Stabilizing alkylglycoside compositions and methods thereof
Inventors
Assignees
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Publication Number
US-8226949-B2
Publication Date
2012-07-24
Expiration Date
Abstract
The present invention relates to alkylglycoside-containing compositions and methods for increasing the stability, reducing the aggregation and immunogenicity, increasing the biological activity, and reducing or preventing fibrillar formation of a peptide, polypeptide, or variant thereof, for example parathyroid hormone (PTH) or PTH analogs, amylin, a monoclonal antibody, insulin, Peptide T or analog thereof, gastrin, gastrin releasing peptides, gastrin releasing peptide-like (GRP) proteins, epidermal growth factor or analog thereof.
Core Innovation
The invention relates to pharmaceutical compositions and methods that use a stabilizing agent comprising at least one alkylglycoside to increase the stability of therapeutic self-associating drugs, including monoclonal antibodies. The stabilizing agent is used to increase stability and to reduce aggregation or reducing immunogenicity, while preserving or increasing biological activity. The described approach is particularly directed to monoclonal antibodies and aims to prevent aggregation and fibril formation associated with reduced stability.
In the described pharmaceutical compositions, a monoclonal antibody is formulated with an alkylglycoside surfactant stabilizing agent, optionally together with a buffering agent and other formulation components. The document emphasizes that alkylglycoside-containing formulations are relevant to critical micelle concentration (CMC) considerations and that reducing aggregation and immunogenicity can occur while maintaining biological activity. The disclosure includes formulation processing such as lyophilization and reconstitution for maintaining performance after processing.
The description further characterizes stability through aggregation-related behavior and performance outcomes, including light-scatter-based aggregation/denaturation proxies and preservation of biological activity. It also addresses immunogenicity reduction using anti-drug antibody measurements, and it supports fibril inhibition and reduced aggregation by multiple characterization approaches. The disclosure includes examples of alkylglycosides and substantially pure alkylglycosides with consideration of anomer composition effects (alpha anomer contamination versus beta anomer purity) to improve stability.
Claims Coverage
Two independent claims are identified. They cover (i) a monoclonal antibody pharmaceutical composition with a stabilizing agent comprising at least one alkylglycoside, and (ii) a method of increasing monoclonal antibody stability by admixing a monoclonal antibody, a stabilizing agent that is at least one alkylglycoside surfactant, and a buffering agent.
Alkylglycoside stabilizing agent for monoclonal antibody stability
A pharmaceutical composition comprising a monoclonal antibody and a stabilizing agent comprising at least one alkylglycoside, for increasing the stability and/or reducing aggregation and/or reducing immunogenicity of the monoclonal antibody.
Admixed buffering formulation with alkylglycoside surfactant
A method for increasing the stability of a monoclonal antibody by admixing the monoclonal antibody, a stabilizing agent, and a buffering agent to form a composition, wherein the stabilizing agent is at least one alkylglycoside surfactant, thereby increasing the stability of the monoclonal antibody.
Overall, the claim coverage centers on using an alkylglycoside surfactant stabilizing agent in monoclonal antibody formulations, with a buffering agent in the method, to increase stability and reduce aggregation and/or immunogenicity.
Stated Advantages
Increasing the stability of a monoclonal antibody.
Reducing aggregation.
Reducing immunogenicity.
Preserving or increasing biological activity.
Maintaining performance after processing such as lyophilization and reconstitution.
Documented Applications
Formulating and stabilizing monoclonal antibody compositions, including increasing stability and reducing aggregation or immunogenicity using alkylglycoside surfactants.
Stabilizing lyophilized (freeze-dried) monoclonal antibody compositions with retained biological activity after reconstitution.
Increasing monoclonal antibody stability by admixing the monoclonal antibody, an alkylglycoside surfactant stabilizing agent, and a buffering agent to form a composition.
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