Claims for Patent: 10,273,444

Summary for Patent: 10,273,444

Title:	Lysis/resealing process and device for incorporating an active ingredient, in particular asparaginase or inositol hexaphosphate, in erythrocytes
Abstract:	A lysis/resealing process for preparing erythrocytes containing active ingredient is provided comprising placing a globular concentrate in suspension in an isotonic solution having a haematocrit level which is equal to or greater than 65%, with refrigeration at 1 to 8.degree. C.; measuring the osmotic fragility based on a sample of erythrocytes from that same globular concentrate, preferably on a sample of the suspension; lysis and internalization procedure of the active ingredient, inside the same chamber, at a temperature maintained at 1 to 8.degree. C., comprising allowing the erythrocyte suspension having a haematocrit level equal to or greater than 65% and a hypotonic lysis solution which is refrigerated at 1 to 8.degree. C., to circulate in a dialysis cartridge; the lysis parameters being adjusted in accordance with the osmotic fragility previously measured; and resealing in a second chamber at a temperature of from 30 to 40.degree. C. by means of a hypertonic solution.
Inventor(s):	Godfrin; Yann (Lyons, FR)
Assignee:	ERYTECH PHARMA (Lyons, FR)
Application Number:	14/089,834
Patent Claims:	1. A lysis and resealing device for preparing erythrocytes which contain an active ingredient, wherein the device comprises a first container and a second container, wherein the first container may be cooled and contains in its internal space a first pouch which can contain an erythrocyte suspension, the lysis device further comprising a dialysis cartridge and a first tube connecting said dialysis cartridge, at one side, to a lysis solution and a second tube connecting said dialysis cartridge, at the other side, to the first pouch, and a pump which can cooperate with said second tube and cause the erythrocyte suspension to circulate from the pouch towards and through the cartridge, wherein the first container maintains the temperature at from +1 to +8.degree. C. in the internal space containing the first pouch, and wherein the second container contains a second pouch in its internal space and maintains the temperature at from +30 to +40.degree. C. in the internal space containing the second pouch; wherein the device comprises a computer which can control the lysis process and the resealing process in accordance with instructions which are input by a device operator, or in accordance with data input by the operator, with reference to the osmotic fragility, the computer being configured in order to establish and adjust the lysis parameters, selected from the flow rate of the erythrocyte suspension, the osmolarity of the lysis solution and both; wherein said computer is connected to the temperature sensors to allow the temperature in the modules and/or at the temperature sensor for the erythrocyte suspension to be controlled; and wherein said computer controls and operates the pumps to control the pressure and flow rate of the suspension through the dialysis cartridge. 2. The lysis and resealing device of claim 1, comprising pumps P1, P2 and P3 and wherein the computer receives, firstly, information from temperature probes, pressure probes and detection devices and, secondly, information relating to the adjustments of the lysis parameters; wherein based on said first and second information, the computer controls pumps P1, P2 and P3; and wherein pump P2 causes fluid to move from the first pouch to the dialysis cartridge, which cartridge is in fluid communication with the second pouch. 3. The lysis and resealing device of claim 2, wherein pumps P1 and P3 have a constant, predetermined flow rate and pump P2 is controlled by the computer in order to cause the flow rate to be varied. 4. The lysis and resealing device of claim 2, wherein the computer controls the temperatures of the first and second containers. 5. A lysis and resealing device for preparing erythrocytes which contain an active ingredient, wherein the device comprises a first container and a second container, wherein the first container may be cooled and contains in its internal space a first pouch which can contain an erythrocyte suspension, the lysis device further comprising a dialysis cartridge and a first tube connecting said dialysis cartridge, at one side, to a lysis solution and a second tube connecting said dialysis cartridge, at the other side, to the first pouch, and a pump which can cooperate with said second tube and cause the erythrocyte suspension to circulate from the pouch towards and through the cartridge, wherein the first container maintains the temperature at from +1 to +8.degree. C. in the internal space containing the first pouch, wherein the device comprises an electronic device for electronically adjusting the flow rate of the erythrocyte suspension through the dialysis cartridge and/or electronically adjusting the osmolarity of the lysis solution as a