Biopharmaceutical compositions

1. A method of treating a disease in a subject, the method comprising:

administering to the subject having the disease a therapeutically effective amount of a composition comprising an anti-IL-5 antibody, the composition comprising:

a) a first antibody comprising the heavy chain amino acid sequence of SEQ ID NO: 1 and the light chain amino acid sequence of SEQ ID NO: 2; and

b) a second antibody comprising the heavy chain amino acid sequence of SEQ ID NO: 1 and the light chain amino acid sequence of SEQ ID NO: 2, except that residue 31 of SEQ ID NO: 2 is replaced with an aspartic acid or an iso-aspartic acid;

wherein the disease is selected from the group consisting of asthma, severe eosinophilic asthma, severe asthma, uncontrolled eosinophilic asthma, eosinophilic asthma, sub-eosinophilic asthma, chronic obstructive pulmonary disease, eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome, nasal polyposis, bullous pemphigoid and eosinophilic esophagitis.

2. The method of claim 1 , wherein 3.3% to 20%, 3.3% to 15%, 3.3% to 17.5%, 3.3% to 12.5%, 3.3% to 10%, or 3.3% to 25% of antibodies in the composition are the second antibody.

3. The method of claim 1 , wherein antibody in the composition is at a concentration of between 75 mg/mL and 100 mg/mL.

4. The method of claim 1 , wherein antibody in the composition is administered to the subject at a dose of 100 mg once every 4 weeks.

5. The method of claim 1 , wherein antibody in the composition is administered to the subject at a dose of 300 mg once every 4 weeks.

6. The method of claim 1 , wherein antibody in the composition is administered to the subject at a dose of 750 mg once every 4 weeks.

7. The method of claim 1 , wherein greater than 50% of the heavy chain C-terminal lysine residue K449 of SEQ ID NO:1 of the composition is deleted.

8. The method of claim 1 , wherein greater than 50% of the heavy chain N-terminal glutamate of SEQ ID NO:1 of the composition is converted to pyro-glutamate.

9. The method of claim 1 , wherein from 0% to 55% of residue M64 of SEQ ID NO: 1 of the composition is oxidized and from 0% to 3% of residue W52 of SEQ ID NO: 1 of the composition is oxidized.

10. The method of claim 1 , wherein from 0% to 55% of residue M64 of SEQ ID NO:1 of the composition is oxidized, from 0% to 55% of residue M254 of SEQ ID NO:1 of the composition is oxidized, from 0% to 55% of residue M360 of SEQ ID NO:1 of the composition is oxidized, from 0% to 55% of residue M430 of SEQ ID NO:1 of the composition is oxidized, and from 0% to 3% of residue W52 of SEQ ID NO:1 of the composition is oxidized.

11. The method of claim 1 , wherein from 0% to 35% of residue 386 of SEQ ID NO: 1 of the composition is replaced with an aspartic acid or an iso-aspartic acid.

12. The method of claim 1 , wherein up to 80% of antibodies in the composition are acidic antibody variants.

13. The method of claim 1 , wherein up to 20% of antibodies in the composition are aggregated antibodies.

14. The method of claim 1 , 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 of SEQ ID NO: 1 and a light chain amino acid sequence of SEQ ID NO:2;

b) 98% or more heavy chain C-terminal lysine deleted variant of the antibody;

c) 95% or more heavy chain N-terminal pyroglutamate variant of the antibody;

d) 6% or less of the antibody wherein residue 31 of SEQ ID NO:2 is replaced with an aspartic acid or an iso-aspartic acid;

e) 4% or less methionine or cysteine oxidated variant;

f) 0.1% or less tryptophan oxidated variant; and

g) 0.4% or less aggregated antibody variant.

15. The method of claim 1 , wherein the composition further comprises:

a) a buffering agent selected from the group consisting of sodium phosphate dibasic heptahydrate, phosphate, citrate, sodium phosphate, potassium phosphate, sodium citrate, and histidine; providing a pH of between 6.8 and 7.2 or a pH of between 6.2 and 6.6;

b) a sugar;

c) polysorbate 80;

d) EDTA; or

e) a combination thereof.

16. The method of claim 1 , wherein the composition is an aqueous liquid formulation comprising:

a) 100 mg/ml antibody;

b) 15.5 mM sodium phosphate dibasic heptahydrate and 4.5 mM citric acid monohydrate at pH 6.3;

c) 12% weight of sucrose to volume;

d) 0.02% weight of polysorbate 80 to volume; and

e) 0.05 mM EDTA.

17. The method of claim 1 , wherein the composition is lyophilized and comprises:

a) 100 mg/mL antibody;

b) 20 mM sodium phosphate dibasic heptahydrate;

c) 12% weight of sucrose to volume; and

d) 0.05% weight of polysorbate 80 to volume.

18. The method of claim 1 , wherein the subject is a human in need thereof.