Self-Buffering Protein Formulations

Abstract

The invention herein described, provides, among other things, self-buffering protein formulations. Particularly, the invention provides self-buffering pharmaceutical protein formulations that are suitable for veterinary and human medical use. The self-buffering protein formulations are substantially free of other buffering agents, stably maintain pH for the extended time periods involved in the distribution and storage of pharmaceutical proteins for veterinary and human medical use. The invention further provides methods for designing, making, and using the formulation. In addition to other advantages, the formulations avoid the disadvantages associated with the buffering agents conventionally used in current formulations of proteins for pharmaceutical use. The invention in these and other respects can be productively applied to a wide variety of proteins and is particularly useful for making and using self-buffering formulations of pharmaceutical proteins for veterinary and medical use, especially, in particular, for the treatment of diseases in human subjects.

Description

REFERENCE TO RELATED APPLICATIONS[0001]This application is a continuation-in-part of and claims full priority benefit of U.S. Provisional Application Ser. No. 60 / 690,582 filed 14 Jun. 2005, which is incorporated herein by reference in its entirety.FIELD OF THE INVENTION[0002]The invention relates to the formulation of proteins, especially pharmaceutical proteins. In particular, it relates to self-buffering biopharmaceutical protein compositions, and to methods for designing, making, and using the compositions. It further relates to pharmaceutical protein compositions for veterinary and / or for human medical use, and to methods relating thereto.BACKGROUND OF THE INVENTION[0003]Many aspects of pharmaceutical production and formulation processes are pH sensitive. Maintaining the correct pH of a finished pharmaceutical product is critical to its stability, effectiveness, and shelf life, and pH is an important consideration in designing formulations for administration that will be accepta...

AI Technical Summary

Benefits of technology

[0056]39. A method for treating a subject comprising administering to a subject in an amount and by a route effective for treatment a composition according to any of the foregoing or the following, including a reconstituted lyophilate.

Problems solved by technology

Although there are many buffers in general use, only a limited number are suitable for biological applications and, of these, fewer still are acceptable for pharmaceutical processes and formulations.

As a result, it often is challenging to find a buffer that not only will be effective at maintaining pH but also will meet all the other requirements for a given pharmaceutical process, formulation, or product.

The challenge of finding a suitable buffer for pharmaceutical use can be especially acute for pharmaceutical proteins.

Proteins are susceptible to a variety of pH sensitive reactions that are deleterious to their efficacy, typically many more than affect small molecule drugs.

Buffering agents that catalyze reactions that inactivate and / or degrade one or more other ingredients, moreover, cannot be used in pharmaceutical formulations.

Buffers for pharmaceutical use must have not only the buffer capacity required to maintain correct pH, but also they must not buffer so strongly that their administration deleteriously perturbs a subject's physiological pH.

For instance, buffers that sublime or evaporate, such as acetate and imidazole, generally cannot be relied upon to maintain pH during lyophilization and in the reconstituted lyophilization product.

Other buffers that crystallize out of the protein amorphous phase, such as sodium phosphate, cannot be relied upon to maintain pH in processes that require freezing.

For instance, several otherwise useful buffers, such as citrate at low or high concentration and acetate at high concentration, are undesirably painful when administered parenterally.

They all have undesirable limitations and disadvantages.

And they all have the inherent disadvantage of being an additional ingredient in the formulation, which complicates the formulation process, poses a risk of deleteriously affecting other ingredients, stability, shelf-life, and acceptability to the end user.

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