Formulation for Anti-alpha4beta7 antibody

Abstract

Antibody formulations are described comprising a mixture of a non-reducing sugar, an anti-α4β7 antibody and at least one amino acid. The disclosed formulations have improved stability, reduced aggregate formation, and may retard degradation of the anti-α4β7 antibody therein or exhibit any combinations thereof. The present invention further provides a safe dosing regimen of these antibody formulations that is easy to follow, and which results in a therapeutically effective amount of the anti-α4β7 antibody in vivo.

Description

RELATED APPLICATIONS[0001]This application claims the benefit of U.S. Provisional Application 61 / 585,859 filed on Jan. 12, 2012, U.S. Provisional Application 61 / 550,545 filed on Oct. 24, 2011, and U.S. Provisional Application 61 / 481,533 filed on May 2, 2011. The entire contents of the foregoing applications are hereby incorporated by reference.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 Apr. 30, 2012, is named 92596614.txt and is 17,047 bytes in size.BACKGROUND OF THE INVENTION[0003]Advances in biotechnology have made it possible to produce a variety of proteins for pharmaceutical applications using recombinant DNA techniques. Because proteins are larger and more complex than traditional organic and inorganic drugs (i.e. possessing multiple functional groups in addition to complex three-dimensional structures), the fo...

AI Technical Summary

Benefits of technology

[0009]The invention relates to the identification of a non-reducing sugar and at least one amino acid, as useful excipients for formulating anti-α4β7 antibody formulations whose instability makes them susceptible to deamidation, oxidation, isomerization and / or aggregation. The formulation improves stability, reduces aggregate formation and retards degradation of the antibody therein.

[0013]In some aspects, the formulation can minimize immunogenicity of the anti-α4β7 antibody.

[0025]In some aspects the method of treatment with the anti-α4β7 antibody formulation, the dose, or the dose regimen can minimize immunogenicity of the anti-α4β7 antibody.

[0028]The dosing regimen can result in mucosal healing in patients suffering from moderate to severely active ulcerative colitis.

Problems solved by technology

Because proteins are larger and more complex than traditional organic and inorganic drugs (i.e. possessing multiple functional groups in addition to complex three-dimensional structures), the formulation of such proteins poses special problems.

Proteins may suffer from a lack of stability, and monoclonal and polyclonal antibodies in particular may be relatively unstable (See e.g., Wang et al., J.

A large number of formulation options are available, and not one approach or system is suitable for all proteins.

In fact, even in the case of purified antibodies, the antibody structures may be heterogeneous, which further complicates the formulation of such systems.

Physical instability can result from denaturation, aggregation, precipitation or adsorption, for example.

Consequences of chemical or physical instability of therapeutic protein include a lowering of the effective administered dose, decreased safety of the therapy due to, for example irritation or immunological reactivity, and more frequent manufacturing due to short shelf life.

However, the aforementioned patents and publications do not disclose specific formulations of the anti-α4β7 antibody or the specific doses and dose regimens described and claimed herein.

Importantly, the aforementioned patents do not disclose formulations, doses, and dose regimens that provide for the methods of treatment (supported by clinical trial data) described and claimed herein.

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