High concentration anti-c5 antibody formulations
AssigneeAlexion Pharmaceuticals, Inc.
InventorsStephan ORTIZ, Jillian GENTILE, Leena PHILOMINATHAN, Eric ROUTHIER, Bruce MASON
Life of this patent
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Abstract
The present disclosure relates to stable aqueous solutions comprising a high concentration of an anti-C5 antibody (e.g., ravulizumab) and methods for preparing the solutions. The disclosure also provides methods for treating or preventing complement-associated disorders, such as paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS), using the solutions. Also featured were therapeutic kits containing one or more of the solutions and a means for administering the solutions to a patient in need such a treatment.
Claims23
A stable aqueous solution comprising:
- (a) an anti-C5 antibody at a concentration of about 100 mg/mL, wherein the anti-C5 antibody comprises a heavy chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:19, a heavy chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:18, a heavy chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:3, a light chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:4, a light chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:5, and a light chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:6;
- (b) about 50 mM Phosphate Buffer;
- (c) about 5% sucrose;
- and
- (d) about 25 mM Arginine.
A stable aqueous solution comprising:
- (a) an anti-C5 antibody, wherein the anti-C5 antibody comprises a heavy chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:19, a heavy chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:18, a heavy chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:3, a light chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:4, a light chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:5, and a light chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:6;
- (b) about 50 mM Phosphate Buffer;
- (c) about 5% sucrose;
- (d) about 0.05% Polysorbate 80;
- and
- (e) about 25 mM Arginine.
15-20. (canceled)
(canceled)
A method for producing a stable concentrated antibody solution comprising an anti-C5 antibody comprising a heavy chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:23, a heavy chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:19, a heavy chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:3, a light chain CDR1 comprising the amino acid sequence depicted in SEQ ID NO:4, a light chain CDR2 comprising the amino acid sequence depicted in SEQ ID NO:5, and a light chain CDR3 comprising the amino acid sequence depicted in SEQ ID NO:6, at a concentration of 100 mg/mL, 50 mM Phosphate Buffer, 5% sucrose;
- and 25 mM Arginine, the method comprising:
- i) providing a first aqueous solution comprising the anti-C5 antibody, the first aqueous solution having a first formulation and comprising no more than 10 mg/mL of the anti-C5 antibody;
- ii) subjecting the first aqueous solution to diafiltration into a formulation comprising 50 mM Phosphate Buffer, 5% sucrose, and 25 mM Arginine, at pH 7.4 to thereby produce a second aqueous solution, wherein the second aqueous solution has a second formulation as a result of the diafiltration;
- and
- iii) concentrating the second aqueous solution to produce a stable concentrated antibody solution comprising 100 mg/mL of the anti-C5 antibody, 50 mM Phosphate Buffer, 5% sucrose;
- and 25 mM Arginine.
26-29. (canceled)
(canceled)
Dependencies are inferred from the claim text.