Clinical preparation of anti-TIGIT antibody

Abstract

The present disclosure relates to pharmaceutical formulations of anti-TIGIT monoclonal antibodies suitable for co-administration and combination with anti-PD-L1 monoclonal antibodies. The present disclosure also relates to articles of manufacture comprising such pharmaceutical formulations, methods of treating cancer using the pharmaceutical formulations, and the use of the pharmaceutical formulations for treating cancer or the manufacture of medicaments for treating cancer. The present disclosure also relates to articles of manufacture comprising a single dose of an anti-TIGIT monoclonal antibody or both an anti-TIGIT monoclonal antibody and an anti-PD-L1 monoclonal antibody, and methods of treating cancer using such articles of manufacture and the formulations contained therein.

Description

[Technical field]

[0001] Related Applications

[0001] This application claims priority to and the benefit of U.S. Provisional Patent Application No. 63 / 292,863 (filed December 22, 2021), U.S. Provisional Patent Application No. 63 / 383,451 (filed November 11, 2022), and U.S. Provisional Patent Application No. 63 / 387,229 (filed December 13, 2022), the entire contents of which are incorporated herein by reference.

[0002] Technical Field

[0002] The present disclosure is in the field of pharmaceutical formulations comprising anti-TIGIT monoclonal antibodies, which are suitable for co-administration and combination with anti-PD-L1 monoclonal antibodies.

[0003] Sequence Listing

[0003] This disclosure includes a Sequence Listing that has been submitted electronically in XML format, the entire contents of which are incorporated herein by reference. A copy of said XML was created on December 21, 2022, is named 000218-0047-WO1_SL.xml, and is 26,125 bytes in size.

[0004] background

[0004] Cancer is the leading cause of death in the world, with approximately 9,958,130 deaths worldwide in 2020. In North America, the number of new cases was estimated at 2,556,860 (1,372,000 men and 1,184,860 women) and 699,274 cancer deaths. Similar data for Central and Eastern Europe in 2020 showed 1,314,193 new cases (657,259 men; 656,934 women) and 695,828 cancer deaths (Global Cancer Observatory, December, 2020). For most malignancies, existing treatments are ineffective in improving quality of life, delaying disease progression, extending survival, or curing patients.

[0005]

[0005] Immunotherapy has been established as a treatment strategy for cancer, improving the prognosis of many patients suffering from various cancers. Moreover, combinations of immunotherapies have proven to be more effective in treating cancer. In fact, the FDA has granted Breakthrough Therapy Designation (BTD) to the combination of tiragolumab and atezolizumab as a first-line treatment for non-small cell lung cancer. Immunotherapy is typically infused into patients over several hours. Patients receiving combination therapy must respond to two separate infusions for longer periods (if the treatments are administered on the same day) or more frequently (if the treatments are administered on different days). Thus, there is a need in the art for combination therapies that can be either co-administered or combined. Such co-administration or combination would reduce patient burden and improve patient compliance. There is also a need in the art for therapies that can be administered more quickly than intravenous infusion (e.g., subcutaneous injection). Summary of the Invention

[0006]

[0006] In some aspects, the disclosure provides a liquid pharmaceutical formulation comprising an anti-TIGIT monoclonal antibody and an anti-PD-L1 monoclonal antibody. In some embodiments, the liquid pharmaceutical formulation comprises: (a) 18 mg / mL to 176 mg / mL of an anti-TIGIT monoclonal antibody; (b) 54 mg / mL to 137.5 mg / mL of an anti-PD-L1 monoclonal antibody; (c) 5 mM to 30 mM histidine buffer; (d) 120 mM to 320 mM sucrose; and (e) 0.02% (w / v) to 0.08% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.4 to 6.2; wherein the anti-TIGIT monoclonal antibody is HVR-H1 comprising the amino acid sequence of SEQ ID NO:1; HVR-H2 comprising the amino acid sequence of SEQ ID NO:2; and HVR-H3 comprising the amino acid sequence of SEQ ID NO:3. and HVR-L3 comprising the amino acid sequence of SEQ ID NO:6; and a light chain variable region comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:10; HVR-H2 comprising the amino acid sequence of SEQ ID NO:11; and HVR-H3 comprising the amino acid sequence of SEQ ID NO:12; and a light chain variable region comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:13; HVR-L2 comprising the amino acid sequence of SEQ ID NO:14; and HVR-L3 comprising the amino acid sequence of SEQ ID NO:15.

[0007] In some embodiments, the liquid pharmaceutical formulation comprises: (a) 18 mg / mL to 176 mg / mL of an anti-TIGIT monoclonal antibody; (b) 54 mg / mL to 137.5 mg / mL of an anti-PD-L1 monoclonal antibody; (c) 5 mM to 30 mM histidine buffer; (d) 120 mM to 320 mM sucrose; and (e) 0.02% (w / v) to 0.08% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation has a pH characterized by a pH of about 5.2 to 6.1. in some embodiments, the formulation comprises: (a) 30 mg / mL to 50 mg / mL of anti-TIGIT monoclonal antibody; (b) 70 mg / mL to 90 mg / mL of anti-PD-L1 monoclonal antibody; (c) 15 mM to 25 mM histidine buffer; (d) 200 mM to 280 mM sucrose; and (e) 0.04% (w / v) to 0.08% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.5 to 6.1. In some embodiments, the formulation comprises: (a) 30 mg / mL to 50 mg / mL of anti-TIGIT monoclonal antibody; (b) 70 mg / mL to 90 mg / mL of anti-PD-L1 monoclonal antibody; (c) 15 mM to 25 mM histidine buffer; (d) 200 mM to 280 mM sucrose; and (e) 0.04% (w / v) to 0.08% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.6 to 6.0. In some embodiments, the formulation comprises: (a) 36 mg / mL to 44 mg / mL of anti-TIGIT monoclonal antibody; (b) 72 mg / mL to 88 mg / mL of anti-PD-L1 monoclonal antibody; (c) 18 mM to 22 mM histidine buffer; (d) 220 mM to 260 mM sucrose; and (e) 0.05% (w / v) to 0.07% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.7 to 5.9.In some embodiments, the formulation comprises: (a) 36 mg / mL to 44 mg / mL of anti-TIGIT monoclonal antibody; (b) 72 mg / mL to 88 mg / mL of anti-PD-L1 monoclonal antibody; (c) 15 mM to 25 mM histidine buffer; (d) 200 mM to 280 mM sucrose; and (e) 0.04% (w / v) to 0.08% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.5 to 6.1. In some embodiments, the formulation comprises (a) 40 mg / mL of anti-TIGIT monoclonal antibody; (b) 80 mg / mL of anti-PD-L1 monoclonal antibody; (c) 20 mM histidine buffer; (d) 240 mM sucrose; and (e) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.5. In some embodiments, the formulation comprises (a) 40 mg / mL of anti-TIGIT monoclonal antibody; (b) 80 mg / mL of anti-PD-L1 monoclonal antibody; (c) 20 mM histidine buffer; (d) 240 mM sucrose; and (e) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.6. In some embodiments, the formulation comprises (a) 40 mg / mL of anti-TIGIT monoclonal antibody; (b) 80 mg / mL of anti-PD-L1 monoclonal antibody; (c) 20 mM histidine buffer; (d) 240 mM sucrose; and (e) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.7. In some embodiments, the formulation comprises (a) 40 mg / mL of anti-TIGIT monoclonal antibody; (b) 80 mg / mL of anti-PD-L1 monoclonal antibody; (c) 20 mM histidine buffer; (d) 240 mM sucrose; and (e) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.8.

[0008]

[0008] In another aspect, the disclosure provides a liquid pharmaceutical formulation suitable for subcutaneous injection, comprising an anti-TIGIT monoclonal antibody, an anti-PD-L1 monoclonal antibody, and hyaluronidase. In some embodiments, the liquid pharmaceutical formulation comprises: (a) 18 mg / mL to 75 mg / mL of an anti-TIGIT monoclonal antibody; (b) 54 mg / mL to 137.5 mg / mL of an anti-PD-L1 monoclonal antibody; (c) 12 mM to 28 mM histidine buffer; (d) 100 mM to 300 mM sucrose; and (e) 0.02% (w / v) to 0.08% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.4 to 6.2; wherein the anti-TIGIT monoclonal antibody is HVR-H1 comprising the amino acid sequence of SEQ ID NO:1; HVR-H2 comprising the amino acid sequence of SEQ ID NO:2; and HVR-H3 comprising the amino acid sequence of SEQ ID NO:3. and HVR-L3 comprising the amino acid sequence of SEQ ID NO:6; and a light chain variable region comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:10; HVR-H2 comprising the amino acid sequence of SEQ ID NO:11; and HVR-H3 comprising the amino acid sequence of SEQ ID NO:12; and a light chain variable region comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:13; HVR-L2 comprising the amino acid sequence of SEQ ID NO:14; and HVR-L3 comprising the amino acid sequence of SEQ ID NO:15.

[0009]

[0009] In another aspect, the present disclosure provides a liquid pharmaceutical formulation suitable for subcutaneous injection, comprising an anti-TIGIT monoclonal antibody, an anti-PD-L1 monoclonal antibody, and hyaluronidase. In some embodiments, the liquid pharmaceutical formulation comprises: (a) 30 mg / mL to 60 mg / mL of an anti-TIGIT monoclonal antibody; (b) 60 mg / mL to 120 mg / mL of an anti-PD-L1 monoclonal antibody; (c) 500 U / mL to 2600 U / mL of hyaluronidase; (d) 5 mM to 30 mM histidine buffer; (e) 180 mM to 320 mM sucrose; and (f) 0.03% (w / v) to 0.08% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.2 to 6.1; wherein the anti-TIGIT monoclonal antibody is HVR-H1 comprising the amino acid sequence of SEQ ID NO:1; HVR-H2 comprising the amino acid sequence of SEQ ID NO:2; and HVR-L1 comprising the amino acid sequence of SEQ ID NO:4; HVR-L2 comprising the amino acid sequence of SEQ ID NO:5; and HVR-L3 comprising the amino acid sequence of SEQ ID NO:6; the anti-PD-L1 monoclonal antibody comprises a heavy chain variable region comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:10; HVR-H2 comprising the amino acid sequence of SEQ ID NO:11; and HVR-H3 comprising the amino acid sequence of SEQ ID NO:12; and a light chain variable region comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:13; HVR-L2 comprising the amino acid sequence of SEQ ID NO:14; and HVR-L3 comprising the amino acid sequence of SEQ ID NO:15.

[0010]

[0010] In some embodiments, the formulation comprises (a) 35 mg / mL to 55 mg / mL of anti-TIGIT monoclonal antibody; (b) 70 mg / mL to 110 mg / mL of anti-PD-L1 monoclonal antibody; (c) 1400 U / mL to 2600 U / mL hyaluronidase; (d) 5 mM to 25 mM histidine buffer; (e) 180 mM to 320 mM sucrose; and (f) 0.04% (w / v) to 0.08% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.5 to 5.8.

[0011]

[0011] In some embodiments, the formulation comprises (a) 30 mg / mL to 60 mg / mL of anti-TIGIT monoclonal antibody; (b) 60 mg / mL to 120 mg / mL of anti-PD-L1 monoclonal antibody; (c) 1000 U / mL to 3000 U / mL hyaluronidase; (d) 15 mM to 25 mM histidine buffer; (e) 200 mM to 280 mM sucrose; and (f) 0.04% (w / v) to 0.08% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.2 to 6.1. In some embodiments, the formulation comprises: (a) 35 mg / mL to 45 mg / mL of anti-TIGIT monoclonal antibody; (b) 70 mg / mL to 90 mg / mL of anti-PD-L1 monoclonal antibody; (c) 1500 U / mL to 2500 U / mL of hyaluronidase; (d) 18 mM to 22 mM histidine buffer; (e) 220 mM to 260 mM sucrose; and (f) 0.05% (w / v) to 0.07% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.5 to 5.8. In some embodiments, the formulation comprises: (a) 40 mg / mL to 50 mg / mL of anti-TIGIT monoclonal antibody; (b) 80 mg / mL to 100 mg / mL of anti-PD-L1 monoclonal antibody; (c) 1500 U / mL to 2500 U / mL of hyaluronidase; (d) 18 mM to 22 mM histidine buffer; (e) 220 mM to 260 mM sucrose; and (f) 0.05% (w / v) to 0.07% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.5 to 5.8.

[0012]

[0012] In some embodiments, the formulation comprises (a) 30 mg / mL anti-TIGIT monoclonal antibody; (b) 60 mg / mL anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.5 to 5.8. In some embodiments, the formulation comprises: (a) 30 mg / mL of anti-TIGIT monoclonal antibody; (b) 60 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.5. In some embodiments, the formulation comprises: (a) 30 mg / mL of anti-TIGIT monoclonal antibody; (b) 60 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.6. In some embodiments, the formulation comprises: (a) 30 mg / mL of anti-TIGIT monoclonal antibody; (b) 60 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.7. In some embodiments, the formulation comprises: (a) 30 mg / mL of anti-TIGIT monoclonal antibody; (b) 60 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.8.

[0013]

[0013] In some embodiments, the formulation comprises (a) 35 mg / mL anti-TIGIT monoclonal antibody; (b) 70 mg / mL anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.5 to 5.8. In some embodiments, the formulation comprises: (a) 35 mg / mL of anti-TIGIT monoclonal antibody; (b) 70 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.5. In some embodiments, the formulation comprises: (a) 35 mg / mL of anti-TIGIT monoclonal antibody; (b) 70 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.6. In some embodiments, the formulation comprises: (a) 35 mg / mL of anti-TIGIT monoclonal antibody; (b) 70 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.7. In some embodiments, the formulation comprises: (a) 35 mg / mL of anti-TIGIT monoclonal antibody; (b) 70 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.8.

[0014]

[0014] In some embodiments, the formulation comprises (a) 40 mg / mL anti-TIGIT monoclonal antibody; (b) 80 mg / mL anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.5 to 5.8. In some embodiments, the formulation comprises: (a) 40 mg / mL of anti-TIGIT monoclonal antibody; (b) 80 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.5. In some embodiments, the formulation comprises: (a) 40 mg / mL of anti-TIGIT monoclonal antibody; (b) 80 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.6. In some embodiments, the formulation comprises: (a) 40 mg / mL of anti-TIGIT monoclonal antibody; (b) 80 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.7. In some embodiments, the formulation comprises: (a) 40 mg / mL of anti-TIGIT monoclonal antibody; (b) 80 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.8.

[0015]

[0015] In some embodiments, the formulation comprises (a) 45 mg / mL anti-TIGIT monoclonal antibody; (b) 90 mg / mL anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.5 to 5.8. In some embodiments, the formulation comprises: (a) 45 mg / mL of anti-TIGIT monoclonal antibody; (b) 90 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.5. In some embodiments, the formulation comprises: (a) 45 mg / mL of anti-TIGIT monoclonal antibody; (b) 90 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.6. In some embodiments, the formulation comprises: (a) 45 mg / mL of anti-TIGIT monoclonal antibody; (b) 90 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.7. In some embodiments, the formulation comprises: (a) 45 mg / mL of anti-TIGIT monoclonal antibody; (b) 90 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.8.

[0016]

[0016] In some embodiments, the formulation comprises (a) 50 mg / mL anti-TIGIT monoclonal antibody; (b) 100 mg / mL anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.5 to 5.8. In some embodiments, the formulation comprises: (a) 50 mg / mL of anti-TIGIT monoclonal antibody; (b) 100 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.5. In some embodiments, the formulation comprises: (a) 50 mg / mL of anti-TIGIT monoclonal antibody; (b) 100 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.6. In some embodiments, the formulation comprises: (a) 50 mg / mL of anti-TIGIT monoclonal antibody; (b) 100 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.7. In some embodiments, the formulation comprises: (a) 50 mg / mL of anti-TIGIT monoclonal antibody; (b) 100 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.8.

[0017]

[0017] In some embodiments, the formulation comprises (a) 55 mg / mL anti-TIGIT monoclonal antibody; (b) 110 mg / mL anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.5 to 5.8. In some embodiments, the formulation comprises: (a) 55 mg / mL of anti-TIGIT monoclonal antibody; (b) 110 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.5. In some embodiments, the formulation comprises: (a) 55 mg / mL of anti-TIGIT monoclonal antibody; (b) 110 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.6. In some embodiments, the formulation comprises: (a) 55 mg / mL of anti-TIGIT monoclonal antibody; (b) 110 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.7. In some embodiments, the formulation comprises: (a) 55 mg / mL of anti-TIGIT monoclonal antibody; (b) 110 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.8.

[0018]

[0018] In some embodiments, the heavy chain variable region of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 16. In some embodiments, the light chain variable region of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 17. In some embodiments, the heavy chain variable region of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 16 and the light chain variable region of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 17. In some embodiments, the anti-PD-L1 monoclonal antibody is an IgG antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is an IgG1 or IgG4 antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is a full-length antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is a full-length IgG antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is a full-length IgG antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is a full-length IgG1 antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is a full-length human IgG1 antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is a full-length humanized IgG antibody. The anti-PD-L1 monoclonal antibody may be an antibody fragment. In some embodiments, the anti-PD-L1 monoclonal antibody is a Fab, Fab', F(ab') 2 , Fv fragment, or scFv fragment. In some embodiments, the anti-PD-L1 monoclonal antibody is a human antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is a humanized antibody.

[0019] In another aspect, the present disclosure provides a liquid pharmaceutical formulation comprising an anti-TIGIT monoclonal antibody and suitable for co-administration with an anti-PD-L1 monoclonal antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is an anti-PD-L1 monoclonal antibody disclosed above. In some embodiments, the liquid pharmaceutical formulation comprises: (a) 18 mg / mL to 176 mg / mL of an anti-TIGIT monoclonal antibody; (b) 5 mM to 30 mM histidine acetate; (c) 100 mM to 320 mM sucrose; and (d) 0.01% (w / v) to 0.08% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.0 to 6.0; the anti-TIGIT monoclonal antibody comprises a heavy chain variable region comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2; and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3; and a light chain variable region comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0020] In another aspect, the present disclosure provides a liquid pharmaceutical formulation comprising an anti-TIGIT monoclonal antibody and suitable for co-administration with an anti-PD-L1 monoclonal antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is an anti-PD-L1 monoclonal antibody disclosed above. In some embodiments, the liquid pharmaceutical formulation comprises: (a) 18 mg / mL to 75 mg / mL of an anti-TIGIT monoclonal antibody; (b) 5 mM to 30 mM histidine acetate; (c) 100 mM to 320 mM sucrose; and (d) 0.01% (w / v) to 0.08% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.0 to 6.0; the anti-TIGIT monoclonal antibody comprises a heavy chain variable region comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2; and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3; and a light chain variable region comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0021]

[0021] In some embodiments, the formulation comprises (a) 144 mg / mL to 176 mg / mL of anti-TIGIT monoclonal antibody; (b) 5 mM to 25 mM histidine buffer; (c) 180 mM to 320 mM sucrose; and (d) 0.05% (w / v) to 0.08% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.2 to 5.8. In some embodiments, the formulation comprises (a) 160 mg / mL of anti-TIGIT monoclonal antibody; (b) 20 mM histidine buffer; (c) 240 mM sucrose; and (d) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.5.

[0022]

[0022] In some embodiments, the liquid pharmaceutical formulation comprises (a) 50 mg / mL to 70 mg / mL of anti-TIGIT monoclonal antibody; (b) 15 mM to 25 mM histidine buffer; (c) 200 mM to 280 mM sucrose; and (d) 0.02% (w / v) to 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.2 to 5.8. In some embodiments, the liquid pharmaceutical formulation comprises (a) 54 mg / mL to 66 mg / mL of anti-TIGIT monoclonal antibody; (b) 18 mM to 22 mM histidine buffer; (c) 220 mM to 260 mM sucrose; and (d) 0.03% (w / v) to 0.05% (w / v) of polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.4 to 5.6. In some embodiments, the formulation comprises (a) 60 mg / mL of anti-TIGIT monoclonal antibody; (b) 20 mM histidine buffer; (c) 240 mM sucrose; and (d) 0.04 percent (w / v) of polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.5.

[0023] In a further aspect, the present disclosure provides a liquid pharmaceutical formulation suitable for subcutaneous injection and comprising an anti-TIGIT monoclonal antibody. In some embodiments, the liquid pharmaceutical formulation comprises: (a) 18 mg / mL to 176 mg / mL of an anti-TIGIT monoclonal antibody; (b) 500 U / mL to 2600 U / mL of hyaluronidase; (c) 5 mM to 30 mM histidine buffer; (d) 180 mM to 320 mM sucrose; and (e) 0.03% (w / v) to 0.08% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.2 to 6.0; the anti-TIGIT monoclonal antibody comprises a heavy chain variable region comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:1; HVR-H2 comprising the amino acid sequence of SEQ ID NO:2; and HVR-H3 comprising the amino acid sequence of SEQ ID NO:3, and a light chain variable region comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:4; HVR-L2 comprising the amino acid sequence of SEQ ID NO:5; and HVR-L3 comprising the amino acid sequence of SEQ ID NO:6.

[0024]

[0024] In some embodiments, the liquid pharmaceutical formulation comprises (a) 144 mg / mL to 176 mg / mL of anti-TIGIT monoclonal antibody; (b) 1400 U / mL to 2600 U / mL of hyaluronidase; (c) 5 mM to 25 mM histidine buffer; (d) 180 mM to 320 mM sucrose; and (e) 0.04% (w / v) to 0.08% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.2 to 5.8. In some embodiments, the formulation comprises (a) 160 mg / mL of anti-TIGIT monoclonal antibody; (b) 2000 U / mL of hyaluronidase; (c) 20 mM histidine buffer; (d) 240 mM sucrose; and (e) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.5.

[0025] In some embodiments, the hyaluronidase is a recombinant human hyaluronidase. In some embodiments, the hyaluronidase is a human soluble PH20 hyaluronidase glycoprotein, such as rHuPH20.

[0026]

[0026] In some embodiments of any of the above formulations, the histidine buffer is histidine acetate.

[0027]

[0027] In some embodiments of any of the above formulations, the formulation further comprises a stabilizer. In some embodiments, the stabilizer is selected from the group consisting of methionine, glycine, alanine, proline, taurine, betaine, octopine, glutamate, sarcosine, γ-aminobutyric acid, and trimethylamine N-oxide. In some embodiments, the stabilizer is methionine. In some embodiments, the concentration of the stabilizer is about 0 mM to about 15 mM. In some embodiments, the concentration of the stabilizer is about 5 mM to about 15 mM. In some embodiments, the concentration of the stabilizer is about 10 mM.

[0028]

[0028] In an additional aspect, the disclosure provides an article of manufacture comprising a liquid pharmaceutical formulation disclosed herein. In some embodiments, the article of manufacture is a vial. In some embodiments, the vial is a single dose vial. In some embodiments, the vial is stoppered with a chlorobutyl elastomer stopper. In some embodiments, the article of manufacture is a prefilled syringe. In some embodiments, the article of manufacture is a syringe pump. In some embodiments, the article of manufacture is a subcutaneous administration device. In some embodiments, the subcutaneous administration device is selected from the group consisting of a syringe, a syringe pump, an injection device, an infusion pump, a syringe pen, a needleless device, an autoinjector, and a subcutaneous patch delivery system. In some embodiments, the subcutaneous administration device is a syringe. In some embodiments, the subcutaneous administration device is a syringe pump. In some embodiments, the subcutaneous administration device is an injection device. In some embodiments, the subcutaneous administration device is an infusion pump. In some embodiments, the subcutaneous administration device is a syringe pen. In some embodiments, the subcutaneous administration device is a needleless device. In some embodiments, the subcutaneous administration device is an autoinjector. In some embodiments, the subcutaneous administration device is a subcutaneous patch delivery system.

[0029] In some embodiments, the article of manufacture comprises about 3 mL to about 30 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manufacture comprises about 3 mL to about 60 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manufacture comprises about 10 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manufacture comprises about 7 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manufacture comprises about 6.5 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manufacture comprises about 21 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manufacture comprises about 50 mL of the liquid pharmaceutical formulation.

[0030]

[0030] In additional aspects, the disclosure provides an article of manufacture comprising a formulation comprising 18 mg / mL to 176 mg / mL of an anti-TIGIT monoclonal antibody. In some embodiments, the formulation comprises 144 mg / mL to 176 mg / mL of an anti-TIGIT monoclonal antibody. In some embodiments, the formulation comprises 160 mg / mL of an anti-TIGIT monoclonal antibody. In some embodiments, the article of manufacture further comprises a formulation comprising an anti-PD-L1 monoclonal antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is atezolizumab.

[0031]

[0031] In a further aspect, the disclosure provides an article of manufacture comprising a formulation comprising (a) 30 mg / mL to 60 mg / mL of anti-TIGIT monoclonal antibody and (b) 60 mg / mL to 120 mg / mL of anti-PD-L1 monoclonal antibody. In some embodiments, the formulation comprises (a) 35 mg / mL to 55 mg / mL of anti-TIGIT monoclonal antibody and (b) 70 mg / mL to 110 mg / mL of anti-PD-L1 monoclonal antibody. In some embodiments, the formulation comprises (a) 30 mg / mL of anti-TIGIT monoclonal antibody and (b) 60 mg / mL of anti-PD-L1 monoclonal antibody. In some embodiments, the formulation comprises (a) 35 mg / mL of anti-TIGIT monoclonal antibody and (b) 70 mg / mL of anti-PD-L1 monoclonal antibody. In some embodiments, the formulation comprises (a) 40 mg / mL of anti-TIGIT monoclonal antibody and (b) 80 mg / mL of anti-PD-L1 monoclonal antibody. In some embodiments, the formulation comprises (a) 45 mg / mL of anti-TIGIT monoclonal antibody and (b) 90 mg / mL of anti-PD-L1 monoclonal antibody. In some embodiments, the formulation comprises (a) 50 mg / mL of anti-TIGIT monoclonal antibody and (b) 100 mg / mL of anti-PD-L1 monoclonal antibody. In some embodiments, the formulation comprises (a) 55 mg / mL of anti-TIGIT monoclonal antibody and (b) 110 mg / mL of anti-PD-L1 monoclonal antibody.

[0032]

[0032] In another aspect, the disclosure provides an article of manufacture comprising a formulation comprising 880 mg / mL of anti-TIGIT monoclonal antibody. In some embodiments, the formulation further comprises 1875 mg or 2000 mg of anti-PD-L1 monoclonal antibody. In some embodiments, the formulation further comprises 1875 mg of anti-PD-L1 monoclonal antibody. In some embodiments, the formulation further comprises 2000 mg of anti-PD-L1 monoclonal antibody. In some embodiments, the formulation further comprises anti-PD-L1 monoclonal antibody. In some embodiments, the formulation further comprises hyaluronidase.

[0033] In an additional aspect, the disclosure provides an article of manufacture comprising 880 mg of an anti-TIGIT monoclonal antibody and 1875 mg or 2000 mg of an anti-PD-L1 monoclonal antibody. In some embodiments, the formulation further comprises hyaluronidase.

[0034]

[0034] In some embodiments, the formulations included in the articles of manufacture of the present disclosure further comprise hyaluronidase. In some embodiments, the formulations included in the articles of manufacture of the present disclosure further comprise hyaluronidase, and the hyaluronidase is between 500 U / mL and 2600 U / mL. In some embodiments, the hyaluronidase is between 1400 U / mL and 2600 U / mL. In some embodiments, the hyaluronidase is at 2000 U / mL. In some embodiments, the hyaluronidase is recombinant human hyaluronidase. In some embodiments, the recombinant hyaluronidase is human soluble PH20 hyaluronidase glycoprotein, such as rHuPH20.

