Formulations of single domain antigen binding molecules
AssigneeWyeth
InventorsJason E. Fernandez, Daniel A. Dixon, Andrea Paulson
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Abstract
The invention relates to formulations of single domain antigen binding molecules, e.g., nanobody molecules, in particular formulations of TNF-binding nanobody molecules. The single domain antigen binding molecules can include one or more single binding domains that interact with, e.g., bind to, one or more target proteins. The formulations are useful, e.g., as pharmaceutical formulations. Method of preparing, and using the formulations described herein, to treat, e.g., TNF-associated disorders, are also disclosed.
Claims30
A formulation comprising:
- (a) a TNF-binding nanobody molecule at a concentration from about 10 mg/mL to about 250 mg/mL;
- (b) a lyoprotectant chosen from sucrose, sorbitol, or trehalose at a concentration of about 5% to about 10%;
- (c) a surfactant chosen from polysorbate-80 or poloxamer-188 at a concentration of about 0.01% to 0.6%;
- and
- (d) a buffer chosen from Histidine buffer at a concentration about 10 to about 20 mM, or a Tris buffer at a concentration about 20 mM such that the pH of the formulation is about 5.0 to 7.5,
- wherein the TNF-binding nanobody molecule in the formulation retains at least about 70% of its binding activity after storage for at least three months at 4° C.
A method or process of preparing a formulation of a TNF-binding nanobody, comprising:
- expressing the TNF-binding nanobody in a cell culture;
- purifying the TNF-binding nanobody by passing the TNF-binding nanobody through at least one of a chromatography purification step, or an ultrafiltration/diafiltration steps;
- adjusting the concentration of the TNF-binding nanobody to about 10 to 250 mg/mL in a formulation containing sucrose at a concentration of about 5% to about 10%;
- polysorbate-80 at a concentration of about 0.01%, 0.02%;
- and a Histidine buffer at a concentration about 10 to about 20 mM or a Tris buffer at a concentration about 20 mM, such that the pH of the formulation is about 5 to 7.5.
A method of preparing a reconstituted formulation containing a TNF-binding nanobody molecule, comprising:
- lyophilizing a mixture of a TNF-binding nanobody molecule and a lyoprotectant, a surfactant, and a buffer, thereby forming a lyophilized mixture;
- and
- reconstituting the lyophilized mixture in a diluent, thereby preparing the formulation, wherein the reconstituted formulation comprises (a) a TNF-binding nanobody molecule at a concentration of about 10 mg/mL to about 130 mg/mL;
- (b) a lyoprotectant selected from the group consisting of sucrose or trehalose at a concentration of about 5% to about 10%;
- (c) polysorbate-80 as the surfactant at a concentration of about 0.01% to 0.02%;
- and (d) a Histidine buffer at a concentration about 10 to about 20 mM, or a Tris buffer at a concentration about 20 mM, such that the pH of the formulation is about 5.0 to 7.5.
Dependencies are inferred from the claim text.