Polynucleotide compositions containing amino acids

Abstract

The present invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides formulations containing amino acids.

We claim: 
     
         1 . A pharmaceutical composition comprising at least one amino acid and at least one polynucleotide encoding a polypeptide of interest, wherein the polynucleotide comprises at least one chemical modification. 
     
     
         2 . The pharmaceutical composition of  claim 1 , wherein the chemical modification is selected from the group consisting of the chemical modifications of Table 4. 
     
     
         3 . The pharmaceutical composition of  claim 2 , wherein the chemical modification is selected from the group consisting of uridine modifications of Table 4. 
     
     
         4 . The pharmaceutical composition of  claim 1 , wherein the polynucleotide comprises two chemical modifications and wherein the two chemical modifications are selected from the group consisting of the chemical modifications of Table 4. 
     
     
         5 . The pharmaceutical composition of  claim 4 , wherein the first chemical modification is a uridine modification of Table 4 and the second modification is a cytidine modification of Table 4. 
     
     
         6 . The pharmaceutical composition of  claim 1 , wherein the polynucleotide comprises a poly-A tail. 
     
     
         7 . The pharmaceutical composition of  claim 1 , wherein the polynucleotide comprises at least one 5′ cap structure. 
     
     
         8 . The pharmaceutical composition of  claim 1 , wherein the polynucleotide is purified. 
     
     
         9 . The pharmaceutical composition of  claim 1 , wherein the polynucleotide comprises at least two regions and wherein at least one region is codon-optimized. 
     
     
         10 . The pharmaceutical composition of  claim 1 , wherein the at least one amino acid is an essential amino acid. 
     
     
         11 . The pharmaceutical composition of  claim 10 , wherein the essential amino acid is leucine. 
     
     
         12 . The pharmaceutical composition of  claim 11 , further comprising at least one amino acid selected from the group consisting of histidine, isoleucine, lysine, methionine, phenylalanine, threonine, tryptophan and valine. 
     
     
         13 . The pharmaceutical composition of  claim 1 , wherein the at least one amino acid is a branched chain amino acid. 
     
     
         14 . The pharmaceutical composition of  claim 13 , wherein the branched chain amino acid is selected from the group consisting of leucine, isoleucine and valine. 
     
     
         15 . The pharmaceutical composition of  claim 14 , wherein the branched chain amino acid is leucine. 
     
     
         16 . The pharmaceutical composition of  claim 13 , further comprising at least one amino acid selected from the group consisting of histidine, isoleucine, lysine, methionine, phenylalanine, threonine, tryptophan and valine. 
     
     
         17 . A method for producing a protein of interest in a mammalian cell or tissue comprising administration of the pharmaceutical composition of any of  claims 1 - 19  to said mammalian cell or tissue. 
     
     
         18 . The method of  claim 17 , where administration is selected from the group consisting of Auricular (Otic), Buccal, Caudal Block, Conjunctival, Cutaneous, Dental, Electro-Osmosis, Endocervical, Endosinusial, Endotracheal, Enteral, Epidural, Extra-Amniotic, Extracorporeal, Hemodialysis, Inhalation, Implantation, Infiltration, Infusion, Interstitial, Intra-Abdominal, Intra-Amniotic, Intra-Arterial, Intra-Articular, Intrabiliary, Intrabronchial, Intrabursal, Intracardiac, Intracartilaginous, Intracaudal, Intracavernous, Intracavitary, Intracerebral, Intracisternal, Intracorneal, Intracoronal, Intracoronary, Intracorporus Cavernosum, Intradermal, Intradiscal, Intraductal, Intraduodenal, Intradural, Intraepidermal, Intraesophageal, Intragastric, Intragingival, Intraileal, Intralesional, Intraluminal, Intralymphatic, Intramedullary, Intrameningeal, Intramuscular, Intraocular, Intraovarian, Intrapericardial, Intraperitoneal, Intrapleural, Intraprostatic, Intrapulmonary, Intrasinal, Intraspinal, Intrasynovial, Intratendinous, Intratesticular, Intrathecal, Intrathoracic, Intratracheal, Intratubular, Intratumor, Intratympanic, Intrauterine, Intravascular, Intravenous, Intravenous Bolus, Intravenous Drip, Intraventricular, Intravesical, Intravitreal, lontophoresis, Irrigation, Laryngeal, Nasal, Nasogastric, Nerve Block, Occlusive Dressing Technique, Ophthalmic, Oral, Oropharyngeal, Other, Parenteral, Percutaneous, Perfusion (Biliary), Perfusion (Cardiac), Periarticular, Peridural, Perineural, Periodontal, Photoperesis, Rectal, Respiratory (Inhalation), Retrobulbar, Spinal, Soft Tissue, Subarachnoid, Subconjunctival, Subcutaneous, Sublingual, Submucosal, Topical, Transdermal, Transmucosal, Transplacental, Transtracheal, Transtympanic, Ureteral and Vaginal. 
     
