Virus purification

1. A process for producing a sterile lentiviral vector pharmaceutical composition, the process comprising a filter-sterilisation step and a concentration step, wherein the filter-sterilisation step is not the final step in the production process, wherein the filter-sterilisation step occurs prior to the concentration step, wherein the filter-sterilisation step is performed using a sterilising filter with a maximum pore size of 0.2 μm, wherein the concentration step is performed in aseptic conditions, wherein the lentiviral vector pharmaceutical composition comprises a lentiviral vector derived from Equine infectious anaemia virus (EIAV), wherein the lentiviral vector comprises a nucleotide sequence encoding ATP-binding cassette, sub-family A, member 4 (ABCA4) protein or myosin VIIA (MYO7A) protein, and wherein the lentiviral vector pharmaceutical composition is suitable for ex vivo administration or administration to a patient.

2. The process according to claim 1 , wherein concentration of the lentiviral vector pharmaceutical composition is performed using an ultrafiltration step.

3. The process according to claim 2 , wherein the lentiviral vector comprises a nucleotide sequence encoding ABCA4 protein, and wherein the lentiviral vector pharmaceutical composition is suitable for ex vivo administration or for administration to a patient with Stargardt disease.

4. The process according to claim 2 , wherein the lentiviral vector comprises a nucleotide sequence encoding MYO7A protein, and wherein the lentiviral vector pharmaceutical composition is suitable for ex vivo administration or for administration to a patient with Usher syndrome.

5. The process according to claim 1 , wherein the lentiviral vector is pseudotyped with envelope glycoprotein of Vesicular stomatisis virus (VSV-G).

6. The process according to claim 1 , wherein the lentiviral vector is a non-replicating and/or self-inactivating vector.

7. The process according to claim 1 , wherein the nucleotide sequence encoding ABCA4 protein or MYO7A protein is under control of a cytomegalovirus (CMV) promoter.

8. The process according to claim 1 , wherein a preparation comprising the lentiviral vector is diluted prior to the filter-sterilisation step.

9. A process for producing a sterile bulk lentiviral vector product, the process comprising the following steps (i) to (vi) in chronological order:

(i) culturing cells that produce a lentiviral vector, wherein the lentiviral vector is derived from EIAV, and wherein the lentiviral vector comprises a nucleotide sequence encoding ABCA4 protein or MYO7A protein;

(ii) harvesting the lentiviral vector-containing supernatant;

(iii) optionally clarifying the supernatant;

(iv) purifying the lentiviral vector to give a lentiviral vector preparation;

(v) filter-sterilising the lentiviral vector preparation using a sterilising filter with a maximum pore size of 0.22 μm; and

(vi) concentrating the lentiviral vector preparation using an ultrafiltration step to produce the bulk lentiviral product, wherein step (vi) is performed under aseptic conditions; and wherein step (vi) is the final step in the process;

wherein the lentiviral vector preparation is suitable for ex vivo administration or for administration to a patient.

10. The process according to claim 9 , wherein step (v) is the penultimate step in the process.

11. The process according to claim 9 , wherein the lentiviral vector comprises a nucleotide sequence encoding ABCA4 protein, and wherein the lentiviral vector preparation is suitable for ex vivo administration or for administration to a patient with Stargardt disease.

12. The process according to claim 9 , wherein the lentiviral vector comprises a nucleotide sequence encoding MYO7A protein, and wherein the lentiviral vector preparation is suitable for ex vivo administration or for administration to a patient with Usher syndrome.

13. The process according to claim 9 , wherein the lentiviral vector is pseudotyped with VSV-G.

14. The process according to claim 9 , wherein the lentiviral vector is a non-replicating and/or self-inactivating vector.

15. The process according to claim 9 , wherein the nucleotide sequence encoding ABCA4 protein or MYO7A protein is under control of a CMV promoter.

16. The process according to claim 9 , wherein the lentiviral vector preparation is diluted prior to filter-sterilisation.

17. The process according to claim 9 , wherein step (iii) is performed by filter clarification.

18. The process according to claim 9 , wherein step (iv) is performed using a method or combination of methods selected from chromatography, ultrafiltration/diafiltration, and centrifugation.

19. The process according to claim 9 , wherein step (iv) includes one or more buffer exchange steps.

20. The process according to claim 19 , wherein the buffer exchange comprises exchange of the ultrafiltration/diafiltration retentate with formulation buffer.

21. The process according to claim 9 , wherein a nucleic acid degradation step is carried out at any point up to and including step (iv).