CD25 antibodies
Inventors
Gip, Phung Tu • Li, Bing • Greving, Matthew P. • LUNDBERG, Matt • Srinivasan, Mohan
Assignees
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Publication Number
US-12215163-B2
Publication Date
2025-02-04
Expiration Date
Abstract
Provided herein are antibodies that specifically bind to CD25. Also provided herein are methods of making the antibodies described, and methods of use thereof. For example, the CD25 antibodies may be used therapeutically to treat cancer or autoimmune diseases, and in certain aspects: disrupt the trimerization of the beta, gamma, and alpha (CD25) chains of the IL-2 receptor, bind to a different epitope than to which Daclizumab or Baciliximab bind, exhibit a higher affinity of binding to CD25 at a pH lower than 7.4, when compared to the affinity of binding to CD25 at a pH of 7.4, and/or exhibit a higher affinity of binding to CD25 at a pH of about 6.5.
Core Innovation
The document describes anti-CD25 monoclonal human antibodies, including human, chimeric, and humanized antibodies, and antibody fragments. The antibodies are defined by variable regions comprising CDRH1, CDRH2, CDRH3, and CDRL1, CDRL2, CDRL3, with specific sequence coverage described by tables and figures and organized by antibody clone IDs and SEQ ID references.
A central technical feature is a monoclonal CD25 antibody that binds to human CD25 and is defined by specific amino acid sequences of the heavy chain and light chain variable-region CDRs. The disclosure provides extensive sequence data for exemplary CD25 monoclonal antibody variants and clone families, including AH04507, AH04522, AH04526, AH04527, AH04734, AH04750, AH05214, AH05247, AH05249, AH05251, AH05256, AH05257, AH05258, AH05259, AH05268, AH05271, AH05274, AH05280, AH05285, AH05286, BL_592, BP003, and BP003T.
The antibodies are described as binding human CD25 without disrupting IL-2 binding to CD25 and/or without altering IL-2/JAK3/STAT5 signaling, and as binding a different epitope relative to 7G7B6 and distinguishing from daclizumab and basiliximab. Additional characterization includes selective disruption of IL-2 receptor chain trimerization involving beta, gamma, and alpha, enhanced binding affinity for CD25 in acidic pH conditions lower than 7.4, and ADCC characterization with reported fold-change lysis over baseline.
Claims Coverage
The provided claim content centers on one independent feature set, with dependent refinements relating to epitope/disruption behavior, pH-dependent binding, sequence identity scope, and therapeutic use. The independent feature is grounded in specified heavy-chain and light-chain variable-region CDR amino acid sequences set forth in tables.
Human CD25-binding monoclonal antibody defined by heavy-chain and light-chain CDR amino acid sequences
A monoclonal CD25 antibody that binds to human CD25 comprising amino acid sequences of complementarity determining regions of the heavy chain variable regions (CDRH1, CDRH2, and CDRH3) and amino acid sequences of light chain variable regions (CDRL1, CDRL2, and CDRL3) as set forth in the table below.
Antibody that does not disrupt IL-2 ligand binding to the CD25 alpha chain and binds a different epitope than 7G7B6
A monoclonal CD25 antibody of claim 1 that does not disrupt the binding of the IL-2 ligand to the alpha chain of the IL-2 receptor (CD25), and binds to a different epitope than to which 7G7B6 binds.
Antibody that does not disrupt IL-2 ligand binding to the CD25 alpha chain but disrupts IL-2 receptor chain trimerization
A monoclonal CD25 antibody of claim 1 that does not disrupt the binding of the IL-2 ligand to the alpha chain of the IL-2 receptor (CD25), but does disrupt the trimerization of the beta, gamma, and alpha (CD25) chains of the IL-2 receptor.
Higher affinity at lower pH than 7.4
A monoclonal CD25 antibody of claim 1 that binds to CD25 with higher affinity at pH lower than 7.4 than at pH 7.4.
Antibody defined by a set of variable heavy chain sequences and sequence identity thresholds
An antibody that includes variable heavy chain amino acid sequences presented in SEQ ID NOS: 2, 4, 6, 8, 17, 19, 21, 23, 32, 38, 44, 46, 48, 56, 60-107, 114, 157, 190, 195, 230, 235, 251, 265, 269, 398, 413, 421, 422, 424, 425, 431-460, 473, 601, 603-606, 608, 611, 615, 617, 619, 868, 869, 936-940, 942, 943, 945-952, 954, 955, 973, 977, 984, 986, 987, 992, 995, 997, 1003-1008, 1010-1015, 1017, 1018, 1020, 1021, 1023, 1025-1027, 1029-1035, 1074, 1075, 1118, 1119, 1123-1128, 1137-1139, 1165-1172, 1174-1179, 1181-1185, 1187, 1188, 1190-1197, 1218, 1220, 1222, 1223-1241, 1313-1318, 1321-1343, 1387-1389, 1395, 1416, 1417, 1419, 1420, 1442-1445, 1453-1455, 1448, 1474, 1496, humanized versions thereof, or an amino acid sequence comprising at least a 80%, at least a 85%, at least a 90%, or at least a 95% sequence identity thereto.
Therapeutic use by administering a therapeutically effective amount
The antibody of claim 1 for treating a subject by administering a therapeutically effective amount.
Across the provided claim content, the invention is anchored in CD25-binding monoclonal antibody variable-region CDR amino acid sequences (heavy and light chains) as enumerated in tables, with further scope narrowing or expansion via functional disruption characteristics, pH-dependent binding comparison, sequence identity coverage, and therapeutic use language.
Stated Advantages
Not explicitly described in patent.
Documented Applications
Treating cancer using anti-CD25 (IL-2 receptor alpha chain) antibodies, including depleting approaches for regulatory T cells [procedural detail omitted for safety].
Treating autoimmune disease using anti-CD25 (IL-2 receptor alpha chain) antibodies [procedural detail omitted for safety].
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