RESOURCES

Where research scientists come to find up to date resources on antibody discovery against challenging membrane protein targets.

Category: news

Live Tutorial: 6 Steps to Success in Discovering Monoclonal Antibodies Against Multipass Membrane Proteins

Thursday, October 29, 2020
Watch video

Integral Molecular has a 95% success rate of discovering high-affinity monoclonal antibodies against multipass membrane proteins despite the structural complexity and low immunogenicity of these targets. Here, we present some of the lessons we have learned throughout numerous discovery campaigns against these historically intractable targets, including GPCRs, ion channels and transporters.

What you’ll learn:

The 6 key steps to success in discovering high-quality, functional MAbs

How to use Lipoparticles with native-conformation antigen for effective immunization, screening and panning

How to access conserved and difficult epitopes

Totient Leverages Integral Molecular’s Membrane Proteome Array to Advance Cancer Therapeutic Discovery

PHILADELPHIA – Integral Molecular and Totient announce a partnership leveraging Integral Molecular’s Membrane Proteome Array (MPA) target identification technology to advance the discovery of antibodies for cancer therapy. Totient reconstructs antibodies from tertiary lymphoid structures (TLS), which are structures formed in tissues affected by autoimmunity, infections, and cancer, collected from patients experiencing exceptional immune responses. The MPA will pinpoint the binding targets for a panel of these antibodies from its array of 6,000 human membrane proteins. The agreement includes milestones paid to Integral Molecular upon successful antibody development goals.

Starting with over 50,000 samples, Totient has reconstructed antibodies against both known and novel extracellular oncology targets. These human-derived antibodies are high-affinity and bind tissue-specific antigens.

“Integral’s MPA technology enables us to rapidly identify native targets which might be missed by other screening methods,” said Deniz Kural, PhD, CEO and co-founder of Totient. “We are excited about uncovering additional targets that can be exploited in cancer therapy.”

MPA technology was developed by Integral Molecular as a comprehensive, high-throughput approach to detect binding of antibodies, cells, and other biologics to membrane protein targets for early de-risking of drug development.

The MPA is the largest library of human membrane proteins, covering 94% of the membrane proteome and includes nearly all G protein-coupled receptors (GPCRs), ion channels, and transporters. In addition to identifying new targets, the MPA is used to rapidly assess therapeutic antibodies for off-target binding that may present safety liabilities.

About Integral Molecular

Integral Molecular (www.integralmolecular.com) is the industry leader in discovering and characterizing therapeutic antibodies against membrane proteins, an important group of drug targets found on the surfaces of cells and viruses. Integral Molecular’s technologies have been integrated into the drug discovery pipelines of over 400 biotech and pharmaceutical companies to help discover new therapies for cancer, diabetes, autoimmune disorders and viral threats such as SARS-CoV-2, Ebola, Zika, and dengue virus.

About Totient

Totient is an AI-driven biotechnology company that leverages tertiary lymphoid structures (TLS) to identify novel tissue-specific antigens and develop matching high-affinity antibody therapeutics. Totient uses machine learning and immunoinformatics technology to pull critical insights from large, complex datasets, to quickly and accurately assemble the most potent antibody candidates. The unique applicability of the Totient platform allows the company to remain flexible and develop therapeutics for cancer, autoimmune disease, infections, and viruses. For more information visit www.totient.bio.

Integral Molecular Awarded Grant from the Commonwealth of Pennsylvania to Advance COVID-19 Research

PHILADELPHIA – Integral Molecular has been awarded $521,723 from the Commonwealth of Pennsylvania to leverage its technologies in the global fight against COVID-19. Integral Molecular is at the forefront of the fight against COVID-19, with their technologies being used by over 100 laboratories worldwide to advance COVID-19 vaccine and therapeutic development. This grant will enable Integral Molecular and its partners to develop therapeutics and vaccines with broad specificity against SARS-CoV-2 variants.

“As a founding member and leader in the Philadelphia biotechnology community, Integral Molecular brings 20 years of virology experience and unique tools to the fight against COVID-19,” said Christopher Molineaux, President and CEO of Life Sciences PA. “We are proud that the science being done in Pennsylvania is having an impact on a global scale.”

The scientific team at Integral Molecular has mobilized four of its technology platforms against the virus. This includes using its MPS Antibody Discovery platform to generate broadly reactive antibodies against SARS-CoV-2 and other coronaviruses. SARS-CoV-2 Reporter Virus Particles (RVPs) have been adopted by vaccine companies to safely test for neutralizing immune responses in patients and vaccinees. Integral Molecular’s Membrane Protein Array (MPA) is being used to rapidly screen the specificity of SARS-CoV-2 antibodies to advance the most promising candidates, and Shotgun Mutagenesis Epitope Mapping is being used to optimize vaccine and antibody design, so that resulting therapeutics and vaccines recognize emerging SARS-CoV-2 variants.