[0035]

[0035] In some embodiments, an article of manufacture of the present disclosure comprises about 3 mL to about 60 mL of an anti-TIGIT monoclonal antibody and one or more of hyaluronidase, histidine buffer, sucrose, and polysorbate 20. In some embodiments, an article of manufacture of the present disclosure comprises about 10 mL of an anti-TIGIT monoclonal antibody and one or more of hyaluronidase, histidine buffer, sucrose, and polysorbate 20. In some embodiments, an article of manufacture of the present disclosure comprises about 7 mL of an anti-TIGIT monoclonal antibody and one or more of hyaluronidase, histidine buffer, sucrose, and polysorbate 20.

[0036] In some embodiments, an article of manufacture of the present disclosure comprises about 6.5 mL of an anti-TIGIT monoclonal antibody and one or more of hyaluronidase, histidine buffer, sucrose, and polysorbate 20. In some embodiments, an article of manufacture of the present disclosure comprises about 21 mL of an anti-TIGIT monoclonal antibody and one or more of hyaluronidase, histidine buffer, sucrose, and polysorbate 20.

[0037] In an additional aspect, the disclosure provides an article of manufacture comprising a subcutaneous administration device that contains and delivers a fixed dose of 880 mg of an anti-TIGIT monoclonal antibody to a patient. In some embodiments, the subcutaneous administration device further delivers a fixed dose of 1875 mg or 2000 mg of an anti-PD-L1 monoclonal antibody to the patient. In some embodiments, the subcutaneous administration device is a syringe pump.

[0038]

[0037] In some embodiments of any of the above aspects, the heavy chain variable region (VH) of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 7. In some embodiments of any of the above aspects, the light chain variable region (VL) of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 9. In some embodiments of any of the above aspects, the heavy chain variable region of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 7, and the light chain variable region of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 9. In some embodiments of any of the above aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 18. In some embodiments of any of the above aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 19. In some embodiments of any of the above aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 24. In some embodiments of any of the above aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 25. In some embodiments of any of the above aspects, the light chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 18, and the light chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 19, and the light chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 24, and the light chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 25, and the light chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is tiragolumab.

[0039]

[0038] In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is an IgG antibody. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is an IgG1 or IgG4 antibody. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is a full-length antibody. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is a full-length IgG antibody. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is a full-length IgG1 antibody. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is a full-length human IgG1 antibody. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is a full-length humanized IgG1 antibody. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is an antibody fragment. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is a Fab, Fab', F(ab') 2 , Fv or scFv fragment. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is a human antibody. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody is a humanized antibody. In some embodiments of any of the above aspects, the anti-TIGIT monoclonal antibody inhibits or blocks the interaction of CD226 with TIGIT.

[0040]

[0039] In some embodiments of any of the above aspects, the anti-PD-L1 monoclonal antibody comprises a heavy chain variable region comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 10; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 11; and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 12, and a light chain variable region comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 13; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 14; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 15. In some embodiments of any of the above aspects, the heavy chain variable region of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 16. In some embodiments of any of the above aspects, the light chain variable region of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 17. In some embodiments of any of the above aspects, the heavy chain variable region of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 16, and the light chain variable region of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 17. In some embodiments of any of the above aspects, the heavy chain of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO:21. In some embodiments of any of the above aspects, the heavy chain of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO:22. In some embodiments of any of the above aspects, the light chain of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO:23. In some embodiments of any of the above aspects, the heavy chain of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO:21 and the light chain of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO:23. In some embodiments of any of the above aspects, the heavy chain of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO:22 and the light chain of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO:23. In some embodiments of any of the above aspects, the anti-PD-L1 antibody is atezolizumab. In some embodiments of any of the above aspects, the anti-PD-L1 monoclonal antibody is an IgG antibody. In some embodiments of any of the above aspects, the anti-PD-L1 monoclonal antibody is an IgG1 or IgG4 antibody.In some embodiments of any of the above aspects, the anti-PD-L1 monoclonal antibody is a full-length antibody.In some embodiments of any of the above aspects, the anti-PD-L1 monoclonal antibody is an antibody fragment.In some embodiments of any of the above aspects, the anti-PD-L1 monoclonal antibody is a Fab, Fab', F(ab'). 2 , Fv, or scFv fragment. In some embodiments of any of the above aspects, the anti-PD-L1 monoclonal antibody is a human antibody. In some embodiments of any of the above aspects, the anti-PD-L1 monoclonal antibody is a humanized antibody.

[0041] In an additional aspect, the disclosure provides an article of manufacture comprising a subcutaneous administration device that contains and delivers a fixed dose of 880 mg of tiragolumab to a patient. In some embodiments, the subcutaneous administration device further delivers a fixed dose of 1875 mg or 2000 mg of atezolizumab to the patient. In some embodiments, the subcutaneous administration device is a syringe pump.

[0042]

[0041] In an additional aspect, the present disclosure provides a method of treating cancer in a subject in need of cancer treatment, comprising administering to the subject a therapeutically effective amount of a liquid pharmaceutical formulation comprising an anti-TIGIT monoclonal antibody and an anti-PD-L1 monoclonal antibody disclosed herein.

[0043]

[0042] In a further aspect, the present disclosure provides a method of treating cancer in a subject in need of cancer treatment, comprising administering to the subject a therapeutically effective amount of a liquid pharmaceutical formulation comprising an anti-TIGIT monoclonal antibody disclosed herein, and administering to the subject a therapeutically effective amount of an anti-PD-1 monoclonal antibody or an anti-PD-L1 monoclonal antibody. In some embodiments, the anti-PD-1 monoclonal antibody or anti-PD-L1 monoclonal antibody and the liquid pharmaceutical formulation comprising an anti-TIGIT monoclonal antibody are administered simultaneously. In some embodiments, the anti-PD-1 monoclonal antibody or anti-PD-L1 monoclonal antibody and the liquid pharmaceutical formulation comprising an anti-TIGIT monoclonal antibody are mixed within 24 hours prior to administration to the subject. In some embodiments, the anti-PD-1 monoclonal antibody or anti-PD-L1 monoclonal antibody and the liquid pharmaceutical formulation comprising an anti-TIGIT monoclonal antibody are mixed during administration to the subject.

[0044] In some embodiments of any of the methods of treating cancer, the method comprises administering an anti-PD-1 antibody. In some embodiments, the anti-PD-1 antibody is selected from the group consisting of lambrolizumab (MK-3475), nivolumab (MDX-1106), vembrolizumab, cemiplimab, and dostarlimab.

[0045]

[0044] In some embodiments, the method of the invention comprises administering an anti-PD-L1 monoclonal antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is selected from the group consisting of atezolizumab (MPDL3280A), durvalumab (MEDI4736), avelumab, and MDX-1105. In some embodiments, the anti-PD-L1 monoclonal antibody comprises a heavy chain variable region comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 10; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 11; and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 12, and a light chain variable region comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 13; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 14; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 15. In some embodiments, the heavy chain variable region (VH) of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 16. In some embodiments, the light chain variable region (VL) of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 17. In some embodiments, the heavy chain variable region of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 16, and the light chain variable region of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 17. In some embodiments, the heavy chain of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 21. In some embodiments, the heavy chain of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 22. In some embodiments, the light chain of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 21, and the light chain of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 23. In some embodiments, the heavy chain of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 22, and the light chain of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 23.

[0046]

[0045] In some embodiments, the anti-PD-L1 monoclonal antibody or the anti-PD-1 monoclonal antibody is an IgG antibody. In some embodiments, the anti-PD-L1 monoclonal antibody or the anti-PD-1 monoclonal antibody is an IgG1 or IgG4 antibody. In some embodiments, the anti-PD-L1 monoclonal antibody or the anti-PD-1 monoclonal antibody is a full-length antibody. In some embodiments, the anti-PD-L1 monoclonal antibody or the anti-PD-1 monoclonal antibody is a full-length IgG antibody. In some embodiments, the anti-PD-L1 monoclonal antibody or the anti-PD-1 monoclonal antibody is a full-length IgG1 antibody. In some embodiments, the anti-PD-L1 monoclonal antibody or the anti-PD-1 monoclonal antibody is a full-length human IgG1 antibody. In some embodiments, the anti-PD-L1 monoclonal antibody or the anti-PD-1 monoclonal antibody is a full-length humanized IgG antibody. The anti-PD-L1 monoclonal antibody or the anti-PD-1 monoclonal antibody may be an antibody fragment. In some embodiments, the anti-PD-L1 monoclonal antibody or the anti-PD-1 monoclonal antibody is a Fab, Fab', F(ab') 2 , Fv fragment, or scFv fragment. In some embodiments, the anti-PD-L1 monoclonal antibody or the anti-PD-1 monoclonal antibody is a human antibody. In some embodiments, the anti-PD-L1 monoclonal antibody or the anti-PD-1 monoclonal antibody is a humanized antibody.

[0047]

[0046] In some embodiments, the liquid pharmaceutical formulation is administered intravenously. In some embodiments, the liquid pharmaceutical formulation is administered subcutaneously.

[0048]

[0047] In some embodiments, the cancer is selected from the group consisting of lung cancer, non-small cell lung cancer, renal cell carcinoma, urothelial cancer, ureteral cancer, urethral cancer, colorectal cancer, colon cancer, rectal cancer, kidney cancer, sarcoma, ovarian cancer, breast cancer, cervical cancer, fallopian tube cancer, endometrial cancer, uterine cancer, pancreatic cancer, gastric cancer, bladder cancer, esophageal cancer, mesothelioma, melanoma, head and neck cancer, thyroid cancer, sarcoma, prostate cancer, penile cancer, glioblastoma, thymic cancer, esophageal cancer, nasopharyngeal cancer, mesothelioma, liver cancer, biliary tract cancer, HPV-positive cancer, leukemia, lymphoma, brain cancer, neuroendocrine cancer, myeloma, mycosis fungoides, Merkel cell carcinoma, hematological tumors, mismatch repair deficient (dMMR) cancer, and microsatellite instability high (MSI-H) cancer.

[0049]

[0048] In some embodiments, the cancer is selected from the group consisting of bladder cancer, muscle-invasive bladder cancer, urothelial carcinoma, ureter cancer, urethral cancer, ureteral urothelial carcinoma, urethral urothelial carcinoma, kidney cancer, renal pelvis cancer, renal cell carcinoma, clear cell renal carcinoma, rectal cancer, colon cancer, colorectal cancer, sarcoma, osteosarcoma, leiomyosarcoma, pleomorphic sarcoma, myxofibrosarcoma, liposarcoma, chondrosarcoma, lung cancer, non-small cell lung cancer, fallopian tube cancer, peritoneal cancer, esophageal cancer, esophageal squamous cell carcinoma, mesothelioma, pleural mesothelioma, peritoneal mesothelioma, Breast cancer, ovarian cancer, cervical cancer, adenosquamous carcinoma of the cervix, breast cancer, triple-negative breast cancer, HER2-positive breast cancer, HER2-negative breast cancer, estrogen receptor-positive breast cancer, progesterone receptor-positive breast cancer, luminal B breast cancer, lymphoma, T-cell lymphoma, B-cell lymphoma, nasal lymphoma, non-Hodgkin's lymphoma, follicular lymphoma, penile cancer, prostate cancer, castration-resistant prostate cancer, endometrial cancer, uterine cancer, myeloma , multiple myeloma, head and neck cancer, prostate cancer, melanoma, cutaneous melanoma, Merkel cell carcinoma, pancreatic cancer, hepatocellular carcinoma, gastric cancer, gastroesophageal junction adenocarcinoma, glioblastoma, glioblastoma multiforme, mycosis fungoides, HPV positive cancer, HPV related cervical cancer, HPV related anal squamous cell carcinoma, HPV related penile squamous cell carcinoma, HPV related vulvar squamous cell carcinoma, vulvar cancer, vaginal cancer, anal cancer, oropharyngeal cancer, oropharyngeal squamous cell carcinoma, leukemia, acute myeloid leukemia The present invention relates to a method for treating or preventing pulmonary hypertension, atherosclerosis, and / or pulmonary edema. The present invention relates to a method for treating or preventing pulmonary hypertension, atherosclerosis, and / or pulmonary edema. The present invention relates to a method for treating or preventing pulmonary hypertension, atherosclerosis, and / or pulmonary edema.

[0050]

[0049] In some embodiments, the cancer is selected from the group consisting of Merkel cell carcinoma, urothelial carcinoma, renal cell carcinoma, non-small cell lung cancer, breast cancer, triple-negative breast cancer, hepatocellular carcinoma, melanoma, Hodgkin's lymphoma, head and neck cancer, colorectal cancer, gastric cancer, cervical cancer, primary mediastinal large B-cell lymphoma, cutaneous squamous cell carcinoma, basal cell carcinoma, bladder cancer, endometrial cancer, esophageal cancer, malignant pleural mesothelioma, cancers with high tumor mutation burden (TMB), mismatch repair deficient (dMMR) cancers, and microsatellite instability high (MSI-H) cancers.

[0051]

[0050] In some embodiments, the cancer is lung cancer, non-small cell lung cancer, bronchogenic carcinoma, breast cancer, triple-negative breast cancer, estrogen receptor positive breast cancer, HER2 positive breast cancer, metastatic lobular breast cancer, ductal carcinoma, cervical cancer, fallopian tube cancer, fallopian tube serous adenocarcinoma, ovarian cancer, ovarian endometrioid tumor, ovarian serous adenocarcinoma, ovarian mucinous carcinoma, uterine cancer, endometrial cancer, skin cancer, melanoma, cutaneous melanoma, Merkel cell carcinoma, head and neck cancer, squamous cell carcinoma of the head and neck, blood system tumors, leukemia, myeloid leukemia, acute myeloid leukemia, myeloid leukemia, chronic lymphocytic leukemia, myelomonocytic leukemia, thyroid cancer, thyroid cancer, thymic carcinoma, neuroendocrine carcinoma, pheochromocytoma, glioma, glioblastoma multiforme, paraganglioma, lymphoma, B cell lymphoma, Hodgkin lymphoma, B cell non-Hodgkin lymphoma, non-Hodgkin lymphoma, cutaneous T cell lymphoma, diffuse large B cell lymphoma, follicular lymphoma, marginal zone lymphoma, pancreatic cancer, pancreatic ductal adenocarcinoma, rectal cancer, colon cancer, colorectal cancer, urinary tract cancer, genitourinary cancer, mesothelioma, pleural mesothelioma, Peritoneal mesothelioma, sarcoma, chondrosarcoma, clear cell sarcoma, liposarcoma, myxoid / round cell liposarcoma, synovial sarcoma, alveolar soft part sarcoma, gliosarcoma, uterine carcinosarcoma, kidney cancer, non-clear cell kidney cancer, renal cell carcinoma, bladder cancer, urothelial carcinoma, muscle invasive bladder cancer, non-muscle invasive bladder cancer, HER2 positive bladder cancer, gallbladder cancer, gastric cancer, esophageal cancer, esophageal squamous cell carcinoma, gastrointestinal cancer, gastroesophageal cancer, gastroesophageal junction cancer, HER2 positive gastric cancer, primary peritoneal cancer, cutaneous squamous cell carcinoma, prostate cancer, prostate adenocarcinoma, castration resistant prostate The cancer is selected from the group consisting of urogenital cancer, ureteral urothelial carcinoma, renal pelvis urothelial carcinoma, urethral urothelial carcinoma, appendix cancer, penile cancer, anal canal cancer, hepatocellular carcinoma, hepatocellular carcinoma, unresectable liver and intrahepatic bile duct cancer, biliary tract cancer, cholangiocarcinoma, intrahepatic cholangiocarcinoma, extrahepatic bile duct cancer, HPV-related cancer, HPV-related anal squamous cell carcinoma, HPV-related cervical squamous cell carcinoma, HPV-related penile squamous cell carcinoma, HPV-related vulvar squamous cell carcinoma, nasopharyngeal carcinoma, pharyngeal squamous cell carcinoma, hypopharyngeal squamous cell carcinoma, oral squamous cell carcinoma, and mycosis fungoides.

[0052]

[0051] In some embodiments, the cancer is selected from the group consisting of urothelial carcinoma, non-small cell lung cancer (NSCLC), breast cancer, triple-negative breast cancer, hepatocellular carcinoma, and melanoma.

[0053]

[0052] In some embodiments, the cancer is selected from the group consisting of multiple myeloma, cervical cancer, esophageal cancer, esophageal squamous cell carcinoma, lung cancer, non-small cell lung cancer, glioblastoma, endometrial cancer, ovarian cancer, squamous cell carcinoma, and head and neck cancer.

[0054]

[0053] In some embodiments, the cancer is selected from the group consisting of cervical cancer, head and neck squamous cell carcinoma, head and neck cancer, non-small cell lung cancer, non-squamous non-small cell lung cancer, esophageal squamous cell carcinoma, esophageal cancer, breast cancer, triple-negative breast cancer, gastric cancer, gastroesophageal junction adenocarcinoma, multiple myeloma, non-Hodgkin's lymphoma, B-cell lymphoma, liver cancer, bladder cancer, urothelial carcinoma, pancreatic cancer, and pancreatic adenocarcinoma.

[0055] In some embodiments, the cancer is a solid tumor. In some embodiments, the cancer is a hematological cancer.

[0056]

[0055] The patent or application file contains at least one drawing in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee. [Brief description of the drawings]

[0057] [Figure 1A-1B]

[0056] Figure 1 shows the degradation of polysorbate 20 (PS20) as measured by fatty acid mass spectrometry (FAMS). Figure 1A shows a table of fatty acid production (e.g., lauric acid, myristic acid) measured in ng / mL / week at 25°C and 40°C. Figure 1B is a graph showing the degradation rate of PS20 at 25°C by FAMS comparison. aTIGIT refers to α-TIGIT. [Figures 2A-2D]

[0057] Figures 2A-2D are graphs showing the concentration of anti-TIGIT monoclonal antibody (tiragolumab) over time at different temperatures (-20°C (Figure 2A), 5°C (Figure 2B), 25°C (Figure 2C), and 40°C (Figure 2D)) as measured by an evaporative light scattering detector (ELSD). "Solid" refers to striped symbols and is used for formulations containing PS20. "Hollow" refers to unfilled symbols and is used for formulations containing PX188. [Figures 3A-3H]

[0058] Graphs showing the stability of anti-TIGIT monoclonal antibody (tiragolumab) by measuring aggregate formation and low molecular weight species (LMWS) over time or by measuring the formation of charge isomers under acidic or basic conditions. Figure 3A.I (aggregates), Figure 3A.II (main), Figure 3A.III (low molecular weight species (LMWS)): Aggregates and LMWS were measured at 5 °C using size exclusion chromatography. Figure 3B.I (acidic), Figure 3B.II (main), Figure 3B.III (basic): Charge isomers were measured at 5 °C using imaging capillary isoelectric focusing (ICIEF). Figure 3C.I (aggregates), Figure 3C.II (main), Figure 3C.III (LMWS): Aggregates and LMWS were measured at -20 °C using size exclusion chromatography. Figure 3D.I (acidic), Figure 3D.II (main), Figure 3D.III (basic): Charge isomers were measured at -20 °C using ICIEF. Figure 3E.I (aggregates), Figure 3E.II (main), Figure 3E.III (LMWS): Aggregates and LMWS were measured at 25 °C using size exclusion chromatography. Figure 3F.I (acidic), Figure 3F.II (main), Figure 3F.III (basic): Charge isomers were measured at 25 °C using ICIEF. Figure 3G.I (aggregates), Figure 3G.II (main), Figure 3G.III (LMWS): Aggregates and LMWS were measured at 40 °C using size exclusion chromatography. Figure 3H.I (acidic), Figure 3H.II (main), Figure 3H.III (basic): Charge isomers were measured at 40 °C using ICIEF. [Figure 4I-4II]

[0059] 4A-4C are graphs showing the stability of anti-TIGIT monoclonal antibody (tiragolumab) at various protein concentrations, pH, detergent concentrations, histidine acetate concentrations, sucrose concentrations, and detergent types (e.g., PS20 or PX188) as measured by size exclusion chromatography (SEC) for high molecular weight species (HMWS) and low molecular weight species (LMWS) (Figure 4.II) or imaging capillary isoelectric focusing (ICIEF) for the formation of charge isomers in acidic or basic conditions (Figure 4.I). [Diagram 5]

[0060] This is a graph showing the stability of an anti-TIGIT monoclonal antibody formulation (60 mg / mL anti-TIGIT monoclonal antibody (tiragolumab), 20 mM histidine acetate, 120 mM sucrose, pH 5.5, in 25 cc 316 L Mini-Can) after seven freeze-thaw cycles, as measured by SEC main peak and shown as a percentage. [Figure 6]

[0061] Size Exclusion Chromatography (SEC) of a high concentration tiragolumab formulation stored for 1 year at -20° C. This high concentration formulation ("PH3 DS"; 60 mg / mL tiragolumab in 20 mM HisOAc, 240 mM sucrose, 10 mM methionine, 0.04% PS20, pH 5.5) was evaluated at TO and after 91 days, 9 months, and 12 months of storage at -20° C. "HisOAc" = histidine acetate and "RS" = Rep. Stability (400L run). [Figure 7]

[0062] Capillary electrophoresis (CE) of a high concentration tiragolumab formulation stored at -20°C for 1 year. This high concentration formulation ("PH3 DS"; 60 mg / mL tiragolumab in 20 mM HisOAc, 240 mM sucrose, 10 mM methionine, 0.04% PS20, pH 5.5) was evaluated at TO and after 91 days, 9 months, and 12 months of storage at -20°C. The slight difference seen in one of the LMW peaks may be due to assay variability. "HisOAc" = histidine acetate and "RS" = replicate stability (400L run). [Figure 8A-8D]

[0063] Figures 8A-8D show the stability of tiragolumab drug product (DP; 60 mg / ml tiragolumab, 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.4 mg / ml polysorbate 20, pH 5.5) with different infusion systems. Figure 8A shows the stability of setup 1: PVC bag, PVC set, PC and PEU infusion aid, PES I line filter. Figure 8B shows the stability of setup 2: PO bag, PE set, PC and PTFE infusion aid, PES inline filter. Figure 8C shows the stability of setup 3: PE bag, PBD set, PC and PUR infusion aid, PSU inline filter. Figure 8D shows the stability of setup 4: PP bag, PUR set, PC and FEP infusion aid, PES inline filter. In Figures 8A-8D, the following abbreviations are used: CL = clear, CO = colorless, FEP = fluorinated ethylene, HMW = high molecular weight, IE-HPLC = ion-exchange high performance liquid chromatography, LIQ = liquid, LMW = low molecular weight, NT = untested, PBD = polybutadiene, PC = polycarbonate, PE = polyethylene, PES = polyethersulfone, PEU = polyetherurethane, PFFP = virtually particle-free, PO = polyolefin, PP = polypropylene, PSU = polysulfone, PTFE = polytetrafluoroethylene, PUR = polyurethane, PVC = polyvinyl chloride, SE-UPLC = size-exclusion ultra-performance liquid chromatography, UV = ultraviolet. a UV protein content was used for pharmaceutical and high-dose samples. w SE-UHPLC with a standard curve was used for protein concentration determination. [Figure 9A-9C]

[0064] Figures 9A-9C show the stability of dosing solutions for co-infusion of Tiragolumab and Tecentriq® (atezolizumab) drug products using different infusion systems. Figure 9A shows the stability of Setup 1: PVC bag, PVC set, PC and PEU infusion aids, PES in-line filter. Figure 9B shows the stability of Setup 2: PO bag, PE set, PC and PTFE infusion aids, PES in-line filter. Figure 9C shows the stability of Setup 3: PO bag, PBD set, PC and PUR infusion aids, PSU in-line filter. In Figures 9A-9C, the following abbreviations are used: CL = clear, CO = colorless, FEP = fluorinated ethylene, HMW = high molecular weight, IE-HPLC = ion exchange high performance liquid chromatography, LIQ = liquid, LMW = low molecular weight, N / A = not applicable, NT = not tested, PBD = polybutadiene, PC = polycarbonate, PE = polyethylene, PES = polyethersulfone, PEU = polyetherurethane, PFFP = substantially particle free, PO = polyolefin, PP = polypropylene, PSU = polysulfone, PTFE = polytetrafluoroethylene, PUR = polyurethane, PVC = polyvinyl chloride, SE-UPLC = size exclusion ultra-performance liquid chromatography, UV = ultraviolet. a A hydrophilic interaction chromatography (HILIC) assay was developed to measure the protein content of Tiragolumab and Tecentriq® (atezolizumab). b An alternative IE-HPLC method was developed to allow quantification of both Tiragolumab and Tecentriq® (atezolizumab) charge variants. [Figure 10]

[0065] 1 is a graph showing the viscosity of various concentrations of Tiragolumab in different buffers and storage conditions. "HisOAc" = histidine acetate; "ArgSucc" = arginine succinate; "Expon." = exponential curve fit. [Figure 11]

[0066] FIG. 1 provides measurements of stability of different tiragolumab formulations (Formulation 1 - 160 mg / mL tiragolumab in 20 mM HisOAc, 240 mM sucrose, 10 mM methionine, 0.06% PS20, pH 5.5; Formulation 2 - 176 mg / mL tiragolumab in 30 mM HisOAc, 180 mM sucrose, 5 mM methionine, 0.08% PS20, pH 5.5) after different freeze-thaw cycles in different formulations. [Figure 12A-12B]

[0067] Figures 12A and 12B show size exclusion chromatography (SEC) of high concentration (Figure 12A) and ultra-high concentration (Figure 12B) tiragolumab formulations. The high concentration formulation ("60mg / ml tira"; 60mg / mL tiragolumab in 20mM HisOAc, 240mM sucrose, 10mM methionine, 0.04% PS20, pH 5.5) was evaluated after storage at 40°C for 7, 14, 30, and 60 days, and the ultra-high concentration formulation ("160mg / ml tira"; 160mg / mL tiragolumab in 20mM HisOAc, 240mM sucrose, 10mM methionine, 0.06% PS20, pH 5.5) was evaluated at T0 and after storage at 40°C for 2 weeks, 3 weeks, and 1 month. [Figure 13A-13B]

[0068] Ion exchange chromatography (IEC) of high concentration (FIG. 13A) and ultra-high concentration (FIG. 13B) tiragolumab formulations are shown. The high concentration formulation ("60 mg / ml tira"; 60 mg / mL tiragolumab in 20 mM HisOAc, 240 mM sucrose, 10 mM methionine, 0.04% PS20, pH 5.5) was evaluated at T0 and after storage at 40° C. for 14 and 30 days, and the ultra-high concentration formulation ("160 mg / ml tira"; 160 mg / mL tiragolumab in 20 mM HisOAc, 240 mM sucrose, 10 mM methionine, 0.06% PS20, pH 5.5) was evaluated at T0 and after storage at 40° C. for 2 weeks, 3 weeks, and 1 month. [Figure 14]

[0069] 1 is a graph showing hyaluronidase activity over time (90 days) after storage at 25° C. for a pH 5.2 or pH 5.5 formulation. [Figure 15A-15B]

