Biopharmaceutical compositions comprising interleukin-5 antibody
The present disclosure relates to compositions, for treating interleukin 5 (IL-5) mediated diseases, and related methods.
1. A composition comprising a mixture of antibodies, the composition comprising:
(i) an antibody having a heavy chain amino acid sequence as shown in SEQ ID NO: 1 and a light chain amino acid sequence as shown in SEQ ID NO: 2; and,
(ii) an antibody having a heavy chain amino acid sequence as shown in SEQ ID NO: 1 and a light chain amino acid sequence as shown in SEQ ID NO: 2, except that residue 31 of SEQ ID NO: 2 is replaced with either an aspartic acid or an iso-aspartic acid.
2. The composition according to claim 1 , wherein the antibody of (ii) comprises from 3.3% to 25% of the composition.
3. A composition according to claim 2 wherein the composition has at least 0.70 IL-5 specific antigen binding activity compared with a reference standard composition, the reference standard composition comprising:
(a) an antibody having a heavy chain amino acid sequence as shown in SEQ ID NO: 1 and a light chain amino acid sequence as shown in SEQ ID NO: 2;
(b) ≥98% HC C-terminal lysine deleted variant of the antibody of (a);
(c) ≥95% HC N-terminal pyroglutamate variant of the antibody of (a);
(d) 5.2% of the antibody of (a) wherein residue 31 of SEQ ID NO: 2 is replaced with either an aspartic acid or an iso-aspartic acid;
(e) 0.9% of the antibody of (a) wherein residue M64 of SEQ ID NO: 1 is oxidized;
(f) 0.1% of the antibody of (a) wherein residue W52 of SEQ ID NO: 1 is oxidized; and,
(g) 0.4% aggregated antibodies of the reference standard composition.
4. A pharmaceutical composition comprising a composition according to claim 2 and a pharmaceutically acceptable carrier.
5. A composition according to claim 2 wherein the antibody is at a concentration of between 75 mg/mL to 100 mg/mL.
6. The composition of claim 2 , wherein the composition further comprises:
(a) ≥92% amino terminal pyroglutamate residue at amino acid residue 1 of the antibodies of the mixture of antibodies;
(b) ≥90% carboxy terminal glycine amino acid residue at amino acid residue 448 of the antibodies of the mixture of antibodies;
(c) from 1.5% to 6% of residue 386 of SEQ ID NO: 1 is replaced with either an aspartic acid or an iso-aspartic acid;
(d) from 0% to 1% of residue W52 of SEQ ID NO: 1 is oxidized;
(e) from 0.5% to 1.5% of residue M64 of SEQ ID NO: 1 is oxidized;
(f) from 2.5% to 4.5% of residue M254 of SEQ ID NO: 1 is oxidized;
(g) from 0.4% to 0.8% of residue M430 of SEQ ID NO: 1 is oxidized; and,
(h) from 3.3% to 6.6% of residue 31 of SEQ ID NO: 2 is replaced with either an aspartic acid or an iso-aspartic acid.
7. The composition according to claim 2 , where in the antibody of (ii) comprises from 3.3% to 6.6% of the composition.
8. The composition of claim 2 , wherein greater than 50% of the heavy chain C-terminal lysine residue K449 is deleted.
9. The composition according to claim 2 , wherein the composition comprises from 0.5% to 55% of residue M64 of SEQ ID NO: 1 is oxidized and from 0% to 3% of residue W52 of SEQ ID NO: 1 is oxidized.
10. The composition according to claim 2 , wherein the composition comprises from 0.5% to 55% of residue M64 of SEQ ID NO:1 is oxidized, from 2.5% to 55% of residue M254 of SEQ ID NO:1 is oxidized, from 0.4% to 55% of residue M360 of SEQ ID NO:1 is oxidized, from 0.4% to 55% of residue M430 of SEQ ID NO:1 is oxidized, and 0% to 3% of wherein residue W52 of SEQ ID NO:1 is oxidized.
11. The composition according to claim 2 , wherein the composition comprises from 1.5% to 35% antibodies with residue 386 of SEQ ID NO: 1 replaced with either an aspartic acid or an iso-aspartic acid.
12. The composition according to claim 2 , wherein the composition further comprises from 0.4% to 20% aggregated antibodies of the composition.