“Our technologies enable us to predict and test virus mutations that can result in resistance to treatments or vaccines,” said Benjamin Doranz, PhD, President and CEO of Integral Molecular. “Containing this pandemic is our immediate goal, but the challenge ahead is to prevent its recurrence in the future.”

Integral Molecular is honored to receive grant funding through the COVID-19 Vaccines, Treatments and Therapies (CV-VTT) program, administered by Dennis Davin, Secretary of the Department of Community and Economic Development (DCED) of the Commonwealth of Pennsylvania.

Integral Molecular & Fierce Bio Present: De-risk Antibody and CAR-T Safety by Identifying Off-target Specificity Webinar

Fierce Bio Webinar

The long-held assumption that antibodies are exquisitely specific is being re-examined since 25% of monoclonal antibodies (MAbs) show polyspecificity and bind unintended targets.

This Fierce webinar brings together experts with experience in biotech, pharma, and the FDA to discuss the latest technologies and strategies to optimize IND safety data packages.

Topics to be discussed include:

Best practices to identify safe lead candidates early in development

Traditional approaches such as tissue cross-reactivity (TCR) studies and other in vitro toxicology assays

Emerging technologies including Integral Molecular’s Membrane Proteome Array (MPA), which tests the specificity of antibodies and CAR-T cells across an array of 6,000 native membrane proteins

 

 

Humanized Chicken Antibody Technology to Drive Next Generation of Integral Molecular’s MPS Antibody Discovery Platform

PHILADELPHIA – Integral Molecular announces the development of Humanized Chicken Antibody Technology (hCAT) and the incorporation of hCAT into the company’s industry-leading MPS antibody discovery platform for multipass membrane proteins. The innovation of hCAT lies in the ability to isolate fully humanized antibodies directly from immunized animals, reducing the time and effort needed for antibody discovery.

The MPS platform uses chickens as a source of antibodies to unlock difficult drug targets that have been inaccessible using conventional animal hosts, such as mice and rabbits. hCAT enables the isolation of antibodies that are already fully humanized and bind with high (picomolar) affinity. This streamlines the antibody discovery process and reduces the need for downstream engineering. Antibodies isolated using hCAT in many cases are more human (i.e. germline human) than antibodies isolated directly from humans.

“Antibody humanization and engineering are often necessary for the development of therapeutic antibodies but can be incredibly time consuming,” said Ross Chambers, Vice President of Antibody Discovery at Integral Molecular. “Our hCAT technology now allows us to harness the robust immune response of chickens and to isolate, humanize, and affinity-mature those antibodies all in one step.”

Integral Molecular unveiled Humanized Chicken Antibody Technology at the PEGS Protein Engineering and Cell Therapy Summit, which debuted the use of hCAT to discover high-affinity lead antibodies against oncology targets Claudin 6 and Claudin 18.2.

About Integral Molecular

Integral Molecular (www.integralmolecular.com) is the industry leader in discovering and characterizing therapeutic antibodies against membrane proteins, an important group of drug targets found on the surfaces of cells and viruses. Integral Molecular’s technologies have been integrated into the drug discovery pipelines of over 300 biotech and pharmaceutical companies to help discover new therapies for cancer, diabetes, auto-immune disorders and viral threats such as SARS-CoV-2, Ebola, Zika, and dengue virus.

Science Center to Honor Leaders of Innovation Community at Annual Nucleus Awards

Benjamin Doranz Nucleus Award
PHILADELPHIA–(August 20, 2020) – The University City Science Center will recognize three local leaders during its annual Nucleus Awards event on September 22, 2020, presented by CSL Behring. This year’s class of honorees includes Benjamin Doranz, President & CEO of Integral Molecular, Aurora Archer, Founder & CEO of Bellatrix Group and Co-Host of The Opt-In Podcast, and Sylvester Mobley, CEO of Coded by Kids. The awards will be presented to the recipients during a one-hour virtual event hosted by WHYY’s Tracey Matisak.

Each fall, Nucleus brings together the region’s leaders and groundbreakers in innovation, all while supporting Philadelphia’s future as a hub of innovation and discovery. Funds raised through Nucleus help sustain Science Center programs, which in 2019 alone supported the growth of 118 businesses; convened more than 39,000 attendees across 475 events; and engaged over 370 middle and high school students through its STEM education initiatives.

“This year’s honorees exemplify the very best of what our region’s entrepreneurial ecosystem has to offer in our shared pursuit of improving the lives of people around the world,” says Bill Mezzanotte, M.D., M.P.H., Executive Vice President, Head of R&D and Chief Medical Officer for CSL Behring – company sponsor of this year’s Nucleus Awards – and member of the University City Science Center Board of Directors.

