Botulinum toxin pharmaceutical compositions formulated with recombinant albumin
A botulinum toxin pharmaceutical composition comprising a botulinum toxin and a non-pasteurized recombinant albumin. In some embodiments, the pharmaceutical composition comprises a reduced amount of recombinant albumin aggregates.
1 . A pharmaceutical composition comprising a botulinum toxin and a non-pasteurized recombinant albumin.
2 . The pharmaceutical composition of claim 1 , wherein the recombinant albumin has been incubated at about 30° C. for about 14 days.
3 . The pharmaceutical composition of claim 1 , wherein the recombinant albumin has been incubated at about 57° C. for about 50 hours.
4 . The pharmaceutical composition of claim 1 , wherein the botulinum toxin is present as a botulinum toxin complex.
5 . The pharmaceutical composition of claim 1 , wherein the botulinum toxin is present as a pure botulinum toxin.
6 . The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition has an enhanced potency.
7 . The pharmaceutical composition of claim 1 , wherein the botulinum toxin is selected from the group consisting of botulinum toxins types A, B, C 1 , D, E, F and G.
8 . A pharmaceutical composition, comprising:
(a) a botulinum toxin, and;
(b) a recombinant albumin, wherein less than 9% of the recombinant albumin is in an aggregate form.
9 . The pharmaceutical composition of claim 8 , wherein less than 5% of the recombinant albumin is in an aggregate form.
10 . The pharmaceutical composition of claim 8 , wherein less than 4% of the recombinant albumin is in an aggregate form.
11 . The pharmaceutical composition of claim 8 , wherein about 2% of the recombinant albumin is in an aggregate form.
12 . The pharmaceutical composition of claim 8 , wherein the botulinum toxin is present as a botulinum toxin complex.
13 . The pharmaceutical composition of claim 8 , wherein the botulinum toxin is present as a pure botulinum toxin.
14 . The pharmaceutical composition of claim 8 , wherein the pharmaceutical composition has an enhanced potency or stability.
15 . The pharmaceutical composition of claim 8 , wherein the botulinum toxin is selected from the group consisting of botulinum toxin types A, B, C, D, E, F and G.
16 . The pharmaceutical composition of claim 8 , wherein the recombinant albumin is non-pasteurized.
17 . A pharmaceutical composition comprising a botulinum toxin and a non-pasteurized recombinant albumin, wherein less than 5% of the recombinant albumin is in an aggregate form.
18 . The pharmaceutical composition of claim 17 , wherein about 2% of the recombinant albumin is in an aggregate form.
19 . A process for making a pharmaceutical composition in a form for reconstitution, the process comprising the steps of:
(a) culturing a Clostridium botulinum bacterium;
(b) cultivating the Clostridium botulinum bacterium;
(c) fermenting the Clostridium botulinum bacterium in a fermentation medium;
(d) harvesting a botulinum toxin from the Clostridium botulinum;
(e) purifying the botulinum toxin; and
(f) compounding the botulinum toxin with a recombinant albumin, wherein the compounding step results in a solid pharmaceutical composition in a form for reconstitution.
20 . The process of claim 19 , wherein the compounding step (f) includes compounding the botulinum toxin and the recombinant albumin with at least one ingredient selected form the group consisting of a sodium chloride, an octanoate, an N-acetyltryptophan, a zinc chloride, and a polysorbate.
21 . The process of claim 19 , wherein the compounding step (f) includes compounding the botulinum toxin and the recombinant albumin with a sodium chloride, octanoate, and polysorbate.
22 . The process of claim 21 , wherein for every 100 units of botulinum toxin, there is about 400-600 ug of recombinant albumin, about 10-16 ug of octanoate, and about 0.01-0.07 ug of polysorbate.
23 . The process of claim 21 , wherein for every 100 units of botulinum toxin, there is about 450-550 ug of recombinant albumin, about 12-14 ug of octanoate, and about 0.03-0.05 ug of polysorbate.
24 . The process of claim 21 , wherein for every 100 units of botulinum toxin, there is about 500 ug of recombinant albumin, about 13 ug of octanoate, and about 0.04 ug of polysorbate.
25 . The process of claim 19 , wherein the botulinum toxin is present as a botulinum toxin complex.
26 . The process of claim 19 , wherein the botulinum toxin is present as a pure botulinum toxin.
27 . The process of claim 19 , wherein the pharmaceutical composition has an enhanced potency or stability.
28 . The process of claim 19 , wherein the botulinum toxin is selected from the group consisting of botulinum toxins types A, B, C 1 , D, E, F and G.
29 . The process of claim 19 , wherein the recombinant albumin is non-pasteurized.
30 . The process of claim 19 , 20 , 21 , 22 , 23 or 24 , wherein less than 5% of the recombinant albumin is in an aggregate form.
31 . The process of claim 19 , 20 , 21 , 22 , 23 or 24 , further comprising a step of
(g) drying compounded composition of step (f).
32 . The process of claim 31 , wherein the drying comprises vacuum-drying.
33 . The process of claim 31 , wherein the drying comprises freeze-drying (lyophilization or freeze drying).
34 . The process of claim 31 , wherein the drying comprises lyophilization.
35 . A pharmaceutical composition made by the process of claim 19 .
36 . A pharmaceutical composition made by the process of claim 31 .
37 . The pharmaceutical composition of claim 1 , 8 or 17 wherein the composition is in a dry state.
38 . The pharmaceutical composition of claim 1 , 8 or 17 wherein the composition is in a dry state due to vacuum-drying.
39 . The pharmaceutical composition of claim 1 , 8 or 17 wherein the composition is in a dry state due to freeze-drying.
40 . The pharmaceutical composition of claim 1 , 8 or 17 wherein the composition is in a dry state due to lyophilization.