[0070] 15A and 15B are graphs showing the percentage of high molecular weight fraction (HMWF, FIG. 15A ) and low molecular weight fraction (LMWF, FIG. 15B ) over time as measured by size exclusion chromatography for tiragolumab (Tira), atezolizumab (Atezo), or a combination of tiragolumab and atezolizumab at various pHs (e.g., 5.4, 5.8, 6.2). [Figure 16A-16B]

[0071] 16A is a graph showing the ratio of the main peak of tiragolumab (Tira; FIG. 16A) to the main peak of atezolizumab (Atezo; FIG. 16B) over time, as measured by ion exchange chromatography at pH 5.4, 5.8, and 6.2. [Figure 17A-17B]

[0072] 17A-17B are graphs showing the percentage of low molecular weight fraction (LMWF, "pre-peak", FIG. 17A - sum of change over time before the peak) and high molecular weight fraction (HMWF, FIG. 17B - sum of change over time of HMWF) over time for tiragolumab (Tira), atezolizumab (Atezo), or a combination of tiragolumab and atezolizumab, as measured by CE-SDS at various pHs (e.g., 5.4, 5.8, 6.2). [Figure 18]

[0073] 18 shows a treatment protocol using the formulation of the present disclosure. In FIG. 18, the following abbreviations are used: Atezo = Atezolizumab; ECOG = Eastern Cooperative Oncology Group; IV = intravenous; PD = progressive disease; PK = pharmacokinetics; PS = performance status; Q3W = every 3 weeks; SC = subcutaneous; TBD = undetermined; Tira = Tiragolumab. a Single dose of co-mixed Tiragolumab SC and Atezolizumab SC (abdominal). a Three cycles of co-mixed Tiragolumab SC and Atezolizumab SC Q3W (thigh). a Three cycles of co-mixed Tiragolumab SC and Atezolizumab SC Q3W (abdominal). [Figure 19]

[0074] A treatment protocol is shown using one of the formulations disclosed herein (40 mg / mL tiragolumab, 80 mg / mL atezolizumab, 20 mM histidine acetate, 240 mM sucrose, 0.06% (w / v) polysorbate 20, pH 5.8). In Figure 19, the following abbreviations are used: CPI = checkpoint inhibitor; EAC = esophageal adenocarcinoma; ECOG PS = Eastern Cooperative Oncology Group performance status; ESCC = esophageal squamous cell carcinoma; FDC = fixed-dose combination; GEJ = gastroesophageal junction cancer; HCC = hepatocellular carcinoma; IMC = internal monitoring committee; IV = intravenous; NSCLC = non-small cell lung cancer; PD = progressive disease; PD-L1 = programmed death ligand-1; Q3W = every 3 weeks; RCC = renal cell carcinoma; SCCHN = head and neck squamous cell carcinoma; UBC = urothelial bladder cancer; mets = metastases; * = Enrollment is limited to subjects with EAC, ESCC, GEJ, HCC, melanoma, NSCLC, RCC, SCCHN, UBC. Additional tumor types may be added as PD-L1 cutoffs become available. [Figure 20]

[0075] 20 shows a treatment protocol using the formulation of the present disclosure. The following abbreviations are used in Figure 20: Atezo = Atezolizumab; ECOG = Eastern Cooperative Oncology Group; IV = intravenous; PD = progressive disease; PK = pharmacokinetics; PS = performance status; Q3W = every 3 weeks; SC = subcutaneous; TBD = undetermined; Tira = tiragolumab. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0058] General

[0076] The practice of the methods and the preparation and use of the compositions disclosed herein employ, unless otherwise indicated, conventional techniques within the skill of the art in molecular biology, biochemistry, chromatin structure and analysis, computational chemistry, cell culture, recombinant DNA, and related fields, which techniques are fully explained in the literature. See, for example, Sambrook et al. MOLECULAR CLONING: A LABORATORY MANUAL, 2nd ed., Cold Spring Harbor Laboratory Press, 1989 and 3rd ed., 2001; Ausubel et al., CURRENT PROTOCOLS IN MOLECULAR BIOLOGY, John Wiley & Sons, New York, 1987 and regularly updated; METHODS IN ENZYMOLOGY series, Academic Press, San Diego; Wolffe, CHROMATIN STRUCTURE AND FUNCTION, 3rd ed., Academic Press, San Diego, 1998; METHODS IN ENZYMOLOGY, Vol. 304, "Chromatin" (eds. P. M. Wassarman and A. P. Wolffe), Academic Press, San Diego, 1999; and METHODS IN MOLECULAR BIOLOGY, Vol. 119, "Chromatin See, for example, "P.B. Becker, Ed., Humana Press, Totowa, 1999."

[0059]

[0077] The term "herein" refers to the entire disclosure.

[0060]

[0078] Any embodiment described herein may be combined with one or more embodiments disclosed herein, including those described in different aspects of the disclosure and in different parts of this specification (including those embodiments described only in the examples), unless expressly prohibited or inappropriate, and combinations of embodiments are not limited to the specific combinations claimed through dependent claims (including multiple dependent claims).

[0061]

[0079] All publications, patents, and published patent applications mentioned in this disclosure are expressly incorporated herein by reference. In the case of conflict, the present specification, including specific definitions, will control.

[0062]

[0080] Throughout this specification, the word "comprise" or variations thereof (such as "comprises" or "comprising"), which are synonymous with "including," "containing," or "characterized by," are inclusive or open-ended and do not exclude additional, unrecited elements or method steps.

[0063]

[0081] Throughout this specification, when a composition is described as having, including, or comprising a particular component (or variations thereof), it is contemplated that the composition consists essentially of or consists of the recited components. Similarly, when a method or process is described as having, including, or comprising a particular process step, the method consists essentially of or consists of the recited processing steps. Furthermore, unless otherwise stated or the context clearly indicates otherwise, the order of steps or order for performing certain actions is not important so long as the compositions and methods described herein are operable. Moreover, two or more steps or actions may be performed simultaneously.

[0064]

[0082] The term "consisting of" excludes any element, step or ingredient not specifically listed.

[0065]

[0083] The term "consisting essentially of" limits the scope of the disclosure to the specified materials or steps and those that do not materially affect the basic and novel characteristic(s) of the disclosure.

[0066]

[0084] Examples following the term "example" or "for example" are not meant to be exhaustive or limiting.

[0067]

[0085] The articles "a", "an" and "the" are used herein to refer to one or to more than one (i.e. to at least one) of the grammatical object of the article. By way of example, "an element" means one element or more than one element.

[0068]

[0086] As used herein, the term "about" modifying the amount of a component, parameter, calculation or measurement in a composition used in a method of the present disclosure refers to variations in numerical quantities that may occur, for example, due to common measuring and liquid handling procedures used to produce isolated polypeptides or pharmaceutical compositions in the real world, inadvertent errors in these procedures, differences in the manufacture, source or purity of components used to produce the compositions of the present invention or to carry out the methods of the present invention, and the like, that do not substantially affect the chemical or physical properties of the compositions or methods of the present disclosure. Such variations may be within 10%, more typically within 5%, of a given value or range. The term "about" also includes amounts that vary due to different equilibrium conditions of a composition resulting from a particular initial mixture. The paragraph includes the equivalent of the amount, whether or not modified by the term "about." Reference herein to "about" a value or parameter includes (and describes) a particular embodiment with respect to the value or parameter itself. For example, a statement of "about X" includes a statement of "X." A numerical range includes the numbers defining the range.

[0069]

[0087] As used herein, the term "or" means "and / or" unless the context clearly indicates otherwise.

[0070]

[0088] Notwithstanding that the numerical ranges and parameters setting forth the broad scope of the present disclosure are approximations, the numerical values ​​set forth in the specific examples are reported as precisely as possible. However, any numerical value inherently contains certain errors necessarily resulting from the standard deviation found in their respective testing measurements. Furthermore, the description of numerical values ​​is not limited to the specifically recited value, but also includes numerical values ​​that one of ordinary skill in the art would normally round to in the context of significant digits. Moreover, all ranges disclosed herein are to be understood to encompass all subranges contained therein. For example, a recited range of "1 to 10" shall be deemed to include all subranges between a minimum value of 1 and a maximum value of 10 (including the boundaries), i.e., all subranges beginning with a minimum value of 1 or more (e.g., 1 to 6.1) and ending with a maximum value of 10 or less (e.g., 5.5 to 10). Furthermore, the disclosure of a range shall be deemed to disclose the endpoints of that range.

[0071]

[0089] Exemplary methods and materials are described herein, although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure. The materials, methods, and examples are illustrative only and are not intended to be limiting.

[0072] definition

[0090] As used herein, "administering" a substance, compound, agent, or composition to a subject or "administration of" it to a subject refers to contacting the substance, compound, agent, or composition with the subject or with a cell, tissue, organ, or bodily fluid of the subject. Such administration can be performed using any of a variety of methods known to those of skill in the art. For example, the substance, compound, agent, or composition can be administered orally or parenterally, such as by injection. In some embodiments, the substance, compound, agent, or composition is administered subcutaneously. In some embodiments, the substance, compound, agent, or composition is administered intravenously. Also, administration can be, for example, administered once, multiple times, and / or over one or more extended periods of time. In some embodiments, administration includes both direct administration, including self-administration, and indirect administration, including the act of prescribing a drug. For example, as used herein, a physician who instructs a subject to self-administer a drug or to have another medication administered to them, and / or who provides a prescription for a drug to a subject, is administering a drug to a subject.

[0073]

[0091] As used herein, the term "antibody" or "Ab" is used in the broadest sense and specifically includes monoclonal antibodies (including full-length monoclonal antibodies), polyclonal antibodies, multispecific antibodies (e.g., bispecific antibodies), and antibody fragments, so long as they exhibit the desired biological activity. An "isolated" antibody is one that has been identified, separated, and / or recovered from a component of its natural environment. Contaminant components of its natural environment are substances that would interfere with research, diagnostic, or therapeutic uses of the antibody, and may include enzymes, hormones, and other proteinaceous or non-proteinaceous solutes. In some embodiments, the antibody is purified (1) to greater than 95%, and in some embodiments greater than 99%, by weight of the antibody, as measured, for example, by the Lowry method; (2) to a degree sufficient to obtain at least 15 residues of N-terminal or internal amino acid sequence, for example, by using a spinning cup sequenator; or (3) to homogeneity, for example, by SDS-PAGE under reducing or non-reducing conditions using Coomassie blue or silver staining. Isolated antibody includes the antibody in situ within recombinant cells since at least one component of the antibody's natural environment will not be present. Ordinarily, however, isolated antibody will be prepared by at least one purification step.

[0074]

[0092] The terms "anti-TIGIT antibody", "anti-TIGIT monoclonal antibody" and "antibody that specifically binds to TIGIT" are used interchangeably herein and refer to an antibody that can bind to TIGIT with sufficient affinity so as to be useful as a diagnostic and / or therapeutic agent for targeting TIGIT. In some embodiments, the extent of binding of an anti-TIGIT antibody to an unrelated non-TIGIT protein is less than about 10% of the binding of the antibody to TIGIT, e.g., as measured by radioimmunoassay (RIA). In certain embodiments, an antibody that binds to TIGIT has an affinity of 1 μM, ≦100 nM, ≦10 nM, ≦1 nM, ≦0.1 nM, ≦0.01 nM or ≦0.001 nM (e.g., 10 -8 M or less, e.g. 10 -8 M~10 -13 M, e.g. 10 -9 M~10-13 In certain embodiments, the anti-TIGIT antibody binds to an epitope on TIGIT that allows for cross-species reactivity, such as an epitope of TIGIT that is conserved among TIGITs of different species, or an epitope comprising amino acid residues Ser78, Ser80, and Lys82.

[0075]

[0093] The terms "anti-PD-L1 antibody," "anti-PD-L1 monoclonal antibody," and "antibody that specifically binds to PD-L1" are used interchangeably herein and refer to an antibody that can bind to PD-L1 with sufficient affinity such that it is useful as a diagnostic and / or therapeutic agent in targeting PD-L1. In some embodiments, the extent of binding of an anti-PD-L1 antibody to an unrelated, non-PD-L1 protein is less than about 10% of the binding of the antibody to PD-L1 as measured, for example, by radioimmunoassay (RIA). In certain embodiments, an antibody that binds to PD-L1 has an affinity of 1 μM, ≦100 nM, ≦10 nM, ≦1 nM, ≦0.1 nM, ≦0.01 nM, or ≦0.001 nM (e.g., 10 -8 M or less, e.g. 10 -8 M~10 -13 M, e.g. 10 -9 M~10 -13 M) in which the antibody binds to a PD-L1 epitope that is conserved among PD-L1 from different species, or an epitope on PD-L1 that is capable of cross-species reactivity.

[0076]

[0094] The term "antibody fragment" as used herein refers to a portion of an intact antibody, preferably the antigen binding and / or variable region of the intact antibody. Examples of antibody fragments include Fab, Fab', F(ab') 2These include F(ab') and Fv fragments; diabodies; linear antibodies (see U.S. Pat. No. 5,641,870, Example 2; Zapata et al., Protein Eng. 8(10):1057-1062

[1995] ); single-chain antibody molecules; and multispecific antibodies formed from antibody fragments. Papain digestion of antibodies produces two identical antigen-binding fragments, called "Fab" fragments, and a residual "Fc" fragment, reflecting their ability to crystallize readily. The Fab fragment consists of an entire L chain, the variable region domain of the H chain (VH), and the first constant domain (CH1) of one heavy chain. Each Fab fragment is monovalent with respect to antigen binding, i.e., it has a single antigen-binding site. Pepsin treatment of antibodies produces a single large F(ab') fragment. 2 The resulting fragment corresponds roughly to two disulfide-linked Fab fragments, each of which has antigen-binding activity and still has the ability to cross-link antigen. Fab' fragments differ from Fab fragments in that they have a few additional residues at the carboxy terminus of the CH1 domain including one or more cysteines from the antibody hinge region. Fab'-SH is the designation herein for Fab' in which the cysteine ​​residues of its constant domains bear a free thiol group. F(ab') 2 Antibody fragments have been produced as pairs of Fab' fragments with hinge cysteines between them. Other chemical couplings of antibody fragments are also known. The Fc fragment contains the carboxy-terminal portions of both H chains held together by disulfides. The effector functions of the antibody are determined by sequences within the Fc region, but this region is also the portion recognized by the Fc receptors (FcR) found on certain cell types. "EU format as described by Edelman" or "EU numbering" or "EU index" refers to the residue numbering of the human Fc domain as described by Edelman GM et al. (Proc. Natl. Acad. USA (1969), 63, 78-85, incorporated herein by reference in its entirety).

[0077]

[0095] The term "buffer" as used herein refers to a reagent that can resist changes in pH due to the addition of acid or base, and keep the pH in a solution relatively stable. Non-limiting examples of buffers include histidine, arginine, acetate, citrate, succinate, gluconate, phosphate, or combinations thereof. Other non-limiting examples include histidine, acetate, histidine acetate, histidine hydrochloride, histidine acetate and arginine, citrate, citric acid, sodium acetate, sodium citrate, arginine succinate, phosphate, disodium phosphate dihydrate, and sodium dihydrogen phosphate dihydrate, or combinations thereof.

[0078]

[0096] The term "atezolizumab," as used herein, refers to the anti-PD-L1 monoclonal antagonist antibody having the International Nonproprietary Name (INN) List 112 (WHO Drug Information, Vol. 28, No. 4, 2014, p. 488) or CAS Registry Number 1380723-44-3.

[0079]

[0097] The term "cancer" as used herein refers to a disease caused by the uncontrolled division of abnormal cells in a part of the body. Cancer may be locally advanced or metastatic. In some cases, cancer is locally advanced. In some cases, cancer is metastatic. In some cases, cancer is recurrent. In some cases, cancer may become unresectable (e.g., unresectable locally advanced or metastatic cancer).

[0098] The term "chimeric" antibody, as used herein, refers to an antibody in which a portion of the heavy and / or light chain is derived from a particular source or species, while the remainder of the heavy and / or light chain is derived from a different source or species.

[0080]

[0099] The terms "full-length antibody", "intact antibody" and "whole antibody" are used interchangeably herein and refer to a substantially complete antibody, as opposed to an antibody fragment. Specifically, a whole antibody includes an antibody having a heavy chain and a light chain, including an Fc region. The constant domain may be a native sequence constant domain (e.g., a human native sequence constant domain) or an amino acid sequence variant thereof. It is known in the art that C-terminal clipping of antibodies by carboxypeptidases occurs during antibody expression. Such clipped antibodies are substantially complete, despite the removal of one or more C-terminal amino acid residues, and are therefore considered to be full-length antibodies. In some cases, an intact antibody may have one or more effector functions. In some embodiments, an intact antibody retains all effector functions. Optionally, one or more effector functions of the antibody may be modified or removed.

[0081]

[0100] As used herein, the term "effector function" refers to a biochemical event resulting from the interaction of the Fc region of an antibody with an Fc receptor or another effector molecule (e.g., Fc receptor-like (FcRL) molecule, complement component C1q, and tripartite motif-containing protein 21 (TRIM21)). Effector functions include, but are not limited to, antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cell-mediated phagocytosis (ADCP), complement-dependent cytotoxicity (CDC), and the like. The term "ADCC" or "antibody-dependent cell-mediated cytotoxicity" as used herein refers to a cell-mediated reaction in which nonspecific cytotoxic cells expressing FcγR recognize bound antibody on a target cell and subsequently cause lysis of the target cell. ADCC correlates with binding to FcγRIIIa; increased binding to FcγRIIIa increases ADCC activity. The term "ADCP" or "antibody-dependent cell-mediated phagocytosis" as used herein refers to a cell-mediated reaction in which non-specific cytotoxic cells expressing FcγR recognize bound antibodies on target cells and subsequently phagocytose the target cells. The term "CDC" or "complement-dependent cytotoxicity" as used herein refers to an effector function triggered by the binding of antibodies to antigens on target cells, leading to activation of the classical complement pathway, which activates a series of cascades involving complement-related proteins in the blood.

[0082]

[0101] The term "human antibody" as used herein refers to an antibody having an amino acid sequence corresponding to that of an antibody produced by a human and / or an antibody made using any of the techniques known in the art for making human antibodies. "Human antibody" specifically excludes humanized antibodies that contain non-human antigen-binding residues. Human antibodies can be generated using a variety of techniques known in the art, including phage display libraries, mouse hybridomas, transgenic animals (e.g., mice), and single B-cell techniques. See, e.g., Lu et al., J. Biomed. Sci., 27:1 (2020); Hoogenboom and Winter, J. Mol. Biol., 227:381 (1991); Marks et al., J. Mol. Biol., 222:581 (1991). Each of these references is incorporated herein by reference in its entirety. Also available for the preparation of human monoclonal antibodies are the methods described in Cole et al., Monoclonal Antibodies and Cancer Therapy, Alan R. Liss, p. 77 (1985); Boerner et al., J. Immunol., 147(1):8695 (1991). See also van Dijk and van de Winkel, Curr. Opin. Pharmacol., 5:368-74 (2001). Human antibodies can be prepared by administering antigen to transgenic animals (e.g., immunized xenomouse) that have been engineered to produce human antibodies in response to antigen challenge (e.g., XENOMOUSE). TM(See U.S. Patent Nos. 6,075,181 and 6,150,584 for techniques). Other transgenic animals for human antibody production are also known in the art, including, for example, HuMAb mice, UntiMAb mice, Transchromo mice, VelocImmune mice, OmniRat, OmniMouse, Harbour Mouse, Kymouse, MeMo mice, AlivaMab mice, and the like. See, for example, Brueggemann et al., Arch. Immunol. Ther. Exp. (Warsz.) 2015, vol. 63(2): 101-108. Additional techniques are also known in the art. See, for example, Li et al., Proc. Natl. Acad. Sci. USA, 103: 3557-3562 (2006) for human antibodies generated by human B cell hybridoma technology.

[0083]

[0102] As used herein, a "humanized" antibody refers to a chimeric antibody that contains both human and non-human antibody sequences. Typically, a humanized antibody contains minimal sequence derived from a non-human immunoglobulin. For example, a humanized antibody includes a human immunoglobulin (recipient antibody) in which hypervariable region residues of the recipient are replaced by residues from a hypervariable region of a non-human species (donor antibody) such as mouse, rat, rabbit or non-human primate having the desired specificity, affinity and capacity. In some cases, certain framework region (FR) residues of the human immunoglobulin are replaced by corresponding non-human residues. Furthermore, humanized antibodies may contain residues that are not found in the recipient antibody or the donor antibody. These modifications are made to further improve antibody performance. In general, a humanized antibody will contain substantially all of at least one, and typically two, variable domains, in which all or substantially all of the hypervariable loops correspond to those of a non-human immunoglobulin and all or substantially all of the FRs are those of human immunoglobulin sequences. A humanized antibody optionally also comprises at least a portion of an immunoglobulin constant region (Fc), typically that of a human immunoglobulin. For further details, see Jones et al., Nature 321:522-525 (1986); Riechmann et al., Nature 332:323-329 (1988); and Presta, Curr. Op. Struct. Biol. 2:593-596 (1992). See also Vaswani and Hamilton, Ann. Allergy, Asthma & Immunol. 1:105-115 (1998); Harris, Biochem. Soc. Transactions 23:1035-1038 (1995); Hurle and Gross, Curr. Op. Biotech. 5:428-433 (1994).

[0084]

[0103] The term "hyaluronidase" as used herein refers to an enzyme that catalyzes the degradation of hyaluronic acid (also called hyaluronan). Hyaluronidase temporarily hydrolyzes hyaluronic acid, a component of the subcutaneous matrix, and reduces the viscosity of the extracellular matrix of the subcutaneous tissue, improving the delivery of drugs administered subcutaneously in the systemic circulation. In some embodiments, the hyaluronidase is recombinant human hyaluronidase. In some embodiments, recombinant human hyaluronidase is administered subcutaneously.

[0085]

[0104] As used herein, the term "hypervariable region", "HVR" or "HV" refers to a region of an antibody variable domain that is hypervariable in sequence and / or forms structurally defined loops. Generally, an antibody contains six HVRs, three in the VH (H1, H2, H3) and three in the VL (L1, L2, L3). In natural antibodies, H3 and L3 show the highest diversity among the six HVRs, and H3 in particular is thought to play a unique role in conferring high specificity to antibodies. See, for example, Xu et al., Immunity 13:37-45 (2000); Johnson and Wu, Methods in Molecular Biology 248:1-25 (Lo, ed., Human Press, Totowa, NJ, 2003). For example, natural camelid antibodies consisting of only heavy chains are functional and stable even without light chains. See, e.g., Hamers-Casterman et al., Nature 363:446-448 (1993); Sheriff et al., Nature Struct. Biol. 3:733-736 (1996).

[0086]

[0105] Several delineations of HVRs are in use in the art and are encompassed herein. Kabat complementarity determining regions (CDRs) are based on sequence variability and are one of the most commonly used definitions (Kabat et al., Sequences of Proteins of Immunological Interest, 5th Ed. Public Health Service, National Institutes of Health, Bethesda, MD. (1991)). Chothia instead refers to the location of structural loops (Chothia and Lesk, J. Mol. Biol. 196:901-917 (1987)). AbM HVRs are a compromise between the Kabat HVRs and the Chothia structural loops, and are the basis of the Oxford The IMGT numbering system is used in Molecular's AbM antibody modeling software. The "contact" HVRs are based on the analysis of available complex crystal structures. The IMGT numbering system was created by taking into account the high degree of conservation of the V-domain structure and by integrating knowledge gained by the analysis of multiple sources, including the alignment of over 5000 sequences, literature data on the framework (FR) and complementarity determining regions (CDR), structural data from X-ray diffraction studies, and characterization of the CDR hypervariable loops. The residues from each of these HVRs are listed in Table 1 below. TIFF2025500483000002.tif112170

[0087]

[0106] Unless otherwise specified, HVRs are determined according to Kabat et al., supra. HVRs may include "extended HVRs" as follows: residues 24-36 or 24-34 (L1), residues 46-56 or 50-56 (L2) and residues 89-97 or 89-96 (L3) in VL, and residues 26-35 (H1), residues 50-65 or 49-65 (H2) and residues 93-102, 94-102 or 95-102 (H3) in VH, each according to Kabat numbering.

[0088]

[0107] The term "monoclonal antibody" as used herein refers to an antibody obtained from a single clone or cell line of cells that produces a population of substantially homogeneous antibodies, i.e., the individual antibodies produced by the cells are identical, except for possible naturally occurring mutations that may be present in minor amounts. Monoclonal antibodies are highly specific and directed against a single antigen. Furthermore, in contrast to polyclonal antibody preparations, which typically contain different antibodies directed against different determinants (epitopes), each monoclonal antibody is directed against a single determinant on the antigen. Monoclonal antibodies may be human, humanized, or chimeric.

[0089]

[0108] The term "stabilizer" as used herein refers to an agent that reduces or minimizes the oxidation of a composition. Non-limiting examples of stabilizers include methionine, glycine, alanine, proline, taurine, betaine, octopine, glutamate, sarcosine, gamma-aminobutyric acid, and trimethylamine N-oxide.

[0090]

[0109] The terms "subject" and "patient" are used interchangeably herein and refer to a human in need of treatment. Thus, the term "subject" or "patient" as used herein refers to a human patient or subject to whom the compositions of the present disclosure may be administered. In some embodiments, the subject is in need of treatment for cancer.

[0091]

[0110] The term "surfactant" as used herein refers to an agent that reduces the surface tension between two liquids, between a gas and a liquid, or between a liquid and a solid. In some embodiments, surfactants prevent protein loss due to surface adsorption. In some embodiments, surfactants minimize the likelihood of formation of soluble aggregates and / or insoluble protein particles. Surfactants can be ionic, non-ionic, zwitterionic, or a combination thereof. Non-limiting examples of surfactants include polysorbates (e.g., polysorbate 20 and polysorbate 80), poloxamers (e.g., poloxamer 188), triton, octyl glucoside, polyethyl glycol, myristamidopropyl-dimethylamine, palmidopropyl-dimethylamine, isostearamidopropyl-dimethylamine, polypropyl glycol, copolymers of ethylene, copolymers of propylene glycol, sodium dodecyl sulfate, sodium lauryl sulfate, lauryl-sulfobetaine, myristyl-sulfobetaine, linoleyl-sulfobetaine, stearyl-sulfobetaine, lauroamidopropyl-betaine, cocamidopropyl-betaine, linoleamidopropyl-betaine, myristamidopropyl-betaine, palmidopropyl-betaine, isostearamidopropyl-betaine, sodium methyl cocoyl-taurate, sodium methyl oleyl-taurate, and mixtures thereof.

