Antibody molecules to pd-l1 and uses thereof
AssigneesNovartis AG, Dana-Farber Cancer Institute, Inc., President and Fellows of Harvard College
InventorsGordon James Freeman, Arlene Helen Sharpe, Gerhard Johann Frey, Hwai Wen Chang, Jennifer Marie Mataraza, Glenn Dranoff
Life of this patent
Estimating the term…
Abstract
Antibody molecules that specifically bind to PD-L1 are disclosed. Combination therapies comprising the anti-PD-L1 antibody molecules are also disclosed. The anti-PD-L1 antibody molecules can be used to treat, prevent and/or diagnose cancerous or infectious conditions and disorders.
Claims38
-4. (canceled)
An isolated antibody molecule capable of binding to human Programmed Death-Ligand 1 (PD-L1), comprising:
- (a) a heavy chain variable region (VH) comprising a VHCDR1 amino acid sequence of SEQ ID NO:
- 4;
- a VHCDR2 amino acid sequence of SEQ ID NO:
- 5, and a VHCDR3 amino acid sequence of SEQ ID NO:
- 3;
- and a light chain variable region (VL) comprising a VLCDR1 amino acid sequence of SEQ ID NO:
- 12, a VLCDR2 amino acid sequence of SEQ ID NO:
- 13, and a VLCDR3 amino acid sequence of SEQ ID NO:
- 14;
- (b) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO:
- 1;
- a VHCDR2 amino acid sequence of SEQ ID NO:
- 2;
- and a VHCDR3 amino acid sequence of SEQ ID NO:
- 3;
- and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO:
- 9, a VLCDR2 amino acid sequence of SEQ ID NO:
- 10, and a VLCDR3 amino acid sequence of SEQ ID NO:
- 11;
- (c) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO:
- 195;
- a VHCDR2 amino acid sequence of SEQ ID NO:
- 5, and a VHCDR3 amino acid sequence of SEQ ID NO:
- 3;
- and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO:
- 12, a VLCDR2 amino acid sequence of SEQ ID NO:
- 13, and a VLCDR3 amino acid sequence of SEQ ID NO:
- 14;
- and
- (d) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO:
- 195;
- a VHCDR2 amino acid sequence of SEQ ID NO:
- 2;
- and a VHCDR3 amino acid sequence of SEQ ID NO:
- 3;
- and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO:
- 9, a VLCDR2 amino acid sequence of SEQ ID NO:
- 10, and a VLCDR3 amino acid sequence of SEQ ID NO:
- 11.
-17. (canceled)
-56. (canceled)
-73. (canceled)
-93. (canceled)
-97. (canceled)
-101. (canceled)
-105. (canceled)
(canceled)
(canceled)
An isolated nucleic acid encoding the antibody heavy or light chain variable region of an antibody molecule capable of binding to human Programmed Death Ligand-1 (PD-L1), wherein the antibody molecule comprises:
- (a) a heavy chain variable region (VH) comprising a VHCDR1 amino acid sequence of SEQ ID NO:
- 4;
- a VHCDR2 amino acid sequence of SEQ ID NO:
- 5, and a VHCDR3 amino acid sequence of SEQ ID NO:
- 3;
- and a light chain variable region (VL) comprising a VLCDR1 amino acid sequence of SEQ ID NO:
- 12, a VLCDR2 amino acid sequence of SEQ ID NO:
- 13, and a VLCDR3 amino acid sequence of SEQ ID NO:
- 14;
- (b) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO:
- 1;
- a VHCDR2 amino acid sequence of SEQ ID NO:
- 2;
- and a VHCDR3 amino acid sequence of SEQ ID NO:
- 3;
- and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO:
- 9, a VLCDR2 amino acid sequence of SEQ ID NO:
- 10, and a VLCDR3 amino acid sequence of SEQ ID NO:
- 11;
- (c) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO:
- 195;
- a VHCDR2 amino acid sequence of SEQ ID NO:
- 5, and a VHCDR3 amino acid sequence of SEQ ID NO:
- 3;
- and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO:
- 12, a VLCDR2 amino acid sequence of SEQ ID NO:
- 13, and a VLCDR3 amino acid sequence of SEQ ID NO:
- 14;
- and
- (d) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO:
- 195;
- a VHCDR2 amino acid sequence of SEQ ID NO:
- 2;
- and a VHCDR3 amino acid sequence of SEQ ID NO:
- 3;
- and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO:
- 9, a VLCDR2 amino acid sequence of SEQ ID NO:
- 10, and a VLCDR3 amino acid sequence of SEQ ID NO:
- 11.
