Binding members to pd-l1
AssigneeCell Medica Switzerland AG
InventorsAbdijapar Shamshiev, Titus Kretzschmar, Miriam Droste, Douglas Phillips
Life of this patent
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Abstract
The present invention relates to anti-PD-L1 binding members and in particular to monovalent, high potency PD-L1-binding antibody fragments being highly stable and soluble. Such binding members may be used in the treatment of cancer and inflammatory diseases as well as in diagnostics. Also provided are related nucleic acids, vectors, cells, and compositions.
Claims42
A binding member having a binding specificity to PD-L1, the binding member having one or more of the following properties:
- (a) binds human PD-L1 with a binding dissociation equilibrium constant (KD) of lower than 10 pM as measured by Kinetic Exclusion Assay under the conditions indicated in Example 4 for monovalent or in Example 9 for bivalent format;
- (b) binds to an epitope on PD-L1 which impedes human PD-L1 interaction with both human PD-1 and human CD80;
- (c) cross-reacts with monkey PD-L1;
- (d) binds monkey PD-L1, with a binding affinity at least as strong, more preferably at least twice as strong for monkey PD-L1 as for human PD-L1;
- (e) does not bind to human PD-L2 or human B7-H3;
- (f) inhibits tumor growth in an HCC827 human lung cancer model;
- (g) forms less than 3% of dimers after 1 or 2 weeks of storage at 37° C. at a concentration of 10 mg/ml in PBS at pH 7.2 in the scFv format.
The binding member of any one of the preceding claims, comprising
- (i) a variable light chain having at least 90% sequence identity to SEQ ID NO:
- 1;
- and/or
- (ii) a variable heavy chain having at least 90% sequence identity to SEQ ID NO:
- 2 or variants thereof, respectively.
The binding member of any one of the preceding claims, further comprising a linker sequence, wherein the linker sequence is the sequence set forth in SEQ ID NO:
- 10, or variants thereof.
A binding member competing with the binding member disclosed herein for binding to human PD-L1.
The binding member, nucleic acid molecule, vector or host cell for use of 27, wherein the PD-L1-mediated disease is cancer, such as at least one of NSCLC (non-small cell lung carcinoma), urothelial cancer, melanoma, renal cell carcinoma, Hodgkin's lymphoma, head and neck squamous cell carcinoma, ovarian cancer, gastrointestinal cancer, hepatocellular cancer, glioma, breast cancer, lymphoma, small cell lung carcinoma, myelodysplastic syndromes, prostate cancer, bladder cancer, cervical cancer, non-clear cell kidney cancer, colorectal cancer, sarcomas, colon cancer, kidney cancer, lung cancer, pancreatic cancer or gastric cancer, skin cancer, uterine cancer, glioblastoma, leukemia, carcinoma, Merkel cell carcinoma or renal cell carcinoma (RCC), blood cancer, multiple myeloma, lymphoblastic leukemia (ALL), B cell leukemia, chronic lymphocytic leukemia, non-Hodgkin's lymphoma, and ovarian cancer;
- or wherein said disease is systemic lupus erythematosus, or wherein said disease is systemic lupus erythematosus, sepsis, stroke, pathogen infection or an autoimmune disorder.
Dependencies are inferred from the claim text.