Claims for Patent: 10,583,155

Summary for Patent: 10,583,155

Title:	Stable, highly pure L-cysteine compositions for injection and methods of use
Abstract:	The subject matter described herein is directed to stable L-cysteine compositions for injection, comprising: L-cysteine or a pharmaceutically acceptable salt thereof and/or hydrate thereof in an amount from about 10 mg/mL to about 100 mg/mL; Aluminum in an amount from about 1.0 parts per billion (ppb) to about 250 ppb; cystine in an amount from about 0.01 wt % to about 2 wt % relative to L-cysteine; pyruvic acid in an amount from about 0.01 wt % to about 2 wt % relative to L-cysteine; a pharmaceutically acceptable carrier, comprising water; headspace O.sub.2 that is less than 1.0%; dissolved oxygen present in the carrier in an amount from about 0.01 parts per million (ppm) to about 1 ppm, wherein the composition is enclosed in a single-use container having a volume of from 10 mL to 100 mL. Also described are compositions for a total parenteral nutrition regimen and methods for their use.
Inventor(s):	Maloney; John (Salisbury, NC), Koganti; Aruna (Lenoir, NC), Koneru; Phanesh (Waxhaw, NC)
Assignee:	Exela Pharma Sciences, LLC (Lenoir, NC)
Application Number:	16/665,702
Patent Litigation and PTAB cases:	See patent lawsuits and PTAB cases for patent 10,583,155
Patent Claims:	1. A method of treating a subject having an adverse health condition that is responsive to L-cysteine administration, said method comprising: parenterally administering to said subject a parenteral composition comprising a mixture of one or more amino acids, intravenous fluid, and a stable L-cysteine composition, wherein said stable L-cysteine composition contributes to said parenteral composition: a therapeutically effective amount of L-cysteine or a pharmaceutically acceptable salt thereof and/or hydrate thereof; per Liter of said stable L-cysteine composition, from about 1.0 mcg to about 250 mcg of Aluminum; not more than about 2.0 wt % of cystine relative to L-cysteine; and, not more than about 2.0 wt % of pyruvic acid relative to L-cysteine. 2. The method of claim 1, wherein said stable L-cysteine composition contributes Aluminum in an amount less than 200 mcg/L. 3. The method of claim 1, wherein said stable L-cysteine composition contributes Aluminum in an amount less than 150 mcg/L. 4. The method of claim 1, wherein said parenteral composition is a total parenteral nutrition (TPN) composition. 5. The method of claim 1, wherein said intravenous fluid is selected from the group consisting of isotonic saline, glucose solution, glucose saline, dextrose solution, crystalline amino acid solution, and lipids, and combinations thereof. 6. The method of claim 1, wherein said intravenous fluid is selected from the group consisting of isotonic saline, dextrose solution, and crystalline amino acid solution, and combinations thereof. 7. The method of claim 1, wherein said parenteral composition further comprises one or more amino acids selected from the group consisting of leucine, isoleucine, lysine, valine, phenylalanine, histidine, threonine, methionine, tryptophan, alanine, arginine, glycine, proline, serine, and tyrosine. 8. The method of claim 1, wherein said administering comprises administration once or twice daily. 9. The method of claim 8, wherein said parenterally administering delivers about 120 mg/kg/day to about 160 mg/kg/day L-cysteine, or a pharmaceutically acceptable salt thereof and/or hydrate thereof. 10. The method of claim 8, wherein said parenterally administering delivers about 80 mg/kg/day to about 120 mg/kg/day L-cysteine, or a pharmaceutically acceptable salt thereof and/or hydrate thereof. 11. The method of claim 8, wherein said parenterally administering delivers about 40 mg/kg/day to about 80 mg/kg/day L-cysteine, or a pharmaceutically acceptable salt thereof and/or hydrate thereof. 12. The method of claim 8, wherein said parenterally administering delivers about 45 mg/kg/day to about 60 mg/kg/day L-cysteine, or a pharmaceutically acceptable salt thereof and/or hydrate thereof. 