[0092]

[0111] As used herein, the term "effective amount" refers to at least the minimum amount of a substance, compound, drug or composition, such as an antibody, required to affect a measurable improvement of a particular disorder. The therapeutically effective amount herein may vary depending on factors such as the patient's condition, age, sex, and weight, and the ability of the substance, compound, drug or composition, such as an antibody, to induce a desired response in an individual. Appropriate amounts and administration regimens can be determined using common techniques in the art. A therapeutically effective amount is also an amount in which the therapeutically beneficial effects outweigh the toxic or adverse effects of the treatment. Beneficial or desired results include clinical results such as reduction of one or more symptoms caused by the disease, improvement of the quality of life of the disease sufferer, reduction of the dose of other drugs required to treat the disease, enhancement of the effect of another drug, for example by targeting, delay of disease progression, and / or prolonged survival. In the case of cancer or tumors, a therapeutically effective amount of a drug may be effective to reduce the number of cancer cells; reduce the size of the tumor; inhibit (i.e., slow to some extent, preferably stop) cancer cell invasion into peripheral organs; inhibit (i.e., slow to some extent, preferably stop) tumor metastasis; inhibit tumor growth to some extent; alleviate to some extent one or more symptoms associated with the disorder, and / or maintain remission. A therapeutically effective amount may be administered in one or more administrations. In the present disclosure, a therapeutically effective amount of a drug, compound, or pharmaceutical composition is an amount sufficient to directly or indirectly achieve therapeutic treatment. As understood in the clinical context, a therapeutically effective amount of a drug, compound, or pharmaceutical composition may or may not be achieved in combination with another drug, compound, or pharmaceutical composition. Thus, a "therapeutically effective amount" may be considered in the context of administering one or more therapeutic agents, and a single agent may be considered to be given in a therapeutically effective amount when a desired result may or has been achieved in combination with one or more other agents.

[0093]

[0112] The term "tonicity agent" as used herein refers to an agent that affects the osmotic gradient of a composition. In some embodiments, a tonicity agent is added to a composition to achieve isotonicity, where the osmotic pressure of the composition is the same as compared to a reference composition. In some embodiments, the composition may be isotonic with the subject's blood or other bodily fluid. The tonicity agent may be a salt. In some embodiments, the tonicity agent is a polyol, such as a sugar or sugar alcohol. Non-limiting examples of tonicity agents include fructose, mannose, maltose, lactose, arabinose, xylose, ribose, rhamnose, galactose, glucose, sucrose, trehalose, sorbose, melezitose, raffinose, mannitol, xylitol, erythritol, threitol, sorbitol, glycerol, sodium chloride, and potassium chloride.

[0094]

[0113] As used herein, "treatment" (and variations thereof, such as "treat" or "treating") refers to a clinical intervention intended to alter the natural history of the individual or cells being treated during the course of clinical pathology. Desired effects of treatment include slowing the rate of disease progression, improving or mitigating the condition, preventing cancer recurrence, preventing metastasis, and achieving remission or improving prognosis. For example, an individual suffering from cancer is considered to have been successfully "treated" if one or more symptoms associated with the cancer are alleviated or eliminated, such as inhibiting (or destroying) the proliferation of cancer cells, reducing symptoms caused by the cancer, improving the quality of life of the cancer sufferer, reducing the dosage of other drugs required to treat the cancer, slowing the progression of the cancer, and / or prolonging the survival of the individual.

[0095]

[0114] The term "variable region" or "variable domain" as used herein refers to the domain of an antibody heavy or light chain involved in binding the antibody to an antigen. The heavy and light chain variable domains (VH and VL, respectively) of natural antibodies generally have similar structures, with each domain comprising four conserved framework regions (FR) and three hypervariable regions (HVR). (See, e.g., Kindt et al. Kuby Immunology, 6th ed., WH Freeman and Co., p. 91 (2007)). Although a VH domain is usually paired with a VL domain, a single VH or VL domain may be sufficient to confer antigen-binding specificity. Furthermore, antibodies that bind to a particular antigen can be isolated using the VH or VL domain of an antibody that binds to that antigen, and a library of complementary VL or VH domains, respectively, can be screened. See, e.g., Portolano et al, J. Immunol. 150:880-887 (1993); Clarkson et al, Nature 352:624-628 (1991).

[0096]

[0115] The term "vial" as used herein refers to a small container for storing a pharmaceutical formulation. In some embodiments, the vial is stoppered with a chlorobutyl elastomer stopper. In some embodiments, the vial is glass. In some embodiments, the vial is plastic.

[0097] Overview

[0116] The present disclosure relates to anti-TIGIT monoclonal antibody formulations, articles of manufacture, and methods of treatment suitable for co-administration or combination with anti-PD-L1 monoclonal antibodies to shorten patient treatment times and thus increase patient compliance. Therapeutic proteins, such as therapeutic antibodies, are large and have complex surface chemistry. Thus, different therapeutic proteins (such as therapeutic antibodies) interact differently with the components of a pharmaceutical formulation, and a formulation that confers stability to one therapeutic antibody may not confers stability to another therapeutic antibody. Indeed, it is known in the art that the hydrophobicity of the CDR loops of an antibody is a key determinant of the aggregation tendency of an antibody. See, for example, Perchiacca et al., Annu. Rev. Chem. Biomol. Eng. 3:263-286, 2012. Antibodies that bind to different antigens have different CDR residues and therefore different surface chemistries. As a result, different antibodies often require different formulation components to confer stability and / or bioavailability. The present disclosure provides an anti-TIGIT monoclonal antibody pharmaceutical formulation that can be co-administered with or include an anti-PD-L1 monoclonal antibody without adversely affecting the stability and / or bioavailability of either antibody. Such a formulation is unexpected given the state of the art. The present disclosure also provides a stable, highly concentrated anti-TIGIT formulation that shortens administration time from hours to minutes, thereby improving patient convenience and compliance. The present disclosure also provides a stable, highly concentrated anti-TIGIT formulation suitable for subcutaneous administration that shortens administration time from hours to minutes, thereby improving patient convenience and compliance.

[0098] Pharmaceutical preparations

[0117] A first aspect of the present disclosure provides a liquid pharmaceutical formulation comprising: (a) an anti-TIGIT monoclonal antibody; (b) a buffer; (c) a tonicity agent; and (d) a surfactant, wherein the liquid pharmaceutical formulation has a pH of about 5.4 to about 6.2. In some embodiments, the liquid pharmaceutical formulation is suitable for co-administration with an anti-PD-L1 monoclonal antibody.

[0099]

[0118] Another aspect of the present disclosure provides a liquid pharmaceutical formulation comprising: (a) an anti-TIGIT monoclonal antibody, (b) an anti-PD-L1 monoclonal antibody, (c) a buffer, (d) an isotonicity agent, and (e) a surfactant, wherein the liquid pharmaceutical formulation has a pH of about 5.4 to about 6.2.

[0100]

[0119] In some embodiments, the anti-TIGIT monoclonal antibody comprises a heavy chain variable region comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2; and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3, and a light chain variable region comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0101]

[0120] In some embodiments, the anti-TIGIT monoclonal antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7. In some embodiments, the anti-TIGIT monoclonal antibody comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO: 9. In some embodiments, the anti-TIGIT monoclonal antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 9. In some embodiments of any of the above aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 18. In some embodiments of any of the above aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 19. In some embodiments of any of the above aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 24. In some embodiments of any of the above aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 25. In some embodiments of any of the above aspects, the light chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 18, and the light chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 19, and the light chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 24, and the light chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20. In some embodiments of any of the above aspects, the heavy chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 25, and the light chain of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 20. In some embodiments, the anti-TIGIT monoclonal antibody is tiragolumab. In some embodiments, the anti-TIGIT monoclonal antibody is tiragolumab.Tiragolumab is listed in the WHO Drug Information (International Nonproprietary Names for Pharmaceutical Substances), proposed INN: List 117, Volume 31, Number 2, published June 9, 2017 (see page 343). In some embodiments, tiragolumab has the CAS Registry Number 1918185-84-8.

[0102]

[0121] In some embodiments, the anti-TIGIT monoclonal antibody is an IgG antibody. The anti-TIGIT monoclonal antibody may be an IgG1 antibody, an IgG2 antibody, an IgG3 antibody, or an IgG4 antibody. In some embodiments, the anti-TIGIT monoclonal antibody is an IgG1 or IgG4 antibody. In some embodiments, the anti-TIGIT monoclonal antibody is an IgG1 antibody. In some embodiments, the anti-TIGIT monoclonal antibody is a wild-type IgG1 antibody. In some embodiments, the anti-TIGIT monoclonal antibody comprises a human IgG1 Fc region comprising one or more amino acid modifications. In some embodiments, the anti-TIGIT monoclonal antibody is an IgG4 antibody. In some embodiments, the anti-TIGIT monoclonal antibody is a wild-type IgG4 antibody. In some embodiments, the anti-TIGIT monoclonal antibody comprises a human IgG4 Fc region comprising one or more amino acid modifications. In some embodiments, the anti-TIGIT monoclonal antibody is an antagonist antibody. In some cases, the anti-TIGIT monoclonal antibody may have one or more effector functions. In some embodiments, the anti-TIGIT monoclonal antibody retains all effector functions. Optionally, one or more effector functions of the anti-TIGIT monoclonal antibody may be altered or removed.

[0103]

[0122] In some embodiments, the anti-TIGIT monoclonal antibody is a human antibody. In some embodiments, the anti-TIGIT monoclonal antibody is a humanized antibody. In some embodiments, the anti-TIGIT monoclonal antibody is a full-length antibody. In some embodiments, the anti-TIGIT monoclonal antibody is a full-length IgG antibody. In some embodiments, the anti-TIGIT monoclonal antibody is a full-length IgG1 antibody. In some embodiments, the anti-TIGIT monoclonal antibody is a full-length human IgG1 antibody. The anti-TIGIT monoclonal antibody may be an antibody fragment. In some embodiments, the anti-TIGIT monoclonal antibody is a Fab, Fab', F(ab') 2 In some embodiments, the anti-TIGIT monoclonal antibody is a Fab fragment. In some embodiments, the anti-TIGIT monoclonal antibody is a Fab' fragment. In some embodiments, the anti-TIGIT monoclonal antibody is a F(ab') 2 In some embodiments, the anti-TIGIT monoclonal antibody is an Fv fragment. In some embodiments, the anti-TIGIT monoclonal antibody is an scFv fragment. In some embodiments, the anti-TIGIT monoclonal antibody is a diabody. In some embodiments, the anti-TIGIT monoclonal antibody is a linear antibody. In some embodiments, the anti-TIGIT monoclonal antibody is a single-chain antibody molecule. In some embodiments, the anti-TIGIT monoclonal antibody is a multispecific antibody, e.g., a multispecific antibody formed from antibody fragments.

[0104]

[0123] In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 75 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 25 mg / mL to about 75 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 30 mg / mL to about 75 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 35 mg / mL to about 75 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 40 mg / mL to about 75 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 45 mg / mL to about 75 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 50 mg / mL to about 75 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 55 mg / mL to about 75 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 60 mg / mL to about 75 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 65 mg / mL to about 75 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 70 mg / mL to about 75 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 70 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 65 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 60 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 55 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 45 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 40 mg / mL.In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 35 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 30 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 25 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 45 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 30 mg / mL to about 45 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 45 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 45 mg / mL to about 75 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 50 mg / mL to about 70 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 55 mg / mL to about 65 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 60 mg / mL to about 65 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 55 mg / mL to about 60 mg / mL.

[0105]

[0124] In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 180 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 160 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 140 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 120 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 100 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 80 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 60 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 40 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 40 mg / mL to about 180 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 60 mg / mL to about 180 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 80 mg / mL to about 180 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 100 mg / mL to about 180 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 120 mg / mL to about 180 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 140 mg / mL to about 180 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 160 mg / mL to about 180 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 30 mg / mL to about 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 40 mg / mL to about 160 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 40 mg / mL to about 140 mg / mL.In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 40 mg / mL to about 120 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 40 mg / mL to about 100 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 40 mg / mL to about 80 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 40 mg / mL to about 60 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 50 mg / mL to about 70 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 150 mg / mL to about 170 mg / mL.

[0106]

[0125] In some embodiments of any of the above formulations, the concentration of the anti-TIGIT monoclonal antibody is about 18 mg / mL to about 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 19 mg / mL to about 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 21 mg / mL to about 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 22 mg / mL to about 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 23 mg / mL to about 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 24 mg / mL to about 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 25 mg / mL to about 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 26 mg / mL to about 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 27 mg / mL to about 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 28 mg / mL to about 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 29 mg / mL to about 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 30 mg / mL to about 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 31 mg / mL to about 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 32 mg / mL to about 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 33 mg / mL to about 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 34 mg / mL to about 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 35 mg / mL to about 50 mg / mL.In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 36 mg / mL to about 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 37 mg / mL to about 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 38 mg / mL to about 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 39 mg / mL to about 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 40 mg / mL to about 50 mg / mL.

[0107]

[0126] In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 25 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 30 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 35 mg / mL. In certain embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 40 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 45 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 55 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 60 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 65 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 70 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 75 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 80 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 85 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 90 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 95 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 100 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 105 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 110 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 115 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 120 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 125 mg / mL.In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 130 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 135 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 140 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 145 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 150 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 155 mg / mL. In certain embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 160 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 165 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 170 mg / mL. In certain embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 175 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 180 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 185 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 190 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 195 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 200 mg / mL.

[0108]

[0127] In some embodiments of any of the above formulations, the concentration of the anti-TIGIT monoclonal antibody is about 31 mg / mL to about 49 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 32 mg / mL to about 48 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 33 mg / mL to about 47 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 34 mg / mL to about 46 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 35 mg / mL to about 45 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 36 mg / mL to about 44 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 37 mg / mL to about 43 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 38 mg / mL to about 42 mg / mL.In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 39 mg / mL to about 41 mg / mL.

[0109]

[0128] In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 18 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 23 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 25 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 30 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 32 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 35 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 37 mg / mL. In certain embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 40 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 43 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 45 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 48 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 53 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 55 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 60 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 65 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 70 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 75 mg / mL.

[0110]

[0129] In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 75 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 25 mg / mL to 75 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 30 mg / mL to 75 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 35 mg / mL to 75 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 40 mg / mL to 75 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 45 mg / mL to 75 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 50 mg / mL to 75 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 55 mg / mL to 75 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 60 mg / mL to 75 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 65 mg / mL to 75 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 70 mg / mL to about 75 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 70 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 65 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 60 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 55 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 45 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 40 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 35 mg / mL.In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 30 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 25 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 25 mg / mL to 45 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 30 mg / mL to 45 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 35 mg / mL to 45 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 45 mg / mL to 75 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 50 mg / mL to 70 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 55 mg / mL to 65 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 60 mg / mL to 65 mg / mL.In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 55 mg / mL to 60 mg / mL.

[0111]

[0130] In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 180 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 160 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 140 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 120 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 100 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 80 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 60 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 40 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 40 mg / mL to 180 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 60 mg / mL to 180 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 80 mg / mL to 180 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 100 mg / mL to 180 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 120 mg / mL to 180 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 140 mg / mL to 180 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 160 mg / mL to 180 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 30 mg / mL to 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 40 mg / mL to 160 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 40 mg / mL to 140 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 40 mg / mL to 120 mg / mL.In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 40 mg / mL to 100 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 40 mg / mL to 80 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 40 mg / mL to 60 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 50 mg / mL to 70 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 150 mg / mL to 170 mg / mL.

[0112]

[0131] In some embodiments of any of the above formulations, the concentration of the anti-TIGIT monoclonal antibody is 18 mg / mL to 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 19 mg / mL to 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 21 mg / mL to 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 22 mg / mL to 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 23 mg / mL to 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 24 mg / mL to 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 25 mg / mL to 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 26 mg / mL to 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 27 mg / mL to 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 28 mg / mL to 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 29 mg / mL to 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 30 mg / mL to 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 31 mg / mL to 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 32 mg / mL to 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 33 mg / mL to 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 34 mg / mL to 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 35 mg / mL to 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 36 mg / mL to 50 mg / mL.In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 37 mg / mL to 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 38 mg / mL to 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 39 mg / mL to 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 40 mg / mL to 50 mg / mL.

[0113]

[0132] In some embodiments of any of the above formulations, the concentration of the anti-TIGIT monoclonal antibody is 31 mg / mL to 49 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 32 mg / mL to 48 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 33 mg / mL to 47 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 34 mg / mL to 46 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 35 mg / mL to 45 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 36 mg / mL to 44 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 37 mg / mL to 43 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 38 mg / mL to 42 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is between 39 mg / mL and 41 mg / mL.

[0114]

[0133] In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 18 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 23 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 25 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 28 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 30 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 32 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 35 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 37 mg / mL. In a particular embodiment, the concentration of the anti-TIGIT monoclonal antibody is 40 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 43 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 45 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 48 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 53 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 55 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 60 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 65 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 70 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 75 mg / mL.

[0115]

[0134] In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 25 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 30 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 35 mg / mL. In certain embodiments, the concentration of the anti-TIGIT monoclonal antibody is 40 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 45 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 55 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 60 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 65 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 70 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 75 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 80 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 85 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 90 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 95 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 100 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 105 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 110 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 115 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 120 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 125 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 130 mg / mL.In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 135 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 140 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 145 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 150 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 155 mg / mL. In certain embodiments, the concentration of the anti-TIGIT monoclonal antibody is 160 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 165 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 170 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 175 mg / mL. In certain embodiments, the concentration of the anti-TIGIT monoclonal antibody is 176 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 180 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 185 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 190 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 195 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 200 mg / mL.

[0116]

[0135] In some embodiments, the anti-PD-L1 monoclonal antibody comprises a heavy chain variable region comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 10; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 11; and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 12, and a light chain variable region comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 13; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 14; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 15.

[0117]

[0136] In some embodiments, the anti-PD-L1 monoclonal antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 16. In some embodiments, the anti-PD-L1 monoclonal antibody comprises a light chain variable region comprising the amino acid sequence of SEQ ID NO: 17. In some embodiments, the anti-PD-L1 monoclonal antibody comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 16, and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 17. In some embodiments of any of the above aspects, the heavy chain of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 21. In some embodiments of any of the above aspects, the heavy chain of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 22. In some embodiments of any of the above aspects, the light chain of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 23. In some embodiments of any of the above aspects, the heavy chain of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 21, and the light chain of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 23. In some embodiments of any of the above aspects, the heavy chain of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 22, and the light chain of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 23. In some embodiments, the anti-PD-L1 monoclonal antibody is atezolizumab. In some embodiments, the anti-PD-L1 monoclonal antibody is atezolizumab.

[0118]

[0137] In some embodiments, the anti-PD-L1 monoclonal antibody is an IgG antibody. The anti-PD-L1 monoclonal antibody may be an IgG1 antibody, an IgG2 antibody, an IgG3 antibody, or an IgG4 antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is an IgG1 or IgG4 antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is an IgG1 antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is an IgG4 antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is an antagonist antibody. In some cases, the anti-PD-L1 monoclonal antibody may have one or more effector functions. In some embodiments, the anti-PD-L1 monoclonal antibody retains all effector functions. Optionally, one or more effector functions of the anti-PD-L1 monoclonal antibody may be modified or removed.

[0119]

[0138] In some embodiments, the anti-PD-L1 monoclonal antibody is a human antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is a humanized antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is a full-length antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is a full-length IgG antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is a full-length IgG1 antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is a full-length human IgG1 antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is a full-length humanized IgG antibody. The anti-PD-L1 monoclonal antibody may be an antibody fragment. In some embodiments, the anti-PD-L1 monoclonal antibody is a Fab, Fab', F(ab') 2 , Fv or scFv fragments. In some embodiments, the anti-PD-L1 monoclonal antibody is a Fab fragment. In some embodiments, the anti-PD-L1 monoclonal antibody is a Fab' fragment. In some embodiments, the anti-PD-L1 monoclonal antibody is a F(ab') 2In some embodiments, the anti-PD-L1 monoclonal antibody is a Fv fragment. In some embodiments, the anti-PD-L1 monoclonal antibody is an scFv fragment. In some embodiments, the anti-PD-L1 monoclonal antibody is a diabody. In some embodiments, the anti-PD-L1 monoclonal antibody is a linear antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is a single chain antibody molecule. In some embodiments, the anti-PD-L1 monoclonal antibody is a multispecific antibody, such as a multispecific antibody formed from antibody fragments. In some embodiments, the anti-PD-L1 monoclonal antibody is atezolizumab, which is commercially available as Tecentriq®. Atezolizumab is listed in the WHO Drug Information (International Nonproprietary Names), proposed INN:List 112, Volume 28, Issue 4, 2014 (see page 488). In some embodiments, atezolizumab has the CAS registry number 1380723-44-3.

[0120]

[0139] In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is about 60 mg / mL to about 100 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is about 60 mg / mL to about 90 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is about 60 mg / mL to about 80 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is about 60 mg / mL to about 70 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is about 70 mg / mL to about 100 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is about 80 mg / mL to about 100 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is about 90 mg / mL to about 100 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is about 70 mg / mL to about 90 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is about 70 mg / mL to about 80 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is about 65 mg / mL to about 95 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is about 75 mg / mL to about 85 mg / mL.

[0121]

[0140] In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is about 60 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is about 65 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is about 70 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is about 75 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is about 80 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is about 85 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is about 90 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is about 95 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is about 100 mg / mL.

[0122]

[0141] In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is between 60 mg / mL and 100 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is between 60 mg / mL and 90 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is between 60 mg / mL and 80 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is between 60 mg / mL and 70 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is between 70 mg / mL and 100 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is between 80 mg / mL and 100 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is between 90 mg / mL and 100 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is between 70 mg / mL and 90 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is between 70 mg / mL and 80 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is between 65 mg / mL and 95 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is between 75 mg / mL and 85 mg / mL.

[0123]

[0142] In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is 60 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is 65 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is 70 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is 75 mg / mL. In certain embodiments, the concentration of the anti-PD-L1 monoclonal antibody is 80 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is 85 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is 90 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is 95 mg / mL. In some embodiments, the concentration of the anti-PD-L1 monoclonal antibody is 100 mg / mL.

[0124]

[0143] The liquid pharmaceutical formulation of the present disclosure comprises a buffer. In some embodiments, the buffer is an acid salt. In some embodiments, the buffer comprises histidine, arginine, acetate, citrate, succinate, gluconate, phosphate, or a combination thereof. In some embodiments, the buffer comprises histidine, arginine, acetate, citrate, succinate, gluconate, phosphate, or an acid salt form thereof. In some embodiments, the buffer is selected from the group consisting of histidine, acetate, histidine acetate, histidine hydrochloride, histidine acetate, and arginine, citrate, citric acid, sodium acetate, sodium citrate, arginine succinate, phosphate, disodium phosphate dihydrate, and sodium dihydrogen phosphate dihydrate. In some embodiments, the buffer is histidine. In some embodiments, the buffer is acetate. In some embodiments, the buffer is histidine acetate. In some embodiments, the buffer is histidine hydrochloride. In some embodiments, the buffer is histidine acetate and arginine. In some embodiments, the buffer is citrate. In some embodiments, the buffer is citric acid. In some embodiments, the buffer is sodium acetate. In some embodiments, the buffer is sodium citrate. In some embodiments, the buffer is arginine succinate. In some embodiments, the buffer is phosphate. In some embodiments, the buffer is disodium phosphate dihydrate. In some embodiments, the buffer is sodium dihydrogen phosphate dihydrate.

[0125]

[0144] Those skilled in the art will understand that depending on the other components and pH of the composition, a buffer added in the form of a salt may be converted (or partially converted) into the form of an acid (or vice versa) and thus be present in the composition in either the form of a salt, the form of an acid, or a mixture of both. For example, when sodium citrate is added to a composition in a solution, it may remain in the form of a citrate salt, be converted to citric acid, or be present as a mixture of citrate salt and citric acid forms. Similarly, when citric acid is added to a composition in a solution, it may remain in the form of citric acid, be converted to citrate salt, or be present as a mixture of citric acid and citrate salt forms. Thus, when determining the concentration of a buffer in a composition, those skilled in the art will consider both the form of a salt and the form of an acid when determining the buffer concentration. For example, when a composition includes a certain concentration of citrate salt, those skilled in the art will include both the form of citrate salt and the form of citric acid in the composition when determining the buffer concentration.

[0126]

[0145] In some embodiments, the buffer concentration is about 10 mM to about 30 mM. In some embodiments, the buffer concentration is about 15 mM to about 25 mM. In some embodiments, the buffer concentration is about 12 mM to about 28 mM. In some embodiments, the buffer concentration is about 10 mM. In some embodiments, the buffer concentration is about 15 mM. In some embodiments, the buffer concentration is about 20 mM. In some embodiments, the buffer concentration is about 25 mM. In some embodiments, the buffer concentration is about 30 mM.

[0127]

[0146] In some embodiments, the buffer concentration is 10 mM to 30 mM. In some embodiments, the buffer concentration is 15 mM to 25 mM. In some embodiments, the buffer concentration is 12 mM to 28 mM. In some embodiments, the buffer concentration is 10 mM. In some embodiments, the buffer concentration is 15 mM. In some embodiments, the buffer concentration is 20 mM. In some embodiments, the buffer concentration is 25 mM. In some embodiments, the buffer concentration is 30 mM.

[0128]

[0147] The liquid pharmaceutical formulation of the present disclosure comprises an isotonicity agent. In some embodiments, the isotonicity agent is a salt or a polyol. In some embodiments, the isotonicity agent is a salt. In some embodiments, the isotonicity agent is a polyol. In some embodiments, the polyol is a sugar or a sugar alcohol. In some embodiments, the polyol is a sugar. In some embodiments, the polyol is a sugar alcohol. In some embodiments, the isotonicity agent is a sugar alcohol selected from the group consisting of mannitol, xylitol, erythritol, threitol, sorbitol, and glycerol. In some embodiments, the sugar alcohol is mannitol. In some embodiments, the sugar alcohol is xylitol. In some embodiments, the sugar alcohol is erythritol. In some embodiments, the sugar alcohol is threitol. In some embodiments, the sugar alcohol is sorbitol. In some embodiments, the sugar alcohol is glycerol.

[0129]

[0148] In some embodiments, the tonicity agent is a reducing sugar. In some embodiments, the reducing sugar is selected from the group consisting of fructose, mannose, maltose, lactose, arabinose, xylose, ribose, rhamnose, galactose, and glucose. In some embodiments, the reducing sugar is fructose. In some embodiments, the reducing sugar is mannose. In some embodiments, the reducing sugar is maltose. In some embodiments, the reducing sugar is lactose. In some embodiments, the reducing sugar is arabinose. In some embodiments, the reducing sugar is xylose. In some embodiments, the reducing sugar is ribose. In some embodiments, the reducing sugar is rhamnose. In some embodiments, the reducing sugar is galactose. In some embodiments, the reducing sugar is glucose.

[0130]

[0149] In some embodiments, the tonicity agent is a non-reducing sugar. In some embodiments, the non-reducing sugar is selected from the group consisting of sucrose, trehalose, sorbose, melezitose, and raffinose. In some embodiments, the non-reducing sugar is sucrose. In some embodiments, the non-reducing sugar is trehalose. In some embodiments, the non-reducing sugar is sorbose. In some embodiments, the non-reducing sugar is melezitose. In some embodiments, the non-reducing sugar is raffinose. In certain embodiments, the tonicity agent is sucrose.

[0131]

[0150] In some embodiments, the tonicity agent is a salt. In some embodiments, the salt is sodium chloride or potassium chloride. In some embodiments, the salt is sodium chloride. In some embodiments, the salt is potassium chloride.

[0132]

[0151] In some embodiments, the tonicity agent is selected from the group consisting of sodium chloride, mannitol, sucrose, glucose, glycerol, and potassium chloride. In some embodiments, the tonicity agent is sodium chloride. In some embodiments, the tonicity agent is mannitol. In some embodiments, the tonicity agent is sucrose. In some embodiments, the tonicity agent is glucose. In some embodiments, the tonicity agent is glycerol. In some embodiments, the tonicity agent is potassium chloride.

