapping of antibody epitopes on a GPCR. J AM CHEM SOC 131(20), 6952-6954.


Drug Discovery Amino Acid Substitution antibodies antibody discovery biologics High-throughput Antibodies Monoclonal antibodies G coupled protein receptor Transporter Membrane proteins Ion Channel Show 12 more tags Show less

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Antibody Discovery

Price on request
MPS is the only MAb discovery platform specifically built for multipass membrane protein targets. Our technologies enable robust immune responses against conserved proteins and employ deep screening, resulting in a >95% success rate. Our MPS Antibody Discovery Platform delivers large panels of functional MAbs as compared to small panels of non-functional MAbs delivered produced by traditional discovery platforms. Advantages of our MPS Antibody Discovery Platform: 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: Isolates diverse panels of MAbs to find rare agonists/antagonists • Access to Conserved Epitopes: Provides high-titer responses, even for highly conserved proteins by using chickens for immunization, enabling maximal epitope coverage and MAb developability and dual specificity for human and rodent orthologs • Optimized Antigen Expression: We engineer target proteins for increased expression, stability, and enhanced surface trafficking, using proprietary techniques Case Studies Learn more about our State-specific GLUT4 Mabs for Diabetes • Learn more about Antagonist MAbs against the GPCR CB1 for NASH liver disease • Learn more about Agonist and antagonist MAbs targeting the P2X7 ion channel for autoimmune disorders • Learn more about Highly specific MAbs against the tight junction protein Claudin-6 for solid tumors Select Publications Featuring MPS Antibody Discovery TUCKER, ET AL. 2018. Isolation of state-dependent monoclonal antibodies against the 12-transmembrane domain glucose transporter 4 using virus-like particles. PNAS 115(22):E4990-E4999. • HUSTON-PATERSON, ET AL. 2016. Screening the Membrane Proteome A High-Throughput Platform for Identifying Membrane Protein Antibody Targets. GENETIC ENGINEERING NEWS VOL. 36, NO. 15. • VAN DER WONING, ET AL. 2016. DNA immunization combined with scFv phage display identifies antagonistic GCGR specific antibodies and reveals new epitopes on the small extracellular loops. MABS 8(6):1126–1135. • GRIFFITHS, ET AL. 2016. i-bodies, Human Single Domain Antibodies That Antagonize Chemokine Receptor CXCR4. J BIO CHEM 291(24):12641-57. • DORANZ, ET AL. 2015. Optimizing Membrane Protein Expression: Improving Surface Expression and Stability for Antibody and Vaccine Discovery. GENETIC ENGINEERING NEWS VOL. 35, NO. 15. • FONG, ET AL. 2014. Exposure of epitope residues on the outer face of the chikungunya virus envelope trimer determines antibody neutralizing efficacy. JOURNAL OF VIROLOGY 88(24):14364-14379. • ADAM, ET AL. 2014. Membrane Protein Solutions for Antibody Discovery. GENETIC ENGINEERING & BIOTECHNOLOGY NEWS VOL. 34, NO. 8. • BERDOUGO, ET AL. 2012. Isolating Membrane Protein Antibodies. GENETIC ENGINEERING & BIOTECHNOLOGY NEWS VOL. 33, NO. 6. • BERDOUGO, ET AL. 2011. Maximal Humanization of Monoclonal Abs. GENETIC ENGINEERING & BIOTECHNOLOGY NEWS VOL. 31, NO. 14. • BANIK AND DORANZ, 2009. Antibody strategies for membrane protein targets. DRUG DISCOVERY & DEVELOPMENT VOL 12, NO. 9.


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Lipoparticle Production

Price on request

Lipoparticles are virus-like particles that concentrate and present conformationally intact membrane proteins on non-infectious particles. This enables complex membrane proteins to be manipulated as soluble, high-concentration proteins for antibody immunization and screening.

The Lipoparticle ‘Advantage’ for Antibody Discovery: 

• Lipoparticles concentrate proteins at 10-100× (~50-200 pmol/mg) the concentration of cells or membrane preps, resulting in robust immune responses and more successful antibody screens

• Lipoparticles display properly folded membrane proteins in their native cellular membrane, providing the ability to elicit and screen for conformational, functional antibodies

• Lipoparticles are ~150 nm, the size of most viruses, so are optimal targets for dendritic cells in vivo and surface attachment for phage display

Applications of Lipoparticles include:

• Immunization

• Phage/yeast display

• Antibody screening by ELISA

• Kinetic analysis by biosensor

• Radioligand and fluorescent binding assays

Custom Lipoparticles

• Lipoparticles are typically customized to incorporate customer specified membrane proteins

• Each Lipoparticle batch is assessed using rigorous quality-control metrics to ensure homogeneity, purity, and target protein integrity

• Hundreds of membrane proteins have been successfully incorporated into Lipoparticles, which can be modified with biotin or fluorescence for detection

ReadyReceptor Lipoparticles

Pre-validated Lipoparticles contain optimized, highly expressed membrane proteins and are available for rapid delivery.

ReadyReceptor Lipoparticles are produced and validated using the same stringent quality metrics employed for Custom Lipoparticle production.

See all ReadyReceptor Lipoparticles.

Case Studies 

Learn how Lipoparticles rescued a CX3CR1 discovery campaign and enabled a clinical stage antibody

Learn how Argenx used Lipoparticles to isolate antibodies with diverse epitopes against the GPCR glucagon receptor

Learn how AdAlta used our CXCR4 Lipoparticles to isolate i-bodies

Learn how Pfizer used Lipoparticles to target the CXCR4 pathway in leukemia

Select publications that feature Lipoparticles

Tucker ET AL. 2018. Isolation of state-dependent monoclonal antibodies against the 12-transmembrane domain glucose transporter 4 using virus-like particles. PNAS 115(22):E4990-E4999.

Fong ET AL. 2014. Exposure of epitope residues on the outer face of the Chikungunya virus envelope trimer determines antibody neutralizing efficacy. J VIROL 88(24)14364-14379.

Willis ET AL. 2008. Virus-like particles as quantitative probes of membrane protein interactions. BIOCHEMISTRY 47(27):6988-6990.

Endres ET AL. 1997. Targeting of HIV- and SIV-infected cells by CD4-chemokine receptor pseudotypes. SCIENCE 278(5342): 1462-1464.





GPCR membrane protein Ion Channel Transporter

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