Anti-PVRIG Antibody Formulations for Stable Liquid Delivery
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Solution Overview
Problem
Current therapeutic strategies for cancer and autoimmune diseases face challenges in effectively modulating costimulatory signals to enhance immune responses without compromising immune defense against pathogens, and there is a need for biomarkers to identify patient populations that would benefit from anti-PVRIG antibody treatment.
Innovation Solution
Development of stable liquid pharmaceutical formulations of anti-PVRIG antibodies, including specific heavy and light chain variable domains, histidine, NaCl, L-arginine, and polysorbate 80, with a pH range of 5.5 to 7.0, for use alone or in combination with anti-PD-1 antibodies, and the use of biomarkers such as activated DC cells, effector memory CD8 positive T cells, and NK-T cells to determine treatment efficacy and patient populations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If costimulatory signals are blocked to treat autoimmune diseases and transplant rejection, then immune responses are modulated, but the immune system's ability to defend against pathogens is compromised
Solution Approach 1:
The patent applies local quality by developing formulations with specific pH ranges (5.5-7.0) and containing particular excipients (histidine, NaCl, L-arginine, polysorbate 80) that optimize antibody stability and function in specific contexts, allowing selective modulation of costimulatory pathways while preserving pathogen defense
Solution Approach 2:
The patent employs parameter changes by optimizing formulation parameters including pH (5.5-7.0), buffer concentration (10-100 mM histidine), salt concentration (30-100 mM NaCl), and stabilizer concentrations (20-150 mM L-arginine, 0.005-0.1% polysorbate 80) to enhance antibody stability and efficacy, enabling precise control over immune modulation while maintaining safety
2Reliability
If monoclonal antibodies are used to block costimulatory molecules, then therapeutic effects are achieved, but formulation stability and storage requirements become challenging
Solution Approach 1:
The patent uses intermediary substances including histidine buffer, NaCl, L-arginine, and polysorbate 80 as mediators that protect the monoclonal antibody from degradation, aggregation, and denaturation during storage and administration, thereby maintaining therapeutic efficacy without compromising formulation stability
Solution Approach 2:
The patent creates a composite pharmaceutical formulation combining the monoclonal antibody with multiple excipients (histidine, NaCl, L-arginine, polysorbate 80) that work synergistically to enhance stability, solubility, and shelf-life while maintaining therapeutic function
Data Source
AI summary
The present invention is directed to anti-PVRIG antibodies and stable liquid pharmaceutical formulations thereof. The present invention is directed to monotherapy and combination treatments with anti-PVRIG antibodies and anti-PD-1 antibodies, in particular nivolumab, using stable liquid pharmaceutical formulations thereof. The present invention also provides biomarkers for use in determining populations for treatment with anti-PVRIG antibodies and such biomarkers include, for example PVRIG and/or PVRL2 expression.