Pathogen-inactivated red blood cell compositions
The present invention provides pathogen-inactivated red blood cell compositions suitable for infusion into a subject.
1. A composition comprising:
(a) red blood cells, wherein the red blood cells have covalently reacted with an electrophilic group of a pathogen-inactivating compound;
(b) a quencher comprising a thiol group that is capable of reacting with the pathogen inactivating compound; and
(c) a final additive solution;
wherein the red blood cells have a Median Corpuscular Fragility value greater than 150 mOsm after 35 days at 4° C., wherein the red blood cells have a Packed Cell Volume of greater than 50%, and wherein the composition is suitable for infusion into a subject.
2. The composition of claim 1 , wherein the electrophilic group is selected from the group consisting of a mustard, a mustard intermediate, and a mustard equivalent.
3. The composition of claim 1 , wherein the electrophilic group comprises an aziridine, an aziridinium ion, a mono- or bis-(haloethyl)amine, a mono- or bis-(mesylethyl)amine, or a mono- or bis-(tosylethyl)amine.
4. The composition of claim 1 , wherein the electrophilic group has covalently reacted with the cell surface of the red blood cells.
5. The composition of claim 1 , wherein the pathogen-inactivating compound is β-alanine, N-(acridin-9-yl), 2-[bis(2-chloroethyl)amino]ethyl ester.
6. The composition of claim 1 , wherein the quencher comprises cysteine or a derivative of cysteine.
7. The composition of claim 6 , wherein the quencher is glutathione or a pharmaceutically acceptable salt thereof.
8. The composition of claim 1 , wherein the quencher is at a concentration of less than about 10 mM.
9. The composition of claim 1 , wherein the quencher is at a concentration of less than about 8 mM.
10. The composition of claim 1 , wherein the quencher is at a concentration of less than about 6 mM.
11. The composition of claim 1 , wherein the red blood cells have a Packed Cell Volume of greater than 55%.
12. The composition of claim 11 , wherein the red blood cells have a Packed Cell Volume of greater than 60%.
13. The composition of claim 1 , wherein the red blood cells have an average antibody binding capacity (ABC) of less than about 50,000.
14. The composition of claim 13 , wherein the red blood cells have an average antibody binding capacity (ABC) of less than about 40,000.
15. The composition of claim 1 , wherein the red blood cells have an average antibody binding capacity (ABC) of between about 25,000 and 70,000.
16. The composition of claim 15 , wherein the red blood cells have an average antibody binding capacity (ABC) of between about 35,000 and 45,000.
17. The composition of claim 1 , wherein the final additive solution comprises one or more of sodium chloride, adenine, glucose, and mannitol.
18. The composition of claim 17 , wherein the final additive solution further comprises phosphate.
19. The composition of claim 17 , wherein the final additive solution further comprises citrate.
20. The composition of claim 1 , further comprising one or more degradation products of the pathogen-inactivating compound.
21. The composition of claim 20 , wherein the one or more degradation products of the pathogen-inactivating compound comprise one or more hydrolysis products of the pathogen-inactivating compound.
22. The composition of claim 20 , wherein the one or more degradation products of the pathogen-inactivating compound comprise an acridine.
23. The composition of claim 1 , wherein the final additive solution is an additive solution selected from the group consisting of AS-1, AS-3, SAG-M, Erythrosol, AS-5, PAGGS-M, and MAP.
24. The composition of claim 1 , wherein the red blood cells have a Median Corpuscular Fragility value greater than 150 mOsm after 42 days at 4° C.
25. The composition of claim 7 , wherein the quencher is glutathione monosodium salt.
26. The composition of claim 1 , wherein the pathogen-inactivating compound is β-alanine, N-(acridin-9-yl), 2-[bis(2-chloroethyl)amino]ethyl ester, and wherein the quencher is glutathione monosodium salt.
27. The composition of claim 26 , further comprising an acridine degradation product of the pathogen-inactivating compound.