RESOURCES

Integral Molecular Awarded $3.5M Contract from NIH to Study Ebola and Hepatitis C Virus Antibody Response

PHILADELPHIA–(BUSINESS WIRE)–Integral Molecular, Inc. has been awarded a five year $3.5 million contract to study the human immune response to Ebola virus and hepatitis C virus (HCV). This award enables Integral Molecular to understand how human antibodies protect (or fail to protect) against these viruses. Using its proprietary Shotgun Mutagenesis Epitope Mapping technology, Integral Molecular will identify how antibodies target binding structures, or epitopes, on Ebola and HCV, which will facilitate the development of vaccines and therapeutics against these major health threats.

This award from the National Institute of Allergy and Infectious Diseases (NIAID, part of the National Institutes of Health) is the second NIAID contract awarded to Integral Molecular for epitope mapping. Under the recently completed first contract, Integral Molecular used Shotgun Mutagenesis to map over 280 antibody epitope binding sites on the envelope proteins of dengue virus, chikungunya virus, and HCV, exceeding the original project goals and providing some of the largest epitope data sets available for any viral pathogen. Many of these epitopes have now been published in major scientific journals and deposited in NIAID’s central Immune Epitope database (immuneepitope.org). Among the antibodies discovered and characterized by Integral Molecular are some of the most potent antibodies against chikungunya virus isolated to date, providing a potential therapeutic treatment for this debilitating viral disease.

“Understanding the full range of antibody epitopes targeted by the human immune system is vital for designing effective vaccines and antibody-based therapeutics against viruses,” said Dr. Benjamin Doranz, President of Integral Molecular. “With this contract we will isolate and characterize new human antibodies against Ebola and HCV envelope proteins. High resolution epitope maps that describe how the most effective antibodies bind and neutralize these viruses will increase our understanding of how these viral proteins function and how they can be inhibited.”

Shotgun Mutagenesis Epitope Mapping analyzes hundreds to thousands of variants of a target protein, each with a single defined amino acid substitution, to rapidly identify the binding residues that form antibody epitopes. The technology analyzes proteins directly within living human cells, allowing epitope mapping of complex proteins in their native conformation. Integral Molecular also offers Shotgun Mutagenesis services for epitope mapping and protein engineering on a fee-for-service basis to the research community.

About Integral Molecular
Integral Molecular is a research-driven biotechnology company creating a pipeline of therapeutic antibodies against under-exploited membrane protein targets, including GPCRs, ion channels, transporters and viral envelope proteins using its proprietary MPS Discovery Engine®. This platform is built on the company’s Lipoparticle and Shotgun Mutagenesis technologies and over 10 years of experience optimizing membrane proteins, enabling the isolation, characterization, and engineering of monoclonal antibodies against otherwise intractable membrane protein targets. The company currently has therapeutic programs focused on pain, autoimmunity and infectious diseases.

Integral Molecular, Inc.
Benjamin Doranz, 215-966-6061
bdoranz@integralmolecular.com

Integral Molecular Announces Patent Allowance for Dengue Research Technology

PHILADELPHIA–(BUSINESS WIRE)–Integral Molecular, a leader in membrane protein research, announces the issuance of a new composition patent protecting dengue reporter virus particles (RVPs). The invention relates to the company’s chimeric and codon-optimized flavivirus replicons, expression plasmids, and RVPs used for infectivity, neutralization, enhancement and structure-function studies of dengue virus (DENV) and its envelope protein (prM/E). U.S. Patent No 8,691,961, was issued by the USPTO on April 8, 2014, furthering the company’s commitment to the discovery of drugs and vaccines against this widespread virus.

“The dengue virus RVPs are enabling faster and more accurate quantification of dengue sera and antibody neutralization and enhancement,” said Benjamin Doranz, Chief Scientific Officer at Integral Molecular. “The technology is also being used in our structural studies of DENV envelope, for instance, to identify the exact residues responsible for mediating its folding, triggering, and fusion.”

Integral Molecular has a long standing interest in dengue research, and has epitope mapped over 150 monoclonal antibodies targeting dengue envelope proteins as part of an ongoing contract funded by the National Institute of Allergy and Infectious Diseases (NIAID). This work has been described in numerous publications, including seven publications in the past two years, providing important insights into the functionality of DENV prM/E. Viral epitopes were mapped using the company’s Shotgun Mutagenesis technology which enables vaccine researchers to identify immunodominant regions of a target pathogen. Integral Molecular has similarly used its Shotgun Mutagenesis technology to map antibody epitopes on diverse viral pathogens, including chikungunya, hepatitis B, hepatitis C, HIV, and respiratory syncytial viruses. Integral Molecular offers dengue virus RVPs that retain antigenic equivalence to wild-type virions by incorporating prM/E proteins from DENV serotypes 1, 2, 3, or 4. DENV RVPs feature a reporter gene that provides a rapid and convenient read-out of infectivity, and are validated for both antibody neutralization and enhancement studies. Epitope mapping of anti-viral antibodies by Shotgun Mutagenesis is offered on a fee-for-service basis.

