23-05-2019 дата публикации
Номер: US20190153113A1
Принадлежит:
The present invention relates to antigen-binding compounds that inhibit CD39. The invention also relates to cells producing such compounds; methods of making such compounds, and antibodies, fragments, variants, and derivatives thereof; pharmaceutical compositions comprising the same; methods of using the compounds to diagnose, treat or prevent diseases, e.g. cancer. 1. An antibody that specifically binds human CD39 (NTPDase1) at the surface of a cell without binding to CD39-L1 , -L2 , -L3 or -L4 polypeptides , and that is capable of neutralizing the ATPase activity of human CD39 (NTPDase1) without substantially inducing or increasing the internalization of cell surface CD39 , wherein the antibody substantially lacks binding to human CD16 , CD32a , CD32b and CD64 polypeptides wherein the Vcomprises:{'sub': 1', '2', '3', '1', '2', '3, '(a) a CDR1 capable of contacting the N-terminal domain of CD39, wherein the residues at Kabat position 31, 32 and 33 have the formula XXX, wherein Xrepresents a histidine or asparagine, Xrepresents an aromatic residue, and Xrepresents glycine or another amino acid that avoids steric hindrance;'}{'sub': 1', '2', '3', '4', '5', '6', '7', '8', '9', '10', '11', '12', '13', '1', '2', '3', '4', '5', '6', '7', '8', '9', 'H', '10', '11', 'H', '12', '13, '(b) a CDR2-FR3 segment capable of contacting the C-terminal domain of CD39, wherein the residues at Kabat position 59-71 have the formula XXXXXXXXXXXXX(SEQ ID NO: 12), wherein Xrepresents a tyrosine, each of X, X, X, Xand Xeach represent any amino acid, Xrepresents glycine or another residue which does not introduce steric hindrance that reduces antigen binding, Xrepresents any amino acid, Xrepresents phenylalanine or another hydrophobic residue capable of maintaining the beta-strand position and Vdomain structure integrity, Xrepresents alanine, valine, leucine, threonine, or a hydrophobic residue, Xrepresents phenylalanine or another hydrophobic residue capable of maintaining the beta-strand ...
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