Liquid Anti-BAFFR Antibody Composition for Shelf-Stable High Dosing
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Solution Overview
Problem
Existing pharmaceutical compositions of anti-BAFFR antibodies suffer from chemical and physical instabilities during storage, leading to antibody aggregation and reduced shelf life, which can cause safety concerns and decreased biological activity.
Innovation Solution
Formulating anti-BAFFR antibodies in an aqueous composition with specific pH, stabilizers, surfactants, and buffering agents to maintain high concentrations with minimal aggregation, suitable for subcutaneous administration.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If anti-BAFFR antibodies are formulated at high concentrations to reduce dosing volume, then dosing efficiency is improved, but antibody aggregation increases during storage
Solution Approach 1:
The patent introduces specific excipients as intermediary substances to mediate between the high concentration requirement and aggregation prevention. These include surfactants (polysorbate 20, poloxamer 188) that act as molecular mediators to prevent antibody-antibody interactions, stabilizers (sucrose, trehalose, mannitol) that provide a protective environment, and amino acids (arginine, histidine) that maintain proper folding and prevent aggregation even at high concentrations up to 165 mg/mL
Solution Approach 2:
The patent systematically optimizes multiple formulation parameters simultaneously: pH (5.0-7.0, preferably 6.0-6.5), ionic strength, temperature, and excipient concentrations. By changing these parameters in combination, the formulation achieves a state where high antibody concentration does not lead to aggregation, resolving the contradiction between dosing efficiency and stability
2Duration of action of stationary object
If antibodies are stored for extended periods to ensure supply availability, then patient access is improved, but chemical and physical instability increases
Solution Approach 1:
The patent applies preliminary protective actions by incorporating stabilizers and antioxidants into the formulation before storage. These pre-added substances (sucrose, trehalose, mannitol, arginine, histidine) create a protective matrix that prevents degradation pathways from initiating, allowing the antibody to maintain biological activity throughout extended storage periods
Solution Approach 2:
The formulation includes excipients that act as cushioning agents against potential degradation. The surfactants and stabilizers provide a buffer against chemical and physical stressors that may occur during storage, ensuring that even under varying conditions, the antibody maintains its structure and function throughout the shelf life
3Stability of the object's composition
If lyophilisates are used to improve storage stability, then aggregation is reduced, but reconstitution time and complexity increase
Solution Approach 1:
The patent extracts the stability-enhancing properties of lyophilization (aggregation prevention) while removing the need for the complex reconstitution process. By using a carefully designed aqueous formulation with stabilizers and surfactants, the product achieves comparable stability in a ready-to-use liquid form, eliminating the reconstitution step entirely
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 formulation achieves stability and bioactivity of anti-BAFFR antibodies, allowing for high concentrations with low aggregation, even after prolonged storage, and enables convenient subcutaneous administration.
Implementation Method 1
Pharmaceutical compositions formulated to contain high concentration of antibody may, however, have short shelf lives and the formulated antibodies may loose biological activity resulting from chemical and physical instabilities during the storage. Among those, aggregation, deamidation and oxidation are known to be the most common causes of antibody degradation.
Implementation Method 2
The aqueous compositions of the invention comprise high concentration of anti-BAFFR antibodies, but no or essentially no aggregated antibodies and are thus particularly suitable for subcutaneous administration. In one embodiment, the present disclosure relates to aqueous compositions having a pH of 5.0-7.0 and comprising (i) a non-fucosylated anti-BAFFR antibody
Implementation Method 3
In one embodiment, the present disclosure relates to aqueous compositions having a pH of 5.0-7.0 and comprising (i) a non-fucosylated anti-BAFFR antibody wherein the antibody has a concentration of 18 - 165 mg/mL, and wherein said anti-BAFFR antibody includes heavy chain CDR1, CDR2 and CDR3 of SEQ ID NOs 3, 4 and 5 respectively, and light chain CDR1, CDR2 and CDR3 of SEQ ID NOs: 6, 7 and 8, (ii) a stabilizer, (iii) a buffering agent, (iv) a surfactant
Data Source
AI summary
Anti-BAFFR antibodies are formulated as liquid formulation comprising a high concentration of the antibody active ingredient for delivery to a patient without high levels of antibody aggregation. The aqueous pharmaceutical composition may include one or more sugars, a buffering agent, a surfactant, and/or a free amino acid.