Compositions of stable Anti-pd1 antibody protein

Description

1 / 50 “ANTI-PD1 ANTIBODY STABLE PROTEIN COMPOSITIONS” FIELD OF THE INVENTION

[001] The present invention generally relates to the preparation of stable anti-PD1 antibody compositions and their application in a medicament. The present invention relates to a pharmaceutical composition comprising an anti-PD1 antibody, a buffer, a sugar or sugar alcohol, and a surfactant. FUNDAMENTALS OF THE INVENTION

[002] Programmed cell death protein 1 (PD-1) is a 288-amino acid cell surface molecule that has been designated as an immunoglobulin superfamily membrane protein in humans. This protein is expressed on T cells, pro-B cells, and myeloid-derived dendritic cells, leading to the downregulation of the proliferation and activity of these cells (Yamane, Hiromichi et al. American journal of cancer research vol. 5,4 1553-7. March 15, 2015).

[003] Several anti-PD1 and PDL1 antibodies targeting PD-1 or PD-L1 have been approved and marketed. There are published documents disclosing anti-PD1 formulations, for example:

[004] US9220776B2 and its equivalent families disclose liquid and lyophilized formulations of pembrolizumab comprising a histidine buffer, polysorbate 80 and sucrose;

[005] WO2021123202A1 discloses liquid pharmaceutical compositions comprising: an anti-human PD1 antibody, trehalose or a sugar alcohol; a nonionic surfactant; and histidine buffer;

[006] US10786567B2 and its equivalent families disclose formulations of an anti-PD1 antibody containing sodium acetate, α,α-trehalose dihydrate and polysorbate 20, pH 5.2;

[007] WO 2018 / 028383 A1 describes a pharmaceutical formulation comprising an anti-PD1 antibody, citrate, histidine, mannitol, sodium chloride, Petition 870260076824, dated 07 / 31 / 2026, page 9 / 108 2 / 50 edetate and polysorbate 20 or polysorbate 80, with pH 5.5 to 6.5;

[008] WO 2018 / 187057 A1 discloses a pharmaceutical composition comprising an anti-PD1 antibody, histidine, sucrose, proline and polysorbate 80, with a pH of 6.0;

[009] WO 2018 / 204368 A1 describes formulations of an anti-PD1 antibody comprising a buffer, a stabilizer, a nonionic surfactant and an antioxidant;

[010] WO 2019 / 142149 discloses a pharmaceutical composition comprising an anti-PD1 antibody, histidine, sucrose, polysorbate 20 and EDTA, with a pH of 6.5; and

[011] WO 2019 / 171253 A1 describes a pharmaceutical composition comprising an anti-PD1 antibody, a disaccharide, a buffer, a chelating agent and a polysorbate, with a pH of 4.5 to 5.5.

[012] The present inventors conducted intensive studies in an effort to address an unmet need for a stable anti-PD1 antibody composition and discovered that a combination of a buffer, a sugar or sugar alcohol, and a surfactant in the correct proportions unexpectedly results in a composition that is stable and convenient for clinical use. SUMMARY OF THE INVENTION

[013] One objective of the present invention is to provide a stable anti-PD-1 antibody composition.

[014] Another objective of the present invention is to provide a stable liquid pharmaceutical composition comprising: (a) a human anti-PD1 antibody; (b) a sugar, for example, a non-reducing sugar; (c) a buffer; and (d) a non-ionic surfactant. Petition 870260076824, dated 07 / 31 / 2026, page 10 / 108 3 / 50

[015] Yet another objective of the present invention is to provide a stable anti-PD-1 antibody composition in which the anti-PD1 antibody is at a concentration in the range of about 5 mg / mL to about 30 mg / mL.

[016] Yet another objective of the present invention is to provide a stable anti-PD-1 antibody composition in which the non-reducing sugar is sucrose, trehalose or mannitol, preferably trehalose, more preferably α,α-trehalose dihydrate.