13. The method of claim 8, wherein said parenterally administering delivers about 30 mg/kg/day to about 45 mg/kg/day L-cysteine, or a pharmaceutically acceptable salt thereof and/or hydrate thereof. 14. The method of claim 8, wherein said parenterally administering delivers about 15 mg/kg/day to about 30 mg/kg/day L-cysteine, or a pharmaceutically acceptable salt thereof and/or hydrate thereof. 15. The method of claim 8, wherein said parenterally administering delivers about 7 mg/kg/day to about 10 mg/kg/day L-cysteine, or a pharmaceutically acceptable salt thereof and/or hydrate thereof. 16. The method of claim 8, wherein said parenterally administering delivers about 4 mg/kg/day to about 7.5 mg/kg/day L-cysteine, or a pharmaceutically acceptable salt thereof and/or hydrate thereof. 17. The method of claim 1, wherein said subject is a preterm infant or less than about 1 month of age. 18. The method of claim 1, wherein said subject has an age of 1 month to 1 year. 19. The method of claim 1, wherein said subject has an age of 1 year to 11 years. 20. The method of claim 1, wherein said subject has an age of 12 years to 17 years. 21. The method of claim 1, wherein said subject is an adult. 22. The method of claim 17, wherein said administering delivers about 15 mg of said L-cysteine per gram of said one or more amino acids, and said L-cysteine composition contributes not more than 0.21 mcg/kg/day of Aluminum. 23. The method of claim 1, wherein said adverse health condition results from the inability to convert methionine to L-cysteine. 24. The method of claim 1, wherein said adverse health condition is the need for total parenteral nutrition (TPN). 25. The method of claim 1, wherein said adverse health condition is selected from the group consisting of short bowel syndrome, gastrointestinal fistula, bowel obstruction, prolonged bowel rest, severe malnutrition, significant weight loss and/or hypoproteinaemia, and a condition that precludes oral or enteral feeding. 26. The method of claim 1, wherein said adverse health condition is selected from the group consisting of the need for total parenteral nutrition (TPN), osteoarthritis, rheumatoid arthritis, angina, chronic bronchitis, chronic obstructive pulmonary disease (COPD), influenza, acute respiratory distress syndrome (ARDS), and diabetes. 27. A method of treating a subject having an adverse health condition that is responsive to L-cysteine administration, said method comprising: parenterally administering to said subject a parenteral composition comprising a mixture comprising a stable L-cysteine composition, wherein said stable L-cysteine composition contributes to said parenteral composition: a therapeutically effective amount of L-cysteine or a pharmaceutically acceptable salt thereof and/or hydrate thereof; per Liter of said stable L-cysteine composition, not more than 150 mcg of Aluminum; cystine relative to L-cysteine not more than about 2.0 wt %; and, pyruvic acid relative to L-cysteine not more than about 2.0 wt %. 28. A total parenteral nutritional composition comprising a mixture of: a stable L-cysteine composition, wherein said stable L-cysteine composition contributes to said total parenteral nutritional composition: L-cysteine or a pharmaceutically acceptable salt thereof and/or hydrate thereof; per Liter of said stable L-cysteine composition, from about 10 mcg to about 250 mcg of Aluminum; cystine in an amount from about 0.001 wt % to about 2.0 wt % relative to L-cysteine; pyruvic acid in an amount from about 0.001 wt % to about 2.0 wt % relative to L-cysteine; one or more amino acids selected from the group consisting of: leucine, isoleucine, lysine, valine, phenylalanine, histidine, threonine, methionine, tryptophan, alanine, arginine, glycine, proline, serine, and tyrosine; and, a pharmaceutically acceptable carrier, comprising water. 29. The total parenteral nutritional composition of claim 28, wherein the amount of L-Cysteine is from about 15 mg to about 40 mg per gram of said amino acids. 30. The total parenteral nutritional composition of claim 28, comprising said L-Cysteine from about 20 mg/mL to about 80 mg/mL of said parenteral nutritional composition.