[0133]

[0152] In some embodiments, the concentration of the isotonicity agent is about 100 mM to about 300 mM. In some embodiments, the concentration of the isotonicity agent is about 120 mM to about 280 mM. In some embodiments, the concentration of the isotonicity agent is about 140 mM to about 280 mM. In some embodiments, the concentration of the isotonicity agent is about 160 mM to about 280 mM. In some embodiments, the concentration of the isotonicity agent is about 180 mM to about 280 mM. In some embodiments, the concentration of the isotonicity agent is about 200 mM to about 280 mM. In some embodiments, the concentration of the isotonicity agent is about 220 mM to about 280 mM. In some embodiments, the concentration of the isotonicity agent is about 240 mM to about 280 mM. In some embodiments, the concentration of the isotonicity agent is about 260 mM to about 280 mM. In some embodiments, the concentration of the isotonicity agent is about 220 mM to about 260 mM. In some embodiments, the concentration of the isotonicity agent is about 230 mM to about 250 mM. In some embodiments, the concentration of the isotonicity agent is about 200 mM to about 260 mM. In some embodiments, the concentration of the isotonicity agent is about 180 mM to about 300 mM. In some embodiments, the concentration of the isotonicity agent is about 200 mM to about 300 mM. In some embodiments, the concentration of the isotonicity agent is about 220 mM to about 300 mM. In some embodiments, the concentration of the isotonicity agent is about 240 mM to about 300 mM. In some embodiments, the concentration of the isotonicity agent is about 250 mM to about 300 mM.

[0134]

[0153] In some embodiments, the concentration of the tonicity agent is about 100 mM. In some embodiments, the concentration of the tonicity agent is about 110 mM. In some embodiments, the concentration of the tonicity agent is about 120 mM. In some embodiments, the concentration of the tonicity agent is about 130 mM. In some embodiments, the concentration of the tonicity agent is about 140 mM. In some embodiments, the concentration of the tonicity agent is about 150 mM. In some embodiments, the concentration of the tonicity agent is about 160 mM. In some embodiments, the concentration of the tonicity agent is about 170 mM. In some embodiments, the concentration of the tonicity agent is about 180 mM. In some embodiments, the concentration of the tonicity agent is about 190 mM. In some embodiments, the concentration of the tonicity agent is about 200 mM. In some embodiments, the concentration of the tonicity agent is about 210 mM. In some embodiments, the concentration of the tonicity agent is about 220 mM. In some embodiments, the concentration of the tonicity agent is about 230 mM. In certain embodiments, the concentration of the tonicity agent is about 240 mM. In some embodiments, the concentration of the tonicity agent is about 250 mM. In some embodiments, the concentration of the tonicity agent is about 260 mM. In some embodiments, the concentration of the tonicity agent is about 270 mM. In some embodiments, the concentration of the tonicity agent is about 280 mM. In some embodiments, the concentration of the tonicity agent is about 290 mM. In some embodiments, the concentration of the tonicity agent is about 300 mM.

[0135]

[0154] In some embodiments, the concentration of the isotonicity agent is 100 mM to 300 mM. In some embodiments, the concentration of the isotonicity agent is 120 mM to 280 mM. In some embodiments, the concentration of the isotonicity agent is 140 mM to 280 mM. In some embodiments, the concentration of the isotonicity agent is 160 mM to 280 mM. In some embodiments, the concentration of the isotonicity agent is 180 mM to 280 mM. In some embodiments, the concentration of the isotonicity agent is 200 mM to 280 mM. In some embodiments, the concentration of the isotonicity agent is 220 mM to 280 mM. In some embodiments, the concentration of the isotonicity agent is 240 mM to 280 mM. In some embodiments, the concentration of the isotonicity agent is 260 mM to 280 mM. In some embodiments, the concentration of the isotonicity agent is 220 mM to 260 mM. In some embodiments, the concentration of the isotonicity agent is 230 mM to 250 mM. In some embodiments, the concentration of the isotonicity agent is 200 mM to 260 mM. In some embodiments, the concentration of the isotonicity agent is 180 mM to 300 mM. In some embodiments, the concentration of the isotonicity agent is 200 mM to 300 mM. In some embodiments, the concentration of the isotonicity agent is 220 mM to 300 mM. In some embodiments, the concentration of the isotonicity agent is 240 mM to 300 mM. In some embodiments, the concentration of the isotonicity agent is 250 mM to 300 mM.

[0136]

[0155] In some embodiments, the concentration of the tonicity agent is 100 mM. In some embodiments, the concentration of the tonicity agent is 110 mM. In some embodiments, the concentration of the tonicity agent is 120 mM. In some embodiments, the concentration of the tonicity agent is 130 mM. In some embodiments, the concentration of the tonicity agent is 140 mM. In some embodiments, the concentration of the tonicity agent is 150 mM. In some embodiments, the concentration of the tonicity agent is 160 mM. In some embodiments, the concentration of the tonicity agent is 170 mM. In some embodiments, the concentration of the tonicity agent is 180 mM. In some embodiments, the concentration of the tonicity agent is 190 mM. In some embodiments, the concentration of the tonicity agent is 200 mM. In some embodiments, the concentration of the tonicity agent is 210 mM. In some embodiments, the concentration of the tonicity agent is 220 mM. In some embodiments, the concentration of the tonicity agent is 230 mM. In certain embodiments, the concentration of the tonicity agent is 240 mM. In some embodiments, the concentration of the tonicity agent is 250 mM. In some embodiments, the concentration of the tonicity agent is 260 mM. In some embodiments, the concentration of the tonicity agent is 270 mM. In some embodiments, the concentration of the tonicity agent is 280 mM. In some embodiments, the concentration of the tonicity agent is 290 mM. In some embodiments, the concentration of the tonicity agent is 300 mM.

[0137]

[0156] The liquid pharmaceutical formulation comprises a surfactant. In some embodiments, the surfactant is a non-ionic surfactant, an ionic surfactant, a zwitterionic surfactant, or a combination thereof. In some embodiments, the surfactant is a non-ionic surfactant. In some embodiments, the surfactant is an ionic surfactant. In some embodiments, the surfactant is a zwitterionic surfactant.

[0138]

[0157] In some embodiments, the surfactant is a non-ionic surfactant selected from the group consisting of polysorbates, poloxamers, tritons, octyl glucosides, myristamidopropyl-dimethylamine, palmidopropyl-dimethylamine, isostearamidopropyl-dimethylamine, polyethyl glycols, polypropyl glycols, copolymers of ethylene, copolymers of propylene glycol, and combinations thereof. In some embodiments, the surfactant is a polysorbate. Polysorbates are amphiphilic non-ionic surfactants derived from ethoxylated sorbitan or isosorbide (a derivative of sorbitol) esterified with fatty acids. The polysorbate may be polysorbate 20 or polysorbate 80. In some embodiments, the polysorbate is polysorbate 20. In some embodiments, the polysorbate is polysorbate 80. In some embodiments, the surfactant is a poloxamer. Poloxamers are block copolymers of polyoxyethylene and polyoxypropylene and include poloxamers 101, 105, 108, 122, 123, 124, 181, 182, 183, 184, 185, 188, 212, 215, 217, 231, 234, 235, 237, 238, 282, 284, 288, 331, 333, 334, 335, 338, 401, 402, 403, and 407, poloxamer 105 benzoate, and poloxamer 182 dibenzoate. In some embodiments, the poloxamer is poloxamer 188 or 407. In some embodiments, the poloxamer is poloxamer 188. In some embodiments, the surfactant is triton. In some embodiments, the surfactant is octyl glucoside. In some embodiments, the surfactant is myristamidopropyl-dimethylamine. In some embodiments, the surfactant is palmidopropyl-dimethylamine. In some embodiments, the surfactant is isostearamidopropyl-dimethylamine. In some embodiments, the surfactant is polyethyl glycol. In some embodiments, the surfactant is polypropyl glycol. In some embodiments, the surfactant is a copolymer of ethylene.In some embodiments, the surfactant is a copolymer of propylene glycol.

[0139]

[0158] In some embodiments, the surfactant is selected from the group consisting of polysorbate 20, polysorbate 80, poloxamer 188, and combinations thereof. In particular embodiments, the surfactant is polysorbate 20. In some embodiments, the surfactant is polysorbate 80. In some embodiments, the surfactant is poloxamer 188.

[0140]

[0159] In some embodiments, the surfactant is a zwitterionic surfactant selected from the group consisting of sodium dodecyl sulfate, sodium lauryl sulfate, lauryl-sulfobetaine, myristyl-sulfobetaine, linoleyl-sulfobetaine, stearyl-sulfobetaine, lauroamidopropyl-betaine, cocamidopropyl-betaine, linoleamidopropyl-betaine, myristamidopropyl-betaine, palmidopropyl-betaine, isostearamidopropyl-betaine, sodium methyl cocoyl-taurate, sodium methyl oleyl-taurate, and combinations thereof. In some embodiments, the surfactant is sodium dodecyl sulfate. In some embodiments, the surfactant is sodium lauryl sulfate. In some embodiments, the surfactant is lauryl-sulfobetaine. In some embodiments, the surfactant is myristyl-sulfobetaine. In some embodiments, the surfactant is linoleyl-sulfobetaine. In some embodiments, the surfactant is stearyl-sulfobetaine. In some embodiments, the surfactant is lauramidopropyl-betaine. In some embodiments, the surfactant is cocamidopropyl-betaine. In some embodiments, the surfactant is linoleamidopropyl-betaine. In some embodiments, the surfactant is myristamidopropyl-betaine. In some embodiments, the surfactant is palmidopropyl-betaine. In some embodiments, the surfactant is isostearamidopropyl-betaine. In some embodiments, the surfactant is sodium methyl cocoyl-taurate. In some embodiments, the surfactant is sodium methyl oleyl-taurate.

[0141]

[0160] In some embodiments, the surfactant concentration is about 0.1 mg / mL to about 1 mg / mL. In some embodiments, the surfactant concentration is about 0.2 mg / mL to about 1 mg / mL. In some embodiments, the surfactant concentration is about 0.3 mg / mL to about 1 mg / mL. In some embodiments, the surfactant concentration is about 0.4 mg / mL to about 1 mg / mL. In some embodiments, the surfactant concentration is about 0.5 mg / mL to about 1 mg / mL. In some embodiments, the surfactant concentration is about 0.6 mg / mL to about 1 mg / mL. In some embodiments, the surfactant concentration is about 0.7 mg / mL to about 1 mg / mL. In some embodiments, the surfactant concentration is about 0.8 mg / mL to about 1 mg / mL. In some embodiments, the surfactant concentration is about 0.9 mg / mL to about 1 mg / mL. In some embodiments, the surfactant concentration is about 0.1 mg / mL to about 0.9 mg / mL. In some embodiments, the surfactant concentration is about 0.1 mg / mL to about 0.8 mg / mL. In some embodiments, the surfactant concentration is about 0.1 mg / mL to about 0.7 mg / mL. In some embodiments, the surfactant concentration is about 0.1 mg / mL to about 0.6 mg / mL. In some embodiments, the surfactant concentration is about 0.1 mg / mL to about 0.5 mg / mL. In some embodiments, the surfactant concentration is about 0.1 mg / mL to about 0.4 mg / mL. In some embodiments, the surfactant concentration is about 0.1 mg / mL to about 0.3 mg / mL. In some embodiments, the surfactant concentration is about 0.1 mg / mL to about 0.2 mg / mL. In some embodiments, the surfactant concentration is about 0.2 mg / mL to about 0.9 mg / mL. In some embodiments, the surfactant concentration is about 0.2 mg / mL to about 0.8 mg / mL. In some embodiments, the concentration of the surfactant is about 0.2 mg / mL to about 0.7 mg / mL. In some embodiments, the concentration of the surfactant is about 0.2 mg / mL to about 0.6 mg / mL. In some embodiments, the concentration of the surfactant is about 0.2 mg / mL to about 0.5 mg / mL.In some embodiments, the surfactant concentration is about 0.2 mg / mL to about 0.4 mg / mL. In some embodiments, the surfactant concentration is about 0.2 mg / mL to about 0.3 mg / mL. In some embodiments, the surfactant concentration is about 0.3 mg / mL to about 0.4 mg / mL. In some embodiments, the surfactant concentration is about 0.3 mg / mL to about 0.5 mg / mL. In some embodiments, the surfactant concentration is about 0.3 mg / mL to about 0.6 mg / mL. In some embodiments, the surfactant concentration is about 0.3 mg / mL to about 0.7 mg / mL. In some embodiments, the surfactant concentration is about 0.3 mg / mL to about 0.8 mg / mL. In some embodiments, the surfactant concentration is about 0.3 mg / mL to about 0.9 mg / mL. In some embodiments, the surfactant concentration is about 0.4 mg / mL to about 0.9 mg / mL. In some embodiments, the surfactant concentration is about 0.4 mg / mL to about 0.8 mg / mL. In some embodiments, the surfactant concentration is about 0.4 mg / mL to about 0.7 mg / mL. In some embodiments, the surfactant concentration is about 0.4 mg / mL to about 0.6 mg / mL. In some embodiments, the surfactant concentration is about 0.4 mg / mL to about 0.5 mg / mL. In some embodiments, the surfactant concentration is about 0.5 mg / mL to about 0.6 mg / mL. In some embodiments, the surfactant concentration is about 0.5 mg / mL to about 0.7 mg / mL. In some embodiments, the surfactant concentration is about 0.5 mg / mL to about 0.8 mg / mL. In some embodiments, the surfactant concentration is about 0.5 mg / mL to about 0.9 mg / mL. In some embodiments, the surfactant concentration is about 0.6 mg / mL to about 0.7 mg / mL. In some embodiments, the concentration of the surfactant is about 0.6 mg / mL to about 0.8 mg / mL. In some embodiments, the concentration of the surfactant is about 0.6 mg / mL to about 0.9 mg / mL. In some embodiments, the concentration of the surfactant is about 0.7 mg / mL to about 0.8 mg / mL. In some embodiments, the concentration of the surfactant is about 0.7 mg / mL to about 0.9 mg / mL.In some embodiments, the concentration of the surfactant is from about 0.8 mg / mL to about 0.9 mg / mL.

[0142]

[0161] In some embodiments, the concentration of the surfactant is about 0.1 mg / mL. In some embodiments, the concentration of the surfactant is about 0.2 mg / mL. In some embodiments, the concentration of the surfactant is about 0.3 mg / mL. In some embodiments, the concentration of the surfactant is about 0.4 mg / mL. In some embodiments, the concentration of the surfactant is about 0.5 mg / mL. In certain embodiments, the concentration of the surfactant is about 0.6 mg / mL. In some embodiments, the concentration of the surfactant is about 0.7 mg / mL. In certain embodiments, the concentration of the surfactant is about 0.8 mg / mL. In some embodiments, the concentration of the surfactant is about 0.9 mg / mL. In some embodiments, the concentration of the surfactant is about 1 mg / mL.

[0143]

[0162] In some embodiments, the concentration of the surfactant is from 0.1 mg / mL to 1 mg / mL. In some embodiments, the concentration of the surfactant is from 0.2 mg / mL to 1 mg / mL. In some embodiments, the concentration of the surfactant is from 0.3 mg / mL to 1 mg / mL. In some embodiments, the concentration of the surfactant is from 0.4 mg / mL to 1 mg / mL. In some embodiments, the concentration of the surfactant is from 0.5 mg / mL to 1 mg / mL. In some embodiments, the concentration of the surfactant is from 0.6 mg / mL to 1 mg / mL. In some embodiments, the concentration of the surfactant is from 0.7 mg / mL to 1 mg / mL. In some embodiments, the concentration of the surfactant is from 0.8 mg / mL to 1 mg / mL. In some embodiments, the concentration of the surfactant is from 0.9 mg / mL to 1 mg / mL. In some embodiments, the concentration of the surfactant is from 0.1 mg / mL to 0.9 mg / mL. In some embodiments, the concentration of the surfactant is from 0.1 mg / mL to 0.8 mg / mL. In some embodiments, the concentration of the surfactant is 0.1 mg / mL to 0.7 mg / mL. In some embodiments, the concentration of the surfactant is 0.1 mg / mL to 0.6 mg / mL. In some embodiments, the concentration of the surfactant is 0.1 mg / mL to 0.5 mg / mL. In some embodiments, the concentration of the surfactant is 0.1 mg / mL to 0.4 mg / mL. In some embodiments, the concentration of the surfactant is 0.1 mg / mL to 0.3 mg / mL. In some embodiments, the concentration of the surfactant is 0.1 mg / mL to 0.2 mg / mL. In some embodiments, the concentration of the surfactant is 0.2 mg / mL to 0.9 mg / mL. In some embodiments, the concentration of the surfactant is 0.2 mg / mL to 0.8 mg / mL. In some embodiments, the concentration of the surfactant is 0.2 mg / mL to 0.7 mg / mL. In some embodiments, the concentration of the surfactant is 0.2 mg / mL to 0.6 mg / mL. In some embodiments, the concentration of the surfactant is between 0.2 mg / mL and 0.5 mg / mL. In some embodiments, the concentration of the surfactant is between 0.2 mg / mL and 0.4 mg / mL.In some embodiments, the concentration of the surfactant is 0.2 mg / mL to 0.3 mg / mL. In some embodiments, the concentration of the surfactant is 0.3 mg / mL to 0.4 mg / mL. In some embodiments, the concentration of the surfactant is 0.3 mg / mL to 0.5 mg / mL. In some embodiments, the concentration of the surfactant is 0.3 mg / mL to 0.6 mg / mL. In some embodiments, the concentration of the surfactant is 0.3 mg / mL to 0.7 mg / mL. In some embodiments, the concentration of the surfactant is 0.3 mg / mL to 0.8 mg / mL. In some embodiments, the concentration of the surfactant is 0.3 mg / mL to 0.9 mg / mL. In some embodiments, the concentration of the surfactant is 0.4 mg / mL to 0.9 mg / mL. In some embodiments, the concentration of the surfactant is 0.4 mg / mL to 0.8 mg / mL. In some embodiments, the concentration of the surfactant is 0.4 mg / mL to 0.7 mg / mL. In some embodiments, the concentration of the surfactant is 0.4 mg / mL to 0.6 mg / mL. In some embodiments, the concentration of the surfactant is 0.4 mg / mL to 0.5 mg / mL. In some embodiments, the concentration of the surfactant is 0.5 mg / mL to 0.6 mg / mL. In some embodiments, the concentration of the surfactant is 0.5 mg / mL to 0.7 mg / mL. In some embodiments, the concentration of the surfactant is 0.5 mg / mL to 0.8 mg / mL. In some embodiments, the concentration of the surfactant is 0.5 mg / mL to 0.9 mg / mL. In some embodiments, the concentration of the surfactant is 0.6 mg / mL to 0.7 mg / mL. In some embodiments, the concentration of the surfactant is 0.6 mg / mL to 0.8 mg / mL. In some embodiments, the concentration of the surfactant is 0.6 mg / mL to 0.9 mg / mL. In some embodiments, the concentration of the surfactant is 0.7 mg / mL to 0.8 mg / mL. In some embodiments, the concentration of the surfactant is between 0.7 mg / mL and 0.9 mg / mL. In some embodiments, the concentration of the surfactant is between 0.8 mg / mL and 0.9 mg / mL.

[0144]

[0163] In some embodiments, the concentration of the surfactant is 0.1 mg / mL. In some embodiments, the concentration of the surfactant is 0.2 mg / mL. In some embodiments, the concentration of the surfactant is 0.3 mg / mL. In some embodiments, the concentration of the surfactant is 0.4 mg / mL. In some embodiments, the concentration of the surfactant is 0.5 mg / mL. In certain embodiments, the concentration of the surfactant is 0.6 mg / mL. In some embodiments, the concentration of the surfactant is 0.7 mg / mL. In certain embodiments, the concentration of the surfactant is 0.8 mg / mL. In some embodiments, the concentration of the surfactant is 0.9 mg / mL. In some embodiments, the concentration of the surfactant is 1 mg / mL.

[0145]

[0164] In some embodiments, the liquid pharmaceutical formulation further comprises a stabilizer. In some embodiments, the stabilizer is selected from the group consisting of methionine, glycine, alanine, proline, taurine, betaine, octopine, glutamate, sarcosine, gamma-aminobutyric acid, and trimethylamine N-oxide. In particular embodiments, the stabilizer is methionine. In some embodiments, the stabilizer is glycine. In some embodiments, the stabilizer is alanine. In some embodiments, the stabilizer is proline. In some embodiments, the stabilizer is taurine. In some embodiments, the stabilizer is betaine. In some embodiments, the stabilizer is octopine. In some embodiments, the stabilizer is glutamate. In some embodiments, the stabilizer is sarcosine. In some embodiments, the stabilizer is gamma-aminobutyric acid. In some embodiments, the stabilizer is trimethylamine N-oxide.

[0146]

[0165] In some embodiments, the concentration of the stabilizer is about 5 mM to about 20 mM. In some embodiments, the concentration of the stabilizer is about 5 mM to about 15 mM. In some embodiments, the concentration of the stabilizer is about 8 mM to about 12 mM. In some embodiments, the concentration of the stabilizer is about 9 mM to about 11 mM. In some embodiments, the concentration of the stabilizer is about 5 mM. In some embodiments, the concentration of the stabilizer is about 6 mM. In some embodiments, the concentration of the stabilizer is about 7 mM. In some embodiments, the concentration of the stabilizer is about 8 mM. In some embodiments, the concentration of the stabilizer is about 9 mM. In certain embodiments, the concentration of the stabilizer is about 10 mM. In some embodiments, the concentration of the stabilizer is about 11 mM. In some embodiments, the concentration of the stabilizer is about 12 mM. In some embodiments, the concentration of the stabilizer is about 13 mM. In some embodiments, the concentration of the stabilizer is about 14 mM. In some embodiments, the concentration of the stabilizer is about 15 mM. In some embodiments, the concentration of the stabilizer is about 16 mM. In some embodiments, the concentration of the stabilizer is about 17 mM. In some embodiments, the concentration of the stabilizer is about 18 mM. In some embodiments, the concentration of the stabilizer is about 19 mM. In some embodiments, the concentration of the stabilizer is about 20 mM.

[0147]

[0166] In some embodiments, the concentration of the stabilizer is about 0 mM to about 15 mM. In some embodiments, the concentration of the stabilizer is 5 mM to 20 mM. In some embodiments, the concentration of the stabilizer is 5 mM to 15 mM. In some embodiments, the concentration of the stabilizer is 8 mM to 12 mM. In some embodiments, the concentration of the stabilizer is 9 mM to 11 mM. In some embodiments, the concentration of the stabilizer is 5 mM. In some embodiments, the concentration of the stabilizer is 6 mM. In some embodiments, the concentration of the stabilizer is 7 mM. In some embodiments, the concentration of the stabilizer is 8 mM. In some embodiments, the concentration of the stabilizer is 9 mM. In certain embodiments, the concentration of the stabilizer is 10 mM. In some embodiments, the concentration of the stabilizer is 11 mM. In some embodiments, the concentration of the stabilizer is 12 mM. In some embodiments, the concentration of the stabilizer is 13 mM. In some embodiments, the concentration of the stabilizer is 14 mM. In some embodiments, the concentration of the stabilizer is 15 mM. In some embodiments, the concentration of the stabilizer is 16 mM. In some embodiments, the concentration of the stabilizer is 17 mM. In some embodiments, the concentration of the stabilizer is 18 mM. In some embodiments, the concentration of the stabilizer is 19 mM. In some embodiments, the concentration of the stabilizer is 20 mM.

[0148]

[0167] In some embodiments, the pH of the liquid pharmaceutical formulation is about 4.0 to about 7.0. In some embodiments, the pH of the liquid pharmaceutical formulation is about 4.5 to about 7.0. In some embodiments, the pH of the liquid pharmaceutical formulation is about 5.0 to about 7.0. In some embodiments, the pH of the liquid pharmaceutical formulation is about 5.5 to about 7.0. In some embodiments, the pH of the liquid pharmaceutical formulation is about 6.0 to about 7.0. In some embodiments, the pH of the liquid pharmaceutical formulation is about 6.5 to about 7.0. In some embodiments, the pH of the liquid pharmaceutical formulation is about 4.0 to about 6.5. In some embodiments, the pH of the liquid pharmaceutical formulation is about 4.0 to about 6.0. In some embodiments, the pH of the liquid pharmaceutical formulation is about 4.0 to about 5.5. In some embodiments, the pH of the liquid pharmaceutical formulation is about 4.0 to about 5.0. In some embodiments, the pH of the liquid pharmaceutical formulation is about 4.0 to about 4.5. In some embodiments, the pH of the liquid pharmaceutical formulation is about 4.5 to about 6.5. In some embodiments, the pH of the liquid pharmaceutical formulation is about 4.5 to about 6.0. In some embodiments, the pH of the liquid pharmaceutical formulation is about 4.5 to about 5.5. In some embodiments, the pH of the liquid pharmaceutical formulation is about 4.5 to about 5.0. In some embodiments, the pH of the liquid pharmaceutical formulation is about 5.0 to about 6.5. In some embodiments, the pH of the liquid pharmaceutical formulation is about 5.0 to about 6.0. In some embodiments, the pH of the liquid pharmaceutical formulation is about 5.0 to about 5.5. In some embodiments, the pH of the liquid pharmaceutical formulation is about 5.2 to about 5.8. In some embodiments, the pH of the liquid pharmaceutical formulation is about 5.2 to about 6.1. In some embodiments, the pH of the liquid pharmaceutical formulation is about 5.4 to about 5.5. In some embodiments, the pH of the liquid pharmaceutical formulation is about 5.5 to about 6.5. In some embodiments, the pH of the liquid pharmaceutical formulation is about 5.5 to about 6.0. In some embodiments, the pH of the liquid pharmaceutical formulation is about 5.5 to about 6.1. In some embodiments, the pH of the liquid pharmaceutical formulation is about 5.7 to about 5.9. In some embodiments, the pH of the liquid pharmaceutical formulation is about 6.0 to about 6.5.

[0149]

[0168] In some embodiments, the pH of the liquid pharmaceutical formulation is about 4.0. In some embodiments, the pH of the liquid pharmaceutical formulation is about 4.1. In some embodiments, the pH of the liquid pharmaceutical formulation is about 4.2. In some embodiments, the pH of the liquid pharmaceutical formulation is about 4.3. In some embodiments, the pH of the liquid pharmaceutical formulation is about 4.4. In some embodiments, the pH of the liquid pharmaceutical formulation is about 4.5. In some embodiments, the pH of the liquid pharmaceutical formulation is about 4.6. In some embodiments, the pH of the liquid pharmaceutical formulation is about 4.7. In some embodiments, the pH of the liquid pharmaceutical formulation is about 4.8. In some embodiments, the pH of the liquid pharmaceutical formulation is about 4.9. In some embodiments, the pH of the liquid pharmaceutical formulation is about 5.0. In some embodiments, the pH of the liquid pharmaceutical formulation is about 5.1. In some embodiments, the pH of the liquid pharmaceutical formulation is about 5.2. In some embodiments, the pH of the liquid pharmaceutical formulation is about 5.3. In some embodiments, the pH of the liquid pharmaceutical formulation is about 5.4. In certain embodiments, the pH of the liquid pharmaceutical formulation is about 5.5. In some embodiments, the pH of the liquid pharmaceutical formulation is about 5.6. In some embodiments, the pH of the liquid pharmaceutical formulation is about 5.7. In certain embodiments, the pH of the liquid pharmaceutical formulation is about 5.8. In some embodiments, the pH of the liquid pharmaceutical formulation is about 5.9. In some embodiments, the pH of the liquid pharmaceutical formulation is about 6.0. In some embodiments, the pH of the liquid pharmaceutical formulation is about 6.2. In some embodiments, the pH of the liquid pharmaceutical formulation is about 6.4. In some embodiments, the pH of the liquid pharmaceutical formulation is about 6.5. In some embodiments, the pH of the liquid pharmaceutical formulation is about 6.6. In some embodiments, the pH of the liquid pharmaceutical formulation is about 6.7. In some embodiments, the pH of the liquid pharmaceutical formulation is about 6.8. In some embodiments, the pH of the liquid pharmaceutical formulation is about 6.9. In some embodiments, the pH of the liquid pharmaceutical formulation is about 7.0.

