FreshPatents.com Logo
stats FreshPatents Stats
2 views for this patent on FreshPatents.com
2013: 1 views
2012: 1 views
Updated: April 14 2014
newTOP 200 Companies filing patents this week


    Free Services  

  • MONITOR KEYWORDS
  • Enter keywords & we'll notify you when a new patent matches your request (weekly update).

  • ORGANIZER
  • Save & organize patents so you can view them later.

  • RSS rss
  • Create custom RSS feeds. Track keywords without receiving email.

  • ARCHIVE
  • View the last few months of your Keyword emails.

  • COMPANY DIRECTORY
  • Patents sorted by company.

AdPromo(14K)

Follow us on Twitter
twitter icon@FreshPatents

Self-buffering protein formulations

last patentdownload pdfimage previewnext patent


Title: 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. ...


Browse recent Amgen Inc. patents - Thousand Oaks, CA, US
Inventors: Yatin R. GOKARN, Eva Kras, Richard Louis Remmele, JR., David Brems, Susan Irene Hershenson
USPTO Applicaton #: #20120028877 - Class: 514 11 (USPTO) - 02/02/12 - Class 514 


view organizer monitor keywords


The Patent Description & Claims data below is from USPTO Patent Application 20120028877, Self-buffering protein formulations.

last patentpdficondownload pdfimage previewnext patent

REFERENCE TO RELATED APPLICATIONS

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

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

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 acceptable, as well as safe and effective.

To maintain pH, pharmaceutical processes and formulations use one or more buffering agents. A variety of buffering agents are available for pharmaceutical use. The buffer or buffers for a given application must be effective at the desired pH. They must also provide sufficient buffer capacity to maintain the desired pH for as long as necessary. A good buffer for a pharmaceutical composition must satisfy numerous other requirements as well. It must be appropriately soluble. It must not form deleterious complexes with metal ions, be toxic, or unduly penetrate, solubilize, or absorb on membranes or other surfaces. It should not interact with other components of the composition in any manner which decreases their availability or effectiveness. It must be stable and effective at maintaining pH over the range of conditions to which it will be exposed during formulation and during storage of the product. It must not be deleteriously affected by oxidation or other reactions occurring in its environment, such as those that occur in the processing of the composition in which it is providing the buffering action. If carried over or incorporated into a final product, a buffering agent must be safe for administration, compatible with other components of the composition over the shelf-life of the product, and acceptable for administration to the end user.

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. The conformation and activity of proteins are critically dependent upon pH. Proteins are susceptible to a variety of pH sensitive reactions that are deleterious to their efficacy, typically many more than affect small molecule drugs. For instance, to mention just a few salient examples, the side chain amides of asparagine and glutamine are deamidated at low pH (less than 4.0) and also at neutral or high pH (greater than 6.0). Aspartic acid residues promote the hydrolysis of adjacent peptide bonds at low pH. The stability and disposition of disulfide bonds is highly dependent on pH, particularly in the presence of thiols. Solubility, flocculation, aggregation, precipitation, and fibrillation of proteins are critically dependent on pH. The crystal habit important to some pharmaceutical formulations also is critically dependent on pH. And pH is also an important factor in surface adsorption of many pharmaceutical peptides and proteins.

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. Buffers for pharmaceutical formulations also must be compatible with typically complex formulation processes. 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.

Buffers used to maintain pH in pharmaceutical end-products also must be not only effective at maintaining pH but also safe and acceptable for administration to the subject. 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.

Some buffers have been found to be useful in the formulation of pharmaceutical proteins, such as acetate, succinate, citrate, histidine (imidazole), phosphate, and Tris. 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.

There is a need, therefore, for additional and improved methods of maintaining pH in the production and formulation of pharmaceuticals and in pharmaceutical compositions, particularly in the production and formulation of biopharmaceutical proteins and in biopharmaceutical protein compositions.

SUMMARY

Therefore, it is among the various objects and aspects of the invention to provide, in certain of the preferred embodiments, protein formulations comprising a protein, particularly pharmaceutically acceptable formulations comprising a pharmaceutical protein, that are buffered by the protein itself, that do not require additional buffering agents to maintain a desired pH, and in which the protein is substantially the only buffering agent (i.e., other ingredients, if any, do not act substantially as buffering agents in the formulation).

In this regard and others, it is among the various objects and aspects of the invention to provide, in certain preferred embodiments, self-buffering formulations of a protein, particularly of a pharmaceutical protein, characterized in that the concentration of the formulated protein provides a desired buffer capacity.

It is further among the various objects and aspects of the invention to provide, in certain of the particularly preferred embodiments, self-buffering protein formulations, particularly pharmaceutical protein formulations, in which the total salt concentration is less than 150 mM.

It is further among the various objects and aspects of the invention to provide, in certain of the particularly preferred embodiments, self-buffering protein formulations, particularly pharmaceutical protein formulations, that further comprise one or more polyols and/or one or more surfactants.

