Compositions and Formulations for Increasing Renal Function and Treatment and Prevention of Renal Diseases, and Methods of Production and Use Thereof
Nutritive polypeptides are provided herein. Also provided are various other embodiments including nucleic acids encoding the polypeptides, recombinant microorganisms that make the polypeptides, vectors for expressing the polypeptides, methods of making the polypeptides using recombinant microorganisms, compositions and formulations that comprise the polypeptides, and methods of using the polypeptides, compositions and formulations.
1 .- 44 . (canceled)
45 . A nutritive formulation for the treatment or prevention of a muscle wasting disease, disorder or condition in a human subject suffering from a renal disease, comprising an isolated nutritive polypeptide comprising an amino acid sequence at least about 90% identical over at least about 50 amino acids to a polypeptide sequence selected from the group consisting of SEQID 00001-03909; wherein the nutritive polypeptide is present in an amount sufficient to provide a nutritional benefit to a human subject having or at risk of having reduced protein absorption capacity; wherein the isolated nutritive polypeptide has an aqueous solubility at pH 7 of at least 12.5 g/L and wherein the isolated nutritive polypeptide has a simulated gastric digestion half-life of less than 30 minutes.
46 . The formulation of claim 45 , wherein the polypeptide sequence comprises a ratio of essential amino acid residues to total amino acid residues of at least 34% and wherein the polypeptide sequence is nutritionally complete.
47 . The formulation of claim 45 , wherein the nutritive polypeptide is formulated in a pharmaceutically acceptable carrier, or wherein the nutritive polypeptide is formulated in or as a food or a food ingredient; or wherein the nutritive polypeptide is formulated in or as a beverage or a beverage ingredient.
48 . The formulation of claim 45 , wherein the amino acid sequence encodes an enzyme having a primary activity, and wherein the nutritive polypeptide substantially lacks the primary activity.
49 . The formulation of claim 45 , further comprising a component selected from a tastant, a protein mixture, a polypeptide, a peptide, a free amino acid, a carbohydrate, a lipid, a mineral or mineral source, a vitamin, a supplement, an organism, a pharmaceutical, and an excipient.
50 . The formulation of claim 45 , wherein the formulation is present as a liquid, semi-liquid or gel in a volume not greater than about 500 ml or as a solid or semi-solid in a total mass not greater than about 200 g.
51 .- 64 . (canceled)
65 . A method of treating or reducing the severity of a renal disease in a human subject, comprising administering to the human subject a nutritional formulation in an amount sufficient to treat or prevent the renal disease, wherein the nutritional formulation comprises an isolated nutritive polypeptide comprising an amino acid sequence at least about 90% identical over at least about 50 amino acids to a polypeptide sequence selected from the group consisting of SEQID 00001-03909.
66 . The method of claim 65 , wherein the isolated nutritive polypeptide has an aqueous solubility at pH 7 of at least 12.5, 20, 30, 50, or 100 g/L.
67 . The method of claim 65 , wherein the isolated nutritive polypeptide has a simulated gastric digestion half-life of less than 2, 10, 30, or 60 minutes.
68 . The method of claim 65 , wherein the isolated nutritive polypeptide does not form insoluble aggregates at 95° C., pH 7.1, when present at 10 mg/ml.
69 . The method of claim 65 , wherein the formulation further comprises a pharmaceutically acceptable carrier.
70 . The method of claim 65 , wherein the formulation is present as a liquid, semi-liquid or gel in a volume not greater than about 500 ml or as a solid or semi-solid in a total mass not greater than about 200 g; and wherein the formulation is substantially free of non-comestible products.
71 . The method of claim 65 , wherein the formulation further comprises a component selected from a tastant, a protein mixture, a polypeptide, a peptide, a free amino acid, a carbohydrate, a lipid, a mineral or mineral source, a vitamin, a supplement, an organism, a pharmaceutical, and an excipient.
72 . The method of claim 65 , wherein the human subject is at risk of developing malnutrition or protein malnutrition.
73 . The method of claim 65 , wherein the human subject has chronic renal failure, acute renal failure, glomerulonephritis, glomerulonephrosis, tubular nephritis, interstitial nephritis, or nephrotic syndrome.
74 . The method of claim 65 , wherein the human subject has end-stage renal disease or a nephrotic syndrome.
75 . The method of claim 65 , wherein the human subject has a urea cycle disorder.
76 . The method of claim 65 , wherein the human subject suffers from a muscle wasting condition.
77 . The method of claim 65 , wherein the nutritional formulation is administered as an adjunct to administration of a pharmaceutical composition.
78 . The method of claim 65 , wherein the human subject is suffering from a renal disease and has received one or more doses of a pharmaceutical composition, wherein i) the disease, disorder or condition or ii) the administration of the pharmaceutical composition, or both i) and ii) increases a risk of loss of muscle mass and/or muscle function.