     
         19 . The method of  claim 18 , where administration is intramuscular. 
     
     
         20 . The method of  claim 17 , wherein the pharmaceutical composition comprises at least one inactive ingredient selected from the group consisting of Acetic Acid, Activated Charcoal, Adipic Acid, Alcohol, Alcohol, Dehydrated, Ammonium Acetate, Anhydrous Dextrose, Ascorbic Acid, Benzalkonium Chloride, Benzethonium Chloride, Benzoic Acid, Benzyl Alcohol, Benzyl Benzoate, Butylated Hydroxyanisole, Butylated Hydroxytoluene, Butylparaben, Calcium, Calcium Chloride, Carbon Dioxide, Carboxymethylcellulose, Carboxymethylcellulose Sodium, Castor Oil, Cellulose, Microcrystalline, Chlorobutanol, Chlorobutanol Hemihydrate, Chlorobutanol, Anhydrous, Citric Acid, Citric Acid Monohydrate, Corn Oil, Cottonseed Oil, Creatine, Creatinine, Croscarmellose Sodium, Crospovidone, Dextrose, Diatrizoic Acid, Docusate Sodium, Edetate Calcium Disodium, Edetate Disodium, Edetate Disodium Anhydrous, Edetate Sodium, Ethyl Acetate, Gelatin, Glutathione, Glycerin, Glycine, Hyaluronate Sodium, Hydrochloric Acid, Hydroxide Ion, Lactic Acid, Lactic Acid, Dl-, Lactose, Lactose Monohydrate, Lactose, Hydrous, Lecithin, Magnesium Chloride, Maleic Acid, Mannitol, Meglumine, Metacresol, Methionine, Methylcelluloses, Methylparaben, Monothioglycerol, Myristyl-.Gamma.-Picolinium Chloride, N,N-Dimethylacetamide, Niacinamide, Nitrogen, Peanut Oil, Peg-20 Sorbitan Isostearate, Phenol, Phenylmercuric Nitrate, Phosphoric Acid, Polyethylene Glycol 200, Polyethylene Glycol 300, Polyethylene Glycol 3350, Polyethylene Glycol 4000, Polyglactin, Polylactide, Polysorbate 20, Polysorbate 40, Polysorbate 80, Polyvinyl Alcohol, Potassium Phosphate, Dibasic, Potassium Phosphate, Monobasic, Povidones, Propyl Gallate, Propylene Glycol, Propylparaben, Saccharin Sodium, Saccharin Sodium Anhydrous, Sesame Oil, Sodium Acetate, Sodium Acetate Anhydrous, Sodium Benzoate, Sodium Bicarbonate, Sodium Bisulfite, Sodium Carbonate, Sodium Chlorate, Sodium Chloride, Sodium Chloride Injection, Sodium Citrate, Sodium Formaldehyde Sulfoxylate, Sodium Hydroxide, Sodium Metabisulfite, Sodium Phosphate, Sodium Phosphate, Dibasic, Sodium Phosphate, Dibasic, Anhydrous, Sodium Phosphate, Dibasic, Heptahydrate, Sodium Phosphate, Monobasic, Sodium Phosphate, Monobasic, Anhydrous, Sodium Phosphate, Monobasic, Monohydrate, Sodium Sulfate Anhydrous, Sodium Sulfite, Sodium Tartrate, Sorbitan Monopalmitate, Sorbitol, Sorbitol Solution, Starch, Sucrose, Sulfobutylether .Beta.-Cyclodextrin, Sulfuric Acid, Sulfurous Acid, Tartaric Acid, Thimerosal, Tromantadine, Tromethamine and Urea.