“Congratulations to Ben, Aurora and Sylvester for your outstanding examples of the tangible impact that novel technologies can have on quality of life, economic development and societal welfare.”

BENJAMIN DORANZ
President and CEO of Integral Molecular
Commercialization Award
Sponsored by NewSpring Capital

Ben Doranz is President and CEO of Integral Molecular. Founded in 2001 at the Science Center and current uCity Square resident, Integral Molecular is a founding member of the Philadelphia biotech community with a history of excellence in antibody discovery for difficult to treat diseases and research in emerging viruses. In 2020 Integral Molecular rapidly pivoted its research and development programs in an effort to combat the COVID-19 pandemic. With support from the National Institute of Health and a team of talented scientists, Integral Molecular rapidly adapted many of its platform technologies to launch a suite of research solutions to accelerate the development of SARS-CoV-2 therapeutics. These include Reporter Virus Particles (RVPs) to test for the presence of neutralizing antibodies in vaccinees and technologies to assess the breadth of human immune responses against this virus.

Dr. Doranz co-founded Integral Molecular together with colleagues from the University of Pennsylvania using virus-based technologies. He has led all aspects of the company’s growth since its inception, bringing five different technologies from research to market. His efforts have cultivated a company that is profitable while being actively engaged with the local community. Dr. Doranz is an established life science entrepreneur previously responsible for helping create startups at the Center for Technology Transfer at the University of Pennsylvania. Dr. Doranz earned a Ph.D. in Cellular and Molecular Biology from the University of Pennsylvania, an M.B.A. from the Wharton School of Business at the University of Pennsylvania, and a B.A. from Cornell University.

For more information about Nucleus or to purchase tickets, visit www.ucscNucleus.org.

Integral Molecular Expands its Reporter Virus Technology to Enable Broad Testing for Coronavirus Protection Against Emerging Strains Including D614G

PHILADELPHIA – Integral Molecular has launched an expanded panel of SARS-CoV-2 Reporter Virus Particles (RVP), which includes spike protein variants such as D614G and spike protein from other related coronaviruses. These variants will test the breadth of protection afforded by COVID-19 therapeutics and vaccines against newly emerging or resistant strains of the virus. Virus neutralization testing using RVPs is being adopted by vaccine companies for screening sera from clinical trials to provide rapid and safe testing under standard BSL-2 laboratory conditions.

Viruses mutate and change over time and these mutations can compromise the efficacy of drugs or vaccines through resistance. For example, the D614G variant of SARS-CoV-2, mutated at position 614 of the spike protein, has quickly become the dominant form of the virus in many parts of the world and may have a higher transmission rate than the original virus. As novel or resistant strains emerge, it is critical to keep pace with the changing virus, test for effectiveness against evolving strains, and adapt therapeutics and vaccines accordingly.

“To get ahead of this pandemic, we need to start planning now for how the virus will look tomorrow,” said Benjamin Doranz, President and CEO of Integral Molecular. “Our reporter virus system is extremely agile and RVPs have been rapidly engineered to incorporate emerging sequence variants to provide timely support for drug and vaccine development.”

SARS-CoV-2 is closely related to other coronaviruses that also cause severe illnesses, including SARS (severe acute respiratory syndrome) and MERS (Middle East respiratory syndrome) virus. Integral Molecular’s suite of pseudotyped coronavirus RVPs enables neutralization tests against all three coronaviruses and can be used to identify broadly neutralizing vaccines or therapeutics that have the potential to protect against multiple pathogens.

About Integral Molecular

Integral Molecular (www.integralmolecular.com) is the industry leader in discovering and characterizing therapeutic antibodies against membrane proteins, an important group of drug targets found on the surfaces of cells and viruses. Integral Molecular’s technologies have been integrated into the drug discovery pipelines of over 300 biotech and pharmaceutical companies to help discover new therapies for cancer, diabetes, auto-immune disorders and viral threats such as SARS-CoV-2, Ebola, Zika, and dengue.

Integral Molecular Provides Rapid Safety Testing of COVID-19 Antibody Therapeutics with its Membrane Proteome Array Technology

PHILADELPHIA – Integral Molecular, the leader in discovering and characterizing antibodies against membrane protein and viral targets, is applying its Membrane Proteome Array (MPA) technology for antibody specificity profiling to promote the rapid development of SARS-CoV-2 therapeutic antibodies.

Researchers from Abound Bio and collaborators used the MPA to profile a promising monoclonal antibody that targets and neutralizes SARS-CoV-2 virus with high potency by blocking its binding to the ACE2 protein, the key interaction that drives infection. As described in a recent pre-print on bioRxiv, this antibody did not show off-target binding to any human proteins on the MPA and is being progressed for further development.

