US2018072769A1PendingUtilityA1

Virus filtration

36
Assignee: ALEXION PHARMA INCPriority: Mar 23, 2015Filed: Mar 23, 2016Published: Mar 15, 2018
Est. expiryMar 23, 2035(~8.7 yrs left)· nominal 20-yr term from priority
Inventors:Bianca OlsonSaravanamoorthy RajendranRyan Tedstone
C07K 1/34B01D 71/10B01D 2311/04B01D 71/34C07K 16/18B01D 69/08B01D 71/56B01D 71/68B01D 61/58B01D 2311/18C07K 2317/24C07K 16/065
36
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Claims

Abstract

Provided herein are methods of performing viral filtration on a fluid including a recombinant antibody, and the use of these methods in methods of manufacturing or producing the recombinant antibody.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A method of performing viral filtration, the method comprising:
 (a) adjusting the pH of a fluid comprising a recombinant antibody to between about 5.0 and about 6.7; and   (b) flowing the fluid through a virus filter to produce a filtrate comprising the recombinant antibody.   
     
     
         2 . The method of  claim 1 , wherein (a) comprises adjusting the pH of the fluid to between about 5.0 and about 6.5. 
     
     
         3 . The method of  claim 2 , wherein (a) comprises adjusting the pH of the fluid to between about 5.0 and about 6.0. 
     
     
         4 . The method of  claim 3 , wherein (a) comprises adjusting the pH of the fluid to between about 5.5 and about 6.0. 
     
     
         5 . The method of any one of  claims 1 - 4 , further comprising, prior to (b):
 adding a stabilizing agent to the fluid in an amount sufficient to yield a final concentration of between about 0.1 mM and about 25 mM stabilizing agent in the fluid.   
     
     
         6 . The method of  claim 5 , wherein adding the stabilizing agent to the fluid yields a final concentration of between about 0.1 mM and about 24 mM stabilizing agent in the fluid. 
     
     
         7 . The method of  claim 6 , wherein adding the stabilizing agent to the fluid yields a final concentration of between about 0.1 mM and about 22 mM stabilizing agent in the fluid. 
     
     
         8 . The method of  claim 7 , wherein adding the stabilizing agent to the fluid yields a final concentration of between about 0.1 mM and about 20 mM stabilizing agent in the fluid. 
     
     
         9 . The method of  claim 8 , wherein adding the stabilizing agent to the fluid yields a final concentration of between about 0.1 mM and about 10 mM stabilizing agent in the fluid. 
     
     
         10 . The method of  claim 9 , wherein adding the stabilizing agent to the fluid yields a final concentration of between about 0.1 mM and about 5 mM stabilizing agent in the fluid. 
     
     
         11 . The method of any one of  claims 1 - 10 , further comprising, immediately prior to (b): flowing the fluid through a pre-filter. 
     
     
         12 . The method of  claim 11 , wherein the pre-filter comprises a polyamide membrane. 
     
     
         13 . The method of  claim 11 , wherein the pre-filter is a depth filter. 
     
     
         14 . The method of  claim 13 , wherein the depth filter comprises a porous filtration medium that is anionic and/or hydrophobic. 
     
     
         15 . The method of any one of  claims 11 - 14 , wherein the fluid further comprises between about 5 mM and about 300 mM sodium chloride. 
     
     
         16 . The method of  claim 15 , wherein the fluid comprises between about 50 mM and about 300 mM sodium chloride. 
     
     
         17 . The method of  claim 16 , wherein fluid comprises between about 100 mM and about 300 mM sodium chloride. 
     
     
         18 . The method of  claim 17 , wherein the fluid comprises between about 100 mM and about 250 mM sodium chloride. 
     
     
         19 . A method of performing viral filtration, the method comprising:
 (a) adding a stabilizing agent to a fluid comprising a recombinant antibody in an amount sufficient to yield a final concentration of between about 10 mM and about 100 mM stabilizing agent in the fluid, wherein prior to adding, the fluid has a pH of between about 6.7 and about 8.5; and   (b) flowing the fluid through a virus filter to produce a filtrate comprising the recombinant antibody.   
     
     
         20 . The method of  claim 19 , wherein prior to adding, the fluid has a pH of between about 7.0 and about 7.8. 
     
     
         21 . The method of  claim 20 , wherein prior to adding, the fluid has a pH of between about 7.4 and about 7.8. 
     
