Pharmaceutical compositions of mosunetuzumab and methods of use
The disclosure provides pharmaceutical compositions comprising mosunetuzumab and methods of using the same.
1. A pharmaceutical composition comprising about 1 mg/ml mosunetuzumab, about 10 mM L-histidine, about 240 mM sucrose, about 0.06% (w/v) PS20, and about 10 mM methionine, wherein the pharmaceutical composition has a pH of about 5.8.
2. The pharmaceutical composition of claim 1 , wherein
the pharmaceutical composition is in a unit dosage form.
3. The pharmaceutical composition of claim 1 , wherein mosunetuzumab has a methionine at position 257 of the Fc region (EU numbering), and wherein oxidation of the methionine at position 257 of the Fc region is less than about 10% over two weeks at 40° C.
4. The pharmaceutical composition of claim 2 , wherein the unit dosage form is a liquid formulation for dilution.
5. The pharmaceutical composition of claim 4 , wherein
the liquid formulation for dilution is supplied in a container having a volume of about 50 ml.
6. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition:
(a) has a shelf-life of at least 36 months when stored at 5° C.±3° C. and protected from light;
(b) is stable through one or more freeze-thaw cycles;
(c) is stable for about two weeks or longer at about 25° C.; or
(d) is stable for about 48 months or longer at −20° C.
7. The pharmaceutical composition of claim 6 , wherein stability is assessed by size-exclusion high-performance liquid chromatography (SE-HPLC) or by non-reduced capillary electrophoresis sodium dodecyl sulfate (CE-SDS) assay.
8. The pharmaceutical composition of claim 7 , wherein:
(a) the pharmaceutical composition is determined to be stable if the pharmaceutical composition maintains a purity that is changed by less than 5% as measured by SE-H PLC;
(b) the pharmaceutical composition has a purity of about 85% or higher as assessed by SE-HPLC;
(c) the purity of the pharmaceutical composition as assessed by SE-HPLC is maintained about the same for about 36 months or longer at about 5° C.;
(d) the pharmaceutical composition is determined to be stable if the pharmaceutical composition maintains a purity that is changed by less than 5% as measured by non-reduced CE-SDS assay;
(e) the pharmaceutical composition has a purity of about 75% or higher as assessed by non-reduced CE-SDS assay; or
(f) the purity of the pharmaceutical composition as assessed by non-reduced CE-SDS assay is maintained for about 36 months or longer at about 5° C.
9. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated for administration by infusion after dilution with a normal saline solution comprising 0.45% or 0.9% NaCl.
10. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition further comprises histidine acetate.
11. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated as a drug product (DP).
12. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition is formulated for intravenous administration.
13. The pharmaceutical composition of claim 12 , wherein the pharmaceutical composition is formulated for administration by infusion.
14. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition does not contain a preservative.
15. The pharmaceutical composition of claim 4 , wherein the volume of the liquid formulation for dilution is between 20-40 ml.
16. The pharmaceutical composition of claim 1 , wherein the pharmaceutical composition comprises no more than 1,000 particles having a diameter ≥2 μm per ml as detected by high accuracy liquid particle counting (HIAC).
17. The pharmaceutical composition of claim 4 , wherein the volume of the liquid formulation for dilution is between 0.2-2 ml.