Antibody Coformulations with Succinate Buffer Stability
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Solution Overview
Problem
Formulating stable pharmaceutical compositions of multiple antibodies is challenging due to their susceptibility to degradation and the need for optimal excipients and conditions, which becomes even more complex when combining three or more antibodies, requiring a compromise in formulation conditions.
Innovation Solution
A stable pharmaceutical formulation comprising a plurality of antibodies with a succinate buffer at a pH between 4.5 and 7, along with tonicity agents like amino acids and surfactants such as polysorbate, to maintain stability and effectiveness.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If multiple antibodies are combined in a single formulation to improve therapeutic efficacy, then the diagnostic or therapeutic effectiveness is enhanced, but the formulation stability deteriorates due to susceptibility to degradation and aggregation
Solution Approach 1:
The patent systematically varies formulation parameters including pH (tested ranges from 4.0 to 7.5), buffer composition (succinate, citrate, phosphate buffers), excipient types and concentrations (aminosulfonic acid, polysorbate 80, arginine), and ionic strength to identify conditions that maintain stability of multiple antibody combinations. This parameter optimization approach resolved the contradiction by finding specific parameter sets where multi-antibody formulations remain stable while retaining therapeutic efficacy.
2Reliability
If trial and error methods are used to find optimal excipients and conditions for single antibody formulation, then suitable stabilization conditions can be achieved, but the process becomes time-consuming and challenging
Solution Approach 1:
The patent performs preliminary stability assessments by evaluating the compatibility of multiple antibodies with various excipients and formulation conditions before final formulation development. By pre-screening buffer systems, excipient combinations, and pH ranges, the invention reduces the iterative trial-and-error process and accelerates the formulation development timeline while ensuring stable outcomes.
3Adaptability or versatility
If compromise conditions are used to formulate multiple antibodies in a single composition, then co-formulation is achieved, but the optimal stability for each individual antibody may not be fully realized
Solution Approach 1:
The patent develops composite formulation systems that integrate multiple antibodies with carefully selected excipient combinations including succinate buffer, aminosulfonic acid, polysorbate 80, and arginine. These composite formulations create a synergistic environment that maintains the stability of each individual antibody component while enabling their co-administration in a single composition, thus resolving the contradiction between co-formulation versatility and individual antibody stability.
Data Source
Figure 1a~1c
Figure 2
Figure 3A~3B
AI summary
This invention relates to stable formulations of multiple antibodies comprising a plurality of antibodies and an effective amount of a succinate buffer wherein the pH of the formulation is between about 4.5 and about 7.0.