VARIABLE REGION SEQUENCES OF IL-31 MONOCLONAL ANTIBODIES AND METHODS OF USE
First Claim
1. A monoclonal antibody or antibody fragment that competes for specifically binding to a polypeptide comprising the amino acid sequence of SEQ ID NO:
- 2 wherein the monoclonal antibody comprises a light chain variable region and a heavy chain variable region selected from the group consisting of;
a) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
8 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
9;
b) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
10 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
11;
c) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
12 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
13;
d) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
14 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
15;
e) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
16 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
17;
f) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
18 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
19;
g) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
20 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
21;
h) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
22 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
23;
i) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
24 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
25; and
j) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
26 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
27 and wherein the monoclonal antibody or antibody fragment is used in conjunction with an human IgG4 Fc molecule.
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Accused Products
Abstract
Novel compositions derived from antigen-binding sites of immunoglobulins having affinity for IL-31 are provided. The compositions exhibit immunological binding properties of antibody molecules capable of binding specifically to a human IL-31. CDR regions derived from same or different immunoglobulin moieties are provided. Also provided are single chain polypeptides wherein VH and VL domains are attached. The sFv molecules can include ancillary polypeptide moieties which can be bioactive, or which provide a site of attachment for other useful moieties. The compositions are useful in specific binding assays, affinity purification schemes, drug or toxin targeting, imaging, and genetic or immunological therapeutics for inflammatory diseases. The invention thus provides novel polypeptides, the DNAs encoding those polypeptides, expression cassettes comprising those DNAs, and methods of inducing the production of the polypeptides. The invention further provides the amino acid sequences of the variable regions of the monoclonal antibodies and use of these monoclonal antibody or antibody fragment in conjunction with an human IgG4 Fc molecule.
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Citations
26 Claims
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1. A monoclonal antibody or antibody fragment that competes for specifically binding to a polypeptide comprising the amino acid sequence of SEQ ID NO:
- 2 wherein the monoclonal antibody comprises a light chain variable region and a heavy chain variable region selected from the group consisting of;
a) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
8 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
9;b) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
10 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
11;c) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
12 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
13;d) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
14 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
15;e) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
16 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
17;f) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
18 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
19;g) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
20 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
21;h) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
22 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
23;i) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
24 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
25; andj) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
26 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
27 and wherein the monoclonal antibody or antibody fragment is used in conjunction with an human IgG4 Fc molecule. - View Dependent Claims (9, 11, 13, 15, 17, 18)
- 2 wherein the monoclonal antibody comprises a light chain variable region and a heavy chain variable region selected from the group consisting of;
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2. A method of reducing, blocking, inhibiting, or neutralizing inflammation in a mammal comprising administering to the mammal an monoclonal antibody or antibody fragment that competes for specifically binding to a polypeptide comprising the amino acid sequence of SEQ ID NO:
- 2 wherein the monoclonal antibody comprises a light chain variable region and a heavy chain variable region selected from the group consisting of;
a) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
8 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
9;b) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
10 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
11;c) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
12 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
13;d) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
14 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
15;e) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
16 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
17;f) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
18 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
19;g) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
20 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
21;h) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
22 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
23;i) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
24 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
25; andj) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
26 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
27 and wherein the monoclonal antibody or antibody fragment is used in conjunction with an human IgG4 Fc molecule. - View Dependent Claims (3, 4, 10, 12, 14, 16)
- 2 wherein the monoclonal antibody comprises a light chain variable region and a heavy chain variable region selected from the group consisting of;
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5. A method of reducing, blocking, inhibiting, or neutralizing pruritis in a mammal comprising administering to the mammal an monoclonal antibody or antibody fragment that competes for specifically binding to a polypeptide comprising the amino acid sequence of SEQ ID NO:
- 2 wherein the monoclonal antibody comprises a light chain variable region and a heavy chain variable region selected from the group consisting of;
a) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
8 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
9;b) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
10 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
11;c) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
12 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
13;d) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
14 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
15;e) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
16 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
17;f) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
18 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
19;g) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
20 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
21;h) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
22 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
23;i) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
24 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
25; andj) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
26 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
27 and wherein the monoclonal antibody or antibody fragment is used in conjunction with an human IgG4 Fc molecule. - View Dependent Claims (6, 7)
- 2 wherein the monoclonal antibody comprises a light chain variable region and a heavy chain variable region selected from the group consisting of;
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8. A method of reducing, blocking, inhibiting, or neutralizing scratching in a mammal comprising administering to the mammal an monoclonal antibody or antibody fragment that competes for specifically binding to a polypeptide comprising the amino acid sequence of SEQ ID NO:
- 2 wherein the monoclonal antibody comprises a light chain variable region and a heavy chain variable region selected from the group consisting of;
a) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
8 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
9;b) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
10 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
11;c) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
12 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
13;d) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
14 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
15;e) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
16 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
17;f) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
18 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
19;g) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
22 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
21;h) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
22 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
23;i) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
24 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
25; andj) a light chain variable region comprising the amino acid sequence of SEQ ID NO;
26 and a heavy chain variable region comprising the amino acid sequence of SEQ ID NO;
27 and wherein the monoclonal antibody or antibody fragment is used in conjunction with an human IgG4 Fc molecule.
