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US 2026/0274972 A1Published application
Anti-ccr8 antibodies and uses thereof
AssigneeGilead Sciences, Inc.
InventorsJillian L. Boice, Kelli L. Boyd, Janine Y.N. Fu, Chung-Ming Hsieh, Dorothée Saddier Axe, Nicole T. Schirle Oakdale, Nathan D. Thomsen, Willie D. Wang, Brian M. Weist, Rosanna Win
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Abstract
Provided herein are various embodiments relating to anti-CCR8 binding agents, that bind to CCR8, and uses thereof. Some of the embodiments include antibodies, fragments thereof, variants thereof, derivatives thereof, and binding polypeptides targeting the same that bind CCR8. Such anti-CCR8 binding agents can be used in methods to treat, for example, cancer.
Claims113
An isolated antibody or an antigen-binding fragment thereof that binds to human C-C motif chemokine receptor (CCR8), wherein the antibody or fragment thereof comprises:
- a) a heavy chain variable (VH) region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 214, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 215, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 216, and a light chain variable (VL) region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 217, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 218, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 219;
- b) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 56, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 82, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- c) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 37, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- d) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 83, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- e) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 84, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- f) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 58, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 37, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- g) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 59, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 37, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- h) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 60, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 68, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 89, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- i) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 60, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 69, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 89, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- j) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 68, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 89, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- k) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 69, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 89, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- l) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 60, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 89, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- m) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 60, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 68, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- n) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 60, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 69, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- o) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 68, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- p) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 35, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 60, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- q) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 89, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- r) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 37, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 89, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- s) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- t) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 60, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 68, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 37, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- u) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 60, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 69, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 37, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- v) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 68, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 37, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 391;
- w) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 60, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 37, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- x) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 61, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 37, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- y) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 69, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 37, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- z) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 240, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- or
- aa) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 241, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39.
187 more elements
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A binding polypeptide that indicates the presence of CCR8 expressing cells in a sample obtained from a subject, wherein the binding polypeptide selectively binds to CCR8 and is labeled with a detectable label or moiety, wherein the binding polypeptide comprises:
- a) a heavy chain variable (VH) region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 214, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 215, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 216, and a light chain variable (VL) region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 217, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 218, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 219;
- b) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 56, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 82, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- c) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 37, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- d) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 83, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- e) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 84, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- f) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 58, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 37, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- g) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 59, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 37, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- h) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 60, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 68, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 89, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- i) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 60, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 69, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 89, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- j) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 68, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 89, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- k) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 69, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 89, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- l) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 60, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 89, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- m) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 60, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 68, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- n) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 60, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 69, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- o) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 68, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- p) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 35, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 60, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- q) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 89, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- r) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 37, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 89, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- s) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- t) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 60, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 68, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 37, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- u) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 60, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 69, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 37, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- v) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 68, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 37, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 391;
- w) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 60, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 37, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- x) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 61, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 37, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- y) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 69, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 37, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- z) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 240, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- or
- aa) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 241, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39.
187 more elements
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A binding polypeptide that mediates activity in a diseased microenvironment associated with CCR8 expression in a subject, wherein the binding polypeptide selectively binds to CCR8 and is conjugated or fused to one or more therapeutic agents, wherein the binding polypeptide comprises:
- a) a heavy chain variable (VH) region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 214, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 215, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 216, and a light chain variable (VL) region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 217, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 218, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 219;
- b) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 56, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 82, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- c) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 37, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- d) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 83, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- e) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 84, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- f) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 58, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 37, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- g) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 59, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 37, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- h) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 60, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 68, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 89, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- i) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 60, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 69, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 89, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- j) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 68, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 89, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- k) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 69, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 89, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- l) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 60, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 89, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- m) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 60, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 68, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- n) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 60, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 69, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- o) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 68, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- p) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 35, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 60, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- q) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 89, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- r) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 37, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 89, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- s) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 85, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- t) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 60, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 68, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 37, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- u) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 60, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 69, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 37, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- v) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 68, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 37, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 391;
- w) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 60, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 37, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- x) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 61, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 37, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- y) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 69, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 37, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- z) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 240, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39;
- or
- aa) a VH region comprising an HCDR1 comprising the amino acid sequence of SEQ ID NO:
- 34, an HCDR2 comprising the amino acid sequence of SEQ ID NO:
- 57, an HCDR3 comprising the amino acid sequence of SEQ ID NO:
- 36, and a VL region comprising an LCDR1 comprising the amino acid sequence of SEQ ID NO:
- 241, an LCDR2 comprising the amino acid sequence of SEQ ID NO:
- 38, and an LCDR3 comprising the amino acid sequence of SEQ ID NO:
- 39.
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A method of selecting a subject suspected of having or having cancer for treatment with an anti-CCR8 agent, the method comprising:
- a) obtaining a sample from the subject;
- b) performing the method of claim 0;
- c) comparing the level of the subject's CCR8 or number of CCR8 expressing cells with a threshold level of CCR8 or number of CCR8 expressing cells;
- and
- d) selecting the subject for treatment with an anti-CCR8 agent if the level of the subject's CCR8 or number of CCR8 expressing cells exceed the threshold level of CCR8 or number of CCR8 expressing cells,
- optionally wherein the CCR8 expressing cell is a CCR8+Treg cell.
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Dependencies are inferred from the claim text.