About Integral Molecular
Integral Molecular is a research-driven biotechnology company creating a pipeline of therapeutic antibodies against under-exploited membrane protein targets, including GPCRs, ion channels, transporters and viral envelope proteins using its proprietary MPS Discovery Engine®. This platform is built on the company’s Lipoparticle and Shotgun Mutagenesis technologies and over 10 years of experience optimizing membrane proteins, enabling the isolation, characterization, and engineering of monoclonal antibodies against otherwise intractable membrane protein targets. The company currently has therapeutic programs focused on pain, autoimmunity and infectious diseases.

Integral Molecular
Benjamin Doranz, 215-966-6061
info@integralmolecular.com

Integral Molecular Announces Patent Protecting the Use of Lipoparticles for Antibody Discovery

PHILADELPHIA–(BUSINESS WIRE)–Integral Molecular, a leader in membrane protein antibody discovery, announces the issuance of a new patent protecting the use of Lipoparticles for eliciting antibodies against membrane protein targets. Lipoparticles are an enabling technology for the company’s MPS Discovery Engine® for isolating monoclonal antibodies (MAbs) against membrane protein targets. Lipoparticles are used to generate conformationally-sensitive, inhibitory MAbs against targets such as GPCRs, ion channels and transporters. U.S. Patent No. 8,680,244 was issued by the U.S. Patent and Trademark Office on March 25, 2014, further strengthening the intellectual property position of the MPS platform for the discovery of antibody therapeutics.

The MPS platform has been used to elicit unique antibodies against a number of targets that until now had few or no antibodies against them. Targets include the P2X3 and Kv1.3 ion channels and the Glut4 transporter. Antibodies generated using MPS have been characterized as binding conformational epitopes and having high selectivity for their targets.

“GLUT4 in particular has a highly complex and challenging structure for antibody elicitation,” commented Joseph Rucker, Director of Research and Development at Integral Molecular. “With twelve transmembrane helices and short extracellular loops that are poorly immunogenic, cell-surface antibodies against glucose transporters have been nearly impossible to raise using conventional methods. We are excited that MPS has allowed us to gain access to this target, which is involved in type 2 diabetes.” Integral Molecular is currently employing MPS to discover MAbs against high value membrane protein targets for both internal and customer projects.

About Integral Molecular
Integral Molecular is a research-driven biotechnology company creating a pipeline of therapeutic antibodies against under-exploited membrane protein targets, including GPCRs, ion channels, transporters and viral envelope proteins using its proprietary MPS Discovery Engine®. This platform is built on the company’s Lipoparticle and Shotgun Mutagenesis technologies and over 10 years of experience optimizing membrane proteins, enabling the isolation, characterization, and engineering of monoclonal antibodies against otherwise intractable membrane protein targets. The company currently has therapeutic programs focused on pain, autoimmunity and infectious diseases.

Integral Molecular
Benjamin Doranz
215-966-6061
info@integralmolecular.com

Integral Molecular Identifies Potent Antibody Antagonists Against Ion Channel Pain Target P2X3

PHILADELPHIA–(BUSINESS WIRE)–Integral Molecular, a leader in membrane protein antibody discovery, announces that it has successfully generated potent antibody antagonists targeting the P2X3 ion channel using the MPS Discovery Engine®, its proprietary strategy for antibody elicitation and optimization, in conjunction with Crystal Bioscience’s proprietary GEM technology for isolating unique monoclonal antibodies from immunized chickens.

P2X3 is a validated therapeutic target for pain, but its structural complexity has made it difficult to target using small molecules, and previous approaches using such drugs have failed due to the lack of compound specificity and limited bioavailability. Monoclonal antibodies (MAbs) offer superior specificity and bioavailability, which are paramount to the successful therapeutic inhibition of many membrane protein targets. Thorough characterization of the P2X3 MAbs reveals that they bind conformational epitopes on P2X3 with high specificity and sub-nanomolar affinity. The MAbs also block 90% of neuronal currents in primary cells ex vivo, enabling further development of lead candidates.

“We are extremely excited to have generated inhibitory MAbs that target P2X3. This is an exciting advancement for the chronic pain field where there are limited therapeutic options,” said Joseph Rucker, Director of Research and Development at Integral Molecular. “Because of their structural complexity and conservation, ion channels have been exceptionally challenging to target and inhibit and these P2X3 MAbs represent some of the few inhibitory antibodies against any ion channel. We are eager to move this campaign forward and progress our most promising leads into development to treat neuropathic pain”.

