IP Library › Granted Patent US 8,604,177

Granted Patent B2

US 8,604,177 · App. 13/043,293 · Granted Dec 10, 2013

Interleukin-13 binding proteins

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Quick Facts

Patent No.: US 8,604,177
App. No.: 13/043,293
Granted: Dec 10, 2013
Kind: B2

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Abstract

The present invention encompasses IL-13 binding proteins. Specifically, the invention relates to antibodies that are chimeric, CDR grafted and humanized antibodies. Preferred antibodies have high affinity for hIL-13 and neutralize hIL-13 activity in vitro and in vivo. An antibody of the invention can be a full-length antibody or an antigen-binding portion thereof. Method of making and method of using the antibodies of the invention are also provided. The antibodies, or antibody portions, of the invention are useful for detecting hIL-13 and for inhibiting hIL-13 activity, e.g., in a human subject suffering from a disorder in which hIL-13 activity is detrimental.

Claims (678)

1. An isolated nucleic acid encoding an amino acid sequence of at least one variable domain of an IL-13 binding protein, wherein said at least one variable domain comprises CDR-H1, CDR-H2, and CDR-H3 amino acid sequences independently selected from the group consisting of:

CDR-H1

CDR-H2

CDR-H3

residues 31-35 of

residues 50-66 of

residues 99-105 of

SEQ ID NO.: 32

residues 31-35 of

residues 50-66 of

residues 99-105 of

SEQ ID NO.: 34

residues 31-35 of

residues 50-66 of

residues 99-109 of

SEQ ID NO.: 36

residues 31-35 of

residues 50-66 of

residues 99-109 of

SEQ ID NO.: 38

residues 31-35 of

residues 50-66 of

residues 99-112 of

SEQ ID NO.: 39

residues 31-35 of

residues 50-66 of

residues 99-112 of

SEQ ID NO.: 41

residues 31-35 of

residues 50-66 of

residues 99-100 of

SEQ ID NO.: 42

residues 31-35 of

residues 50-65 of

residues 98-106 of

SEQ ID NO.: 44

residues 31-37 of

residues 52-67 of

residues 100-112 of

SEQ ID NO.: 46

residues 31-37 of

residues 52-67 of

residues 100-112 of

SEQ ID NO.: 48

residues 31-37 of

residues 52-67 of

residues 100-112 of

SEQ ID NO.: 50

residues 31-35 of

residues 50-66 of

residues 99-107 of

SEQ ID NO.: 52

residues 31-35 of

residues 50-65 of

residues 98-107 of

SEQ ID NO.: 54

residues 31-35 of

residues 50-65 of

residues 98-107 of

SEQ ID NO.: 56

residues 31-35 of

residues 50-65 of

residues 98-107 of

SEQ ID NO.: 58

residues 31-35 of

residues 50-65 of

residues 98-107 of

SEQ ID NO.: 60

residues 31-35 of

residues 50-65 of

residues 98-107 of

SEQ ID NO.: 62

SEQ ID NO.: 62.

2. An isolated nucleic acid encoding an amino acid sequence of at least one variable domain of an IL-13 binding protein, wherein said at least one variable domain comprises CDR-L1, CDR-L2, and CDR-L3 amino acid sequences independently selected from the group consisting of:

CDR-L1

CDR-L2

CDR-L3

residues 24-39 of SEQ ID NO.: 33

residues 55-61 of SEQ ID NO.: 33

residues 94-102 of SEQ ID NO.: 33

residues 24-39 of SEQ ID NO.: 35

residues 55-61 of SEQ ID NO.: 35

residues 94-102 of SEQ ID NO.: 35

residues 24-39 of SEQ ID NO.: 37

residues 55-61 of SEQ ID NO.: 37

residues 94-102 of SEQ ID NO.: 37

residues 24-39 of SEQ ID NO.: 40

residues 55-61 of SEQ ID NO.: 40

residues 94-102 of SEQ ID NO.: 40

residues 24-39 of SEQ ID NO.: 43

residues 55-61 of SEQ ID NO.: 43

residues 94-102 of SEQ ID NO.: 43

residues 24-40 of SEQ ID NO.: 45

residues 56-62 of SEQ ID NO.: 45

residues 95-103 of SEQ ID NO.: 45

residues 24-34 of SEQ ID NO.: 47

residues 50-56 of SEQ ID NO.: 47

residues 89-97 of SEQ ID NO.: 47

residues 24-34 of SEQ ID NO.: 49

residues 50-56 of SEQ ID NO.: 49

residues 89-97 of SEQ ID NO.: 49

residues 24-34 of SEQ ID NO.: 51

residues 50-56 of SEQ ID NO.: 51

residues 89-97 of SEQ ID NO.: 51

residues 23-36 of SEQ ID NO.: 53

residues 52-58 of SEQ ID NO.: 53

residues 91-99 of SEQ ID NO.: 53

residues 24-38 of SEQ ID NO.: 55

residues 54-60 of SEQ ID NO.: 55

residues 93-101 of SEQ ID NO.: 55

residues 24-38 of SEQ ID NO.: 57

residues 54-60 of SEQ ID NO.: 57

residues 93-101 of SEQ ID NO.: 57

residues 24-38 of SEQ ID NO.: 59

residues 54-60 of SEQ ID NO.: 59

residues 93-101 of SEQ ID NO.: 59

residues 24-38 of SEQ ID NO.: 61

residues 54-60 of SEQ ID NO.: 61

residues 93-101 of SEQ ID NO.: 61

residues 24-38 of SEQ ID NO.: 63

residues 54-60 of SEQ ID NO.: 63

residues 93-101 of SEQ ID NO.: 63

residues 24-34 of SEQ ID NO: 92

residues 50-56 of SEQ ID NO: 92

residues 89-97 of SEQ ID NO: 92

residues 24-34 of SEQ ID NO: 93

residues 50-56 of SEQ ID NO: 93

residues 89-97 of SEQ ID NO: 93

residues 24-34 of SEQ ID NO: 94

residues 50-56 of SEQ ID NO: 94

residues 89-97 of SEQ ID NO: 94.

3. The isolated nucleic acid according to either claim 1 or claim 2 , encoding an antibody construct amino acid sequence, wherein said antibody construct comprises said binding protein and further comprises a linker polypeptide or an immunoglobulin constant domain.

4. A vector comprising an isolated nucleic acid according to claim 1 or an isolated nucleic acid according to claim 2 , or a combination thereof.

5. The vector of claim 4 wherein said vector is selected from the group consisting of pcDNA, pTT, pTT3, pEFBOS, pBV, pJV, and pBJ.

6. A host cell comprising a vector according to claim 4 .

7. The host cell according to claim 6 , wherein said host cell is a prokaryotic cell.

8. The host cell according to claim 7 , wherein said host cell is E. coli.

9. The host cell according to claim 6 , wherein said host cell is a eukaryotic cell.

10. The host cell according to claim 9 , wherein said eukaryotic cell is selected from the group consisting of a protist cell, an animal cell, a plant cell, and a fungal cell.

11. The host cell according to claim 9 , wherein said eukaryotic cell is an animal cell selected from the group consisting of: a mammalian cell, an avian cell, and an insect cell.

12. The host cell according to claim 9 , wherein said host cell is a CHO cell.

13. The host cell according to claim 9 , wherein said host cell is a COS cell.

14. The host cell according to claim 9 , wherein said host cell is a yeast cell.

15. The host cell according to claim 14 , wherein said yeast cell is Saccharomyces cerevisiae.

16. The host cell according to claim 9 , wherein said host cell is an insect Sf9 cell.

17. A host cell comprising at least one nucleic acid according to either claim 1 or claim 2 .

18. A host cell comprising one or more nucleic acids encoding a polypeptide chain of an IL-13 binding protein, said polypeptide chain comprising CDR-H1, CDR-H2, and CDR-H3 amino acid sequences independently selected from the group consisting of:

CDR-H1

CDR-H2

CDR-H3

residues 31-35 of SEQ ID NO.: 32

residues 50-66 of SEQ ID NO.: 32

residues 99-105 of SEQ ID NO.: 32

residues 31-35 of SEQ ID NO.: 34

residues 50-66 of SEQ ID NO.: 34

residues 99-105 of SEQ ID NO.: 34

residues 31-35 of SEQ ID NO.: 36

residues 50-66 of SEQ ID NO.: 36

residues 99-109 of SEQ ID NO.: 36

residues 31-35 of SEQ ID NO.: 38

residues 50-66 of SEQ ID NO.: 38

residues 99-109 of SEQ ID NO.: 38

residues 31-35 of SEQ ID NO.: 39

residues 50-66 of SEQ ID NO.: 39

residues 99-112 of SEQ ID NO.: 39

residues 31-35 of SEQ ID NO.: 41

residues 50-66 of SEQ ID NO.: 41

residues 99-112 of SEQ ID NO.: 41

residues 31-35 of SEQ ID NO.: 42

residues 50-66 of SEQ ID NO.: 42

residues 99-100 of SEQ ID NO.: 42

residues 31-35 of SEQ ID NO.: 44

residues 50-65 of SEQ ID NO.: 44

residues 98-106 of SEQ ID NO.: 44

residues 31-37 of SEQ ID NO.: 46

residues 52-67 of SEQ ID NO.: 46

residues 100-112 of SEQ ID NO.: 46

residues 31-37 of SEQ ID NO.: 48

residues 52-67 of SEQ ID NO.: 48

residues 100-112 of SEQ ID NO.: 48

residues 31-37 of SEQ ID NO.: 50

residues 52-67 of SEQ ID NO.: 50

residues 100-112 of SEQ ID NO.: 50

residues 31-35 of SEQ ID NO.: 52

residues 50-66 of SEQ ID NO.: 52

residues 99-107 of SEQ ID NO.: 52

residues 31-35 of SEQ ID NO.: 54

residues 50-65 of SEQ ID NO.: 54

residues 98-107 of SEQ ID NO.: 54

residues 31-35 of SEQ ID NO.: 56

residues 50-65 of SEQ ID NO.: 56

residues 98-107 of SEQ ID NO.: 56

residues 31-35 of SEQ ID NO.: 58

residues 50-65 of SEQ ID NO.: 58

residues 98-107 of SEQ ID NO.: 58

residues 31-35 of SEQ ID NO.: 60

residues 50-65 of SEQ ID NO.: 60

residues 98-107 of SEQ ID NO.: 60

residues 31-35 of SEQ ID NO.: 62

residues 50-65 of SEQ ID NO.: 62

residues 98-107 of SEQ ID NO.: 62

and nucleic acids encoding a polypeptide chain of an IL-13 binding protein, said polypeptide chain comprising CDR-L1, CDR-L2, and CDR-L3 amino acid sequences independently selected from the group consisting of:

