High concentration formulations of anti-C5 antibodies
The present disclosure relates to, inter alia, stable aqueous solutions comprising a high concentration of an antibody that binds to human complement component C5 and methods for preparing the solutions. The disclosure also provides methods for treating or preventing complement-associated disorders (for example, age-related macular degeneration or rheumatoid arthritis) using the solutions. Also featured are therapeutic kits containing one or more of the solutions and a means for administering the solutions to a patient in need such a treatment.
1. A stable aqueous solution comprising:
(a) an anti-C5 antibody at a concentration of about 100 mg/mL to about 200 mg/mL, wherein the anti-C5 antibody comprises CDR1, CDR2, and CDR3 domains of a heavy chain comprising the amino acid sequence set forth in SEQ ID NO:13 and CDR1, CDR2, and CDR3 domains of a light chain comprising the amino acid sequence set forth in SEQ ID NO:12,
(b) about 20 mM histidine,
(c) about 50 mM serine,
(d) about 3% (w/v) sorbitol, and
(e) about 1.5% (w/v) mannitol.
2. A stable aqueous solution consisting of:
(a) an anti-C5 antibody at a concentration of about 100 mg/mL to about 200 mg/mL, wherein the anti-C5 antibody comprises CDR1, CDR2, and CDR3 domains of a heavy chain comprising the amino acid sequence set forth in SEQ ID NO:13 and CDR1, CDR2, and CDR3 domains of a light chain comprising the amino acid sequence set forth in SEQ ID NO:12,
(b) about 20 mM histidine,
(c) about 50 mM serine,
(d) about 3% (w/v) sorbitol, and
(e) about 1.5% (w/v) mannitol.
3. The stable aqueous solution of claim 1 , wherein the anti-C5 antibody comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO:13 and a light chain comprising the amino acid sequence set forth in SEQ ID NO:12.
4. The stable aqueous solution of claim 1 , wherein the anti-C5 antibody is eculizumab.
5. The stable aqueous solution of claim 1 , wherein the pH of the solution is between 6.5 and 7.5.
6. The stable aqueous solution of claim 5 , wherein the pH of the solution is 7.0.
7. The stable aqueous solution of claim 1 , wherein the anti-C5 antibody is at a concentration of 100 mg/mL.
8. The stable aqueous solution of claim 1 , wherein the solution is sterile.
9. The stable aqueous solution of claim 1 , wherein the anti-C5 antibody remains at least 97% monomeric during storage at 2° C. to 8° C. for at least six months as determined by SEC-HPLC.
10. The stable aqueous solution of claim 1 , wherein the anti-C5 antibody remains at least 97% monomeric during storage at 2° C. to 8° C. for at least one year as determined by SEC-HPLC.
11. The stable aqueous solution of claim 1 , wherein less than 2% of the anti-C5 antibody in the solution is aggregated as determined by SEC-HPLC.
12. The stable aqueous solution of claim 1 , wherein less than 1% of the anti-C5 antibody in the solution is fragmented as determined by SEC-HPLC.
13. The stable aqueous solution of claim 1 , wherein during storage at 2° C. to 8° C. for at least six months the anti-C5 antibody retains at least 90% of its C5-binding activity, as compared to a reference anti-C5 antibody corresponding to the anti-C5 antibody prior to storage.
14. The stable aqueous solution of claim 1 , wherein during storage at 2° C. to 8° C. for at least six months the anti-C5 antibody retains at least 95% of its ability to inhibit hemolysis, as compared to a reference anti-C5 antibody corresponding to the anti-C5 antibody prior to storage.
15. A stable aqueous solution comprising:
(a) eculizumab,
(b) about 20 mM histidine,
(c) about 50 mM serine,
(d) about 3% (w/v) sorbitol, and
(e) about 1.5% (w/v) mannitol.