It is also further among the various objects and aspects of the invention to provide, in certain of the particularly preferred embodiments, self-buffering formulations comprising a protein, particularly a pharmaceutical protein, in which the total salt concentration is less than 150 mM, that further comprise one or more excipients, including but not limited to, pharmaceutically acceptable salts; osmotic balancing agents (tonicity agents); surfactants, polyols, anti-oxidants; antibiotics; antimycotics; bulking agents; lyoprotectants; anti-foaming agents; chelating agents; preservatives; colorants; and analgesics.

It is additionally among the various objects and aspects of the invention to provide, in certain preferred embodiments, self-buffering protein formulations, particularly pharmaceutical protein formulations, that comprise, in addition to the protein, one or more other pharmaceutically active agents.

Various additional aspects and embodiments of the invention are illustratively described in the following numbered paragraphs. The invention is described by way of reference to each of the items set forth in the paragraphs, individually and/or taken together in any combination. Applicant specifically reserves the right to assert claims based on any such combination.

1. A composition according to any of the following, wherein the composition has been approved for pharmaceutical use by a national or international authority empowered by law to grant such approval preferably the European Agency for the Evaluation of Medical Products, Japan\'s Ministry of Health, Labor and Welfare, China\'s State Drug Administration, United States Food and Drug Administration, or their successor(s) in this authority, particularly preferably the United States Food and Drug Administration or its successor(s) in this authority.

2. A composition according to any of the foregoing or the following, wherein the composition is produced in accordance with good manufacturing practices applicable to the production of pharmaceuticals for use in humans.

3. A composition according to any of the foregoing or the following, comprising a protein, the protein having a buffer capacity per unit volume per pH unit of at least that of approximately: 2.0 or 3.0 or 4.0 or 5.0 or 6.50 or 8.00 or 10.0 or 15.0 or 20.0 or 30.0 or 40.0 or 50.0 or 75.0 or 100 or 125 or 150 or 200 or 250 or 300 or 350 or 400 or 500 mM sodium acetate buffer in pure water over the range of pH 5.0 to 4.0 or pH 5.0 to 5.5, preferably as determined in accordance with the methods described in Example 1 and 2, particularly preferably at least 2.0 mM, especially particularly preferably at least 3.0 mM, very especially particularly preferably at least 4.0 mM or at least 5.0 mM, especially particularly preferably at least 7.5 mM, particularly preferably at least 10 mM, preferably at least 20 mM.

4. A composition according to any of the foregoing or the following wherein, exclusive of the buffer capacity of the protein, the buffer capacity per unit volume per pH unit of the composition is equal to or less than that of 1.0 or 1.5 or 2.0 or 3.0 or 4.0 or 5.0 mM sodium acetate buffer in pure water over the range of pH 4.0 to 5.0 or pH 5.0 to 5.5, preferably as determined in accordance with the methods described in Example 1 and 2, particularly preferably less than that of 1.0 mM, very especially particularly preferably less than that of 2.0 mM, especially particularly preferably less than that of 2.5 mM, particularly preferably less than that of 3.0 mM, preferably less than that of 5.0 mM.

5. A composition according to any of the foregoing or the following comprising a protein wherein over the range of plus or minus 1 pH unit from the pH of the composition, the buffer capacity of the protein is at least approximately: 1.00 or 1.50 or 1.63 or 2.00 or 3.00 or 4.00 or 5.00 or 6.50 or 8.00 or 10.0 or 15.0 or 20.0 or 30.0 or 40.0 or 50.0 or 75.0 or 100 or 125 or 150 or 200 or 250 or 300 or 350 or 400 or 500 or 700 or 1,000 mEq per liter per pH unit, preferably at least approximately 1.00, particularly preferably 1.50, especially particularly preferably 1.63, very especially particularly preferably 2.00, very highly especially particularly preferably 3.00, very especially particularly preferably 5.0, especially particularly preferably 10.0, particularly preferably 20.0.



Download full PDF for full patent description/claims.

Advertise on FreshPatents.com - Rates & Info


You can also Monitor Keywords and Search for tracking patents relating to this Self-buffering protein formulations patent application.
###
monitor keywords



Keyword Monitor How KEYWORD MONITOR works... a FREE service from FreshPatents
1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored.
3. Each week you receive an email with patent applications related to your keywords.  
Start now! - Receive info on patent apps like Self-buffering protein formulations or other areas of interest.
###


Previous Patent Application:
Membrane evaporation for generating highly concentrated protein therapeutics
Next Patent Application:
Vegfr-1/nrp-1 targeting peptides
Industry Class:
Drug, bio-affecting and body treating compositions
Thank you for viewing the Self-buffering protein formulations patent info.
- - - Apple patents, Boeing patents, Google patents, IBM patents, Jabil patents, Coca Cola patents, Motorola patents

Results in 1.0188 seconds


Other interesting Freshpatents.com categories:
Software:  Finance AI Databases Development Document Navigation Error -g2-0.1935
     SHARE
  
           

FreshNews promo


stats Patent Info
Application #
US 20120028877 A1
Publish Date
02/02/2012
Document #
13188329
File Date
07/21/2011
USPTO Class
514/11
Other USPTO Classes
International Class
61K38/02
Drawings
15



Follow us on Twitter
twitter icon@FreshPatents