The antibodies were elicited using Integral Molecular’s Lipoparticle reagents, which provide highly concentrated membrane proteins in their native conformation, and were screened using Crystal Bioscience’s GEM technology.

“The recovery of antibodies with these unique characteristics confirms and extends our previous results, showing that the immunoglobulin repertoire of immunized chickens contains antibodies to epitopes that cannot be accessed using conventional discovery platforms. These data are also a testament to the power of the GEM technology to screen the repertoire and identify antibodies that not only bind the target but are biologically active” said Bill Harriman, Chief Science Officer at Crystal Bioscience. The synergistic application of MPS and GEM technologies results from a fruitful collaboration between the Companies announced last year, which will include more targets in the future.

Integral Molecular Announces Issuance of Third Patent Family, Extending Patent Landscape for Key Lipoparticle Technology

PHILADELPHIA–(BUSINESS WIRE)–Integral Molecular, a leader in membrane protein antibody discovery, announces the issuance of a new patent and patent family protecting the composition of matter for its Lipoparticle technology. Lipoparticles represent a proprietary Integral Molecular technology that feature highly-concentrated membrane proteins in their native conformation for drug and antibody discovery against high-value targets including G protein-coupled receptors (GPCRs), ion channels, and transporters. This represents the third issued patent family surrounding the Lipoparticle technology.

US Patent No. 8,574,590 was granted by the USPTO on November 5, 2013 to Integral Molecular, expanding the company’s landscape of Lipoparticle intellectual property. Integral Molecular is the exclusive world-wide patent holder or licensee of all Lipoparticle patents, and licensed Lipoparticle technology is available only from Integral Molecular. Additional patents covering Lipoparticle technology are pending.

“Complex membrane proteins are exceptionally difficult to study, and there are currently no FDA approved antibody therapeutics against high-value targets such as GPCRs, ion channels and transporters,” said Dr. Benjamin Doranz, President of Integral Molecular. “Lipoparticles have become an established route for membrane protein antibody discovery, and our growing patent landscape strengthens our commitment to the discovery of these therapeutically important antibodies.”

Integral Molecular Launches MPS Platform for Discovery of Antibodies Targeting Membrane Proteins

PHILADELPHIA–(BUSINESS WIRE)–Integral Molecular, Inc., a leader in membrane protein reagents and services, announces the launch of its Membrane Protein Solutions (MPS) antibody discovery platform. MPS enables the isolation, characterization, and engineering of monoclonal antibodies (MAbs) against difficult membrane protein targets including GPCRs, transporters and ion channels. The technology platform harnesses the strength of Integral’s expertise and 10+ years of research experience in membrane protein expression and analysis. MPS applies Integral’s proprietary Lipoparticle and Shotgun Mutagenesis technologies, facilitating high concentration antigen presentation, comprehensive epitope mapping, and antibody engineering for the isolation and advancement of high-value, pre-clinical ready MAbs against a wide variety of membrane proteins.

“Although membrane proteins make up nearly 50% of existing drug targets, there are currently no FDA approved MAbs that target GPCRs, ion channels or transporters” said Benjamin Doranz, President of Integral Molecular. “We are excited to provide the MPS platform for advancing high value preclinical ready MAbs against intractable membrane proteins. The first of our internal programs, against the ion channel P2X3, has resulted in high affinity, inhibitory antibodies that will be developed for the treatment of neuropathic and inflammatory pain, and these MAbs represent some of the few inhibitory antibodies developed against any ion channel.”

The MPS platform has been used at Integral Molecular to develop a pipeline of several dozen MAbs against complex membrane proteins that are involved in a variety of human diseases, including cancer, inflammation, pain, and infectious diseases. The company is seeking partnerships with companies who are interested in working with Integral Molecular to develop these MAbs and isolate antibodies against additional high value targets.

Patent for Nano-scale Detection of Ion Channel Function in Lipoparticles

PHILADELPHIA–(BUSINESS WIRE)–Integral Molecular, Inc., a leader in membrane protein reagents and services, announces a patent allowance covering its technology for cell-free detection of ion channel function. The U.S. patent covers the application of Integral Molecular’s Lipoparticle technology for deriving high concentrations of functional ion channels for drug screening, antibody development, and biomedical research. Ion channels are important therapeutic targets for a wide range of human diseases and comprise approximately 15% of existing drug targets. Lipoparticle technology stems from research conducted at the University of Pennsylvania and published in the journals Science, PNAS, and Journal of Virology . US Patent No. 8,377,691 was issued by the U.S. Patent and Trademark Office on February 19, 2013 to Integral Molecular.