[0150]

[0169] In some embodiments, the liquid pharmaceutical formulation has a pH of 4.0 to 7.0. In some embodiments, the liquid pharmaceutical formulation has a pH of 4.5 to 7.0. In some embodiments, the liquid pharmaceutical formulation has a pH of 5.0 to 7.0. In some embodiments, the liquid pharmaceutical formulation has a pH of 5.5 to 7.0. In some embodiments, the liquid pharmaceutical formulation has a pH of 6.0 to 7.0. In some embodiments, the liquid pharmaceutical formulation has a pH of 6.5 to 7.0. In some embodiments, the liquid pharmaceutical formulation has a pH of 4.0 to 6.5. In some embodiments, the liquid pharmaceutical formulation has a pH of 4.0 to 6.0. In some embodiments, the liquid pharmaceutical formulation has a pH of 4.0 to 5.5. In some embodiments, the liquid pharmaceutical formulation has a pH of 4.0 to 5.0. In some embodiments, the liquid pharmaceutical formulation has a pH of 4.0 to 4.5. In some embodiments, the liquid pharmaceutical formulation has a pH of 4.5 to 6.5. In some embodiments, the liquid pharmaceutical formulation has a pH of 4.5 to 6.0. In some embodiments, the liquid pharmaceutical formulation has a pH of 4.5 to 5.5. In some embodiments, the liquid pharmaceutical formulation has a pH of 4.5 to 5.0. In some embodiments, the liquid pharmaceutical formulation has a pH of 5.0 to 6.5. In some embodiments, the liquid pharmaceutical formulation has a pH of 5.0 to 6.0. In some embodiments, the liquid pharmaceutical formulation has a pH of 5.0 to 5.5. In some embodiments, the liquid pharmaceutical formulation has a pH of 5.2 to 5.8. In some embodiments, the liquid pharmaceutical formulation has a pH of 5.2 to 6.1. In some embodiments, the liquid pharmaceutical formulation has a pH of 5.4 to 5.5. In some embodiments, the liquid pharmaceutical formulation has a pH of 5.5 to 6.5. In some embodiments, the liquid pharmaceutical formulation has a pH of 5.5 to 6.0. In some embodiments, the liquid pharmaceutical formulation has a pH of 5.5 to 6.1. In some embodiments, the pH of the liquid pharmaceutical formulation is 5.7 to 5.9. In some embodiments, the pH of the liquid pharmaceutical formulation is 6.0 to 6.5.

[0151]

[0170] In some embodiments, the liquid pharmaceutical formulation has a pH of 4.0. In some embodiments, the liquid pharmaceutical formulation has a pH of 4.1. In some embodiments, the liquid pharmaceutical formulation has a pH of 4.2. In some embodiments, the liquid pharmaceutical formulation has a pH of 4.3. In some embodiments, the liquid pharmaceutical formulation has a pH of 4.4. In some embodiments, the liquid pharmaceutical formulation has a pH of 4.5. In some embodiments, the liquid pharmaceutical formulation has a pH of 4.6. In some embodiments, the liquid pharmaceutical formulation has a pH of 4.7. In some embodiments, the liquid pharmaceutical formulation has a pH of 4.8. In some embodiments, the liquid pharmaceutical formulation has a pH of 4.9. In some embodiments, the liquid pharmaceutical formulation has a pH of 5.0. In some embodiments, the liquid pharmaceutical formulation has a pH of 5.1. In some embodiments, the liquid pharmaceutical formulation has a pH of 5.2. In some embodiments, the liquid pharmaceutical formulation has a pH of 5.3. In some embodiments, the liquid pharmaceutical formulation has a pH of 5.4. In certain embodiments, the liquid pharmaceutical formulation has a pH of 5.5. In some embodiments, the liquid pharmaceutical formulation has a pH of 5.6. In some embodiments, the liquid pharmaceutical formulation has a pH of 5.7. In certain embodiments, the liquid pharmaceutical formulation has a pH of 5.8. In some embodiments, the liquid pharmaceutical formulation has a pH of 5.9. In some embodiments, the liquid pharmaceutical formulation has a pH of 6.0. In some embodiments, the liquid pharmaceutical formulation has a pH of 6.2. In some embodiments, the liquid pharmaceutical formulation has a pH of 6.4. In some embodiments, the liquid pharmaceutical formulation has a pH of 6.5. In some embodiments, the liquid pharmaceutical formulation has a pH of 6.6. In some embodiments, the liquid pharmaceutical formulation has a pH of 6.7. In some embodiments, the liquid pharmaceutical formulation has a pH of 6.8. In some embodiments, the liquid pharmaceutical formulation has a pH of 6.9. In some embodiments, the liquid pharmaceutical formulation has a pH of 7.0.

[0152]

[0171] In some embodiments, the anti-TIGIT monoclonal antibody and the anti-PD-L1 monoclonal antibody are in a ratio of about 1:2. For example, if the anti-TIGIT monoclonal antibody is present at a concentration of about 40 mg / ml, the anti-PD-L1 monoclonal antibody is present at a concentration of about 80 mg / ml. Similarly, if the anti-TIGIT monoclonal antibody is present at a concentration of 40 mg / ml, the anti-PD-L1 monoclonal antibody is present at a concentration of 80 mg / ml.

[0153]

[0172] In some embodiments, the liquid pharmaceutical formulation further comprises hyaluronidase. In some embodiments, the hyaluronidase is recombinant human hyaluronidase. In some embodiments, the hyaluronidase is human soluble PH20 hyaluronidase glycoprotein. In certain embodiments, the hyaluronidase is rHuPH20.

[0154]

[0173] In some embodiments, the concentration of hyaluronidase is about 1000 U / mL to about 7000 U / mL. In some embodiments, the concentration of hyaluronidase is about 1000 U / mL to about 6000 U / mL. In some embodiments, the concentration of hyaluronidase is about 1000 U / mL to about 5000 U / mL. In some embodiments, the concentration of hyaluronidase is about 1000 U / mL to about 4000 U / mL. In some embodiments, the concentration of hyaluronidase is about 1000 U / mL to about 3000 U / mL. In some embodiments, the concentration of hyaluronidase is about 1000 U / mL to about 2000 U / mL. In some embodiments, the concentration of hyaluronidase is about 1000 U / mL to about 1500 U / mL. In some embodiments, the concentration of hyaluronidase is about 1500 U / mL to about 3000 U / mL. In some embodiments, the concentration of hyaluronidase is about 1500 U / mL to about 2500 U / mL. In some embodiments, the concentration of hyaluronidase is about 1500 U / mL to about 2000 U / mL. In some embodiments, the concentration of hyaluronidase is about 1800 U / mL to about 2200 U / mL.

[0155]

[0174] In some embodiments, the concentration of hyaluronidase is about 1000 U / mL. In some embodiments, the concentration of hyaluronidase is about 1500 U / mL. In certain embodiments, the concentration of hyaluronidase is about 2000 U / mL. In some embodiments, the concentration of hyaluronidase is about 2500 U / mL. In some embodiments, the concentration of hyaluronidase is about 3000 U / mL. In some embodiments, the concentration of hyaluronidase is about 3500 U / mL. In some embodiments, the concentration of hyaluronidase is about 4000 U / mL. In some embodiments, the concentration of hyaluronidase is about 4500 U / mL. In some embodiments, the concentration of hyaluronidase is about 5000 U / mL. In some embodiments, the concentration of hyaluronidase is about 5500 U / mL. In some embodiments, the concentration of hyaluronidase is about 6000 U / mL. In some embodiments, the concentration of hyaluronidase is about 6500 U / mL. In some embodiments, the concentration of hyaluronidase is about 7000 U / mL.

[0156]

[0175] In some embodiments, the concentration of hyaluronidase is 1000 U / mL to 7000 U / mL. In some embodiments, the concentration of hyaluronidase is 1000 U / mL to 6000 U / mL. In some embodiments, the concentration of hyaluronidase is 1000 U / mL to 5000 U / mL. In some embodiments, the concentration of hyaluronidase is 1000 U / mL to 4000 U / mL. In some embodiments, the concentration of hyaluronidase is 1000 U / mL to 3000 U / mL. In some embodiments, the concentration of hyaluronidase is 1000 U / mL to 2000 U / mL. In some embodiments, the concentration of hyaluronidase is 1000 U / mL to 1500 U / mL. In some embodiments, the concentration of hyaluronidase is between 1500 U / mL and 3000 U / mL. In some embodiments, the concentration of hyaluronidase is between 1500 U / mL and 2500 U / mL. In some embodiments, the concentration of hyaluronidase is between 1500 U / mL and 2000 U / mL. In some embodiments, the concentration of hyaluronidase is between 1800 U / mL and 2200 U / mL.

[0157]

[0176] In some embodiments, the concentration of hyaluronidase is 1000 U / mL. In some embodiments, the concentration of hyaluronidase is about 1500 U / mL. In certain embodiments, the concentration of hyaluronidase is 2000 U / mL. In some embodiments, the concentration of hyaluronidase is 2500 U / mL. In some embodiments, the concentration of hyaluronidase is 3000 U / mL. In some embodiments, the concentration of hyaluronidase is 3500 U / mL. In some embodiments, the concentration of hyaluronidase is 4000 U / mL. In some embodiments, the concentration of hyaluronidase is 4500 U / mL. In some embodiments, the concentration of hyaluronidase is 5000 U / mL. In some embodiments, the concentration of hyaluronidase is 5500 U / mL. In some embodiments, the concentration of hyaluronidase is 6000 U / mL. In some embodiments, the concentration of hyaluronidase is 6500 U / mL. In some embodiments, the concentration of hyaluronidase is 7000 U / mL.

[0158]

[0177] In some embodiments, the liquid pharmaceutical formulation comprises 50 mg / mL to 70 mg / mL of anti-TIGIT monoclonal antibody, 15 mM to 25 mM of buffer, 230 to 250 mM of tonicity agent, 5 mM to 15 mM of stabilizer, 0.3 mg / mL to 0.5 mg / mL of surfactant, and a pH of 5.4 to 5.6. In some embodiments, the liquid pharmaceutical formulation comprises 50 mg / mL to 70 mg / mL of anti-TIGIT monoclonal antibody, 15 mM to 25 mM of histidine acetate, 230 to 250 mM of sucrose, 5 mM to 15 mM of methionine, 0.3 mg / mL to 0.5 mg / mL of polysorbate 20, and a pH of 5.4 to 5.6. In some embodiments, the liquid pharmaceutical formulation comprises 55 mg / mL to 65 mg / mL of anti-TIGIT monoclonal antibody, 18 mM to 22 mM of buffer, 235 to 245 mM of tonicity agent, 8 mM to 12 mM of stabilizer, 0.35 mg / mL to 0.45 mg / mL of surfactant, and a pH of 5.45 to 5.55. In some embodiments, the liquid pharmaceutical formulation comprises 55 mg / mL to 65 mg / mL of anti-TIGIT monoclonal antibody, 18 mM to 22 mM of histidine acetate, 235 to 245 mM of sucrose, 8 mM to 12 mM of methionine, 0.35 mg / mL to 0.45 mg / mL of polysorbate 20, and a pH of 5.45 to 5.55.

[0159]

[0178] In some embodiments, the liquid pharmaceutical formulation comprises about 50 mg / mL to about 70 mg / mL of anti-TIGIT monoclonal antibody, about 15 mM to about 25 mM of buffer, about 230 mM to about 250 mM of tonicity agent, about 5 mM to about 15 mM of stabilizer, about 0.3 mg / mL to about 0.5 mg / mL of surfactant, and a pH of about 5.4 to 5.6. In some embodiments, the liquid pharmaceutical formulation comprises about 50 mg / mL to about 70 mg / mL of anti-TIGIT monoclonal antibody, about 15 mM to about 25 mM of histidine acetate, about 230 mM to about 250 mM of sucrose, about 5 mM to about 15 mM of methionine, about 0.3 mg / mL to about 0.5 mg / mL of polysorbate 20, and a pH of about 5.4 to 5.6. In some embodiments, the liquid pharmaceutical formulation comprises about 55 mg / mL to about 65 mg / mL of anti-TIGIT monoclonal antibody, about 18 mM to about 22 mM of buffer, about 235 mM to about 245 mM of tonicity agent, about 8 mM to about 12 mM of stabilizer, about 0.35 mg / mL to about 0.45 mg / mL of surfactant, and a pH of about 5.45 to about 5.55. In some embodiments, the liquid pharmaceutical formulation comprises about 55 mg / mL to about 65 mg / mL of anti-TIGIT monoclonal antibody, about 18 mM to about 22 mM of histidine acetate, about 235 mM to about 245 mM of sucrose, about 8 mM to about 12 mM of methionine, about 0.35 mg / mL to about 0.45 mg / mL of polysorbate 20, and a pH of about 5.45 to about 5.55.

[0160]

[0179] In some embodiments, the liquid pharmaceutical formulation comprises 60 mg / mL of anti-TIGIT monoclonal antibody, 20 mM buffer, 240 mM tonicity agent, 10 mM stabilizer, 0.4 mg / mL surfactant, and a pH of 5.5. In some embodiments, the liquid pharmaceutical formulation comprises 60 mg / mL of anti-TIGIT monoclonal antibody, 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.4 mg / mL polysorbate 20, and a pH of 5.5. Converting mg / mL to % (w / v) is within the skill of the art. For example, 0.4 mg / mL polysorbate 20 corresponds to 0.04% (w / v) polysorbate 20.

[0161]

[0180] In some embodiments, the liquid pharmaceutical formulation comprises about 60 mg / mL of anti-TIGIT monoclonal antibody, about 20 mM buffer, about 240 mM tonicity agent, about 10 mM stabilizer, about 0.4 mg / mL surfactant, and a pH of about 5.5. In some embodiments, the liquid pharmaceutical formulation comprises about 60 mg / mL of anti-TIGIT monoclonal antibody, about 20 mM histidine acetate, about 240 mM sucrose, about 10 mM methionine, about 0.4 mg / mL polysorbate 20, and a pH of about 5.5.

[0162]

[0181] In some embodiments, the liquid pharmaceutical formulation comprises 150 mg / mL to 170 mg / mL of anti-TIGIT monoclonal antibody, 15 to 25 mM buffer, 230 to 250 mM isotonicity agent, 5 to 15 mM stabilizer, 0.5 to 0.7 mg / mL surfactant, and a pH of 5.4 to 5.6. In some embodiments, the liquid pharmaceutical formulation comprises 150 mg / mL to 170 mg / mL of anti-TIGIT monoclonal antibody, 15 to 25 mM histidine acetate, 230 to 250 mM sucrose, 5 to 15 mM methionine, 0.5 to 0.7 mg / mL polysorbate 20, and a pH of 5.4 to 5.6. In some embodiments, the liquid pharmaceutical formulation comprises 155-165 mg / mL of anti-TIGIT monoclonal antibody, 18-22 mM buffer, 235-245 mM isotonicity agent, 8-12 mM stabilizer, 0.55-0.65 mg / mL surfactant, and a pH of 5.45-5.55. In some embodiments, the liquid pharmaceutical formulation comprises 155-165 mg / mL of anti-TIGIT monoclonal antibody, 18-22 mM histidine acetate, 235-245 mM sucrose, 8-12 mM methionine, 0.55-0.65 mg / mL polysorbate 20, and a pH of 5.45-5.55.

[0163]

[0182] In some embodiments, the liquid pharmaceutical formulation comprises about 150 to about 170 mg / mL of an anti-TIGIT monoclonal antibody, about 15 to about 25 mM of a buffer, about 230 to about 250 mM of an isotonicity agent, about 5 to about 15 mM of a stabilizer, about 0.5 to about 0.7 mg / mL of a surfactant, and a pH of about 5.4 to about 5.6. In some embodiments, the liquid pharmaceutical formulation comprises about 150 to about 170 mg / mL of an anti-TIGIT monoclonal antibody, about 15 to about 25 mM of histidine acetate, about 230 to about 250 mM of sucrose, about 5 to about 15 mM of methionine, about 0.5 to about 0.7 mg / mL of polysorbate 20, and a pH of about 5.4 to about 5.6. In some embodiments, the liquid pharmaceutical formulation comprises about 155 to about 165 mg / mL of an anti-TIGIT monoclonal antibody, about 18 to about 22 mM of a buffer, about 235 to about 245 mM of an isotonicity agent, about 8 to about 12 mM of a stabilizer, about 0.55 to about 0.65 mg / mL of a surfactant, and a pH of about 5.45 to about 5.55. In some embodiments, the liquid pharmaceutical formulation comprises about 155 to about 165 mg / mL of an anti-TIGIT monoclonal antibody, about 18 to about 22 mM of histidine acetate, about 235 to about 245 mM of sucrose, about 8 to about 12 mM of methionine, about 0.55 to about 0.65 mg / mL of polysorbate 20, and a pH of about 5.45 to about 5.55.

[0164]

[0183] In some embodiments, the liquid pharmaceutical formulation comprises 160 mg / mL of anti-TIGIT monoclonal antibody, 20 mM buffer, 240 mM tonicity agent, 10 mM stabilizer, 0.6 mg / mL surfactant, and a pH of 5.5. In some embodiments, the liquid pharmaceutical formulation comprises 160 mg / mL of anti-TIGIT monoclonal antibody, 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.6 mg / mL polysorbate 20, and a pH of 5.5. In some embodiments, the liquid pharmaceutical formulation comprises 176 mg / mL of anti-TIGIT monoclonal antibody, 30 mM histidine acetate, 180 mM sucrose, 5 mM methionine, 0.8 mg / mL polysorbate 20, and a pH of 5.5.

[0165]

[0184] In some embodiments, the liquid pharmaceutical formulation comprises about 160 mg / mL of anti-TIGIT monoclonal antibody, about 20 mM buffer, about 240 mM isotonicity agent, about 10 mM stabilizer, about 0.6 mg / mL of surfactant, and a pH of about 5.5. In some embodiments, the liquid pharmaceutical formulation comprises about 160 mg / mL of anti-TIGIT monoclonal antibody, about 20 mM histidine acetate, about 240 mM sucrose, about 10 mM methionine, about 0.6 mg / mL of polysorbate 20, and a pH of about 5.5. In some embodiments, the liquid pharmaceutical formulation comprises about 176 mg / mL of anti-TIGIT monoclonal antibody, about 30 mM histidine acetate, about 180 mM sucrose, about 5 mM methionine, about 0.8 mg / mL of polysorbate 20, and a pH of about 5.5.

[0166]

[0185] In some embodiments, the liquid pharmaceutical formulation comprises 150-170 mg / mL anti-TIGIT monoclonal antibody, 1000-3000 U / mL hyaluronidase, 15-25 mM buffer, 230-250 mM isotonicity agent, 5-15 mM stabilizer, 0.5-0.7 mg / mL surfactant, and a pH of 5.4-5.6. In some embodiments, the liquid pharmaceutical formulation comprises 150 mg / mL-170 mg / mL anti-TIGIT monoclonal antibody, 1000-3000 U / mL hyaluronidase, 15-25 mM histidine acetate, 230-250 mM sucrose, 5-15 mM methionine, 0.5-0.7 mg / mL polysorbate 20, and a pH of 5.4-5.6. In some embodiments, the liquid pharmaceutical formulation comprises 155-165 mg / mL of anti-TIGIT monoclonal antibody, 1500-2500 U / mL of hyaluronidase, 18-22 mM of buffer, 235-245 mM of tonicity agent, 8-12 mM of stabilizer, 0.55-0.65 mg / mL of surfactant, and a pH of 5.45-5.55. In some embodiments, the liquid pharmaceutical formulation comprises 155-165 mg / mL of anti-TIGIT monoclonal antibody, 1500-2500 U / mL of hyaluronidase, 18-22 mM of histidine acetate, 235-245 mM of sucrose, 8-12 mM of methionine, 0.55-0.65 mg / mL of polysorbate 20, and a pH of 5.45-5.55.

[0167]

[0186] In some embodiments, the liquid pharmaceutical formulation comprises about 150 to about 170 mg / mL of anti-TIGIT monoclonal antibody, about 1000 to about 3000 U / mL of hyaluronidase, about 15 to about 25 mM of buffer, about 230 to about 250 mM of isotonicity agent, about 5 to about 15 mM of stabilizer, about 0.5 to about 0.7 mg / mL of surfactant, and a pH of about 5.4 to 5.6. In some embodiments, the liquid pharmaceutical formulation comprises about 150 to about 170 mg / mL of anti-TIGIT monoclonal antibody, about 1000 to about 3000 U / mL of hyaluronidase, about 15 to about 25 mM histidine acetate, about 230 to about 250 mM sucrose, about 5 to about 15 mM methionine, about 0.5 to about 0.7 mg / mL of polysorbate 20, and a pH of about 5.4 to about 5.6. In some embodiments, the liquid pharmaceutical formulation comprises about 155 to about 165 mg / mL of anti-TIGIT monoclonal antibody, about 1500 to about 2500 U / mL of hyaluronidase, about 18 to about 22 mM of buffer, about 235 to about 245 mM of isotonicity agent, about 8 to about 12 mM of stabilizer, about 0.55 to about 0.65 mg / mL of surfactant, and a pH of about 5.45 to about 5.55. In some embodiments, the liquid pharmaceutical formulation comprises about 155 to about 165 mg / mL of anti-TIGIT monoclonal antibody, about 1500 to about 2500 U / mL of hyaluronidase, about 18 to about 22 mM histidine acetate, about 235 to about 245 mM sucrose, about 8 to about 12 mM methionine, about 0.55 to about 0.65 mg / mL of polysorbate 20, and a pH of about 5.45 to about 5.55.

[0168]

[0187] In some embodiments, the liquid pharmaceutical formulation comprises 160 mg / mL anti-TIGIT monoclonal antibody, 2000 U / mL hyaluronidase, 20 mM buffer, 240 mM tonicity agent, 10 mM stabilizer, 0.6 mg / mL surfactant, and a pH of 5.5. In some embodiments, the liquid pharmaceutical formulation comprises 160 mg / mL anti-TIGIT monoclonal antibody, 2000 U / mL hyaluronidase, 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.6 mg / mL polysorbate 20, and a pH of 5.5.

[0169]

[0188] In some embodiments, the liquid pharmaceutical formulation comprises about 160 mg / mL of anti-TIGIT monoclonal antibody, about 2000 U / mL of hyaluronidase, about 20 mM buffer, about 240 mM of tonicity agent, about 10 mM of stabilizer, about 0.6 mg / mL of surfactant, and a pH of about 5.5. In some embodiments, the liquid pharmaceutical formulation comprises about 160 mg / mL of anti-TIGIT monoclonal antibody, about 2000 U / mL of hyaluronidase, about 20 mM of histidine acetate, about 240 mM of sucrose, about 10 mM of methionine, about 0.6 mg / mL of polysorbate 20, and a pH of about 5.5.

[0170]

[0189] In some embodiments, the liquid pharmaceutical formulation comprises 30-50 mg / mL anti-TIGIT monoclonal antibody, 70 mg / mL-90 mg / mL anti-PD-L1 monoclonal antibody, 15 mM-25 mM buffer, 230 mM-250 mM tonicity agent, 5 mM-15 mM stabilizer, 0.5 mg / mL-0.7 mg / mL surfactant, and a pH of 5.7-5.9. In some embodiments, the liquid pharmaceutical formulation comprises 30 mg / mL to 50 mg / mL of anti-TIGIT monoclonal antibody, 70 mg / mL to 90 mg / mL of anti-PD-L1 monoclonal antibody, 15 mM to 25 mM histidine acetate, 230 mM to 250 mM sucrose, 5 mM to 15 mM methionine, 0.5 mg / mL to 0.7 mg / mL polysorbate 20, and a pH of 5.7 to 5.9. In some embodiments, the liquid pharmaceutical formulation comprises 35 mg / mL to 45 mg / mL of anti-TIGIT monoclonal antibody, 75 mg / mL to 85 mg / mL of anti-PD-L1 monoclonal antibody, 18 mM to 22 mM buffer, 235 mM to 245 mM tonicity agent, 8 mM to 12 mM stabilizer, 0.55 mg / mL to 0.65 mg / mL of surfactant, and a pH of 5.75 to 5.85. In some embodiments, the liquid pharmaceutical formulation comprises 35 mg / mL to 45 mg / mL of anti-TIGIT monoclonal antibody, 75 mg / mL to 85 mg / mL of anti-PD-L1 monoclonal antibody, 18 mM to 22 mM histidine acetate, 235 mM to 245 mM sucrose, 8 mM to 12 mM methionine, 0.55 mg / mL to 0.65 mg / mL polysorbate 20, and a pH of 5.75 to 5.85.

[0171]

[0190] In some embodiments, the liquid pharmaceutical formulation comprises about 30 to about 50 mg / mL of anti-TIGIT monoclonal antibody, 70 mg / mL to 90 mg / mL of anti-PD-L1 monoclonal antibody, about 15 mM to about 25 mM of buffer, about 230 mM to about 250 mM of tonicity agent, about 5 mM to about 15 mM of stabilizer, about 0.5 mg / mL to about 0.7 mg / mL of surfactant, and a pH of about 5.7 to about 5.9. In some embodiments, the liquid pharmaceutical formulation comprises about 30 mg / mL to about 50 mg / mL of anti-TIGIT monoclonal antibody, about 70 mg / mL to about 90 mg / mL of anti-PD-L1 monoclonal antibody, about 15 mM to about 25 mM histidine acetate, about 230 mM to about 250 mM sucrose, about 5 mM to about 15 mM methionine, about 0.5 mg / mL to about 0.7 mg / mL of polysorbate 20, and a pH of about 5.7 to about 5.9. In some embodiments, the liquid pharmaceutical formulation comprises about 35 mg / mL to about 45 mg / mL of anti-TIGIT monoclonal antibody, about 75 mg / mL to about 85 mg / mL of anti-PD-L1 monoclonal antibody, about 18 mM to about 22 mM buffer, about 235 mM to about 245 mM of tonicity agent, about 8 mM to about 12 mM stabilizer, about 0.55 mg / mL to about 0.65 mg / mL of surfactant, and a pH of about 5.75 to about 5.85. In some embodiments, the liquid pharmaceutical formulation comprises about 35 mg / mL to about 45 mg / mL of anti-TIGIT monoclonal antibody, about 75 mg / mL to about 85 mg / mL of anti-PD-L1 monoclonal antibody, about 18 mM to about 22 mM histidine acetate, about 235 mM to about 245 mM sucrose, about 8 mM to about 12 mM methionine, about 0.55 mg / mL to about 0.65 mg / mL of polysorbate 20, and a pH of about 5.75 to about 5.85.

