Antibody Composition for High-Concentration Subcutaneous Delivery
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Solution Overview
Problem
Current methods of delivering anti-PD-1 and/or anti-PD-L1 antibodies for cancer treatment are inconvenient and invasive, necessitating improvements for subcutaneous administration to enhance patient compliance.
Innovation Solution
A pharmaceutical composition comprising nivolumab, histidine, sucrose, polysorbate 80, pentetic acid, methionine, and rHuPH20, designed for subcutaneous delivery using a vial, syringe, auto-injector, or wearable pump.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of operation
If subcutaneous delivery is used to improve patient compliance and reduce administration burden, then injection volume is limited to small volumes (e.g., less than 2 mL), but this limits the amount of antibody that can be delivered in a single injection
Solution Approach 1:
The patent applies preliminary action by pre-formulating the antibody at a high concentration (at least 10 mg/mL, preferably at least 20 mg/mL) before administration. This allows the required total dose to be delivered in a small volume that can be accommodated by subcutaneous injection, thereby enabling easy patient compliance while still achieving the necessary antibody delivery amount.
2Quantity of substance
If antibody concentration is increased to deliver sufficient dose in small volume, then subcutaneous delivery becomes feasible, but aggregation and precipitation of the antibody occur
Solution Approach 1:
The patent introduces antioxidants (such as ascorbic acid, tocopherol, or glutathione) as intermediary substances that mediate between the high antibody concentration and the stability requirement. These antioxidants prevent oxidative aggregation and precipitation of the antibody, enabling the formulation to maintain stability at the high concentrations (at least 10 mg/mL, preferably at least 20 mg/mL) needed for subcutaneous delivery.
3Stability of the object's composition
If conventional excipients are used to maintain antibody stability, then aggregation is reduced, but the formulation lacks sufficient activity to prevent oxidative damage during storage and administration
Solution Approach 1:
The patent applies parameter changes by selecting antioxidants with specific properties (such as ascorbic acid, tocopherol, or glutathione) and optimizing their concentrations in the formulation. These antioxidants provide reliable oxidative protection (preventing at least 50%, preferably at least 75%, more preferably at least 90% oxidation) while maintaining antibody stability during storage and administration, thereby simultaneously improving both stability and reliability parameters.
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 convenient and less invasive administration of anti-PD-1 antibodies, improving patient compliance and treatment experience.
Implementation Method 1
the antioxidant is ascorbic acid, glutathione, or tocopherol
Implementation Method 2
the pharmaceutical composition further comprises an endoglycosidase hydrolase enzyme
Data Source
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AI summary
The disclosure provides pharmaceutical compositions comprising an antibody and at least two antioxidants. In some aspects, pharmaceutical composition is formulated for subcutaneous delivery. In some aspects, the pharmaceutical composition further comprises an endoglycosidase hydrolase enzyme. Other aspects of the present disclosure are directed to methods of subcutaneously delivering the pharmaceutical composition.