TPP-1 formulations and methods for treating CLN2 disease

1. A formulation comprising non-aggregated recombinant human tripeptidyl peptidase-1 (rhTPP1) for intracerebroventricular, intrathecal, or intraocular administration, wherein the rhTPP1 comprises the amino acid sequence of SEQ ID NO: 1 or a fragment thereof, wherein the formulation comprises rhTPP1 at a concentration of from about 25 mg/mL to about 35 mg/mL, further comprising potassium chloride at a concentration of about 0.01 mg/mL to about 1 mg/mL, magnesium chloride hexahydrate at a concentration of about 0.01 mg/mL to about 1 mg/mL, and calcium chloride dehydrate at a concentration of about 0.01 mg/mL to about 1 mg/mL, and wherein the formulation has a pH of 6.5 and the rhTTP1 is not aggregated.

2. The formulation of claim 1 , further comprising sodium phosphate dibasic heptahydrate at a concentration of about 0.01 mg/mL to about 1 mg/mL, sodium phosphate monobasic monohydrate at a concentration of about 0.01 mg/mL to about 1 mg/mL, and sodium chloride at a concentration of about 1 mg/mL to about 20 mg/mL.

3. The formulation of claim 1 , further comprising sodium phosphate dibasic heptahydrate at a concentration of about 0.11 mg/mL, sodium phosphate monobasic monohydrate at a concentration of about 0.08 mg/mL, sodium chloride at a concentration of about 8.77 mg/mL, potassium chloride at a concentration of about 0.22 mg/mL, magnesium chloride hexahydrate at a concentration of about 0.16 mg/mL, and calcium chloride dehydrate at a concentration of about 0.21 mg/mL.

4. The formulation of claim 1 , wherein the formulation is preservative-free.

5. The formulation of claim 1 , wherein the formulation is stable at about 5° C. for at least 6 months.

6. A kit comprising the formulation of claim 1 and a flushing solution.

7. The kit of claim 6 , wherein the flushing solution comprises sodium phosphate dibasic heptahydrate at a concentration of about 0.11 mg/mL, sodium phosphate monobasic monohydrate at a concentration of about 0.08 mg/mL, sodium chloride at a concentration of about 8.77 mg/mL, potassium chloride at a concentration of about 0.22 mg/mL, magnesium chloride hexahydrate at a concentration of about 0.16 mg/mL, and calcium chloride dihydrate at a concentration of about 0.21 mg/mL.

8. The kit of claim 6 , further comprising a reservoir for implantation and a catheter.

9. The kit of claim 6 , further comprising one or more elements selected from the group consisting of an extension line, an in-line filter, a port needle, a syringe, a syringe needle, and combinations thereof.

10. A method of treating Neuronal Ceroid Lipofuscinosis (CLN2) disease comprising administering the formulation of claim 1 to a subject in need thereof.

11. A method of treating Neuronal Ceroid Lipofuscinosis (CLN2) disease comprising administering the formula of claim 1 to a subject in need thereof at a dose of about 300 mg, wherein the dose is administered to the subject at a rate less than or equal to 75 mg/hour.

12. The method of claim 11 , wherein the formulation, composition or dose is administered every other week.

13. The method of claim 11 , wherein the formulation, composition or dose is administered intracerebroventricularly.

14. The method of claim 11 , wherein the formulation, composition or dose is administered intrathecally.

15. The method of claim 11 , wherein the formulation, composition or dose is administered intraocularly.

16. The method of claim 11 , further comprising administering a flushing solution to the subject following administration of the formulation of claim 1 .

17. The method of claim 16 , comprising administering about 0.5 mL to about 5 mL of the flushing solution to the subject.

18. The method of claim 16 , wherein the flushing solution comprises sodium phosphate dibasic heptahydrate at a concentration of about 0.11 mg/mL, sodium phosphate monobasic monohydrate at a concentration of about 0.08 mg/mL, sodium chloride at a concentration of about 8.77 mg/mL, potassium chloride at a concentration of about 0.22 mg/mL, magnesium chloride hexahydrate at a concentration of about 0.16 mg/mL, and calcium chloride dihydrate at a concentration of about 0.21 mg/mL.

19. A method of treating Neuronal Ceroid Lipofuscinosis (CLN2) disease comprising administering the formulation of claim 1 to a subject in need thereof at a dose of rhTPP1 effective to maintain a physiological function or slow or reduce deterioration of a physiological function in the subject, wherein the physiological function is language function, motor function, vision or feeding function.

20. The method of claim 19 , wherein the dose of rhTTP1 is effective to maintain language function or slow or reduce deterioration of language function in the subject and/or maintain motor function or slow or reduce deterioration of motor function in the subject.

21. The method of claim 20 , wherein the deterioration of language function or motor function is a reduction of at least one point compared to previous rating determined before or during treatment as measured using a Weill Cornell Medical College or Hamburg disease rating scale.

22. The method of claim 19 , wherein the dose of rhTPP1 is effective to maintain vision or slow or reduce deterioration of vision in the subject.

23. The method of claim 22 , wherein the deterioration of vision is a reduction of at least one point compared to baseline as measured using a Hamburg disease rating scale.

24. The method of claim 19 , wherein the dose of rhTPP1 is effective to maintain feeding function or slow or reduce deterioration of feeding function in the subject.

25. The method of claim 24 , wherein the deterioration of feeding function is a reduction of at least one point compared to baseline as measured using the Weill Cornell Medical College disease rating scale.