[0172]

[0191] In some embodiments, the liquid pharmaceutical formulation comprises 40 mg / mL anti-TIGIT monoclonal antibody, 80 mg / mL anti-PD-L1 monoclonal antibody, 20 mM buffer, 240 mM tonicity agent, 10 mM stabilizer, 0.6 mg / mL surfactant, and a pH of 5.8. In some embodiments, the liquid pharmaceutical formulation comprises 40 mg / mL anti-TIGIT monoclonal antibody, 80 mg / mL anti-PD-L1 monoclonal antibody, 20 mM histidine acetate, 240 mM sucrose, 10 mM methionine, 0.6 mg / mL polysorbate 20, and a pH of 5.8.

[0173]

[0192] In some embodiments, the liquid pharmaceutical formulation comprises about 40 mg / mL anti-TIGIT monoclonal antibody, 80 mg / mL anti-PD-L1 monoclonal antibody, about 20 mM buffer, about 240 mM tonicity agent, about 10 mM stabilizer, about 0.6 mg / mL surfactant, and a pH of about 5.8. In some embodiments, the liquid pharmaceutical formulation comprises about 40 mg / mL anti-TIGIT monoclonal antibody, about 80 mg / mL anti-PD-L1 monoclonal antibody, about 20 mM histidine acetate, about 240 mM sucrose, about 10 mM methionine, about 0.6 mg / mL polysorbate 20, and a pH of about 5.8.

[0174]

[0193] In some embodiments, the liquid pharmaceutical formulation is formulated to be administered intravenously or subcutaneously. In some embodiments, the liquid pharmaceutical formulation is formulated to be administered intravenously. In some embodiments, the liquid pharmaceutical formulation is formulated to be administered subcutaneously.

[0175]

[0194] In some embodiments, the anti-TIGIT monoclonal antibody in the formulation is not pre-lyophilized.In some embodiments, the anti-PD-L1 monoclonal antibody in the formulation is not pre-lyophilized.

[0176]

[0195] A further aspect of the present disclosure provides a liquid pharmaceutical formulation comprising an anti-TIGIT monoclonal antibody and an anti-PD-L1 monoclonal antibody. In some embodiments, the liquid pharmaceutical formulation comprises: (a) 18 mg / mL to 176 mg / mL of anti-TIGIT monoclonal antibody; (b) 54 mg / mL to 137.5 mg / mL of anti-PD-L1 monoclonal antibody; (c) 5 mM to 30 mM histidine buffer; (d) 120 mM to 320 mM sucrose; and (e) 0.02% (w / v) to 0.08% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.2 to 6.1; and the anti-TIGIT monoclonal antibody is HVR-H1 comprising the amino acid sequence of SEQ ID NO:1; HVR-H2 comprising the amino acid sequence of SEQ ID NO:2; and HVR-H3 comprising the amino acid sequence of SEQ ID NO:3. and HVR-L3 comprising the amino acid sequence of SEQ ID NO:6; the anti-PD-L1 monoclonal antibody comprises a heavy chain variable region comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:10; HVR-H2 comprising the amino acid sequence of SEQ ID NO:11; and HVR-H3 comprising the amino acid sequence of SEQ ID NO:12, and a light chain variable region comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:13; HVR-L2 comprising the amino acid sequence of SEQ ID NO:14; and HVR-L3 comprising the amino acid sequence of SEQ ID NO:15.

[0177]

[0196] In some embodiments, the liquid pharmaceutical formulation comprises 18 mg / mL to 176 mg / mL of anti-TIGIT monoclonal antibody; 54 mg / mL to 137.5 mg / mL of anti-PD-L1 monoclonal antibody; 5 mM to 30 mM histidine buffer; 120 mM to 320 mM sucrose; 0.02% (w / v) to 0.08% (w / v) polysorbate 20, and a pH of about 5.2 to 6.1. In some embodiments, the liquid pharmaceutical formulation comprises 36 mg / mL to 44 mg / mL of anti-TIGIT monoclonal antibody, 72 mg / mL to 88 mg / mL of anti-PD-L1 monoclonal antibody, 15 mM to 25 mM histidine buffer, 200 mM to 280 mM sucrose, 0.04% (w / v) to 0.08% (w / v) polysorbate 20, and a pH of about 5.5 to 6.1. In some embodiments, the liquid pharmaceutical formulation comprises 40 mg / mL of anti-TIGIT monoclonal antibody, 80 mg / mL of anti-PD-L1 monoclonal antibody, 20 mM histidine buffer, 240 mM sucrose, 0.06% (w / v) polysorbate 20, and a pH of about 5.5. In some embodiments, the liquid pharmaceutical formulation comprises 40 mg / mL of anti-TIGIT monoclonal antibody; 80 mg / mL of anti-PD-L1 monoclonal antibody; 20 mM histidine buffer; 240 mM sucrose; 0.06% (w / v) polysorbate 20, and a pH of about 5.6. In some embodiments, the liquid pharmaceutical formulation comprises 40 mg / mL of anti-TIGIT monoclonal antibody; 80 mg / mL of anti-PD-L1 monoclonal antibody; 20 mM histidine buffer; 240 mM sucrose; 0.06% (w / v) polysorbate 20, and a pH of about 5.7. In some embodiments, the liquid pharmaceutical formulation comprises 40 mg / mL anti-TIGIT monoclonal antibody; 80 mg / mL anti-PD-L1 monoclonal antibody; 20 mM histidine buffer; 240 mM sucrose; 0.06% (w / v) polysorbate 20, and a pH of about 5.8.In some embodiments, the liquid pharmaceutical formulation comprises about 18 mg / mL to about 176 mg / mL of anti-TIGIT monoclonal antibody; about 54 mg / mL to about 137.5 mg / mL of anti-PD-L1 monoclonal antibody; about 5 mM to about 30 mM histidine buffer; about 120 mM to about 320 mM sucrose; about 0.02% (w / v) to about 0.08% (w / v) polysorbate 20, and a pH of about 5.2 to 6.1. In some embodiments, the liquid pharmaceutical formulation comprises about 36 mg / mL to about 44 mg / mL of anti-TIGIT monoclonal antibody, about 72 mg / mL to about 88 mg / mL of anti-PD-L1 monoclonal antibody, about 15 mM to about 25 mM histidine buffer, about 200 mM to about 280 mM sucrose, about 0.04% (w / v) to about 0.08% (w / v) polysorbate 20, and a pH of about 5.5 to 6.1. In some embodiments, the liquid pharmaceutical formulation comprises about 40 mg / mL of anti-TIGIT monoclonal antibody, about 80 mg / mL of anti-PD-L1 monoclonal antibody, about 20 mM histidine buffer, about 240 mM sucrose, about 0.06% (w / v) polysorbate 20, and a pH of about 5.8.

[0178]

[0197] Another aspect of the present disclosure provides a liquid pharmaceutical formulation comprising an anti-TIGIT monoclonal antibody and an anti-PD-L1 monoclonal antibody. In some embodiments, the liquid pharmaceutical formulation comprises: (a) 18 mg / mL to 75 mg / mL of anti-TIGIT monoclonal antibody; (b) 54 mg / mL to 137.5 mg / mL of anti-PD-L1 monoclonal antibody; (c) 12 mM to 28 mM histidine buffer; (d) 100 mM to 300 mM sucrose; and (e) 0.02% (w / v) to 0.08% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.4 to 6.2; wherein the anti-TIGIT monoclonal antibody is HVR-H1 comprising the amino acid sequence of SEQ ID NO:1; HVR-H2 comprising the amino acid sequence of SEQ ID NO:2; and HVR-H3 comprising the amino acid sequence of SEQ ID NO:3. and HVR-L3 comprising the amino acid sequence of SEQ ID NO:6; and a light chain variable region comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:10; HVR-H2 comprising the amino acid sequence of SEQ ID NO:11; and HVR-H3 comprising the amino acid sequence of SEQ ID NO:12; and a light chain variable region comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:13; HVR-L2 comprising the amino acid sequence of SEQ ID NO:14; and HVR-L3 comprising the amino acid sequence of SEQ ID NO:15.

[0179]

[0198] In some embodiments, the liquid pharmaceutical formulation comprises: (a) 30 mg / mL to 50 mg / mL of anti-TIGIT monoclonal antibody; (b) 70 mg / mL to 90 mg / mL of anti-PD-L1 monoclonal antibody; (c) 15 mM to 25 mM of histidine acetate; (d) 200 mM to 280 mM of sucrose; and (3) 0.04% (w / v) to 0.08% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of 5.6 to 6.0. In some embodiments, the liquid pharmaceutical formulation comprises: (a) 36 mg / mL to 44 mg / mL of anti-TIGIT monoclonal antibody; (b) 72 mg / mL to 88 mg / mL of anti-PD-L1 monoclonal antibody; (c) 18 mM to 22 mM of histidine acetate; (d) 220 mM to 260 mM of sucrose; and (3) 0.05% (w / v) to 0.07% (w / v) of polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of 5.7 to 5.9.

[0180]

[0199] Another aspect of the disclosure provides a liquid pharmaceutical formulation comprising an anti-TIGIT monoclonal antibody and suitable for co-administration with an anti-PD-L1 monoclonal antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is an anti-PD-L1 monoclonal antibody disclosed above. In some embodiments, the liquid pharmaceutical formulation comprises: (a) 18 mg / mL to 176 mg / mL of an anti-TIGIT monoclonal antibody; (b) 5 mM to 30 mM histidine acetate; (c) 100 mM to 320 mM sucrose; and (d) 0.01% (w / v) to 0.08% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.0 to 6.0; the anti-TIGIT monoclonal antibody comprises a heavy chain variable region comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2; and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3; and a light chain variable region comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6. In some embodiments, the liquid pharmaceutical formulation comprises: (a) about 18 mg / mL to about 176 mg / mL of an anti-TIGIT monoclonal antibody; (b) about 5 mM to about 30 mM histidine acetate; (c) about 100 mM to about 320 mM sucrose; and (d) about 0.01% (w / v) to about 0.08% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.0 to 6.0; the anti-TIGIT monoclonal antibody comprises a heavy chain variable region comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2; and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3; and a light chain variable region comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6.

[0181]

[0200] In some embodiments, the formulation comprises (a) 144 mg / mL to 176 mg / mL of anti-TIGIT monoclonal antibody; (b) 5 mM to 25 mM histidine buffer; (c) 180 mM to 320 mM sucrose; and (d) 0.05% (w / v) to 0.08% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.2 to 5.8. In some embodiments, the formulation comprises (a) 160 mg / mL of anti-TIGIT monoclonal antibody; (b) 20 mM histidine buffer; (c) 240 mM sucrose; and (d) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.5. In some embodiments, the formulation comprises (a) about 144 mg / mL to about 176 mg / mL of an anti-TIGIT monoclonal antibody; (b) 5 mM to 25 mM histidine buffer; (c) about 180 mM to about 320 mM sucrose; and (d) about 0.05% (w / v) to about 0.08% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.2 to 5.8. In some embodiments, the formulation comprises (a) about 160 mg / mL of an anti-TIGIT monoclonal antibody; (b) about 20 mM histidine buffer; (c) about 240 mM sucrose; and (d) about 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.5.

[0182]

[0201] An additional aspect of the present disclosure provides a liquid pharmaceutical formulation suitable for subcutaneous injection and comprising an anti-TIGIT monoclonal antibody. In some embodiments, the liquid pharmaceutical formulation comprises: (a) 18 mg / mL to 176 mg / mL of an anti-TIGIT monoclonal antibody; (b) 500 U / mL to 2600 U / mL of hyaluronidase; (c) 5 mM to 30 mM histidine buffer; (d) 180 mM to 320 mM sucrose; and (e) 0.03% (w / v) to 0.08% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.2 to 6.0; the anti-TIGIT monoclonal antibody comprises a heavy chain variable region comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:1; HVR-H2 comprising the amino acid sequence of SEQ ID NO:2; and HVR-H3 comprising the amino acid sequence of SEQ ID NO:3, and a light chain variable region comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:4; HVR-L2 comprising the amino acid sequence of SEQ ID NO:5; and HVR-L3 comprising the amino acid sequence of SEQ ID NO:6.

[0183]

[0202] In some embodiments, the liquid pharmaceutical formulation comprises 18 mg / mL to 176 mg / mL of an anti-TIGIT monoclonal antibody, (b) 500 U / mL to 2600 U / mL of hyaluronidase, 5 mM to 30 mM histidine buffer, 180 mM to 320 mM sucrose, 0.03% (w / v) to 0.08% (w / v) polysorbate 20, and a pH of about 5.2 to 6.0. In some embodiments, the liquid pharmaceutical formulation comprises 144 mg / mL to 176 mg / mL of anti-TIGIT monoclonal antibody, (b) 1400 U / mL to 2600 U / mL of hyaluronidase, 5 mM to 25 mM histidine buffer, 180 mM to 320 mM sucrose, 0.04 percent (w / v) to 0.08% (w / v) polysorbate 20, and a pH of about 5.2 to 5.8. In some embodiments, the liquid pharmaceutical formulation comprises 160 mg / mL of anti-TIGIT monoclonal antibody, 80 mg / mL of anti-PD-L1 monoclonal antibody, (b) 2000 U / mL of hyaluronidase, 20 mM histidine buffer, 240 mM sucrose, 0.06% (w / v) polysorbate 20, and a pH of about 5.5. In some embodiments, the liquid pharmaceutical formulation comprises 144 mg / mL to 176 mg / mL of anti-TIGIT monoclonal antibody, 5 mM to 25 mM histidine buffer, 180 mM to 320 mM sucrose, 0.05% (w / v) to 0.08% (w / v) polysorbate 20, and a pH of about 5.2 to 5.8. In some embodiments, the liquid pharmaceutical formulation comprises 160 mg / mL of anti-TIGIT monoclonal antibody, 20 mM histidine buffer, 240 mM sucrose, 0.06% (w / v) polysorbate 20, and a pH of about 5.5. In some embodiments, the liquid pharmaceutical formulation comprises about 18 mg / mL to about 176 mg / mL of an anti-TIGIT monoclonal antibody, (b) about 500 U / mL to about 2600 U / mL of hyaluronidase, about 5 mM to about 30 mM histidine buffer, about 180 mM to about 320 mM sucrose, about 0.03% (w / v) to 0.08% (w / v) polysorbate 20, and a pH of about 5.2 to 6.0.In some embodiments, the liquid pharmaceutical formulation comprises about 144 mg / mL to about 176 mg / mL of anti-TIGIT monoclonal antibody, about 5 mM to about 25 mM histidine buffer, about 180 mM to about 320 mM sucrose, about 0.05% (w / v) to about 0.08% (w / v) polysorbate 20, and a pH of about 5.2 to 5.8. In some embodiments, the liquid pharmaceutical formulation comprises about 160 mg / mL of anti-TIGIT monoclonal antibody, about 20 mM histidine buffer, about 240 mM sucrose, about 0.06% (w / v) polysorbate 20, and a pH of about 5.5.

[0184]

[0203] In some embodiments, the hyaluronidase is recombinant human hyaluronidase. In some embodiments, the hyaluronidase is human soluble PH20 hyaluronidase glycoprotein, such as rHuPH20. In some embodiments, the hyaluronidase is human soluble PH20 hyaluronidase glycoprotein. In certain embodiments, the hyaluronidase is rHuPH20.

[0185]

[0204] In another aspect, the disclosure provides a liquid pharmaceutical formulation suitable for subcutaneous injection, comprising an anti-TIGIT monoclonal antibody, an anti-PD-L1 monoclonal antibody, and hyaluronidase. In some embodiments, the liquid pharmaceutical formulation comprises: (a) 30 mg / mL to 60 mg / mL of an anti-TIGIT monoclonal antibody; (b) 60 mg / mL to 120 mg / mL of an anti-PD-L1 monoclonal antibody; (c) 500 U / mL to 2600 U / mL of hyaluronidase; (d) 5 mM to 30 mM histidine buffer; (e) 180 mM to 320 mM sucrose; and (f) 0.03% (w / v) to 0.08% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.2 to 6.1; wherein the anti-TIGIT monoclonal antibody is HVR-H1 comprising the amino acid sequence of SEQ ID NO:1; HVR-H2 comprising the amino acid sequence of SEQ ID NO:2; and HVR-L1 comprising the amino acid sequence of SEQ ID NO:4; HVR-L2 comprising the amino acid sequence of SEQ ID NO:5; and HVR-L3 comprising the amino acid sequence of SEQ ID NO:6; the anti-PD-L1 monoclonal antibody comprises a heavy chain variable region comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO:10; HVR-H2 comprising the amino acid sequence of SEQ ID NO:11; and HVR-H3 comprising the amino acid sequence of SEQ ID NO:12; and a light chain variable region comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO:13; HVR-L2 comprising the amino acid sequence of SEQ ID NO:14; and HVR-L3 comprising the amino acid sequence of SEQ ID NO:15.

[0186]

[0205] In some embodiments, the formulation comprises: (a) 30 mg / mL to 60 mg / mL of anti-TIGIT monoclonal antibody; (b) 60 mg / mL to 120 mg / mL of anti-PD-L1 monoclonal antibody; (c) 1000 U / mL to 3000 U / mL of hyaluronidase; (d) 15 mM to 25 mM histidine buffer; (e) 200 mM to 280 mM sucrose; and (f) 0.04% (w / v) to 0.08% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.2 to 6.1. In some embodiments, the formulation comprises: (a) 35 mg / mL to 45 mg / mL of anti-TIGIT monoclonal antibody; (b) 70 mg / mL to 90 mg / mL of anti-PD-L1 monoclonal antibody; (c) 1500 U / mL to 2500 U / mL of hyaluronidase; (d) 18 mM to 22 mM histidine buffer; (e) 220 mM to 260 mM sucrose; and (f) 0.05% (w / v) to 0.07% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.5 to 5.8. In some embodiments, the formulation comprises: (a) 40 mg / mL to 50 mg / mL of anti-TIGIT monoclonal antibody; (b) 80 mg / mL to 100 mg / mL of anti-PD-L1 monoclonal antibody; (c) 1500 U / mL to 2500 U / mL of hyaluronidase; (d) 18 mM to 22 mM histidine buffer; (e) 220 mM to 260 mM sucrose; and (f) 0.05% (w / v) to 0.07% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.5 to 5.8.

[0187]

[0206] In some embodiments, the formulation comprises: (a) 30 mg / mL of anti-TIGIT monoclonal antibody; (b) 60 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.5 to 5.8. In some embodiments, the formulation comprises: (a) 30 mg / mL of anti-TIGIT monoclonal antibody; (b) 60 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.5. In some embodiments, the formulation comprises: (a) 30 mg / mL of anti-TIGIT monoclonal antibody; (b) 60 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.6. In some embodiments, the formulation comprises: (a) 30 mg / mL of anti-TIGIT monoclonal antibody; (b) 60 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.7. In some embodiments, the formulation comprises: (a) 30 mg / mL of anti-TIGIT monoclonal antibody; (b) 60 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.8.

[0188]

[0207] In some embodiments, the formulation comprises: (a) 35 mg / mL of anti-TIGIT monoclonal antibody; (b) 70 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.5 to 5.8. In some embodiments, the formulation comprises: (a) 35 mg / mL of anti-TIGIT monoclonal antibody; (b) 70 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.5. In some embodiments, the formulation comprises: (a) 35 mg / mL of anti-TIGIT monoclonal antibody; (b) 70 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.6. In some embodiments, the formulation comprises: (a) 35 mg / mL of anti-TIGIT monoclonal antibody; (b) 70 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.7. In some embodiments, the formulation comprises: (a) 35 mg / mL of anti-TIGIT monoclonal antibody; (b) 70 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.8.

[0189]

[0208] In some embodiments, the formulation comprises: (a) 40 mg / mL of anti-TIGIT monoclonal antibody; (b) 80 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.5 to 5.8. In some embodiments, the formulation comprises: (a) 40 mg / mL of anti-TIGIT monoclonal antibody; (b) 80 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.5. In some embodiments, the formulation comprises: (a) 40 mg / mL of anti-TIGIT monoclonal antibody; (b) 80 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.6. In some embodiments, the formulation comprises: (a) 40 mg / mL of anti-TIGIT monoclonal antibody; (b) 80 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.7. In some embodiments, the formulation comprises: (a) 40 mg / mL of anti-TIGIT monoclonal antibody; (b) 80 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.8.

[0190]

[0209] In some embodiments, the formulation comprises: (a) 45 mg / mL of anti-TIGIT monoclonal antibody; (b) 90 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.5 to 5.8. In some embodiments, the formulation comprises: (a) 45 mg / mL of anti-TIGIT monoclonal antibody; (b) 90 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.5. In some embodiments, the formulation comprises: (a) 45 mg / mL of anti-TIGIT monoclonal antibody; (b) 90 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.6. In some embodiments, the formulation comprises: (a) 45 mg / mL of anti-TIGIT monoclonal antibody; (b) 90 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.7. In some embodiments, the formulation comprises: (a) 45 mg / mL of anti-TIGIT monoclonal antibody; (b) 90 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.8.

[0191]

[0210] In some embodiments, the formulation comprises: (a) 50 mg / mL of anti-TIGIT monoclonal antibody; (b) 100 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.5 to 5.8. In some embodiments, the formulation comprises: (a) 50 mg / mL of anti-TIGIT monoclonal antibody; (b) 100 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.5. In some embodiments, the formulation comprises: (a) 50 mg / mL of anti-TIGIT monoclonal antibody; (b) 100 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.6. In some embodiments, the formulation comprises: (a) 50 mg / mL of anti-TIGIT monoclonal antibody; (b) 100 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.7. In some embodiments, the formulation comprises: (a) 50 mg / mL of anti-TIGIT monoclonal antibody; (b) 100 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.8.

[0192]

[0211] In some embodiments, the formulation comprises: (a) 55 mg / mL of anti-TIGIT monoclonal antibody; (b) 110 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.5 to 5.8. In some embodiments, the formulation comprises: (a) 55 mg / mL of anti-TIGIT monoclonal antibody; (b) 110 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.5. In some embodiments, the formulation comprises: (a) 55 mg / mL of anti-TIGIT monoclonal antibody; (b) 110 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.6. In some embodiments, the formulation comprises: (a) 55 mg / mL of anti-TIGIT monoclonal antibody; (b) 110 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.7. In some embodiments, the formulation comprises: (a) 55 mg / mL of anti-TIGIT monoclonal antibody; (b) 110 mg / mL of anti-PD-L1 monoclonal antibody; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.8.

[0193]

[0212] In some embodiments of any of the above formulations, the histidine buffer is histidine acetate.

[0194]

[0213] In some embodiments of any of the above formulations, the heavy chain variable region of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 7. In some embodiments, the heavy chain variable region of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 8. In some embodiments, the light chain variable region of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 9. In some embodiments, the heavy chain variable region of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 7 and the light chain variable region of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 9. In some embodiments, the heavy chain variable region of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 8 and the light chain variable region of the anti-TIGIT monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 9.

[0195]

[0214] In some embodiments of any of the above formulations, the anti-TIGIT monoclonal antibody is an IgG antibody. In some embodiments, the anti-TIGIT monoclonal antibody is an IgG1 or IgG4 antibody. In some embodiments, the anti-TIGIT monoclonal antibody is an IgG1 antibody. In some embodiments, the anti-TIGIT monoclonal antibody is an IgG4 antibody. In some embodiments, the anti-TIGIT monoclonal antibody is a full-length antibody. In some embodiments, the anti-TIGIT monoclonal antibody is a human antibody. In some embodiments, the anti-TIGIT monoclonal antibody is a humanized antibody. In some embodiments, the anti-TIGIT monoclonal antibody is a full-length IgG antibody. In some embodiments, the anti-TIGIT monoclonal antibody is a full-length IgG1 antibody. In some embodiments, the anti-TIGIT monoclonal antibody is a full-length human IgG1 antibody. In some embodiments, the anti-TIGIT monoclonal antibody is a full-length humanized IgG1 antibody. The anti-TIGIT monoclonal antibody may be an antibody fragment. In some embodiments, the anti-TIGIT monoclonal antibody is a Fab, Fab', F(ab') 2In some embodiments, the anti-TIGIT monoclonal antibody is a Fab fragment. In some embodiments, the anti-TIGIT monoclonal antibody is a Fab' fragment. In some embodiments, the anti-TIGIT monoclonal antibody is a F(ab') 2 In some embodiments, the anti-TIGIT monoclonal antibody is an Fv fragment. In some embodiments, the anti-TIGIT monoclonal antibody is an scFv fragment. In some embodiments, the anti-TIGIT monoclonal antibody is a diabody. In some embodiments, the anti-TIGIT monoclonal antibody is a linear antibody. In some embodiments, the anti-TIGIT monoclonal antibody is a single-chain antibody molecule. In some embodiments, the anti-TIGIT monoclonal antibody is a multispecific antibody, e.g., a multispecific antibody formed from antibody fragments.

[0196]

[0215] In some embodiments of any of the above formulations, the anti-TIGIT monoclonal antibody inhibits or blocks the interaction of CD226 with TIGIT.

[0197]

[0216] In some embodiments of any of the above formulations, the heavy chain variable region of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 16. In some embodiments, the light chain variable region of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 17. In some embodiments, the heavy chain variable region of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 16 and the light chain variable region of the anti-PD-L1 monoclonal antibody comprises the amino acid sequence of SEQ ID NO: 17. In some embodiments, the anti-PD-L1 monoclonal antibody is atezolizumab, which is commercially available as Tecentriq®. Atezolizumab is listed in the WHO National Information on Drugs (International Nonproprietary Names), proposed INN: List 112, Vol. 28, No. 4, 2014 (see page 488). In some embodiments, atezolizumab has the CAS Registry Number 1380723-44-3.

[0198]

[0217] In some embodiments of any of the above formulations, the anti-PD-L1 monoclonal antibody is an IgG antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is an IgG1 or IgG4 antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is an IgG1 antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is an IgG4 antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is a full-length antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is a human antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is a humanized antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is a full-length IgG antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is a full-length IgG1 antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is a full-length human IgG1 antibody. In some embodiments, the anti-PD-L1 monoclonal antibody is a full-length humanized IgG antibody.

[0199]

[0218] In some embodiments of any of the above formulations, the formulation further comprises a stabilizer. In some embodiments, the stabilizer is selected from the group consisting of methionine, glycine, alanine, proline, taurine, betaine, octopine, glutamate, sarcosine, gamma-aminobutyric acid, and trimethylamine N-oxide. In certain embodiments, the stabilizer is methionine. In some embodiments, the stabilizer is glycine. In some embodiments, the stabilizer is alanine. In some embodiments, the stabilizer is proline. In some embodiments, the stabilizer is taurine. In some embodiments, the stabilizer is betaine. In some embodiments, the stabilizer is octopine. In some embodiments, the stabilizer is glutamate. In some embodiments, the stabilizer is sarcosine. In some embodiments, the stabilizer is gamma-aminobutyric acid. In some embodiments, the stabilizer is trimethylamine N-oxide. In some embodiments, the concentration of the stabilizer is about 0 mM to about 15 mM. In some embodiments, the concentration of the stabilizer is about 5 mM to about 15 mM. In certain embodiments, the concentration of the stabilizer is about 10 mM. In some embodiments, the concentration of the stabilizer is 0 mM to about 15 mM. In some embodiments, the concentration of the stabilizer is 5 mM to 15 mM. In certain embodiments, the concentration of the stabilizer is 10 mM.