CDR-L1

CDR-L2

CDR-L3

residues 24-39 of SEQ ID NO.: 33

residues 55-61 of SEQ ID NO.: 33

residues 94-102 of SEQ ID NO.: 33

residues 24-39 of SEQ ID NO.: 35

residues 55-61 of SEQ ID NO.: 35

residues 94-102 of SEQ ID NO.: 35

residues 24-39 of SEQ ID NO.: 37

residues 55-61 of SEQ ID NO.: 37

residues 94-102 of SEQ ID NO.: 37

residues 24-39 of SEQ ID NO.: 40

residues 55-61 of SEQ ID NO.: 40

residues 94-102 of SEQ ID NO.: 40

residues 24-39 of SEQ ID NO.: 43

residues 55-61 of SEQ ID NO.: 43

residues 94-102 of SEQ ID NO.: 43

residues 24-40 of SEQ ID NO.: 45

residues 56-62 of SEQ ID NO.: 45

residues 95-103 of SEQ ID NO.: 45

residues 24-34 of SEQ ID NO.: 47

residues 50-56 of SEQ ID NO.: 47

residues 89-97 of SEQ ID NO.: 47

residues 24-34 of SEQ ID NO.: 49

residues 50-56 of SEQ ID NO.: 49

residues 89-97 of SEQ ID NO.: 49

residues 24-34 of SEQ ID NO.: 51

residues 50-56 of SEQ ID NO.: 51

residues 89-97 of SEQ ID NO.: 51

residues 23-36 of SEQ ID NO.: 53

residues 52-58 of SEQ ID NO.: 53

residues 91-99 of SEQ ID NO.: 53

residues 24-38 of SEQ ID NO.: 55

residues 54-60 of SEQ ID NO.: 55

residues 93-101 of SEQ ID NO.: 55

residues 24-38 of SEQ ID NO.: 57

residues 54-60 of SEQ ID NO.: 57

residues 93-101 of SEQ ID NO.: 57

residues 24-38 of SEQ ID NO.: 59

residues 54-60 of SEQ ID NO.: 59

residues 93-101 of SEQ ID NO.: 59

residues 24-38 of SEQ ID NO.: 61

residues 54-60 of SEQ ID NO.: 61

residues 93-101 of SEQ ID NO.: 61

residues 24-38 of SEQ ID NO.: 63

residues 54-60 of SEQ ID NO.: 63

residues 93-101 of SEQ ID NO.: 63

residues 24-34 of SEQ ID NO: 92

residues 50-56 of SEQ ID NO: 92

residues 89-97 of SEQ ID NO: 92

residues 24-34 of SEQ ID NO: 93

residues 50-56 of SEQ ID NO: 93

residues 89-97 of SEQ ID NO: 93

residues 24-34 of SEQ ID NO: 94

residues 50-56 of SEQ ID NO: 94

residues 89-97 of SEQ ID NO: 94.

19. A method of producing a protein capable of binding IL-13, comprising culturing the host cell of claim 6 in culture medium under conditions sufficient for expression of said binding protein.

20. A host cell comprising a first nucleic acid encoding a variable heavy chain (VH) set of 3 CDRs and a second nucleic acid encoding a variable light chain (VL) set of 3 CDRs, wherein said VH set of 3 CDRs is selected from any one of the VH sets in the group below and said VL set of 3 CDRs is selected from any one of the VL sets in the group below:

VH 25C8 CDR Set

VH 25C8 CDR-H1

Residues 31-35 of SEQ ID NO.: 32

VH 25C8 CDR-H2

Residues 50-66 of SEQ ID NO.: 32

VH 25C8 CDR-H3

Residues 99-105 of SEQ ID NO.: 32

VL 25C8 CDR Set

VL 25C8 CDR-L1

Residues 24-39 of SEQ ID NO.: 33

VL 25C8 CDR-L2

Residues 55-61 of SEQ ID NO.: 33

VL 25C8 CDR-L3

Residues 94-102 of SEQ ID NO.: 33

VH 9C11 CDR Set

VH 9C11 CDR-H1

Residues 31-35 of SEQ ID NO.: 34

VH 9C11 CDR-H2

Residues 50-66 of SEQ ID NO.: 34

VH 9C11 CDR-H3

Residues 99-105 of SEQ ID NO.: 34

VL 9C11 CDR Set

VL 9C11 CDR-L1

Residues 24-39 of SEQ ID NO.: 35

VL 9C11 CDR-L2

Residues 55-61 of SEQ ID NO.: 35

VL 9C11 CDR-L3

Residues 94-102 of SEQ ID NO.: 35

VH 21D9 CDR Set

VH 21D9 CDR-H1

Residues 31-35 of SEQ ID NO.: 36

VH 21D9 CDR-H2

Residues 50-66 of SEQ ID NO.: 36

VH 21D9 CDR-H3

Residues 99-109 of SEQ ID NO.: 36

VL 21D9 CDR Set

VL 21D9 CDR-L1

Residues 24-39 of SEQ ID NO.: 37

VL 21D9 CDR-L2

Residues 55-61 of SEQ ID NO.: 37

VL 21D9 CDR-L3

Residues 94-102 of SEQ ID NO.: 37

VH 22D10 CDR Set

VH 22D10 CDR-H1

Residues 31-35 of SEQ ID NO.: 38

VH 22D10 CDR-H2

Residues 50-66 of SEQ ID NO.: 38

VH 22D10 CDR-H3

Residues 99-109 of SEQ ID NO.: 38

VL 22D10 CDR Set

VL 22D10 CDR-L1

Residues 24-39 of SEQ ID NO.: 37

VL 22D10 CDR-L2

Residues 55-61 of SEQ ID NO.: 37

VL 22D10 CDR-L3

Residues 94-102 of SEQ ID NO.: 37

VH 5F1 CDR Set

VH 5F1 CDR-H1

Residues 31-35 of SEQ ID NO.: 39

VH 5F1 CDR-H2

Residues 50-66 of SEQ ID NO.: 39

VH 5F1 CDR-H3

Residues 99-112 of SEQ ID NO.: 39

VL 5F1 CDR Set

VL 5F1 CDR-L1

Residues 24-39 of SEQ ID NO.: 40

VL 5F1 CDR-L2

Residues 55-61 of SEQ ID NO.: 40

VL 5F1 CDR-L3

Residues 94-102 of SEQ ID NO.: 40

VH 5G1 CDR Set

VH 5G1 CDR-H1

Residues 31-35 of SEQ ID NO.: 41

VH 5G1 CDR-H2

Residues 50-66 of SEQ ID NO.: 41

VH 5G1 CDR-H3

Residues 99-112 of SEQ ID NO.: 41

VL 5G1 CDR Set

VL 5G1 CDR-L1

Residues 24-39 of SEQ ID NO.: 40

VL 5G1 CDR-L2

Residues 55-61 of SEQ ID NO.: 40

VL 5G1 CDR-L3

Residues 94-102 of SEQ ID NO.: 40

VH 3H7 CDR Set

VH 3H7 CDR-H1

Residues 31-35 of SEQ ID NO.: 42

VH 3H7 CDR-H2

Residues 50-66 of SEQ ID NO.: 42

VH 3H7 CDR-H3

Residues 99-100 of SEQ ID NO.: 42

VL 3H7 CDR Set

VL 3H7 CDR-L1

Residues 24-39 of SEQ ID NO.: 43

VL 3H7 CDR-L2

Residues 55-61 of SEQ ID NO.: 43

VL 3H7 CDR-L3

Residues 94-102 of SEQ ID NO.: 43

VH 14B2 CDR Set

VH 14B2 CDR-H1

Residues 31-35 of SEQ ID NO.: 44

VH 14B2 CDR-H2

Residues 50-65 of SEQ ID NO.: 44

VH 14B2 CDR-H3

Residues 98-106 of SEQ ID NO.: 44

VL 14B2 CDR Set

VL 14B2 CDR-L1

Residues 24-40 of SEQ ID NO.: 45

VL 14B2 CDR-L2

Residues 56-62 of SEQ ID NO.: 45

VL 14B2 CDR-L3

Residues 95-103 of SEQ ID NO.: 45

VH 13C5 CDR Set

VH 13C5 CDR-H1

Residues 32-38 of SEQ ID NO.: 46

VH 13C5 CDR-H2

Residues 52-67 of SEQ ID NO.: 46

VH 13C5 CDR-H3

Residues 100-112 of SEQ ID NO.: 46

VL 13C5 CDR Set

VL 13C5 CDR-L1

Residues 24-34 of SEQ ID NO.: 47

VL 13C5 CDR-L2

Residues 50-56 of SEQ ID NO.: 47

VL 13C5 CDR-L3

Residues 89-97 of SEQ ID NO.: 47

