Variable region sequences of IL-31 monoclonal antibodies
The present invention relates to methods of treating pruritic diseases, including but not limited to Contact dermatitis, Atopic Dermatitis, Drug induced delayed type cutaneous allergic reactions, Toxic epidermal necrolysis, Cutaneous T cell Lymphoma, Bullous pemphigoid, Alopecia wereata, Vitiligo, Acne Rosacea, Prurigo nodularis, Scleroderma, Herpes simplex virus, or combination thereof by administering IL-31 monoclonal antibodies. The invention provides the hybridomas that generate the monoclonal antibodies and the amino acid sequences of the variable regions of the monoclonal antibodies and chimeric antibodies comprising the amino acid sequences of the light and heavy chain variable regions.
1. A monoclonal antibody or antibody fragment that competes for specifically binding to a polypeptide consisting of the amino acid sequence of SEQ ID NO: 2 wherein the monoclonal antibody is selected from the group consisting of:
a) a monoclonal antibody comprising
i) a heavy chain variable domain comprising a 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; and
ii) a light chain variable domain comprising a 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; and
b) a monoclonal antibody comprising
i) a heavy chain variable domain comprising a 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; and
ii) a light chain variable domain comprising a 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.
2. The monoclonal antibody or antibody fragment according to claim 1 , wherein the monoclonal antibody or antibody fragment inhibits, blocks, or neutralizes the interaction of IL-31 comprising the amino acid sequence of SEQ ID NO:2 from residue 27 to residue 164 with IL-31RA comprising the amino acid sequence of SEQ ID NO:5.
3. The monoclonal antibody or antibody fragment according to claim 2 , wherein the monoclonal antibody or antibody fragment is selected from the group consisting of:
(a) a murine monoclonal antibody or antibody fragment;
(b) a humanized antibody or antibody fragment;
(c) a human monoclonal antibody; and
(d) a chimeric antibody.
4. The monoclonal antibody or antibody fragment of claim 2 , wherein the antibody or antibody fragment comprises PEG.
5. The monoclonal antibody or antibody fragment of claim 1 , wherein the antibody or antibody fragment comprises a radionuclide, enzyme, substrate, cofactor, fluorescent marker, chemiluminescent marker, peptide tag, magnetic particle, or toxin.
6. The monoclonal antibody or antibody fragment according to claim 1 , wherein the antibody or antibody fragment is a Fab molecule or a F(ab′) 2 molecule.
7. The monoclonal antibody or antibody fragment according to claim 1 , wherein the antibody or antibody fragment is a single-chain molecule.
8. The monoclonal antibody or antibody fragment according to claim 1 , wherein the antibody or antibody fragment comprises a human IgG constant region.
9. The monoclonal antibody or antibody fragment according to claim 1 , wherein the antibody or fragment comprises PEG.
10. A pharmaceutical composition comprising the monoclonal antibody or antibody fragment of claim 1 .
11. A monoclonal antibody or antibody fragment comprising
i) a heavy chain variable domain comprising a 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; and
ii) a light chain variable domain comprising a 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.
12. A monoclonal antibody or antibody fragment comprising
i) a heavy chain variable domain comprising a 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; and
ii) a light chain variable domain comprising a 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.
13. A monoclonal antibody or antibody fragment that competes for specifically binding to a polypeptide consistong of the amino acid sequence of SEQ ID NO: 2 wherein the monoclonal antibody comprising 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; and
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.
14. The monoclonal antibody or antibody fragment of claim 13 , wherein the antibody or antibody fragment comprises a radionuclide, enzyme, substrate, cofactor, fluorescent marker, chemiluminescent marker, peptide tag, magnetic particle, or toxin.
15. The monoclonal antibody or antibody fragment according to claim 13 , wherein the antibody or antibody fragment is a Fab molecule or a F(ab′) 2 molecule.
16. The monoclonal antibody or antibody fragment according to claim 13 , wherein the antibody or antibody fragment is a single-chain molecule.
17. A monoclonal antibody or antibody fragment according to claim 13 , wherein the antibody or antibody fragment comprises a human IgG constant region.
18. The monoclonal antibody or antibody fragment according to claim 13 , wherein the antibody or fragment comprises PEG.
19. The monoclonal antibody or antibody fragment according to claim 13 , wherein the antibody or fragment is selected from the group consisting of:
(a) a murine monoclonal antibody or antibody fragment;
(b) a humanized antibody or antibody fragment;
(c) a human monoclonal antibody; and
(d) a chimeric antibody.
20. A pharmaceutical composition comprising the monoclonal antibody or antibody fragment of claim 13 .
21. A monoclonal antibody or antibody fragment comprising
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.
22. A monoclonal antibody or antibody fragment comprising
a) 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.