     
         22 . The method of  claim 21 , wherein prior to adding, the fluid has a pH of about 7.6. 
     
     
         23 . The method of any one of  claims 19 - 22 , wherein adding the stabilizing agent to the fluid yields a final concentration of between about 10 mM and about 90 mM stabilizing agent in the fluid. 
     
     
         24 . The method of  claim 23 , wherein adding the stabilizing agent to the fluid yields a final concentration of between about 10 mM and about 80 mM stabilizing agent in the fluid. 
     
     
         25 . The method of  claim 24 , wherein adding the stabilizing agent to the fluid yields a final concentration of between about 10 mM and about 70 mM stabilizing agent in the fluid. 
     
     
         26 . The method of  claim 25 , wherein adding the stabilizing agent to the fluid yields a final concentration of between about 10 mM and about 60 mM stabilizing agent in the fluid. 
     
     
         27 . The method of  claim 26 , wherein adding the stabilizing agent to the fluid yields a final concentration of between about 10 mM and about 50 mM stabilizing agent in the fluid. 
     
     
         28 . The method of  claim 27 , wherein adding the stabilizing agent to the fluid yields a final concentration of between about 15 mM and about 50 mM stabilizing agent in the fluid. 
     
     
         29 . The method of  claim 28 , wherein adding the stabilizing agent to the fluid yields a final concentration of between about 20 mM and about 50 mM stabilizing agent in the fluid. 
     
     
         30 . The method of any one of  claims 19 - 29 , further comprising: further comprising, immediately prior to (b):
 flowing the fluid through a pre-filter.   
     
     
         31 . The method of  claim 30 , wherein the pre-filter comprises a polyamide membrane. 
     
     
         32 . The method of  claim 30 , wherein the pre-filter is a depth filter. 
     
     
         33 . The method of  claim 32 , wherein the pre-filter comprises a porous filtration medium that is anionic and/or hydrophobic. 
     
     
         34 . The method of any one of  claims 19 - 33 , wherein the fluid comprises between about 1 mM and about 100 mM sodium chloride. 
     
     
         35 . The method of  claim 34 , wherein the fluid comprises between about 1 mM and about 80 mM sodium chloride. 
     
     
         36 . The method of any one of  claims 5 - 35 , wherein the stabilizing agent is selected from the group consisting of arginine, alanine, aspartic acid, glutamic acid, leucine, lysine, histidine, glycine, sucrose, trehalose, mannitol, and sorbitol. 
     
     
         37 . The method of  claim 36 , wherein the stabilizing agent is arginine. 
     
     
         38 . The method of  claim 37 , wherein the arginine is L-arginine HCl or L-arginine. 
     
     
         39 . The method of any one of  claims 1 - 38 , wherein the virus filter comprises a polyethersulfone membrane. 
     
     
         40 . The method of any one of  claims 1 - 38 , wherein the virus filter comprises a polyvinylidene fluoride (PVDF) membrane. 
     
     
         41 . The method of  claim 40 , wherein the PVDF membrane is a hollow fiber membrane. 
     
     
         42 . The method of any one of  claims 1 - 38 , wherein the virus filter comprises a cuprammonium-regenerated cellulose membrane. 
     
     
         43 . The method of  claim 42 , wherein the cuprammonium-regenerated cellulose membrane is a hollow fiber membrane. 
     
     
         44 . The method of any one of  claims 1 - 43 , wherein prior to (a), the fluid comprises between about 0.1 mg/mL and about 25 mg/mL recombinant antibody. 
     
     
         45 . The method of  claim 44 , wherein prior to (a), the fluid comprises between about 0.1 mg/mL and about 15 mg/mL recombinant antibody. 
     
     
         46 . The method of  claim 45 , wherein prior to (a), the fluid comprises between about 1 mg/mL and about 15 mg/mL recombinant antibody. 
     
     
         47 . The method of  claim 46 , wherein prior to (a), the fluid comprises between about 5 mg/mL and about 15 mg/mL recombinant antibody. 
     
     
         48 . The method of any one of  claims 1 - 18 , wherein prior to (a), the pH of the fluid is between about 7.4 and about 7.8. 
     
     
         49 . The method of  claim 48 , wherein, prior to (a), the pH of the fluid is between about 7.5 and about 7.7. 
     
     
         50 . The method of  claim 49 , wherein, prior to (a), the pH of the fluid is about 7.6. 
     
     
         51 . The method of any one of  claims 19 - 35 , wherein the fluid has a pH of between about 7.4 and about 7.8. 
     
