Anti-IL-5 antibodies

1. A human antibody molecule that immunospecifically binds to human IL-5 with an equilibrium affinity constant (K D ) of at least about 40 pM as determined by surface plasmon resonance, wherein the human antibody molecule comprises:

a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 4, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 6, a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 8, a light chain CDR1 comprising the amino acid sequence of SEQ ID NOs: 5, 21, 24, 27, 30, 33, 36, 39, or 66, a light chain CDR2 comprising the amino acid sequence of SEQ ID NOs: 7, 42, or 45, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NOs: 15, 48, 51, 54, 57, 60, or 63.

2. The antibody molecule of claim 1 , wherein the antibody molecule comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 4, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 6, a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 8, and

a. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 5, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 15;

b. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 21, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 15;

c. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 24, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 15;

d. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 27, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 15;

e. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 30, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 15;

f. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 33, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 15;

g. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 36, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 15;

h. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 39, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 15;

i. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 66, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 15;

j. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 5, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 42, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 15;

k. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 5, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 45, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 15;

l. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 5, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 48;

m. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 5, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 51;

n. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 5, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 54;

o. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 5, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 57;

p. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 5, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 60; or

q. a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 5, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 63;

wherein the position of the amino acid residues of the CDR is determined according to AbM.

3. The antibody molecule of claim 2 , wherein the antibody molecule comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 4, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 6, a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 8, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 5, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 15.

4. The antibody molecule of claim 1 , wherein the antibody is an IgG molecule comprising:

a. a S228P mutation in the hinge region;

b. a M252Y mutation, a S254T mutation, and a T256E mutation in the CH2 domain of the heavy chain;

c. a deletion of a heavy chain C-terminal lysine residue; or

d. any combination of a to c.

5. The antibody molecule of claim 4 , wherein the antibody molecule comprises a S228P mutation and a deletion of a heavy chain C-terminal lysine residue.

6. The antibody molecule of claim 4 , wherein the antibody molecule comprises a S228P mutation, a M252Y mutation, a S254T mutation, a T256E mutation, and a deletion of a heavy chain C-terminal lysine residue.

7. The antibody molecule of claim 1 , wherein the antibody molecule comprises an IgG4 heavy chain constant region and a lambda light chain constant region.

8. The antibody molecule of claim 1 , wherein the antibody molecule comprises a heavy chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 18 and

a. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 19;

b. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 23;

c. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 26;

d. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 29;

e. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 32;

f. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 35;

g. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 38;

h. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 41;

i. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 44;

j. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 47;

k. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 50;

l. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 53;

m. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 56;

n. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 59;

o. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 62;

p. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 65; or

q. a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 68.

9. The antibody molecule of claim 1 , wherein the antibody molecule comprises a heavy chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 20 and a light chain comprising an amino acid sequence that is at least 90%, 95%, 96%, 97%, 98%, 99%, or 100% identical to the amino acid sequence of SEQ ID NO: 19.

10. The antibody molecule of claim 1 , wherein the antibody molecule is a Fab fragment, a Fab2 fragment, or a single chain antibody.

11. The antibody molecule of claim 1 , wherein the antibody molecule has one or more of the following properties:

a. reduces binding of IL-5 to the IL-5 receptor;

b. has a serum half-life of at least about 20 days; or

c. binds human and cynomolgus monkey IL-5 but not mouse, rat, or guinea pig IL-5.

12. A pharmaceutical composition comprising the antibody molecule of claim 1 .

13. A nucleic acid molecule encoding the antibody molecule of claim 1 .

14. A vector comprising the nucleic acid molecule of claim 13 .

15. A cell transformed to express the antibody molecule of claim 1 .

16. A method of treating a subject having eosinophilic asthma, hypereosinophilic syndrome, nasal polyposis with eosinophilic involvement, eosinophilic granulomatosis with polyangiitis, atopic dermatitis or eosinophilic esophagitis comprising:

administering to the subject a therapeutically effective amount of the antibody molecule of claim 1 to treat the eosinophilic asthma, hypereosinophilic syndrome, nasal polyposis with eosinophilic involvement, eosinophilic granulomatosis with polyangiitis, atopic dermatitis or eosinophilic esophagitis.

17. The antibody molecule of claim 1 , wherein the antibody molecule comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 16 and

a. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 17;

b. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 22;

c. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 25;

d. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 28;

e. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 31;

f. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 34;

g. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 37;

h. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 40;

i. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 43;

j. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 46;

k. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 49;

l. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 52;

m. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 55;

n. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 58;

o. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 61;

p. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 64; or

q. a light chain variable region comprising the amino acid sequence of SEQ ID NO: 67.

18. The antibody molecule of claim 17 , wherein the antibody molecule comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 16 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 17.

19. The antibody molecule of claim 17 , wherein the antibody molecule comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 16 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 22.

20. The antibody molecule of claim 17 , wherein the antibody molecule comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 16 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 25.

21. The antibody molecule of claim 17 , wherein the antibody molecule comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 16 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 28.

22. The antibody molecule of claim 1 , wherein the antibody molecule comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 4, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 6, a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 8, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 21, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 15.

23. The antibody molecule of claim 1 , wherein the antibody molecule comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 4, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 6, a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 8, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 24, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 15.

24. The antibody molecule of claim 1 , wherein the antibody molecule comprises a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 4, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 6, a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 8, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 27, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 7, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 15.