function of the osmotic fragility of the erythrocytes to be processed that are present in the first pouch, said electronic device receiving instructions input into the device, or data input into the device, as a function of the osmotic fragility, wherein the second container contains a second pouch in its internal space and maintains the temperature at from +30 to +40.degree. C. in the internal space containing the second pouch, and wherein said electronic device also controls the temperature and said pump; wherein the device comprises a computer which can control the lysis process and the resealing process in accordance with instructions which are input by a device operator, or in accordance with data input by the operator, with reference to the osmotic fragility, the computer being configured in order to establish and adjust the lysis parameters, selected from the flow rate of the erythrocyte suspension, the osmolarity of the lysis solution and both; wherein said computer is connected to the temperature sensors to allow the temperature in the modules and/or at the temperature sensor for the erythrocyte suspension to be controlled; and wherein said computer controls and operates the pumps to control the pressure and flow rate of the suspension through the dialysis cartridge. 6. The device according to claim 5, wherein the first pouch is provided with a tube which is connected to the first pouch at the two ends thereof and the first container comprises a pump which can co-operate with that tube and bring about circulation of the contents of the first pouch to and from said first pouch. 7. The device according to claim 5, wherein a tube for injecting the active ingredient is connected to the tube which connects the first pouch to the blood inlet of the dialysis cartridge, the cartridge is connected by a tube to a flask which can contain the lysis solution, and the first container is configured to receive said flask and a pump which can co-operate with the tube in order to cause the lysis solution to circulate towards and through the dialysis cartridge; and the blood outlet of the dialysis cartridge is connected to a tube which opens, or which may open, outside the first container. 8. The device according to claim 7, wherein the tube which opens, or which may open, outside the first container chamber is connected to the second pouch which can collect the erythrocyte suspension which is discharged from the lysis, as well as a resealing solution. 9. The device according to claim 5, wherein said pump which causes the erythrocyte suspension to circulate from the first pouch towards and through the cartridge is electronically controlled to adjust the flow rate. 10. The device according to claim 5, wherein a tube for injecting the active ingredient is connected to the rube which connects the first pouch to the erythrocyte suspension inlet of the dialysis cartridge. 11. The device according to claim 5, wherein the dialysis cartridge is connected by a tube to a flask which can contain the lysis solution, and the refrigerated first container can receive that flask and a pump which can co-operate with the tube in order to cause the lysis solution to circulate towards and through the dialysis cartridge. 12. The device according to claim 5, wherein the first container is capable of maintaining a temperature of from +2 to +6.degree. C. in its internal space. 13. The device according to claim 5, wherein the blood outlet of the dialysis cartridge is connected to an outlet tube which opens, or which may open, outside the first container and a tube for injecting the active ingredient is connected to that outlet tube. 14. The device according to claim 5, wherein the first container is configured to control the pump which conveys the erythrocyte suspension towards the dialysis cartridge. 15. The device according to claim 5, wherein the first container is configured to control the osmolarity of a lysis solution, either in order to dilute and lower the osmolarity, or to increase that osmolarity by a suitable solute being introduced. 16. The device according to claim 5, wherein the lysis process may be controlled electronically and wherein optionally the resealing process may be controlled electronically, and wherein both processes may be controlled in accordance with instructions which are input by the operator, or in accordance with data input by the operator, with reference to the osmotic fragility. 17. The device according to claim 16, further comprising temperature sensors which allow the temperature in the first and second containers and/or at the temperature sensor for the erythrocyte suspension to be controlled. 18. The device according to claim 5, wherein said active ingredient is asparaginase. 19. The device according to claim 5, wherein said active ingredient is inositol phosphate.

Details for Patent 10,273,444

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Recordati Rare Diseases, Inc.	ELSPAR	asparaginase	For Injection	101063	01/10/1978		2024-08-05