-121. (canceled)
A method of treating a cancer or an infectious disease, comprising administering to a subject in need thereof an isolated antibody molecule capable of binding to human Programmed Death Ligand-1 (PD-L1) in an amount effective to treat the cancer or infectious disease, wherein the antibody molecule comprises:
- (a) a heavy chain variable region (VH) comprising a VHCDR1 amino acid sequence of SEQ ID NO:
- 4;
- a VHCDR2 amino acid sequence of SEQ ID NO:
- 5, and a VHCDR3 amino acid sequence of SEQ ID NO:
- 3;
- and a light chain variable region (VL) comprising a VLCDR1 amino acid sequence of SEQ ID NO:
- 12, a VLCDR2 amino acid sequence of SEQ ID NO:
- 13, and a VLCDR3 amino acid sequence of SEQ ID NO:
- 14;
- (b) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO:
- 1;
- a VHCDR2 amino acid sequence of SEQ ID NO:
- 2;
- and a VHCDR3 amino acid sequence of SEQ ID NO:
- 3;
- and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO:
- 9, a VLCDR2 amino acid sequence of SEQ ID NO:
- 10, and a VLCDR3 amino acid sequence of SEQ ID NO:
- 11;
- (c) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO:
- 195;
- a VHCDR2 amino acid sequence of SEQ ID NO:
- 5, and a VHCDR3 amino acid sequence of SEQ ID NO:
- 3;
- and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO:
- 12, a VLCDR2 amino acid sequence of SEQ ID NO:
- 13, and a VLCDR3 amino acid sequence of SEQ ID NO:
- 14;
- and
- (d) a VH comprising a VHCDR1 amino acid sequence of SEQ ID NO:
- 195;
- a VHCDR2 amino acid sequence of SEQ ID NO:
- 2;
- and a VHCDR3 amino acid sequence of SEQ ID NO:
- 3;
- and a VL comprising a VLCDR1 amino acid sequence of SEQ ID NO:
- 9, a VLCDR2 amino acid sequence of SEQ ID NO:
- 10, and a VLCDR3 amino acid sequence of SEQ ID NO:
- 11.
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(canceled)
A method of treating a cancer in a subject, comprising administering to the subject a combination of two, three or more therapeutic agents chosen from two or all of the following categories (i)-(iii):
- (i) an agent that enhances tumor antigen presentation chosen from one or more of:
- a STING agonist, a TLR agonist, an A2AR antagonist, an oncolytic virus, a TIM-3 modulator, a vascular endothelial growth factor receptor (VEGFR) inhibitor, a c-Met inhibitor, a TGFb inhibitor, an IDO/TDO inhibitor, a vaccine, or a bi- or tri-specific cell engager, or a combination thereof;
- (ii) (optionally) an agent that enhances an effector cell response chosen from one or more of:
- a GITR agonist, a PD-1 inhibitor, a PD-L1 inhibitor, an inhibitor of IAP (Inhibitor of Apoptosis Protein), an inhibitor of EGFR (Epidermal Growth Factor Receptor), an inhibitor of target of rapamycin (mTOR), IL-15 or a variant thereof, a CTLA-4 inhibitor, a bispecific antibody molecule that binds to CD3 and a tumor antigen, a CD40 agonist, an OX40 agonist, or a CD27 agonist, or a combination thereof;
- or
- (iii) an agent that decreases tumor immunosuppression chosen from an anti-PD-L1 antibody molecule, and, optionally, one or more of:
- a GITR agonist, an inhibitor of an immune checkpoint molecule chosen from one or more of PD-1, LAG-3, TIM-3 or CTLA-4, a CSF-1/1R inhibitor, an IL-17 inhibitor, an IL-1β inhibitor, a CXCR2 inhibitor, an inhibitor of PI3Kγ or PI3Kδ), (vii) a BAFF-R inhibitor, a MALT-1/BTK inhibitor, a JAK inhibitor, a CRTH2 inhibitor, a VEGFR inhibitor, an IL-15 or a variant thereof, a CTLA-4 inhibitor, an IDO/TDO inhibitor, an A2AR antagonist, a TGFb inhibitor, or a PFKFB3 inhibitor, or a combination thereof,
- thereby treating the cancer.
-141. (canceled)
Dependencies are inferred from the claim text.