[017] Yet another objective of the present invention is to provide a stable anti-PD-1 antibody composition in which the buffer comprises a citrate, L-Histidine, disodium succinate hexahydrate, succinic acid, sodium citrate, glacial acetic acid, citric acid monohydrate and / or adipic acid, preferably L-Histidine, L-Histidine HCl monohydrate and / or succinic acid. An objective of the present invention is to provide a stable anti-PD-1 antibody composition in which the non-ionic surfactant is Sodium Chloride, Disodium edetate dehydrate, Polysorbate 20, Polysorbate 80 or Poloxamer 188, preferably Disodium edetate dihydrate or Polysorbate 80.

[018] An objective of the present invention is to provide a stable anti-PD-1 antibody composition in which the anti-PD-1 antibody is Nivolumab or Pembrolizumab, preferably Pembrolizumab.

[019] Another objective of the present invention is to provide a stable liquid pharmaceutical composition in which sugar is present at a concentration of about 50 mg / ml to about 150 mg / ml.

[020] Yet another objective of the present invention is to provide a stable anti-PD-1 antibody composition in which the buffer is present at a concentration of about 0.05 mM to about 50 mM, preferably 0.05 mM to 25 mM.

[021] Yet another objective of the present invention is to provide a stable anti-PD-1 antibody composition in which a nonionic surfactant is present at a concentration in the range of about 0.01 mg / ml to about 2.0 mg / ml. Petition 870260076824, dated 07 / 31 / 2026, p. 11 / 108 4 / 50

[022] An object of the present invention is to provide a stable anti-PD-1 antibody composition in which the composition has a pH of about 5.2 to about 6.5.

[023] One objective of the present invention is to provide a stable liquid pharmaceutical composition comprising: (a) a human anti-PD1 antibody; (b) a sugar, for example, a non-reducing sugar; (c) a buffer; and (d) a nonionic surfactant, wherein: the non-reducing sugar is sucrose or trehalose or mannitol; the buffer comprises a citrate, L-Histidine, sodium succinate hexahydrate, succinic acid, sodium citrate, citric acid monohydrate or adipic acid; and the nonionic surfactant is disodium edetate dehydrate, polysorbate 20, polysorbate 80 or poloxamer 188.

[024] Another objective of the present invention is to provide a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, α,α-trehalose dihydrate at a concentration of about 50 mg / mL to about 100 mg / mL, L-histidine at a concentration of about 0.5 mM to about 5 mM, L-Histidine HCl monohydrate at a concentration of about 5 mM to about 15 mM, polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, and a pH of about 5.2 to about 6.5, wherein the anti-PD-1 antibody is Pembrolizumab.

[025] The present invention also provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, sucrose at a concentration of about 50 mg / mL to about 100 mg / mL, succinic acid at a concentration of about 5 mM to about 25 mM, disodium edetate dihydrate at a concentration of Petition 870260076824, dated 07 / 31 / 2026, page 12 / 108 5 / 50 at a concentration of approximately 0.01 mg / ml to approximately 1.0 mg / ml, polysorbate 80 at a concentration in the range of approximately 0.05 mg / ml to approximately 2.0 mg / ml, a pH of approximately 5.2 to approximately 6.5, and wherein the anti-PD-1 antibody is pembrolizumab.

[026] The present invention also provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, sucrose at a concentration of about 50 mg / mL to about 100 mg / mL, succinic acid at a concentration of about 0.05 mM to about 2 mM, disodium succinate hexahydrate at a concentration of about 0.5 mM to about 10 mM, polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is pembrolizumab.

[027] The present invention also provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, sucrose at a concentration of about 50 mg / mL to about 100 mg / mL, glacial acetic acid at a concentration of about 5 mM to about 20 mM, polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is Pembrolizumab.

[028] The present invention also provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, Mannitol at a concentration of about 5 mg / mL to about 15 mg / mL, Sodium Chloride at a concentration of about 5 mg / mL to about 10 mg / mL, Citric Acid Monohydrate at a concentration of about 0.5 mM to about 5 mM, Adipic Acid at a concentration of about 5 mM to about 50 mM, Polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is Pembrolizumab. Petition 870260076824, dated 07 / 31 / 2026, page 13 / 108 6 / 50

[029] The present invention also provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, Mannitol at a concentration of about 5 mg / mL to about 15 mg / mL, Sodium Chloride at a concentration of about 5 mg / mL to about 10 mg / mL, Sodium Citrate at a concentration of about 0.1 mM to about 5 mM, Citric Acid Monohydrate at a concentration of about 3 mM to about 15 mM, Polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is Pembrolizumab.

