SBIR-STTR Award

This proposal involves the development and validation of a novel approach to improve and accelerate the discovery of biopharmaceuticals (i.e. vaccines, monoclonal antibodies and other therapeutic proteins). Biopharmaceuticals are used to treat a variety of infectious and chronic diseases. The proposed research is intended to establish a new paradigm for rapidly improving the solubility and physical stability of biopharmaceuticals. The paradigm will be evaluated using one or more vaccine candidates obtained from a pharmaceutical company as well as the protein osteoprotegerin (OPG), which is involved in bone mineralization and osteoporosis. According to the latest Data-Monitor Report published in June, 2008, protein therapeutics represents the second largest segment in pharmaceutical drug discovery. Since 2000, more than 25% of all new drugs approved have been biopharmaceuticals but there development is a time-consuming and costly endeavor. The development of biopharmaceuticals requires that the protein therapeutic is highly soluble since a substantial amount of the protein must be injected in patients via a small volume of solution. Pharmaceutical and biotechnology companies devote significant time and resources developing suitable formulations that allow the desired protein to be concentrated to high levels without inducing instability in the protein. This process of formulation development is often the major bottleneck in the protein therapeutic discovery process. This proposal involves the use of existing technologies and a novel high-throughput technology to provide information regarding a protein's solubility and stability in different solution conditions (formulations). The information will be used to train an artificial neural network program to predict totally new solution conditions that provide improved protein solubility and stability. If successful, this capability will accelerate and improve the ability to develop clinically useful formulations for biopharmaceuticals being developed by pharmaceutical, biotechnology, government and academic communities. It will also benefit any protein expression research organization (expressing aqueous or membrane proteins) that desires improved solubility and physical stability of expressed protein. It will reduce the cost and time required to develop new vaccines, monoclonal antibodies and other protein therapeutics. Soluble Therapeutics, LLC intends to support biopharmaceutical research as a CRO by establishing collaborative relationships with researchers from industry, academia and the government. It is expected that as industrial partners realize the advantages the company's novel technology it will lead to non-exclusive licenses and strategic partnerships.

Public Health Relevance:
This proposal involves the development and validation of a novel approach to improve and accelerate the discovery of biopharmaceuticals (i.e. vaccines, monoclonal antibodies and other therapeutic proteins). Biopharmaceuticals are used to treat a variety of infectious and chronic diseases. The proposed research is intended to establish a new paradigm for rapidly improving the solubility and physical stability of biopharmaceuticals. The paradigm will be evaluated using one or more vaccine candidates obtained from a pharmaceutical company as well as the protein osteoprotegerin (OPG), which is involved in bone mineralization and osteoporosis. According to the latest Data-Monitor Report published in June, 2008, protein therapeutics represents the second largest segment in pharmaceutical drug discovery. Since 2000, more than 25% of all new drugs approved have been biopharmaceuticals but there development is a time-consuming and costly endeavor. The development of biopharmaceuticals requires that the protein therapeutic is highly soluble since a substantial amount of the protein must be injected in patients via a small volume of solution. Pharmaceutical and biotechnology companies devote significant time and resources developing suitable formulations that allow the desired protein to be concentrated to high levels without inducing instability in the protein. This process of formulation development is often the major bottleneck in the protein therapeutic discovery process. This proposal involves the use of existing technologies and a novel high-throughput technology to provide information regarding a protein's solubility and stability in different solution conditions (formulations). If successful, this capability will accelerate and improve the ability to develop clinically useful formulations for biopharmaceuticals being developed by pharmaceutical, biotechnology, government and academic communities. Soluble Therapeutics, LLC intends to support biopharmaceutical research as via contract research by establishing collaborative relationships with researchers from industry, academia and the government. It is expected that as industrial partners realize the advantages the company's novel technology it will lead to non-exclusive licenses and strategic partnerships.