     
         52 . The method of  claim 51 , wherein the fluid has a pH of between about 7.5 and about 7.7. 
     
     
         53 . The method of  claim 52 , wherein the fluid has a pH of about 7.6. 
     
     
         54 . The method of any one of  claims 1 - 14  and  19 - 33 , wherein the fluid comprises between about 55 mM and about 90 mM sodium chloride. 
     
     
         55 . The method of  claim 54 , wherein the fluid comprises about 65 mM sodium chloride. 
     
     
         56 . The method of any one of  claims 1 - 55 , wherein the recombinant antibody comprises one or both of:
 a heavy chain variable domain that comprises a total of between one and six histidines in the set of CDR1, CDR2, and CDR3; and   a light chain variable domain that comprises a total of between one and six histidines in the set of CDR1, CDR2, and CDR3.   
     
     
         57 . The method of  claim 56 , wherein the recombinant antibody comprises a heavy chain variable domain that comprises a total of between one and five histidines in the set of CDR1, CDR2, and CDR3. 
     
     
         58 . The method of  claim 57 , wherein the recombinant antibody comprises a heavy chain variable domain that comprises a total of between one and three histidines in the set of CDR1, CDR2, and CDR3. 
     
     
         59 . The method of  claim 58 , wherein the recombinant antibody comprises a heavy chain variable domain that comprises a total of two histidines in the set of CDR1, CDR2, and CDR3. 
     
     
         60 . The method of  claim 59 , wherein the CDR1 comprises one histidine residue and the CDR2 comprises one histidine residue. 
     
     
         61 . The method of any one of  claims 56 - 60 , wherein the CDR1 comprises a sequence of SEQ ID NO: 1. 
     
     
         62 . The method of any one of  claims 56 - 61 , wherein the CDR2 comprises a sequence of SEQ ID NO: 2. 
     
     
         63 . The method of any one of  claims 56 - 62 , wherein the CDR3 comprises a sequence of SEQ ID NO: 3. 
     
     
         64 . The method of any one of  claims 56 - 62 , wherein the heavy chain variable domain comprises a sequence of SEQ ID NO: 4. 
     
     
         65 . The method of any one of  claims 56 - 64 , wherein the recombinant antibody comprises a heavy chain comprising a sequence of SEQ ID NO: 5. 
     
     
         66 . The method of any one of  claims 56 - 65 , wherein the recombinant antibody comprises a light chain variable region comprising a CDR1 comprising a sequence of SEQ ID NO: 6, a CDR2 comprising a sequence of SEQ ID NO: 7, and a CDR3 comprising a sequence of SEQ ID NO: 8. 
     
     
         67 . The method of any one of  claims 56 - 66 , wherein the recombinant antibody comprises a light chain variable region comprising a sequence of SEQ ID NO: 9. 
     
     
         68 . The method of any one of  claims 56 - 67 , wherein the recombinant antibody comprises a light chain comprising a sequence of SEQ ID NO: 10. 
     
     
         69 . The method of any one of  claims 1 - 55 , wherein the recombinant antibody comprises a heavy chain variable domain comprising a CDR1 comprising a sequence of SEQ ID NO: 11, a CDR2 comprising a sequence of SEQ ID NO: 12, and a CDR3 comprising a sequence of SEQ ID NO: 13. 
     
     
         70 . The method of  claim 69 , wherein the heavy chain variable domain comprises a sequence of SEQ ID NO: 14. 
     
     
         71 . The method of  claim 69  or  70 , wherein the recombinant antibody comprises a heavy chain comprising a sequence of SEQ ID NO: 15. 
     
     
         72 . The method of any one of  claims 69 - 71 , wherein the recombinant antibody comprises a light chain variable domain comprising a CDR1 comprising a sequence of SEQ ID NO: 16, a CDR2 comprising a sequence of SEQ ID NO: 17, and a CDR3 comprising a sequence of SEQ ID NO: 18. 
     
     
         73 . The method of any one of  claims 69 - 72 , wherein the light chain variable domain comprises a sequence of SEQ ID NO: 19. 
     
     
         74 . The method of any one of  claims 69 - 73 , wherein the recombinant antibody comprises a light chain comprising a sequence of SEQ ID NO: 20. 
     
     
         75 . The method of any one of  claims 1 - 74 , wherein the recombinant antibody specifically binds to human complement protein C5.

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