“The Lipoparticle technology overcomes many of the challenges of conventional electrophysiological approaches for screening ion channel targets, which have largely been limited to studies with live cells or reconstituted lipid bilayers,” said Dr. Benjamin Doranz, Chief Scientific Officer at Integral Molecular and the inventor of the technology. “Development and validation of the Lipoparticle ion channel technology enabled Integral Molecular to successfully implement high-throughput screening (HTS) campaigns against ion channels, including the identification of novel anti-influenza lead compounds.”

Integral Molecular offers custom-produced Lipoparticles with user-specified membrane proteins, as well as ReadyReceptor Lipoparticles that contain pre-validated high-concentration membrane protein targets such as GPCRs, transporters, and ion channels. Each lot of Lipoparticles is quality controlled and provided with technical protocols for relevant applications, including antibody screening, biosensor assays, ELISA binding assays, and functional assays. Lipoparticles can be biotinylated or fluorescently labeled to accommodate specialized applications.

Integral Molecular and IntelliCyt Corporation Announce Co-marketing Collaboration

PHILADELPHIA–(BUSINESS WIRE)–Integral Molecular and IntelliCyt Corporation today announced the formation of a collaborative marketing alliance to co-promote Integral’s Shotgun Mutagenesis protein mapping and engineering platform and IntelliCyt’s HTFC Screening System. Co-marketing efforts, including multiple conference presentations and webinars, will highlight the improved productivity and accelerated rate of antibody discovery the paired technologies provide. Both companies are attending the 23rd annual Antibody Engineering conference in San Diego on December 3rd.

“IntelliCyt’s HTFC Screening System has been an enabling technology for us”, commented Ben Doranz, President and CSO at Integral Molecular. “When we made the transition from a traditional HRP-based screening platform to the HTFC Screening System for our Shotgun Mutagenesis process, we were able to streamline workflows, improve reproducibility and generate higher-fidelity data with fewer repeat experiments. We now deliver protein mapping project results to our customers much faster. Our co-marketing efforts will publicize how both platforms, when combined, speed the pace of drug and antibody discovery against complex protein targets.”

“Integral’s adoption of the HTFC Screening System, the ease in transition to using our technology and the great success they’ve had validates the unique value our platform brings to screening efforts in pharmaceutical, biotechnology and life science laboratories”, commented Terry Dunlay, CEO at IntelliCyt. “We’re delighted to partner with Integral Molecular. Our high-throughput flow cytometry system complements Integral’s Shotgun Mutagenesis platform as it enables the generation of high quality data from thousands of wells containing individual mutants expressed in live cells that are typically assayed in a single project. Together, these technologies offer a more rapid and comprehensive path to developing new therapeutic antibodies.”

IntelliCyt’s HTFC Screening System for cell- and bead-based assays is the first flow cytometry-based benchtop analyzer designed for rapid screening. Unlike other screening technologies that provide data on a per well basis, the HTFC Screening System provides information-rich data on a cell by cell basis in 96- and 384-well microplates. This combined with rapid sample delivery and multiplexing capabilities let researchers in many fields screen large libraries in a matter of days.

Integral Molecular’s Shotgun Mutagenesis technology is a high-throughput strategy for protein mapping and engineering by evaluating alanine scan or other customized mutants across an entire target protein. Integral Molecular offers Shotgun Mutagenesis to customers on a fee-for-service basis.

Integral Molecular and Crystal Bioscience Announce Research Collaboration to Develop Novel GPCR and Ion Channel Antibodies

PHILADELPHIA–(BUSINESS WIRE)–Crystal Bioscience and Integral Molecular have launched a research collaboration to generate panels of chicken monoclonal antibodies against undisclosed therapeutic GPCR and ion channel targets. The collaboration will leverage the synergy between Integral Molecular’s Lipoparticle technology for immunization with native conformation multispanning membrane proteins and Crystal’s GEM technology for the recovery of monoclonal antibodies against otherwise conserved proteins raised in immunized chickens.

“We are excited to be working with Crystal Bioscience to develop antibodies in alternative species where there is increased likelihood of success in eliciting antibodies against epitopes conserved in mammals,” said Dr. Joseph Rucker, Director of Research and Development at Integral Molecular. “We believe that this powerful combination of technologies for immunization and screening will culminate in the ability to produce antibodies against therapeutic targets that have been historically difficult to work with due to both their conformational complexity and high conservation.”

“By combining Integral Molecular’s ability to produce high levels of native conformation receptors with Crystal’s ability to leverage avian immune repertoires, we expect to create a robust new path that will make antibody discovery for challenging targets more routine and predictable,” said Dr. Bill Harriman, Chief Science Officer, Crystal Bioscience.

Integral Molecular’s Lipoparticle technology represents a stable, cell-free solution for displaying high concentrations of membrane proteins in their native conformations for antibody and drug discovery applications. Integral Molecular offers custom-produced Lipoparticles containing user-specified membrane proteins, as well as a large selection of ReadyReceptor® Lipoparticles containing pre-validated high-concentration membrane proteins.