VH 29G5 CDR Set

VH 29G5 CDR-H1

Residues 31-37 of SEQ ID NO.: 48

VH 29G5 CDR-H2

Residues 52-67 of SEQ ID NO.: 48

VH 29G5 CDR-H3

Residues 100-112 of SEQ ID NO.: 48

VL 29G5 CDR Set

VL 29G5 CDR-L1

Residues 24-34 of SEQ ID NO.: 49

VL 29G5 CDR-L2

Residues 50-56 of SEQ ID NO.: 49

VL 29G5 CDR-L3

Residues 89-97 of SEQ ID NO.: 49

VH 33C3 CDR Set

VH 33C3 CDR-H1

Residues 31-37 of SEQ ID NO.: 50

VH 33C3 CDR-H2

Residues 52-67 of SEQ ID NO.: 50

VH 33C3 CDR-H3

Residues 100-112 of SEQ ID NO.: 50

VL 33C3 CDR Set

VL 33C3 CDR-L1

Residues 24-34 of SEQ ID NO.: 51

VL 33C3 CDR-L2

Residues 60-66 of SEQ ID NO.: 51

VL 33C3 CDR-L3

Residues 89-97 of SEQ ID NO.: 51

VH 4A8 CDR Set

VH 4A8 CDR-H1

Residues 31-35 of SEQ ID NO.: 52

VH 4A8 CDR-H2

Residues 50-66 of SEQ ID NO.: 52

VH 4A8 CDR-H3

Residues 99-107 of SEQ ID NO.: 52

VL 4A8 CDR Set

VL 4A8 CDR-L1

Residues 23-36 of SEQ ID NO.: 53

VL 4A8 CDR-L2

Residues 52-58 of SEQ ID NO.: 53

VL 4A8 CDR-L3

Residues 91-99 of SEQ ID NO.: 53

VH 1B6 CDR Set

VH 1B6 CDR-H1

Residues 31-35 of SEQ ID NO.: 54

VH 1B6 CDR-H2

Residues 50-65 of SEQ ID NO.: 54

VH 1B6 CDR-H3

Residues 98-107 of SEQ ID NO.: 54

VL 1B6 CDR Set

VL 1B6 CDR-L1

Residues 24-38 of SEQ ID NO.: 55

VL 1B6 CDR-L2

Residues 54-60 of SEQ ID NO.: 55

VL 1B6 CDR-L3

Residues 93-101 of SEQ ID NO.: 55

VH 3E5 CDR Set

VH 3E5 CDR-H1

Residues 31-35 of SEQ ID NO.: 56

VH 3E5 CDR-H2

Residues 50-65 of SEQ ID NO.: 56

VH 3E5 CDR-H3

Residues 98-107 of SEQ ID NO.: 56

VL 3E5 CDR Set

VL 3E5 CDR-L1

Residues 24-38 of SEQ ID NO.: 57

VL 3E5 CDR-L2

Residues 54-60 of SEQ ID NO.: 57

VL 3E5 CDR-L3

Residues 93-101 of SEQ ID NO.: 57

VH 6C8 CDR Set

VH 6C8 CDR-H1

Residues 31-35 of SEQ ID NO.: 58

VH 6C8 CDR-H2

Residues 50-65 of SEQ ID NO.: 58

VH 6C8 CDR-H3

Residues 98-107 of SEQ ID NO.: 58

VL 6C8 CDR Set

VL 6C8 CDR-L1

Residues 24-38 of SEQ ID NO.: 59

VL 6C8 CDR-L2

Residues 54-60 of SEQ ID NO.: 59

VL 6C8 CDR-L3

Residues 93-101 of SEQ ID NO.: 59

VH 5D3 CDR Set

VH 5D3 CDR-H1

Residues 31-35 of SEQ ID NO.: 60

VH 5D3 CDR-H2

Residues 50-65 of SEQ ID NO.: 60

VH 5D3 CDR-H3

Residues 98-107 of SEQ ID NO.: 60

VL 5D3 CDR Set

VL 5D3 CDR-L1

Residues 24-38 of SEQ ID NO.: 61

VL 5D3 CDR-L2

Residues 54-60 of SEQ ID NO.: 61

VL 5D3 CDR-L3

Residues 93-101 of SEQ ID NO.: 61

VH 8B6 CDR Set

VH 8B6 CDR-H1

Residues 31-35 of SEQ ID NO.: 62

VH 8B6 CDR-H2

Residues 50-65 of SEQ ID NO.: 62

VH 8B6 CDR-H3

Residues 98-107 of SEQ ID NO.: 62

VL 8B6 CDR Set

VL 8B6 CDR-L1

Residues 24-38 of SEQ ID NO.: 63

VL 8B6 CDR-L2

Residues 54-60 of SEQ ID NO.: 63

VL 8B6 CDR-L3

Residues 93-101 of SEQ ID NO.: 63

VH 13C5.5L2E Set

VH 13C5.5L2E CDR-H1

Residues 31-37 of SEQ ID NO.: 80

VH 13C5.5L2E CDR-H2

Residues 52-67 of SEQ ID NO.: 80

VH 13C5.5L2E CDR-H3

Residues 100-112 of SEQ ID NO.: 80

VL 13C5.5L2E Set

VL 13C5.5L2E CDR-L1

Residues 24-34 of SEQ ID NO.: 92

VL 13C5.5L2E CDR-L2

Residues 50-56 of SEQ ID NO.: 92

VL 13C5.5L2E CDR-L3

Residues 89-97 of SEQ ID NO.: 92

VH 13C5.5L2F Set