[030] The present invention also provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, L-Histidine at a concentration of about 5 mM to about 15 mM, sodium chloride at a concentration of about 5 mg / mL to about 10 mg / mL, polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is Pembrolizumab.

[031] The present invention also provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, sucrose at a concentration of about 50 mg / mL to about 100 mg / mL, L-histidine at a concentration of about 0.5 mM to about 5 mM, L-histidine HCl monohydrate at a concentration of about 5 mM to about 20 mM, polysorbate 20 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is pembrolizumab.

[032] The present invention also provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, Sucrose at a concentration of about Petition 870260076824, dated 07 / 31 / 2026, page 14 / 108 7 / 50 of 50 mg / ml to about 100 mg / ml, L-Histidine at a concentration of about 0.5 mM to about 5 mM, L-Histidine HCl monohydrate at a concentration of about 5 mM to about 20 mM, Poloxamer 188 at a concentration in the range of about 0.05 mg / ml to about 2.0 mg / ml, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is Pembrolizumab.

[033] The present invention also provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, sucrose at a concentration of about 50 mg / mL to about 100 mg / mL, glacial acetic acid at a concentration of about 0.5 mM to about 10 mM, sodium acetate trihydrate at a concentration of about 2 mM to about 20 mM, polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is pembrolizumab.

[034] The present invention also provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, sucrose at a concentration of about 50 mg / mL to about 100 mg / mL, anhydrous dibasic sodium phosphate at a concentration of about 0.05 mM to 5 mM, monobasic sodium phosphate monohydrate at a concentration of about 5 mM to about 20 mM, polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is pembrolizumab.

[035] The present invention also provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, sucrose at a concentration of about 50 mg / mL to about 100 mg / mL, succinic acid at a concentration of about 1 mM to about 10 mM, sodium succinate hexahydrate at a concentration of about 2 mM to about 20 mM, polysorbate 80 at a concentration in the range Petition 870260076824, dated 07 / 31 / 2026, page 15 / 108 8 / 50 of approximately 0.05 mg / ml to approximately 2.0 mg / ml, a pH of approximately 5.2 to approximately 6.5, and in which the anti-PD-1 antibody is Pembrolizumab.

[036] The present invention also provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, α,α-trehalose dihydrate at a concentration of about 50 mg / mL to about 100 mg / mL, anhydrous dibasic sodium phosphate at a concentration of about 0.05 mM to about 5 mM, monobasic sodium phosphate monohydrate at a concentration of about 5 mM to about 20 mM, polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is Pembrolizumab.

[037] The present invention also provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, α,α-trehalose dihydrate at a concentration of about 50 mg / mL to about 100 mg / mL, sodium acetate trihydrate at a concentration of about 2 mM to about 20 mM, glacial acetic acid at a concentration of about 0.5 mM to about 10 mM, polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is pembrolizumab.

[038] The present invention also provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, α,α-trehalose dihydrate at a concentration of about 50 mg / mL to about 100 mg / mL, succinic acid at a concentration of about 1 mM to about 10 mM, sodium succinate hexahydrate at a concentration of about 2 mM to about 20 mM, polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is pembrolizumab. Petition 870260076824, dated 07 / 31 / 2026, p. 16 / 108 9 / 50

[039] Another objective of the present invention is to provide an anti-PD-1 antibody composition wherein the composition can be administered by intravenous administration or by subcutaneous administration, or a combination thereof.

[040] In one embodiment, the composition and methods of the invention include high concentrations of an anti-PD1 antibody, or antigen-binding moieties thereof, and (a) a sugar, for example, a non-reducing sugar; (b) a buffer; and (c) a non-ionic surfactant.