- 2 wherein the monoclonal antibody comprises a light chain variable region and a heavy chain variable region selected from the group consisting of;
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19. An isolated antibody that binds to human IL31, wherein said antibody is a humanized antibody derived from the monoclonal antibody produced by the hybridoma deposited with the American Type Culture Collection having the ATCC Patent Deposit Designation selected from:
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a) ATCC Patent Deposit Designation PTA-6815; b) ATCC Patent Deposit Designation PTA-6816; c) ATCC Patent Deposit Designation PTA-6829; d) ATCC Patent Deposit Designation PTA-6830; e) ATCC Patent Deposit Designation PTA-6831; f) ATCC Patent Deposit Designation PTA-6871; g) ATCC Patent Deposit Designation PTA-6872; h) ATCC Patent Deposit Designation PTA-6875; and i) ATCC Patent Deposit Designation PTA-6873; and wherein said antibody comprises a heavy chain immunoglobulin constant domain which is a human IgG4. In an embodiment, the human IgG4 constant domain is a mutated form stable in solution and with little or no complement activating activity. In a particular embodiment, the heavy chain immunoglobulin constant region domain is a human IgG4 constant domain with a Ser to Pro mutation at position 241 (Kabat numbering). - View Dependent Claims (20)
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21. An isolated antibody as disclosed herein wherein
a) the heavy chain variable domain comprises first CDR sequence consisting of amino acid sequence SEQ ID NO: - 51, a second CDR sequence consisting of SEQ ID NO;
52 or SEQ ID NO;
57, and a third CDR sequence consisting of SEQ ID NO;
53; andb) the light chain variable domain comprises first CDR sequence consisting of amino acid sequence SEQ ID NO;
54, a second CDR sequence consisting of SEQ ID NO;
55, and a third CDR sequence consisting of SEQ ID NO;
56.
- 51, a second CDR sequence consisting of SEQ ID NO;
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22. An isolated antibody as disclosed herein wherein
a) the heavy chain variable domain comprises first CDR sequence consisting of amino acid sequence SEQ ID NO: - 51, a second CDR sequence consisting of SEQ ID NO;
58, and a third CDR sequence consisting of SEQ ID NO;
59; andb) the light chain variable domain comprises first CDR sequence consisting of amino acid sequence SEQ ID NO;
60, a second CDR sequence consisting of SEQ ID NO;
61, and a third CDR sequence consisting of SEQ ID NO;
62.
- 51, a second CDR sequence consisting of SEQ ID NO;
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23. An isolated antibody as disclosed herein wherein
a) the heavy chain variable domain comprises first CDR sequence consisting of amino acid sequence SEQ ID NO: - 63, a second CDR sequence consisting of SEQ ID NO;
64, and a third CDR sequence consisting of SEQ ID NO;
65; andb) the light chain variable domain comprises first CDR sequence consisting of amino acid sequence SEQ ID NO;
66, a second CDR sequence consisting of SEQ ID NO;
67, and a third CDR sequence consisting of SEQ ID NO;
68.
- 63, a second CDR sequence consisting of SEQ ID NO;
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24. An isolated antibody as disclosed herein wherein
a) the heavy chain variable domain comprises first CDR sequence consisting of amino acid sequence SEQ ID NO: - 69, a second CDR sequence consisting of SEQ ID NO;
70 or SEQ ID NO;
79, and a third CDR sequence consisting of SEQ ID NO;
71; andb) the light chain variable domain comprises first CDR sequence consisting of amino acid sequence SEQ ID NO;
72, a second CDR sequence consisting of SEQ ID NO;
73, and a third CDR sequence consisting of SEQ ID NO;
74.
- 69, a second CDR sequence consisting of SEQ ID NO;
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25. An isolated antibody as disclosed herein wherein
a) the heavy chain variable domain comprises first CDR sequence consisting of amino acid sequence SEQ ID NO: - 75, a second CDR sequence consisting of SEQ ID NO;
76, and a third CDR sequence consisting of SEQ ID NO;
65; andb) the light chain variable domain comprises first CDR sequence consisting of amino acid sequence SEQ ID NO;
77, a second CDR sequence consisting of SEQ ID NO;
78, and a third CDR sequence consisting of SEQ ID NO;
68.
- 75, a second CDR sequence consisting of SEQ ID NO;
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26. An isolated antibody as disclosed herein wherein
a) the heavy chain variable domain comprises first CDR sequence consisting of amino acid sequence SEQ ID NO: - 80, a second CDR sequence consisting of SEQ ID NO;
817, and a third CDR sequence consisting of SEQ ID NO;
82; andb) the light chain variable domain comprises first CDR sequence consisting of amino acid sequence SEQ ID NO;
83, a second CDR sequence consisting of SEQ ID NO;
84, and a third CDR sequence consisting of SEQ ID NO;
85.
- 80, a second CDR sequence consisting of SEQ ID NO;
Specification