[0200]

[0219] In some embodiments of any of the above formulations, the concentration of the anti-TIGIT monoclonal antibody is 18 mg / mL to 176 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 18 mg / mL to 166 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 18 mg / mL to 160 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 18 mg / mL to 156 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 18 mg / mL to 156 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 18 mg / mL to 146 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 18 mg / mL to 136 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 18 mg / mL to 126 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 18 mg / mL to 116 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 18 mg / mL to 106 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 18 mg / mL to 96 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 18 mg / mL to 86 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 18 mg / mL to 76 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 18 mg / mL to 66 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 18 mg / mL to 56 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 18 mg / mL to 46 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 26 mg / mL to 54 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 31 mg / mL to 49 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 36 mg / mL to 44 mg / mL.In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 124 mg / mL to 196 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 134 mg / mL to 186 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 139 mg / mL to 181 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 144 mg / mL to 176 mg / mL.

[0201]

[0220] In some embodiments of any of the above formulations, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 180 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 170 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 160 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 155 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 150 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 145 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 140 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 135 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 130 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 125 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 120 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 115 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 110 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 105 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 100 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 95 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 90 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 85 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 80 mg / mL.In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 75 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 70 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 65 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 60 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 55 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 45 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL to 40 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 25 mg / mL to 55 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 30 mg / mL to 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 35 mg / mL to 45 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 125 mg / mL to 200 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 135 mg / mL to 185 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 140 mg / mL to 180 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 145 mg / mL to 175 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 150 mg / mL to 170 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is between 155 mg / mL and 165 mg / mL.

[0202]

[0221] In some embodiments of any of the above formulations, the concentration of the anti-TIGIT monoclonal antibody is about 18 mg / mL to about 176 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 18 mg / mL to about 166 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 18 mg / mL to about 160 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 18 mg / mL to about 156 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 18 mg / mL to about 156 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 18 mg / mL to about 146 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 18 mg / mL to about 136 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 18 mg / mL to about 126 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 18 mg / mL to about 116 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 18 mg / mL to about 106 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 18 mg / mL to about 96 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 18 mg / mL to about 86 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 18 mg / mL to about 76 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 18 mg / mL to about 66 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 18 mg / mL to about 56 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 18 mg / mL to about 46 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 26 mg / mL to about 54 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 31 mg / mL to about 49 mg / mL.In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 36 mg / mL to about 44 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 124 mg / mL to about 196 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 134 mg / mL to about 186 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 139 mg / mL to about 181 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 144 mg / mL to about 176 mg / mL.

[0203]

[0222] In some embodiments of any of the above formulations, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 180 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 170 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 160 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 155 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 150 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 145 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 140 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 135 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 130 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 125 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 120 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 115 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 110 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 105 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 100 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 95 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 90 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 85 mg / mL.In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 80 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 75 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 70 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 65 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 60 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 55 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 45 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL to about 40 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 25 mg / mL to about 55 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 30 mg / mL to about 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 35 mg / mL to about 45 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 125 mg / mL to about 200 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 135 mg / mL to about 185 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 140 mg / mL to about 180 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 145 mg / mL to about 175 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 150 mg / mL to about 170 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 155 mg / mL to about 165 mg / mL.

[0204]

[0223] In some embodiments of any of the above formulations, the concentration of the anti-TIGIT monoclonal antibody is about 18 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 23 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 28 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 32 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 37 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 40 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 43 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 48 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 53 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 58 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 63 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 68 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 73 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 78 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 83 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 88 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 93 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 98 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 103 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 108 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 113 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 118 mg / mL.In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 123 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 128 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 133 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 138 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 143 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 148 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 153 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 158 ​​mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 160 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 163 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 168 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 173 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 176 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 178 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 183 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 188 mg / mL.

[0205]

[0224] In some embodiments of any of the above formulations, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 25 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 30 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 35 mg / mL. In certain embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 40 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 45 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 55 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 60 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 65 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 70 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 75 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 80 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 85 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 90 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 95 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 100 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 105 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 110 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 115 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 120 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 125 mg / mL.In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 130 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 135 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 140 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 145 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 150 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 155 mg / mL. In certain embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 160 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 165 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 170 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 175 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 180 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 185 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 190 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 195 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 200 mg / mL.

[0206]

[0225] In some embodiments of any of the above formulations, the concentration of the anti-TIGIT monoclonal antibody is 18 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 23 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 28 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 32 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 37 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 40 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 43 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 48 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 53 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 58 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 63 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 68 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 73 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 78 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 83 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 88 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 93 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 98 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 103 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 108 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 113 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 118 mg / mL.In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 123 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 128 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 133 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 138 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 143 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 148 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 153 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 158 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 160 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 163 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 168 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 173 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 176 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 178 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 183 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 188 mg / mL.

[0207]

[0226] In some embodiments of any of the above formulations, the concentration of the anti-TIGIT monoclonal antibody is 20 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 25 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 30 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 35 mg / mL. In certain embodiments, the concentration of the anti-TIGIT monoclonal antibody is 40 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 45 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 55 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 60 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 65 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 70 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 75 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 80 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 85 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 90 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 95 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 100 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 105 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 110 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 115 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 120 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 125 mg / mL.In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 130 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 135 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 140 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 145 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 150 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 155 mg / mL. In certain embodiments, the concentration of the anti-TIGIT monoclonal antibody is 160 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 165 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 170 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 175 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 180 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 185 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 190 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 195 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is 200 mg / mL.

[0208]

[0227] In some embodiments of any of the above formulations, the concentration of the anti-TIGIT monoclonal antibody is about 18 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 23 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 28 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 32 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 37 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 40 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 43 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 48 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 53 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 58 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 63 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 68 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 73 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 78 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 83 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 88 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 93 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 98 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 103 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 108 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 113 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 118 mg / mL.In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 123 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 128 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 133 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 138 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 143 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 148 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 153 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 158 ​​mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 160 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 163 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 168 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 173 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 176 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 178 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 183 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 188 mg / mL.

[0209]

[0228] In some embodiments of any of the above formulations, the concentration of the anti-TIGIT monoclonal antibody is about 20 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 25 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 30 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 35 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 40 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 45 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 50 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 55 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 60 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 65 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 70 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 75 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 80 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 85 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 90 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 95 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 100 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 105 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 110 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 115 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 120 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 125 mg / mL.In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 130 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 135 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 140 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 145 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 150 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 155 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 165 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 170 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 175 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 180 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 185 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 190 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 195 mg / mL. In some embodiments, the concentration of the anti-TIGIT monoclonal antibody is about 200 mg / mL.

[0210]

[0229] In some embodiments, the formulation comprises: (a) 30 mg / mL tiragolumab; (b) 60 mg / mL atezolizumab; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.5 to 5.8. In some embodiments, the formulation comprises (a) 30 mg / mL tiragolumab; (b) 60 mg / mL atezolizumab; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.5. In some embodiments, the formulation comprises (a) 30 mg / mL tiragolumab; (b) 60 mg / mL atezolizumab; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.6. In some embodiments, the formulation comprises (a) 30 mg / mL tiragolumab; (b) 60 mg / mL atezolizumab; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.7. In some embodiments, the formulation comprises (a) 30 mg / mL tiragolumab; (b) 60 mg / mL atezolizumab; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.8.

[0211]

[0230] In some embodiments, the formulation comprises: (a) 35 mg / mL tiragolumab; (b) 70 mg / mL atezolizumab; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.5 to 5.8. In some embodiments, the formulation comprises (a) 35 mg / mL tiragolumab; (b) 70 mg / mL atezolizumab; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.5. In some embodiments, the formulation comprises (a) 35 mg / mL tiragolumab; (b) 70 mg / mL atezolizumab; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.6. In some embodiments, the formulation comprises (a) 35 mg / mL tiragolumab; (b) 70 mg / mL atezolizumab; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.7. In some embodiments, the formulation comprises (a) 35 mg / mL tiragolumab; (b) 70 mg / mL atezolizumab; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.8.

[0212]

[0231] In some embodiments, the formulation comprises (a) 40 mg / mL tiragolumab; (b) 80 mg / mL atezolizumab; (c) 20 mM histidine buffer; (d) 240 mM sucrose; and (e) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.5 to 5.8. In some embodiments, the formulation comprises (a) 40 mg / mL tiragolumab; (b) 80 mg / mL atezolizumab; (c) 20 mM histidine buffer; (d) 240 mM sucrose; and (e) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.5. In some embodiments, the formulation comprises (a) 40 mg / mL tiragolumab; (b) 80 mg / mL atezolizumab; (c) 20 mM histidine buffer; (d) 240 mM sucrose; and (e) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.6. In some embodiments, the formulation comprises (a) 40 mg / mL tiragolumab; (b) 80 mg / mL atezolizumab; (c) 20 mM histidine buffer; (d) 240 mM sucrose; and (e) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.7. In some embodiments, the formulation comprises: (a) 40 mg / mL of tiragolumab; (b) 80 mg / mL of atezolizumab; (c) 20 mM histidine buffer; (d) 240 mM sucrose; and (e) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.8.

[0213]

[0232] In some embodiments, the formulation comprises: (a) 45 mg / mL tiragolumab; (b) 90 mg / mL atezolizumab; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.5 to 5.8. In some embodiments, the formulation comprises (a) 45 mg / mL tiragolumab; (b) 90 mg / mL atezolizumab; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.5. In some embodiments, the formulation comprises (a) 45 mg / mL tiragolumab; (b) 90 mg / mL atezolizumab; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.6. In some embodiments, the formulation comprises (a) 45 mg / mL tiragolumab; (b) 90 mg / mL atezolizumab; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.7. In some embodiments, the formulation comprises (a) 45 mg / mL tiragolumab; (b) 90 mg / mL atezolizumab; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.8.

[0214]

[0233] In some embodiments, the formulation comprises: (a) 50 mg / mL tiragolumab; (b) 100 mg / mL atezolizumab; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.5 to 5.8. In some embodiments, the formulation comprises (a) 50 mg / mL tiragolumab; (b) 100 mg / mL atezolizumab; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.5. In some embodiments, the formulation comprises (a) 50 mg / mL tiragolumab; (b) 100 mg / mL atezolizumab; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.6. In some embodiments, the formulation comprises (a) 50 mg / mL tiragolumab; (b) 100 mg / mL atezolizumab; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.7. In some embodiments, the formulation comprises (a) 50 mg / mL tiragolumab; (b) 100 mg / mL atezolizumab; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.8.

[0215]

[0234] In some embodiments, the formulation comprises: (a) 55 mg / mL tiragolumab; (b) 110 mg / mL atezolizumab; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.5 to 5.8. In some embodiments, the formulation comprises (a) 55 mg / mL tiragolumab; (b) 110 mg / mL atezolizumab; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.5. In some embodiments, the formulation comprises (a) 55 mg / mL tiragolumab; (b) 110 mg / mL atezolizumab; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.6. In some embodiments, the formulation comprises (a) 55 mg / mL of tiragolumab; (b) 110 mg / mL of atezolizumab; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.7. In some embodiments, the formulation comprises (a) 55 mg / mL of tiragolumab; (b) 110 mg / mL of atezolizumab; (c) 2000 U / mL hyaluronidase; (d) 20 mM histidine buffer; (e) 240 mM sucrose; and (f) 0.06% (w / v) polysorbate 20, wherein the liquid pharmaceutical formulation is characterized by a pH of about 5.8.

[0216]

[0235] In some embodiments, the formulation comprises (a) 160 mg / mL tiragolumab; (b) 20 mM histidine buffer; (c) 240 mM sucrose; and (d) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.2 to 5.8. In some embodiments, the formulation comprises (a) 160 mg / mL tiragolumab; (b) 20 mM histidine buffer; (c) 240 mM sucrose; and (d) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.2. In some embodiments, the formulation comprises (a) 160 mg / mL tiragolumab; (b) 20 mM histidine buffer; (c) 240 mM sucrose; and (d) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.3. In some embodiments, the formulation comprises (a) 160 mg / mL tiragolumab; (b) 20 mM histidine buffer; (c) 240 mM sucrose; and (d) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.4. In some embodiments, the formulation comprises (a) 160 mg / mL tiragolumab; (b) 20 mM histidine buffer; (c) 240 mM sucrose; and (d) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.5. In some embodiments, the formulation comprises (a) 160 mg / mL tiragolumab; (b) 20 mM histidine buffer; (c) 240 mM sucrose; and (d) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.6. In some embodiments, the formulation comprises (a) 160 mg / mL tiragolumab; (b) 20 mM histidine buffer; (c) 240 mM sucrose; and (d) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.7. In some embodiments, the formulation comprises (a) 160 mg / mL tiragolumab; (b) 20 mM histidine buffer; (c) 240 mM sucrose; and (d) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.8.

[0217]

[0236] In some embodiments, the formulation comprises (a) 160 mg / mL tiragolumab; (b) 2000 U / mL hyaluronidase; (c) 20 mM histidine buffer; (d) 240 mM sucrose; and (e) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.2 to 5.8. In some embodiments, the formulation comprises (a) 160 mg / mL tiragolumab; (b) 2000 U / mL hyaluronidase; (c) 20 mM histidine buffer; (d) 240 mM sucrose; and (e) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.2. In some embodiments, the formulation comprises (a) 160 mg / mL tiragolumab; (b) 2000 U / mL hyaluronidase; (c) 20 mM histidine buffer; (d) 240 mM sucrose; and (e) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.3. In some embodiments, the formulation comprises (a) 160 mg / mL tiragolumab; (b) 2000 U / mL hyaluronidase; (c) 20 mM histidine buffer; (d) 240 mM sucrose; and (e) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.4. In some embodiments, the formulation comprises (a) 160 mg / mL tiragolumab; (b) 2000 U / mL hyaluronidase; (c) 20 mM histidine buffer; (d) 240 mM sucrose; and (e) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.5. In some embodiments, the formulation comprises (a) 160 mg / mL tiragolumab; (b) 2000 U / mL hyaluronidase; (c) 20 mM histidine buffer; (d) 240 mM sucrose; and (e) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.6.In some embodiments, the formulation comprises (a) 160 mg / mL tiragolumab; (b) 2000 U / mL hyaluronidase; (c) 20 mM histidine buffer; (d) 240 mM sucrose; and (e) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.7. In some embodiments, the formulation comprises (a) 160 mg / mL tiragolumab; (b) 2000 U / mL hyaluronidase; (c) 20 mM histidine buffer; (d) 240 mM sucrose; and (e) 0.06% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.8.

[0218]

[0237] In some embodiments, the formulation comprises (a) 60 mg / mL tiragolumab; (b) 20 mM histidine buffer; (c) 240 mM sucrose; and (d) 0.04 percent (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.2 to 5.8. In some embodiments, the formulation comprises (a) 60 mg / mL tiragolumab; (b) 20 mM histidine buffer; (c) 240 mM sucrose; and (d) 0.04% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.2. In some embodiments, the formulation comprises (a) 60 mg / mL tiragolumab; (b) 20 mM histidine buffer; (c) 240 mM sucrose; and (d) 0.04% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.3. In some embodiments, the formulation comprises (a) 60 mg / mL tiragolumab; (b) 20 mM histidine buffer; (c) 240 mM sucrose; and (d) 0.04% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.4. In some embodiments, the formulation comprises (a) 60 mg / mL tiragolumab; (b) 20 mM histidine buffer; (c) 240 mM sucrose; and (d) 0.04% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.5. In some embodiments, the formulation comprises (a) 60 mg / mL tiragolumab; (b) 20 mM histidine buffer; (c) 240 mM sucrose; and (d) 0.04% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.6. In some embodiments, the formulation comprises (a) 60 mg / mL tiragolumab; (b) 20 mM histidine buffer; (c) 240 mM sucrose; and (d) 0.04% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.7. In some embodiments, the formulation comprises (a) 60 mg / mL tiragolumab; (b) 20 mM histidine buffer; (c) 240 mM sucrose; and (d) 0.04% (w / v) polysorbate 20, and the liquid pharmaceutical formulation is characterized by a pH of about 5.8.

[0219] manufactured goods

[0238] An additional aspect of the present disclosure provides an article of manufacture comprising a liquid pharmaceutical formulation as disclosed herein. In some embodiments, the article of manufacture provides a liquid pharmaceutical formulation comprising: (a) an anti-TIGIT monoclonal antibody; (b) a buffer; (c) a tonicity agent; and (d) a surfactant, wherein the liquid pharmaceutical formulation is characterized by a pH of about 4.0 to about 7.0. In some embodiments, the article of manufacture comprises a liquid pharmaceutical formulation comprising: (a) an anti-TIGIT monoclonal antibody; (b) an anti-PD-L1 monoclonal antibody; (c) a buffer; (d) a tonicity agent; and (e) a surfactant, wherein the liquid pharmaceutical formulation is characterized by a pH of about 4.0 to about 7.0.

[0220]

[0239] In some embodiments, the article of manufacture is a vial. In some embodiments, the vial is a 10 cc vial. In some embodiments, the vial is a 15 cc vial. In some embodiments, the vial is a 20 cc vial. In some embodiments, the vial is a 25 cc vial. In some embodiments, the vial is a 30 cc vial. In some embodiments, the vial is a 35 cc vial. In some embodiments, the vial is a 40 cc vial. In some embodiments, the vial is a 45 cc vial. In some embodiments, the vial is a 50 cc vial. In some embodiments, the vial is a glass vial. In some embodiments, the vial is a plastic vial.

[0221]

[0240] In some embodiments, the vial is stoppered with a chlorobutyl elastomer stopper. In some embodiments, the stopper is a D21-7S stopper. Without being bound by theory, the D21-7S stopper leads to reduced particle formation in the liquid pharmaceutical formulation. In some embodiments, the D21-7S stopper has a thinner stopper septum.

[0222]

[0241] In some embodiments, the article of manufacture is a prefilled syringe. In some embodiments, the prefilled syringe is a 10 cc prefilled syringe. In some embodiments, the prefilled syringe is a 15 cc prefilled syringe. In some embodiments, the prefilled syringe is a 20 cc prefilled syringe. In some embodiments, the prefilled syringe is a 25 cc prefilled syringe. In some embodiments, the prefilled syringe is a 30 cc prefilled syringe. In some embodiments, the prefilled syringe is a 35 cc prefilled syringe. In some embodiments, the prefilled syringe is a 40 cc prefilled syringe. In some embodiments, the prefilled syringe is a 45 cc prefilled syringe. In some embodiments, the prefilled syringe is a 50 cc prefilled syringe.

[0223]

[0242] In some embodiments, the article of manufacture comprises from about 3 mL to about 30 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manufacture comprises from about 3 mL to about 25 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manufacture comprises from about 3 mL to about 20 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manufacture comprises from about 4 mL to about 25 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manufacture comprises from about 4 mL to about 22 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manufacture comprises from about 4 mL to about 20 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manufacture comprises from about 4 mL to about 18 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manufacture comprises from about 4 mL to about 16 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manufacture comprises from about 4 mL to about 14 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manufacture comprises from about 4 mL to about 12 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manufacture comprises from about 4 mL to about 10 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manufacture comprises from about 4 mL to about 8 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manufacture comprises from about 5 mL to about 7 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manufacture comprises from about 5 mL to about 8 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manufacture comprises from about 5 mL to about 10 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manufacture comprises from about 5 mL to about 21 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manufacture comprises from about 5.5 mL to about 7.5 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manufacture comprises from about 6 mL to about 8 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manufacture comprises from about 6 mL to about 10 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manufacture comprises from about 6 mL to about 12 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manufacture comprises from about 8 mL to about 12 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manufacture comprises from about 9 mL to about 11 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manufacture comprises about 15 mL to about 30 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manufacture comprises about 18 mL to about 30 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manufacture comprises about 18 mL to about 28 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manufacture comprises about 18 mL to about 26 mL of the liquid pharmaceutical formulation.In some embodiments, the article of manufacture comprises about 18 mL to about 24 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manufacture comprises about 19 mL to about 23 mL of the liquid pharmaceutical formulation. In some embodiments, the article of manu...

Claims

1. (a) 18 mg / mL to 176 mg / mL of an anti-TIGIT monoclonal antibody; (b) 54 mg / mL to 137.5 mg / mL of an anti-PD-L1 monoclonal antibody; (c) 5 mM to 30 mM histidine buffer; (d) 120 mM to 320 mM sucrose; and (e) A liquid pharmaceutical formulation comprising 0.02% (w / v) to 0.08% (w / v) polysorbate 20 and characterized by a pH of about 5.2 to 6.1, The anti-TIGIT monoclonal antibody comprises a heavy chain variable region comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2; and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3; and a light chain variable region comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6; A liquid pharmaceutical formulation, wherein the anti-PD-L1 monoclonal antibody comprises a heavy chain variable region comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 10; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 11; and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 12; and a light chain variable region comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 13; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 14; and HVR-L3 comprising the amino acid sequence of SEQ ID NO:

15.

2. (a) 18 mg / mL to 75 mg / mL of an anti-TIGIT monoclonal antibody; (b) 54 mg / mL to 137.5 mg / mL of an anti-PD-L1 monoclonal antibody; (c) 12 mM to 28 mM histidine buffer; (d) 100 mM to 300 mM sucrose; and (e) A liquid pharmaceutical formulation comprising 0.02% (w / v) to 0.08% (w / v) polysorbate 20 and characterized by a pH of about 5.4 to 6.2, The anti-TIGIT monoclonal antibody comprises a heavy chain variable region comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2; and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3; and a light chain variable region comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6; A liquid pharmaceutical formulation, wherein the anti-PD-L1 monoclonal antibody comprises a heavy chain variable region comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 10; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 11; and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 12; and a light chain variable region comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 13; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 14; and HVR-L3 comprising the amino acid sequence of SEQ ID NO:

15.

3. (a) 18 mg / mL to 176 mg / mL of an anti-TIGIT monoclonal antibody; (b) 500 U / mL to 2600 U / mL of hyaluronidase; (c) 5 mM to 30 mM histidine buffer; (d) 180 mM to 320 mM sucrose; and (e) A liquid pharmaceutical formulation comprising 0.03% (w / v) to 0.08% (w / v) polysorbate 20 and characterized by a pH of about 5.2 to 6.0, A liquid pharmaceutical formulation, wherein the anti-TIGIT monoclonal antibody comprises a heavy chain variable region comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2; and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3, and a light chain variable region comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and HVR-L3 comprising the amino acid sequence of SEQ ID NO:

6.

4. (a) 30 mg / mL to 60 mg / mL of an anti-TIGIT monoclonal antibody; (b) 60 mg / mL to 120 mg / mL of an anti-PD-L1 monoclonal antibody; (c) 500 U / mL to 2600 U / mL of hyaluronidase; (d) 5 mM to 30 mM histidine buffer; (e) 180 mM to 320 mM sucrose; and (f) A liquid pharmaceutical formulation comprising 0.03% (w / v) to 0.08% (w / v) polysorbate 20 and characterized by a pH of about 5.2 to 6.1, The anti-TIGIT monoclonal antibody comprises a heavy chain variable region comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2; and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3; and a light chain variable region comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and HVR-L3 comprising the amino acid sequence of SEQ ID NO: 6; A liquid pharmaceutical formulation, wherein the anti-PD-L1 monoclonal antibody comprises a heavy chain variable region comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 10; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 11; and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 12; and a light chain variable region comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 13; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 14; and HVR-L3 comprising the amino acid sequence of SEQ ID NO:

15.

5. (a) 18 mg / mL to 176 mg / mL of an anti-TIGIT monoclonal antibody; (b) 5 mM to 30 mM histidine acetate; (c) 100 mM to 320 mM sucrose; and (d) A liquid pharmaceutical formulation comprising 0.01% (w / v) to 0.08% (w / v) polysorbate 20 and characterized by a pH of about 5.0 to 6.0, A liquid pharmaceutical formulation comprising an anti-TIGIT monoclonal antibody comprising a heavy chain variable region comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2; and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3; and a light chain variable region comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and HVR-L3 comprising the amino acid sequence of SEQ ID NO:

6.

6. (a) 18 mg / mL to 75 mg / mL of an anti-TIGIT monoclonal antibody; (b) 5 mM to 30 mM histidine acetate; (c) 100 mM to 320 mM sucrose; and (d) A liquid pharmaceutical formulation comprising 0.01% (w / v) to 0.08% (w / v) polysorbate 20 and characterized by a pH of about 5.0 to 6.0, A liquid pharmaceutical formulation comprising an anti-TIGIT monoclonal antibody comprising a heavy chain variable region comprising HVR-H1 comprising the amino acid sequence of SEQ ID NO: 1; HVR-H2 comprising the amino acid sequence of SEQ ID NO: 2; and HVR-H3 comprising the amino acid sequence of SEQ ID NO: 3; and a light chain variable region comprising HVR-L1 comprising the amino acid sequence of SEQ ID NO: 4; HVR-L2 comprising the amino acid sequence of SEQ ID NO: 5; and HVR-L3 comprising the amino acid sequence of SEQ ID NO:

6.

7. The liquid pharmaceutical formulation according to any one of claims 1 to 6, wherein the anti-TIGIT monoclonal antibody is tiragolumab.

8. The liquid pharmaceutical formulation according to any one of claims 1, 2 and 4, wherein the anti-PD-L1 monoclonal antibody is atezolizumab.

9. The liquid pharmaceutical formulation of claim 1, wherein the anti-TIGIT monoclonal antibody is tiragolumab and the anti-PD-L1 monoclonal antibody is atezolizumab.

10. 7. An article of manufacture comprising the liquid pharmaceutical formulation of any one of claims 1 to 6.

11. 10. Use of the liquid pharmaceutical formulation of any one of claims 1 to 6 in the manufacture of a medicament for treating cancer in a subject in need thereof.

12. 10. The liquid pharmaceutical formulation of claim 1 for use in the treatment of cancer in a subject in need thereof.

13. 10. Use of the liquid pharmaceutical formulation of any one of claims 3, 5, and 6 and a therapeutically effective amount of an anti-PD-1 monoclonal antibody or an anti-PD-L1 monoclonal antibody in the manufacture of a medicament for treating cancer in a subject in need thereof.

14. 10. The liquid pharmaceutical formulation of any one of claims 3, 5, and 6 and a therapeutically effective amount of an anti-PD-1 monoclonal antibody or an anti-PD-L1 monoclonal antibody for use in treating cancer in a subject in need thereof.

15. An article of manufacture comprising a formulation comprising 18 mg / mL to 176 mg / mL of an anti-TIGIT monoclonal antibody.

16. (a) 30 mg / mL to 60 mg / mL of an anti-TIGIT monoclonal antibody; and (b) 60 mg / mL to 120 mg / mL of an anti-PD-L1 monoclonal antibody 1. An article of manufacture, including a formulation comprising:

17. An article of manufacture comprising a formulation containing 880 mg of an anti-TIGIT monoclonal antibody.

18. An article of manufacture comprising a formulation containing 880 mg of an anti-TIGIT monoclonal antibody and 1875 mg or 2000 mg of an anti-PD-L1 monoclonal antibody.

19. An article of manufacture comprising a subcutaneous administration device containing and delivering an 880 mg fixed dose of anti-TIGIT monoclonal antibody to a patient.

20. A therapeutically effective amount of a formulation contained in the article of manufacture of any one of claims 15 to 19 for use in treating cancer in a subject in need thereof.

Images