VH 13C5.5L3F CDR-H1

Residues 31-37 of SEQ ID NO.: 80

VH 13C5.5L3F CDR-H2

Residues 52-67 of SEQ ID NO.: 80

VH 13C5.5L3F CDR-H3

Residues 100-112 of SEQ ID NO.: 80

VL 13C5.5L3F Set

VL 13C5.5L3F CDR-L1

Residues 24-34 of SEQ ID NO.: 93

VL 13C5.5L3F CDR-L2

Residues 50-56 of SEQ ID NO.: 93

VL 13C5.5L2F CDR-L3

Residues 89-97 of SEQ ID NO.: 93

VH 13C5.5L2EL3F Set

VH 13C5.5L2EL3F CDR-H1

Residues 31-37 of SEQ ID NO.: 80

VH 13C5.5L2EL3F CDR-H2

Residues 52-67 of SEQ ID NO.: 80

VH 13C5.5L2EL3F CDR-H3

Residues 100-112 of SEQ ID NO.: 80

VL 13C5.5L2EL3F Set

VH 13C5.5L2EL3F CDR-L1

Residues 24-34 of SEQ ID NO.: 94

VH 13C5.5L2EL3F CDR-L2

Residues 50-56 of SEQ ID NO.: 94

VH 13C5.5L2EL3F CDR-L3

Residues 89-97 of SEQ ID NO.: 94.

21. The host cell according to claim 20 , which produces at least two variable domain CDR sets selected from a group consisting of:

VH 25C8 CDR Set & VL 25C8 CDR Set;

VH 9C11 CDR Set & VL 9C11 CDR Set;

VH 21D9 CDR Set & VL 21D9 CDR Set;

VH 22D10 CDR Set & VL 22D10 CDR Set;

VH 5F1 CDR Set & VL 5F1 CDR Set;

VH 5G1 CDR Set & VL 5G1 CDR Set;

VH 3H7CDR Set & VL 3H7CDR Set;

VH 14B2 CDR Set & VL 14B2 CDR Set;

VH 13C5 CDR Set & VL 13C5 CDR Set;

VH 29G5 CDR Set & VL 29G5 CDR Set;

VH 33C3 CDR Set & VL 33C3 CDR Set;

VH 4A8 CDR Set & VL 4A8 CDR Set;

VH 1B6 CDR Set & VL 1B6 CDR Set;

VH 3E5CDR Set & VL 3E5 CDR Set;

VH 6C8 CDR Set & VL 6C8 CDR Set;

VH 5D3 CDR Set & VL 5D3 CDR Set;

VH 8B6 CDR Set & VL 8B6 CDR Set;

VH 13C5.5L2E CDR set & VL 13C5.5L2E CDR set;

VH 13C5.5L3F CDR set & VL 13C5.5L3F CDR set; and

VH 13C5.5L2EL3F CDR set & VL 13C5.5L2EL3F CDR set.

22. The isolated nucleic acid according to either claim 1 or claim 2 , further encoding a human acceptor framework.

23. The isolated nucleic acid according to claim 22 , wherein said human acceptor framework comprises an amino acid sequence selected from the group consisting of:

SEQ ID NO.: 6

SEQ ID NO.: 7

SEQ ID NO.: 8

SEQ ID NO.: 9

SEQ ID NO.: 10

SEQ ID NO.: 11

SEQ ID NO.: 12

SEQ ID NO.: 13

SEQ ID NO.: 14

SEQ ID NO.: 15

SEQ ID NO.: 16

SEQ ID NO.: 17

SEQ ID NO.: 18

SEQ ID NO.: 19

SEQ ID NO.: 20

SEQ ID NO.: 21

SEQ ID NO.: 22

SEQ ID NO.: 23

SEQ ID NO.: 24

SEQ ID NO.: 25

SEQ ID NO.: 26

SEQ ID NO.: 27

SEQ ID NO.: 28

SEQ ID NO.: 29

SEQ ID NO.: 30

AND

SEQ ID NO.: 31.

24. The isolated nucleic acid according to claim 22 , wherein said human acceptor framework comprises at least one Framework Region amino acid substitution at a key residue, said key residue selected from the group consisting of:

a residue adjacent to a CDR;

a glycosylation site residue;

a rare residue;

a residue capable of interacting with human IL-13;

a residue capable of interacting with a CDR;

a canonical residue;

a contact residue between heavy chain variable region and light chain variable region;

a residue within a Vernier zone; and

a residue in a region that overlaps between a Chothia-defined variable heavy chain CDR1 and

a Kabat-defined first heavy chain framework.