“Integral Molecular’s cutting-edge MPA technology quickly provided us with the reassurance that Abound Bio’s potent, neutralizing antibodies to SARS-CoV-2 did not bind off-target human membrane proteins which could be associated with toxicity,” said John W. Mellors, MD, CEO of Abound Bio.

“Off-target antibody binding can induce serious adverse clinical events,” said Dimiter Dimitrov, PhD, ScD, CSO of Abound Bio. “For this high-priority project, we relied on Integral Molecular’s rapid specificity profiling to rule out liabilities arising from unexpected antibody cross-reactivity in human cells.”

Recent data show that as many as 25% of preclinical antibodies have off-target binding to unintended protein targets, which can lead to serious adverse events in patients. The MPA is a collection of 6,000 membrane proteins expressed in live cells, representing nearly the entire human membrane proteome. The MPA provides specificity results in less than a month, faster than traditional non-clinical safety studies. Rapidly eliminating drug candidates with off-target effects or other liabilities can accelerate the safe progression of therapeutics into the clinic.

With 20 years of excellence in virology research, Integral Molecular has quickly mobilized several of its technologies to combat COVID-19 and recently launched an antibody neutralization test using pseudotyped SARS-CoV-2 reporter viruses.

About Integral Molecular
Integral Molecular (www.integralmolecular.com) is the industry leader in discovering and characterizing therapeutic antibodies against membrane proteins, an important group of drug targets found on the surfaces of cells and viruses. Integral Molecular’s technologies have been integrated into the drug discovery pipelines of over 300 biotech and pharmaceutical companies to help discover new therapies for cancer, diabetes, auto-immune disorders and viral threats such as SARS-CoV-2, Ebola, Zika, and dengue.

About Abound Bio
Abound Bio (aboundbio.com) is an early stage biotechnology company whose mission is to generate novel antibody-based biological therapeutics to meet unmet medical needs in the fields of cancer and infectious disease. Abound Bio is led by world renowned experts in the therapeutic antibody, infectious disease, and cancer space with a significant track record of successful development of biotherapeutics, licensing, and partnerships. Abound Bio’s industry leading antibody libraries offer size and physical property advantages that incorporate diversified binder formats (Fab, scFv, VH) into the appropriate therapeutic platform (ADC, CAR, multispecific).

Integral Molecular Develops Test for Neutralizing Antibodies in COVID-19 Patients and Clinical Trials

PHILADELPHIA – Integral Molecular announces the launch of SARS-CoV-2 Reporter Virus Particles (RVPs) to test patients for the presence of neutralizing antibodies, determine the effectiveness of vaccines, and measure the efficacy of drugs to enable expedited testing of new vaccines and therapeutics. As part of its commitment to supporting COVID-19 research, Integral Molecular will provide scientists with access to samples of SARS-CoV-2 RVPs at no cost.

Traditional diagnostic blood tests can only detect the presence or absence of antibodies. In contrast, SARS-CoV-2 RVPs assess the ability of antibodies to neutralize (block) virus infection. This distinction is crucial since neutralizing antibodies are the ones that typically offer protection from disease. SARS-CoV-2 RVPs eliminate the need to use live virus for neutralization assays and are safe using standard (BSL-2) laboratory conditions, quantitative, and amenable to high-throughput screening.

“With 20 years of virology experience, Integral Molecular is the industry leader in providing RVPs for therapeutic antibody development and vaccine clinical trials,” said Benjamin Doranz, President and CEO of Integral Molecular. “Like our other reporter viruses, we expect that coronavirus RVPs will be used to determine if serum from vaccinees contain protective antibodies, if new therapeutic antibodies can kill the virus, and if convalescent COVID-19 patients have protective serum that can be used in therapy.”

SARS-CoV-2 RVPs contain the coronavirus spike protein, which is the primary target of the human immune response, and carry a non-infectious genome that produces an easily measured fluorescent or light emitting signal upon cellular infection. Integral Molecular has extensive experience producing large-scale batches of quality-controlled RVPs for dengue and Zika viruses (Mattia et al., 2011, and Whitbeck et al., 2020), which are being used as critical reagents in vaccine clinical trials.

Integral Molecular has already begun shipping SARS-CoV-2 RVPs to partners, and will be discussing the SARS-CoV-2 reporter viruses at a webinar on May 12. Partners interested in using SARS-CoV-2 RVPs for their research or diagnostic assays should contact Integral Molecular.

About Integral Molecular
Integral Molecular (www.integralmolecular.com) is the industry leader in discovering and characterizing therapeutic antibodies against membrane proteins, an important group of drug targets found on the surfaces of cells and viruses. Integral Molecular’s technologies have been integrated into the drug discovery pipelines of over 300 biotech and pharmaceutical companies to help discover new therapies for cancer, diabetes, auto-immune disorders and viral threats such as SARS-CoV-2, Ebola, Zika, and dengue.