[041] A stable anti-PD-1 antibody composition of the present invention can be used for the prophylaxis or treatment of a PD-1 mediated disease or disorder, wherein the disease or disorder is preferably cancer; more preferably cancer expressing PD-L1; wherein the disease or disorder is especially preferably breast cancer, lung cancer, stomach cancer, intestinal cancer, kidney cancer, melanoma; especially preferably non-small cell lung cancer, melanoma and kidney cancer. SUMMARY OF THE INVENTION [04 2] One objective of the present invention is to provide a stable anti-PD-1 antibody composition. [04 3] Another objective of the present invention is to provide a stable liquid pharmaceutical composition comprising: (a) a human anti-PD1 antibody; (b) a sugar, for example, a non-reducing sugar; (c) a buffer; and (d) a non-ionic surfactant.

[044] In one embodiment, the present invention provides a composition Petition 870260076824, dated 07 / 31 / 2026, page 17 / 108 10 / 50 stable anti-PD-1 antibody in which the anti-PDI antibody is present at a concentration in the range of about 5 mg / mL to about 30 mg / mL.

[045] In one embodiment, the present invention provides a stable anti-PD-1 antibody composition in which the non-reducing sugar is sucrose, trehalose or mannitol, preferably trehalose, more preferably α,α-trehalose dihydrate.

[046] In one embodiment, the present invention provides a stable anti-PD-1 antibody composition in which the buffer comprises a citrate, L-Histidine, Disodium Succinate Hexahydrate, Succinic Acid, sodium citrate, glacial acetic acid, citric acid monohydrate and / or adipic acid, preferably L-Histidine, L-Histidine HCl monohydrate and / or succinic acid. An object of the present invention is to provide a stable anti-PD-1 antibody composition in which the non-ionic surfactant is Sodium Chloride, Disodium Edetate Dehydrate, Polysorbate 20, Polysorbate 80 or Poloxamer 188, preferably Disodium Edetate Dihydrate or Polysorbate 80.

[047] In one embodiment, the present invention provides a stable anti-PD-1 antibody composition in which the anti-PD-1 antibody is Nivolumab or Pembrolizumab, preferably Pembrolizumab.

[048] In one embodiment, the present invention provides a stable liquid pharmaceutical composition in which sugar is present at a concentration of about 50 mg / ml to about 150 mg / ml.

[049] Yet another embodiment of the present invention is to provide a stable anti-PD-1 antibody composition in which the buffer is present at a concentration of about 0.05 mM to about 50 mM, preferably 0.05 mM to 25 mM.

[050] Yet another embodiment of the present invention is to provide a stable anti-PD-1 antibody composition in which the nonionic surfactant is present at a concentration in the range of about 0.01 mg / ml to about 2.0 mg / ml. Petition 870260076824, dated 07 / 31 / 2026, p. 18 / 108 11 / 50

[051] In one embodiment, the present invention provides a stable anti-PD-1 antibody composition in which the composition has a pH of about 5.2 to about 6.5.

[052] In one embodiment, the present invention provides a stable liquid pharmaceutical composition comprising: (a) a human anti-PD1 antibody; (b) a sugar, for example, a non-reducing sugar; (c) a buffer; and (d) a nonionic surfactant, wherein: the non-reducing sugar is sucrose or trehalose or mannitol; the buffer comprises a citrate, L-Histidine, sodium succinate hexahydrate, succinic acid, sodium citrate, citric acid monohydrate or adipic acid; and the nonionic surfactant is disodium edetate dehydrate, polysorbate 20, polysorbate 80 or poloxamer 188.

[053] In one embodiment, the present invention provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, α,α-trehalose dihydrate at a concentration of about 50 mg / mL to about 100 mg / mL, L-histidine at a concentration of about 0.5 mM to about 5 mM, L-Histidine HCl monohydrate at a concentration of about 5 mM to about 15 mM, polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, and a pH of about 5.2 to about 6.5, wherein the anti-PD-1 antibody is Pembrolizumab.

