SADA-Complex Formulation Stabilizing Tetrameric Structure
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Solution Overview
Problem
Formulating SADA-complexes to maintain stability in tetrameric form while avoiding disassembly to monomers or agglomeration to multimers, which is crucial for effective delivery and minimizing off-target interactions.
Innovation Solution
An aqueous composition comprising a SADA-complex with a SADA domain and additional domains, along with a buffer system, stabilizing agents, and surfactants, is formulated to maintain the SADA-complex predominantly in the tetrameric form, ensuring stability and preventing unwanted multimerization or precipitation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If SADA-complexes are formulated at high concentration to maintain tetrameric form, then plasma half-life is extended, but aggregation and precipitation occur
Solution Approach 1:
The patent applies parameter changes by carefully controlling formulation conditions including pH (5.0-6.5), ionic strength (10-150 mM), and temperature to stabilize the tetrameric form without inducing aggregation. The formulation maintains a specific concentration range and uses these parameter optimizations to prevent harmful aggregation while preserving the long circulation half-life benefit of tetrameric SADA-complexes
Solution Approach 2:
The patent introduces intermediary substances including buffer systems (acetate, citrate, histidine), stabilizing agents (sugars, polyols, amino acids), and surfactants (polysorbates, poloxamers) that mediate between the tetrameric SADA-complex and the formulation environment. These intermediaries prevent aggregation and precipitation while allowing the tetrameric form to maintain its stability and extended plasma half-life
2Reliability
If SADA-complexes are formulated to remain stable in tetrameric form, then delivery efficacy is improved, but formulation complexity increases
Solution Approach 1:
The patent optimizes formulation parameters including pH (5.0-6.5), ionic strength (10-150 mM), and component concentrations to achieve stable tetrameric form. This parameter optimization ensures reliable delivery efficacy while managing formulation complexity through systematic control of critical quality attributes
Solution Approach 2:
The patent employs buffer systems that simultaneously maintain pH stability and ionic strength control, and stabilizing agents that provide both solubility enhancement and tetramer stabilization. This multi-functionality approach improves delivery efficacy while reducing overall formulation complexity by having components serve multiple purposes
3Duration of action of moving object
If SADA-complexes are administered in tetrameric form to extend circulation time, then target binding opportunity increases, but disassembly to monomers occurs
Solution Approach 1:
The patent applies preliminary anti-action by incorporating stabilizing agents and optimizing formulation conditions before administration to prevent disassembly of the tetrameric form. The formulation proactively counteracts the tendency to disassemble into monomers during circulation, ensuring the tetrameric structure remains intact throughout the extended circulation period to maximize target binding opportunities
Solution Approach 2:
The patent controls formulation parameters including pH (5.0-6.5), ionic strength (10-150 mM), and temperature to maintain tetrameric stability during circulation. These parameter optimizations ensure the tetrameric form remains stable throughout the extended circulation time, preventing premature disassembly while preserving the enhanced target binding opportunity
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The composition effectively stabilizes SADA-complexes, maintaining them predominantly in the tetrameric form during storage and use, which enhances their shelf-life and ensures targeted delivery by prolonging circulation time in the bloodstream.
Implementation Method 1
The self-assembling and disassembling (SADA) technology was originally disclosed in WO 2018204873A1, and make use of SADA domains having the property of assembly and disassembly depending on concentration.
Implementation Method 2
b. A buffer-system; wherein the pH is in the range of 5-6
Implementation Method 3
c. One or more stabilizing agents
Implementation Method 4
d. One or more surfactants
Data Source
AI summary
Disclosed are formulations comprising SADA-complex. The formulations provide for a satisfactory shelf-life without excessive disassembly or multimerization of the SADA-complex. Further disclosed is the use of the formulation for treating cancer.