Anti-c-met antibody formulations

Abstract

Provided herein are pharmaceutical formulations comprising a one-armed, anti-c-met antibody and uses of the same.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]This application claims benefit of priority to U.S. Patent Application 61 / 503,513, filed Jun. 30, 2011, the entire contents of which is incorporated herein by reference in its entirety.SEQUENCE LISTING[0002]The instant application contains a Sequence Listing which has been submitted in ASCII format via EFS-Web and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Feb. 16, 2012, is named P4690R1WO.txt and is 22,553 bytes in size.TECHNICAL FIELD[0003]Provided herein are pharmaceutical formulations comprising an anti-c-met antibody and uses of the same.BACKGROUND[0004]Excipients are added to pharmaceutical formulations to aid in the stabilization of the active compound. The compatibility of the excipients with the active compound is crucial for the quality and stability of the pharmaceutical formulation. While excipients are important in the stabilization of the active compound, excipients can cause problems: t...

AI Technical Summary

Benefits of technology

[0021]Provided are methods of making the pharmaceutical formulation described herein.

[0022]In addition, provided herein are articles of manufacture comprising a container with a pharmaceutical formulation described herein (e.g., upon dilution) contained therein. Provided herein are also methods of making the articles of manufacture comprising a pharmaceutical formulation described herein (e.g., upon dilution).

Problems solved by technology

While excipients are important in the stabilization of the active compound, excipients can cause problems: the excipient may degrade and thus lose its mechanism of stabilization or it may produce degradants that interact with the active compound.

Pharmaceutical formulations in which the active compound is a polypeptide, e.g. an antibody, can pose special problems as polypeptides generally are larger and more complex than traditional organic and inorganic molecules (for example, polypeptides possess multiple functional groups, in addition to complex three-dimensional structures).

Excipients are generally stable in aqueous solution; however, excipients in a pharmaceutical polypeptide formulation can interact with the polypeptide to undergo degradation in a formulation and can prevent the stabilization of the protein or the degradants could interact with the polypeptide to pose challenges (such as a loss in activity).

Loss of polysorbate in the pharmaceutical formulation can result in instability of the formulation.

Further, polysorbates can be degraded by oxidation and hydrolysis which can lead to a decrease in the apparent concentration of polysorbate in the pharmaceutical formulation over long shelf life.

These polysorbate degradants are less surface-active than nondegraded polysorbate and hence the chemical and physical stability of the pharmaceutical formulation may be compromised.

For treatment of pathological conditions requiring an antagonistic function, bivalency of an anti-c-met antibody could result in an undesirable agonistic effect, and therefore, the monovalent trait is required to ensure an antagonistic activity upon binding of the anti-c-met antibody to the target for treatment of the pathological condition.

Aggregation of monovalent antibodies (formation of multimer and oligomers) and / or failure to maintain monovalent structure in a pharmaceutical formulation comprising anti-c-met antibodies could lead to an undesirable agonistic effect.

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