Biologically active proteins having increased in vivo and/or in vitro stability
First Claim
1. An unstructured recombinant polymer (URPs), wherein the URP comprising at least about 200 contiguous amino acids, and wherein(a) the sum of glycine (G), aspartate (D), alanine (A), serine (S), threonine (T), glutamate (E) and proline (P) residues contained in the URP, constitutes more than about 80% of the total amino acids of the URP;
- (b) at least 50% of the amino acids of the URP are not present in secondary structure as determined by Chou-Fasman algorithm;
(c) the URP has a Tepitope score equal to or less than −
5;
(d) the URP contains only 3, 4, 5, or 6 different types of amino acids; and
(e) the URP contains greater than 5% glutamic acid and less than 2% lysine or arginine;
wherein incorporation of the URP into a heterologous protein results in a fusion protein having at least a 2-fold increase in apparent molecular weight of the fusion protein as compared to the protein lacking said URP wherein the apparent molecular weight is approximated by size exclusion chromatography, and wherein the fusion protein exhibits an increased half-life as compared to the protein lacking said URP.
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Accused Products
Abstract
The present invention provides unstructured recombinant polymers (URPs) and proteins containing one or more of the URPs. The present invention also provides microproteins, toxins and other related proteinaceous entities, as well as genetic packages displaying these entities. The present invention also provides recombinant polypeptides including vectors encoding the subject proteinaceous entities, as well as host cells comprising the vectors. The subject compositions have a variety of utilities including a range of pharmaceutical applications.
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Citations
13 Claims
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1. An unstructured recombinant polymer (URPs), wherein the URP comprising at least about 200 contiguous amino acids, and wherein
(a) the sum of glycine (G), aspartate (D), alanine (A), serine (S), threonine (T), glutamate (E) and proline (P) residues contained in the URP, constitutes more than about 80% of the total amino acids of the URP; -
(b) at least 50% of the amino acids of the URP are not present in secondary structure as determined by Chou-Fasman algorithm; (c) the URP has a Tepitope score equal to or less than −
5;(d) the URP contains only 3, 4, 5, or 6 different types of amino acids; and (e) the URP contains greater than 5% glutamic acid and less than 2% lysine or arginine; wherein incorporation of the URP into a heterologous protein results in a fusion protein having at least a 2-fold increase in apparent molecular weight of the fusion protein as compared to the protein lacking said URP wherein the apparent molecular weight is approximated by size exclusion chromatography, and wherein the fusion protein exhibits an increased half-life as compared to the protein lacking said URP. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13)
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Specification