Anti-CD38 Subcutaneous Formulation for High-Dose Stability
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Solution Overview
Problem
The existing intravenous administration of anti-CD38 antibodies for treating multiple myeloma and other hematological malignancies is limited by the physico-chemical properties of the antibodies, particularly solubility and stability in liquid formulations, restricting the amount that can be administered.
Innovation Solution
A pharmaceutical composition comprising an anti-CD38 antibody and hyaluronidase, formulated for subcutaneous administration, which includes specific concentrations of anti-CD38 antibody, hyaluronidase, histidine, sorbitol, PS-20, and methionine at a pH of 5.5, enhancing stability and solubility.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If anti-CD38 antibodies are administered via intravenous route, then therapeutic efficacy is achieved, but the amount that can be administered is limited by solubility and stability in liquid formulation
Solution Approach 1:
The patent changes the physical state of the antibody from liquid to solid form through freeze-drying, and modifies formulation parameters by adding specific excipients (mannitol, histidine, polysorbate 20) to enable stable solid-state storage and subsequent reconstitution, thereby overcoming the solubility and stability limitations of liquid formulations
Solution Approach 2:
The patent creates a composite pharmaceutical formulation combining anti-CD38 antibody with multiple excipients (mannitol as stabilizer, histidine as buffer, polysorbate 20 as surfactant) to achieve enhanced stability and solubility characteristics that allow higher doses to be administered
2Reliability
If anti-CD38 antibodies are administered via intravenous route, then therapeutic effect is achieved, but infusion-related reactions occur
Solution Approach 1:
The patent employs a single-use pre-filled syringe system where the antibody is administered quickly and the entire system is discarded after one use, minimizing contamination risk and reducing opportunities for infusion-related reactions to occur during prolonged administration
Solution Approach 2:
The antibody is pre-formulated with stabilizing excipients and stored in a lyophilized state before administration, ensuring optimal stability and reducing the risk of degradation-related adverse reactions during the infusion process
3Quantity of substance
If higher doses of anti-CD38 antibodies are administered, then therapeutic response is improved, but solubility limitations are exceeded
Solution Approach 1:
The patent transitions the formulation from liquid to solid lyophilized form, enabling much higher antibody concentrations to be incorporated without solubility constraints, and allows flexible reconstitution volumes to achieve desired dosing levels
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
Facilitates higher doses of anti-CD38 antibodies for subcutaneous delivery, potentially reducing infusion-related reactions and improving therapeutic response compared to intravenous administration.
Implementation Method 1
A pharmaceutical composition comprising an anti-CD38 antibody and a hyaluronidase
Data Source
AI summary
The present invention relates to subcutaneous formulations of anti-CD38 antibodies and their uses.