Thesaurus Terms:
Academia; Address; Agreement; Biologic Products; Biological Agent; Biological Neural Networks; Biological Products; Biotechnology; Bone Mineralization; Buffers; Businesses; Calcification, Physiological; Chromatography; Chromatography / Separation Science; Chronic Disease; Chronic Illness; Client; Communities; Computer Simulation; Computerized Models; Contracting Opportunities; Contracts; Data; Development; Drug Formulations; Drugs; Excipients; Formulation; Formulations, Drug; Foundations; Future; Government; Industry; Institution; Investigators; Ionic Strengths; Lead; Legal Patent; Letters; Licensing; Marketing; Mathematical Model Simulation; Mathematical Models And Simulations; Measures; Medication; Membrane Proteins; Membrane-Associated Proteins; Methods And Techniques; Methods, Other; Miniaturisations; Miniaturization; Miniaturizations; Moab, Clinical Treatment; Models, Computer; Monitor; Monoclonal Antibodies; Ocif Protein; Opg Protein; Osteoporosis; Patents; Patients; Pb Element; Pharmaceutic Preparations; Pharmaceutical Agent; Pharmaceutical Preparations; Pharmaceuticals; Pharmacologic Substance; Pharmacological Substance; Phase; Physiologic Calcification; Process; Programs (Pt); Programs [publication Type]; Proteins; Publishing; Reporting; Research; Research Contracts; Research Personnel; Research Resources; Researchers; Resources; Sales; Services; Simulation, Computer Based; Sodium Chloride; Sodium Chloride (Nacl); Solubility; Solutions; Surface Proteins; System; System, Loinc Axis 4; Tnfrsf11b; Tnfrsf11b Gene Product; Techniques; Technology; Temperature; Therapeutic; Time; Training; Tumor Necrosis Factor Receptor Superfamily Member 11b; Tumor Necrosis Factor Receptor 11b; Update; Vaccines; Validation; Aqueous; Base; Biopharmaceutical; Biotherapeutic Agent; Chronic Disease/Disorder; Chronic Disorder; Computational Modeling; Computational Models; Computational Simulation; Computer Based Models; Computerized Modeling; Computerized Simulation; Cost; Design; Designing; Drug Development; Drug Discovery; Drug/Agent; Enthalpy; Gene Product; Heavy Metal Pb; Heavy Metal Lead; High Throughput Technology; Improved; In Silico; Light Scattering; Neural Network; New Approaches; New Technology; New Vaccines; Next Generation Vaccines; Novel; Novel Approaches; Novel Strategies; Novel Strategy; Novel Vaccines; Opg Gene Product; Osteoclastogenesis Inhibitory Factor; Osteoprotegerin; Programs; Protein Expression; Public Health Relevance; Salt; Therapeutic Protein; Vaccine Candidate; Virtual Simulation

This proposal involves the development of a high-throughput self-interaction chromatography (SIC) system that will be used by Soluble Therapeutics, LLC, to improve and accelerate the formulation discovery process for biopharmaceuticals (i.e. vaccines, monoclonal antibodies and other therapeutic proteins). Biopharmaceuticals are used to treat a variety of infectious and chronic diseases. According to a Data-Monitor Report published in June, 2008, protein therapeutics represents the second largest segment in pharmaceutical drug discovery. Since 2000, more than 25% of all new drugs approved have been biopharmaceuticals but there development is a time-consuming and costly endeavor. The development of biopharmaceuticals requires that the protein therapeutic is highly soluble since a substantial amount of the protein must be injected in patients via a small volume of solution. Pharmaceutical and biotechnology companies devote significant time and resources developing suitable formulations that allow the desired protein to be concentrated to high levels without inducing instability in the protein. This process of formulation development is often the major bottleneck in the protein therapeutic discovery process. The HSC technology provides a new paradigm for rapidly improving the solubility and physical stability of biopharmaceuticals. The paradigm was validated in phase-1 studies using vaccine candidates obtained from two pharmaceutical companies as well as the proteins osteoprotegerin (involved in bone mineralization and osteoporosis), the cystic fibrosis transmembrane conductance regulator protein (CFTR), the nucleotide-binding domain-1 of CFTR and phospholipase-D1 (a human enzyme responsible for the hydrolysis of phosphatidyl choline). A prototype 2nd generation system was used to improve the solubility and physical stability of each protein by measuring the second virial coefficient (B-value) for the protein in solutions containing different excipients. In addition to developing the 3rd generation system, a second area with significant commercial potential will simultaneously be validated. This involves use of SIC to optimize stabilization of protein complexes and to screen compound or peptide libraries for those that inhibit or augment protein-protein interactions. The development of a 3rd generation, higher throughput system is needed to meet the market demand demonstrated by Soluble Therapeutics via meetings with pharmaceutical and biotechnology company representatives. The proposed technology will accelerate and improve development of clinically useful biopharmaceutical formulations, research conducted by pharmaceutical, biotechnology, government and academic communities. It will also benefit any protein expression research organization (expressing aqueous or membrane proteins) that desires improved solubility and physical stability of expressed protein. It will reduce the cost and time required to develop new vaccines, monoclonal antibodies and other protein therapeutics. Soluble Therapeutics, LLC intends to support biopharmaceutical research as a CRO by establishing collaborative relationships with researchers from industry, academia and the government.

Public Health Relevance:
Protein drugs such as insulin, vaccines and antibody therapies interact with natural biomolecular processes in the human body to prevent and treat disease. A significant number of protein drugs - although identified to be relevant to a disease state - are unable to be taken to market by pharmaceutical companies due to the difficult challenge of identifying a formulation which makes the protein drug physically stable and soluble at high concentration. The proposed research will enable Soluble Therapeutics to more rapidly (and cost effectively) to bring new protein drugs to patients.