25. The isolated nucleic acid according to claim 24 , wherein the key residue is selected from the group consisting of 2L, 15L, 22L, 41L, 42L, 44L, 49L, 50L, 51L, 62L, 71L, 73L, 10H, 44H, 46H, 48H, 67H, 68H, 70H, 72H, 74H, 76H, 83H, 84H, 86H, 87H, and 97H.

26. An isolated nucleic acid encoding an amino acid sequence of at least one variable domain of an IL-13 binding protein, wherein said at least one variable domain comprises an amino acid sequence selected from the group consisting of:

SEQ ID NO.: 70

SEQ ID NO.: 71

SEQ ID NO.: 72

SEQ ID NO.: 73

SEQ ID NO.: 74

SEQ ID NO.: 75

SEQ ID NO.: 76

SEQ ID NO.: 77

SEQ ID NO.: 78

SEQ ID NO.: 79

SEQ ID NO.: 80

SEQ ID NO.: 81

SEQ ID NO.: 82

SEQ ID NO.: 83

SEQ ID NO.: 84

SEQ ID NO.: 85

SEQ ID NO.: 92

SEQ ID NO.: 93

and

SEQ ID NO.: 94.

27. The host cell according to claim 17 , producing an IL-13 binding protein comprising two variable domains, wherein said two variable domains comprise amino acid sequences selected from the group consisting of:

SEQ ID NO.: 70 & SEQ ID NO.: 71,

SEQ ID NO.: 72 & SEQ ID NO.: 73,

SEQ ID NO.: 74 & SEQ ID NO.: 75,

SEQ ID NO.: 76 & SEQ ID NO.: 77,

SEQ ID NO.: 78 & SEQ ID NO.: 79,

SEQ ID NO.: 80 & SEQ ID NO.: 81,

SEQ ID NO.: 82 & SEQ ID NO.: 83,

SEQ ID NO.: 84 & SEQ ID NO.: 85

SEQ ID NO.: 80 & SEQ ID NO.: 92,

SEQ ID NO.: 80 & SEQ ID NO.: 93, AND

SEQ ID NO.: 80 & SEQ ID NO.: 94.

28. The host cell according to claim 27 , wherein said two variable domains comprise amino acid sequences SEQ ID NO:80 and SEQ ID NO:81.

29. An isolated nucleic acid encoding a binding protein amino acid sequence, said binding protein being capable of binding IL-13 and comprising an antigen binding domain, said antigen binding domain comprising six CDRs: CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3, wherein:

CDR-H1 comprises residues 31-37 of SEQ ID NO:80,

CDR-H2 comprises residues 52-67 of SEQ ID NO:80,

CDR-H3 comprises residues 100-112 of SEQ ID NO:80,

CDR-L1 comprises residues 24-34 of SEQ ID NO:81,

CDR-L2 comprises residues 50-56 of SEQ ID NO:81, and

CDR-L3 comprises residues 89-97 of SEQ ID NO:81.

30. The isolated nucleic according to claim 29 , wherein said antigen binding domain comprises a heavy chain variable domain comprising SEQ ID NO:80 and a light chain variable domain comprising SEQ ID NO:81.

Assignments (4)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 17, 2013

From: ABBOTT LABORATORIES

To: ABBVIE INC.

Reel/Frame 030231/0808 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 8, 2011

From: WU, CHENGBIN; ARGIRIADI, MARIA A.; YING, HUA; CUFF, CAROLYN A.; MELIM, TERRY L.; DIXON, RICHARD W.; BELK, JONATHAN P.; CHEN, YAN

To: ABBOTT LABORATORIES

Reel/Frame 025923/0497 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 8, 2011

From: HINTON, PAUL R.; KUMAR, SHANKAR

To: PDL BIOPHARMA, INC.

Reel/Frame 025923/0573 →

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Mar 8, 2011

From: PDL BIOPHARMA, INC.

To: ABBOTT LABORATORIES

Reel/Frame 025923/0587 →