| NSF Org: |
TI Translational Impacts |
| Recipient: |
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| Initial Amendment Date: | September 13, 2016 |
| Latest Amendment Date: | February 8, 2022 |
| Award Number: | 1632420 |
| Award Instrument: | Standard Grant |
| Program Manager: |
Alastair Monk
amonk@nsf.gov (703)292-4392 TI Translational Impacts TIP Directorate for Technology, Innovation, and Partnerships |
| Start Date: | September 15, 2016 |
| End Date: | July 31, 2022 (Estimated) |
| Total Intended Award Amount: | $750,000.00 |
| Total Awarded Amount to Date: | $1,425,999.00 |
| Funds Obligated to Date: |
FY 2017 = $149,999.00 FY 2018 = $526,000.00 |
| History of Investigator: |
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| Recipient Sponsored Research Office: |
9 AUDUBON RD WAKEFIELD MA US 01880-1256 (787)458-6932 |
| Sponsor Congressional District: |
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| Primary Place of Performance: |
PR US 00935-0001 |
| Primary Place of
Performance Congressional District: |
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| Unique Entity Identifier (UEI): |
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| Parent UEI: |
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| NSF Program(s): | SBIR Phase II |
| Primary Program Source: |
01001718DB NSF RESEARCH & RELATED ACTIVIT 01001819DB NSF RESEARCH & RELATED ACTIVIT |
| Program Reference Code(s): |
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| Program Element Code(s): |
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| Award Agency Code: | 4900 |
| Fund Agency Code: | 4900 |
| Assistance Listing Number(s): | 47.084 |
ABSTRACT
The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II project will address ALL of the factors attributing to protein aggregation by determining the: size, identity, extent, mechanism of aggregation and stability, thus addressing Biopharma industry needs. This information is critical to the development of drug pipeline contributing to a $190 BN biologic's market where $87BN in first generation biologics face patent expiration before 2020. A successful technical approach for its implementation will provide essential information for decision making towards which candidates will enter the market, thus increasing the Biopharma valuation and ensuring supply of drugs to patients. In the end, improving the quality of life of patients with chronic diseases.
The proposed project will address the need for a multivariate high-throughput technology to address the risk of protein aggregation, that when adopted in R&D, will increase pipeline approvals, reduce late stage withdrawals and total costs of drug development. Average R&D development costs for the mere 1% of candidates reaching FDA approval have risen to $2.6 BN per product. Protein therapeutic development needs to be guided by a full understanding of protein stability and aggregation.
Research objectives are to: develop our innovative First-in-Class high throughput platform for screening protein therapeutics; develop original software capable of deciphering protein aggregation mechanism, size, identity and extent of aggregated protein and product stability; commercialize the innovative technology platform. Fully automated evaluation of protein candidates during early R&D phase will be conducted. Best-in-class image acquisition technology will be employed towards this end, using a label free chemical mapping technology, dedicated software using auto recognition algorithms, and correlations to decipher protein aggregation. We through the use of its breakthrough technology will determine: the aggregate free candidate under various stressor conditions, optimum formulation conditions for the protein therapeutic, the most stable candidate, and electronic data reporting that establishes accuracy, reproducibility, critical quality attributes of the protein product.
PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH
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PROJECT OUTCOMES REPORT
Disclaimer
This Project Outcomes Report for the General Public is displayed verbatim as submitted by the Principal Investigator (PI) for this award. Any opinions, findings, and conclusions or recommendations expressed in this Report are those of the PI and do not necessarily reflect the views of the National Science Foundation; NSF has not approved or endorsed its content.
Title: ?Novel, Accurate and Reproducible Platform for the Developability Assessment of Protein Therapeutics? ? Award 1632420
Subtopic BM1: Pharmaceutical Manufacturing
PI: Belinda Pastrana, Ph.D.
OVERVIEW:
The broader impact/commercial potential of this Small Business Innovation Research (SBIR) Phase II and IIB projects lies in testing the critical quality attributes of therapeutic proteins, such as deamidation, stability, aggregation and immunogenicity, by validating bioassays. The evaluations are performed for an array of therapeutic protein samples, thus ensuring the safety and efficacy of therapeutic proteins within the biopharma industry. This information is critical for the drug development pipeline, which by the year 2030 will include an $853 BN biologics market growing at 11.5% CAGR worldwide. At present, there are more than 900 new commercial candidates in the drug pipeline of therapeutic proteins. The successful technical implementation of our work will provide essential information for deciding which candidates will enter the market, thus increasing the biopharma valuation and ensuring the supply of needed drugs to patients. The ultimate goal is to improve the quality of life of patients.
INTELLECTUAL MERIT:
The NSF SBIR PII and IIB award has allowed Protein Dynamic Solutions (PDS) to develop ProteinMentor, a breakthrough multi-attribute platform for the testing of therapeutic proteins that allows biopharma to accelerate the time to market. This platform is comprised of a centralized hyperspectral image collection and data management system to support the seamless implementation of PDS proprietary software application modules designed for both R&D and manufacturing operations. Therapeutic proteins are complex, and their drug development cycle is also complex, requiring multiple analytical tools. The average R&D development costs for the mere 1% of candidates reaching FDA approval have risen to $314 M to $2.8 BN per product. Therapeutic protein development needs to be guided by understanding of critical quality attributes to ensure manufacturability, safety and efficacy. Toward that end, we have also been focused on extending the capabilities of the platform to include methods for the assessment of immunogenicity (unwanted immune response) prior to first-in-human trials. These therapeutic proteins may have diverse indications, both acute and chronic, such as heart disease, neurodegenerative disease, Crohn?s disease, rheumatoid arthritis and cancer, among others. Also, ProteinMentor hyperspectral images are obtained of the intact protein in solution, which is not limited by the therapeutic protein formulation, and requires little to no sample preparation. Data integrity is ensured through 21 CFR part 11 compliance.
BROADER IMPACTS:
The research objectives have been met. The objective was to develop a breakthrough technology for the comprehensive comparative assessment of multiple critical quality attributes of an array of therapeutic proteins and validation bioassays dedicated to evaluating immunogenicity (unwanted immune response) risk prior to first-in-human trials. An array of therapeutic proteins designed for different disease indications were characterized under control and forced degradation conditions. Selected therapeutic proteins were evaluated, based on their extent and site of deamidation, loss of stability, and aggregation state, for inducing an unwanted immune response in parallel with multiple dedicated bioassays that are traditionally used. The innovative platform provided understanding of how the state of each therapeutic protein did or did not evoke an unwanted immune response through pro-inflammatory cytokine overexpression, with statistical results that contributed to validating the bioassays. Our new method, which includes a quantum cascade laser microscope, an innovative slide cell array, and dedicated software that implements 2D-COS and 2D-CDS algorithms, provides a detailed amino acid-level resolution analysis of the overexpressed cytokines that resulted from the acclimation of peripheral blood mononuclear cells to validate immunogenicity bioassays. This analysis is performed with the added advantage that the detection is direct and no other reporter or adjuvant was added, eliminating complexities associated with potential artifacts and sample preparation. Multiple provisional patent applications have been filed and issued, and published peer-reviewed manuscripts and an invited chapter in the Encyclopedia of Analytical Chemistry serve as evidence of our accomplishments. Our platform provides a novel, accurate and reproducible solution to meet the needs of the biopharma industry, while ensuring the safety and efficacy of therapeutic proteins for patients.
Last Modified: 10/25/2022
Modified by: Belinda Pastrana
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