Albumin fusion proteins

Abstract

The present invention encompasses albumin fusion proteins. Nucleic acid molecules encoding the albumin fusion proteins of the invention are also encompassed by the invention, as are vectors containing these nucleic acids, host cells transformed with these nucleic acids vectors, and methods of making the albumin fusion proteins of the invention and using these nucleic acids, vectors, and / or host cells. Additionally the present invention encompasses pharmaceutical compositions comprising albumin fusion proteins and methods of treating, preventing, or ameliorating diseases, disorders or conditions using albumin fusion proteins of the invention.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation-in-part of International Application No. PCT / US2005 / 004041, filed Feb. 9, 2005, which claims benefit under 35 U.S.C. §119(e) of U.S. Provisional Application Nos. 60 / 542,274, filed Feb. 9, 2004, 60 / 549,901, filed Mar. 5, 2004, 60 / 556,906, filed Mar. 29, 2004. and 60 / 636,603, filed Dec. 17, 2004, each of which is hereby incorporated by reference in their entirety.REFERENCE TO SEQUENCE LISTING ON COMPACT DISC [0002] This application refers to a “Sequence Listing” listed below, which is provided as an electronic document on three identical compact discs (CD-R), labeled “Copy 1,”“Copy 2,” and “Copy 3.” These compact discs each contain the file “PF612P1 Sequence Listing.txt” (908 kilobytes, created on Jun. 23, 2006), which is incorporated by reference in its entirety. BACKGROUND OF THE INVENTION [0003] The invention relates generally to Therapeutic proteins (including, but not limited to, at least one polype...

AI Technical Summary

Benefits of technology

[0009] The present invention encompasses albumin fusion proteins comprising a Therapeutic protein (e.g., a polypeptide, antibody, or peptide, or fragment or variant thereof) fused to albumin or a fragment (portion) or variant of albumin. The present invention also encompasses polynucleotides comprising, or alternatively consisting of, nucleic acid molecules encoding a Therapeutic protein (e.g., a polypeptide, antibody, or peptide, or fragment or variant thereof) fused to albumin or a fragment (portion) or variant of albumin. The present invention also encompasses polynucleotides, comprising, or alternatively consisting of, nucleic acid molecules encoding proteins comprising a Therapeutic protein (e.g., a polypeptide, antibody, or peptide, or fragment or variant thereof) fused to albumin or a fragment (portion) or variant of albumin, that is sufficient to prolong the shelf life of the Therapeutic protein, to increase the plasma stability of the Therapeutic protein compared to its unfused state, and / or stabilize the Therapeutic protein and / or its activity in solution (or in a pharmaceutical composition) in vitro and / or in vivo. Albumin fusion proteins encoded by a polynucleotide of the invention are also encompassed by the invention, as are host cells transformed with polynucleotides of the invention, and methods of making the albumin fusion proteins of the invention and using these polynucleotides of the invention, and / or host cells.

[0013] In one embodiment, an albumin fusion protein described in Table 1 or 2 has extended shelf life.

Problems solved by technology

The instability in these molecules when formulated for administration dictates that many of the molecules must be lyophilized and refrigerated at all times during storage, thereby rendering the molecules difficult to transport and / or store.

Storage problems are particularly acute when pharmaceutical formulations must be stored and dispensed outside of the hospital environment.

Few practical solutions to the storage problems of labile protein molecules have been proposed.

Upon in vivo administration, therapeutic proteins in their native state or when recombinantly produced, such as interferons and growth hormones, exhibit a short plasma stability due to rapid clearance from the bloodstream.

However, increasing the dosing schedule for administration of the therapeutic protein often results in an increase in injection site reactions, side-effects, and toxicity in the patient.

Similarly, administration of the therapeutic protein at a higher dose also commonly results in an increase in toxicity and side-effects in the patient.

The few practical solutions to increasing plasma stability of therapeutic molecules that have been proposed, including chemical conjugation, have provided limited benefit to the patient.

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