19-12-2013 дата публикации
Номер: US20130336980A1
Автор:
Duffy Karen,
Fursov Natalie,
Hall LeRoy,
Healy Catherine,
Lamb Roberta,
Luo Jinquan,
Malaviya Ravi,
Naso Michael,
Pratta Michael,
Tornetta Mark,
Wheeler John,
Wu Sheng-Jiu
The present invention relates to ST2L antagonists, polynucleotides encoding the antagonists or fragments thereof, and methods of making and using the foregoing. 1) An isolated human or human-adapted antibody antagonist or fragment thereof that specifically binds Domain I (SEQ ID NO: 9) of human ST2L.2) The isolated antibody of claim 1 , wherein the antibody blocks IL-33/ST2L interaction.3) The isolated antibody of claim 2 , wherein the antibody competes for binding to human ST2L (SEQ ID NO: 1) with an isolated antibody comprising a heavy chain variable region (VH) of SEQ ID NO: 47 and a light chain variable region (VL) of SEQ ID NO: 51.4) The isolated antibody of claim 3 , wherein the antibody binds human ST2L at amino acid residues 35-48 of SEQ ID NO: 1 (RCPRQGKPSYTVDW; SEQ ID NO: 210).5) The isolated antibody of claim 4 , wherein the antibody binds human ST2L at amino acid residues T93 and F94 of SEQ ID NO: 1.6) The isolated antibody of having a dissociation constant (K) to human ST2L between about 5×10M to about 7×10M claim 2 , an on rate constant (K) to human ST2L between about 2×10to about 1×10Ms claim 2 , or an off rate constant (K) to human ST2L between about 1×10sto about 1×10s.7Macaca fascicularis) The isolated antibody of having a dissociation constant (K) to (cyno) ST2L (SEQ ID NO: 2) between about 3×10M to about 2×10M claim 6 , an on rate constant (K) to cyno ST2L between about 4×10Msto about 1×10Ms claim 6 , or an off rate constant (K) to cyno ST2L between about 7×10sto about 1×10s.8) The isolated antibody of comprising:{'sub': 1', '2', '3', '4, 'claim-text': [{'sub': '1', 'Xis S, F, D, I, G or V;'}, {'sub': '2', 'Xis Y or D;'}, {'sub': '3', 'Xis A, D or S; and'}, {'sub': '4', 'Xis S, F or I;'}], 'a) a heavy chain complementarity determining region (HCDR) 1 (HCDR1) of SEQ ID NO: 160 (XXXMX); wherein'}{'sub': 5', '6', '7', '8', '9, 'claim-text': [{'sub': '5', 'Xis A, S, T, Y or D;'}, {'sub': '6', 'Xis S, R, E, K, G or A;'}, {'sub': '7', 'Xis S, E or N ...
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