[054] In one embodiment, the present invention provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, sucrose at a concentration of about 50 mg / mL to about 100 mg / mL, succinic acid at a concentration of about 5 mM to about 25 mM, disodium edetate dihydrate in Petition 870260076824, dated 07 / 31 / 2026, page 19 / 108 12 / 50 at a concentration of about 0.01 mg / ml to about 1.0 mg / ml, polysorbate 80 at a concentration in the range of about 0.05 mg / ml to about 2.0 mg / ml, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is pembrolizumab.

[055] In one embodiment, the present invention provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, sucrose at a concentration of about 50 mg / mL to about 100 mg / mL, succinic acid at a concentration of about 0.05 mM to about 2 mM, disodium succinate hexahydrate at a concentration of about 0.5 mM to about 10 mM, polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is pembrolizumab.

[056] In one embodiment, the present invention provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, sucrose at a concentration of about 50 mg / mL to about 100 mg / mL, glacial acetic acid at a concentration of about 5 mM to about 20 mM, polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is Pembrolizumab.

[057] In one embodiment, the present invention provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, Mannitol at a concentration of about 5 mg / mL to about 15 mg / mL, Sodium Chloride at a concentration of about 5 mg / mL to about 10 mg / mL, Citric Acid Monohydrate at a concentration of about 0.5 mM to about 5 mM, Adipic Acid at a concentration of about 5 mM to about 50 mM, Polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is Pembrolizumab. Petition 870260076824, dated 07 / 31 / 2026, page 20 / 108 13 / 50

[058] In one embodiment, the present invention provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, Mannitol at a concentration of about 5 mg / mL to about 15 mg / mL, Sodium Chloride at a concentration of about 5 mg / mL to about 10 mg / mL, Sodium Citrate at a concentration of about 0.1 mM to about 5 mM, Citric Acid Monohydrate at a concentration of about 3 mM to about 15 mM, Polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is Pembrolizumab.

[059] In one embodiment, the present invention provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, L-Histidine at a concentration of about 5 mM to about 15 mM, sodium chloride at a concentration of about 5 mg / mL to about 10 mg / mL, polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is Pembrolizumab.

[060] In one embodiment, the present invention provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, sucrose at a concentration of about 50 mg / mL to about 100 mg / mL, L-histidine at a concentration of about 0.5 mM to about 5 mM, L-histidine HCl monohydrate at a concentration of about 5 mM to about 20 mM, polysorbate 20 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is pembrolizumab.

[061] In one embodiment, the present invention provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, Sucrose in a Petition 870260076824, dated 07 / 31 / 2026, page 21 / 108 14 / 50 concentration of about 50 mg / ml to about 100 mg / ml, L-Histidine at a concentration of about 0.5 mM to about 5 mM, L-Histidine HCl monohydrate at a concentration of about 5 mM to about 20 mM, Poloxamer 188 at a concentration in the range of about 0.05 mg / ml to about 2.0 mg / ml, a pH of about 5.2 to about 6.5, and where the anti-PD-1 antibody is Pembrolizumab.

[062] In one embodiment, the present invention provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, sucrose at a concentration of about 50 mg / mL to about 100 mg / mL, glacial acetic acid at a concentration of about 0.5 mM to about 10 mM, sodium acetate trihydrate at a concentration of about 2 mM to about 20 mM, polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is pembrolizumab.

[063] In one embodiment, the present invention provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, sucrose at a concentration of about 50 mg / mL to about 100 mg / mL, anhydrous dibasic sodium phosphate at a concentration of about 0.05 mM to 5 mM, monobasic sodium phosphate monohydrate at a concentration of about 5 mM to about 20 mM, polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is pembrolizumab.

[064] In one embodiment, the present invention provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, sucrose at a concentration of about 50 mg / mL to about 100 mg / mL, succinic acid at a concentration of about 1 mM to about 10 mM, sodium succinate hexahydrate Petition 870260076824, dated 07 / 31 / 2026, p. 22 / 108 15 / 50 at a concentration of about 2 mM to about 20 mM, polysorbate 80 at a concentration in the range of about 0.05 mg / ml to about 2.0 mg / ml, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is pembrolizumab.

[065] In one embodiment, the present invention provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, α,α-trehalose dihydrate at a concentration of about 50 mg / mL to about 100 mg / mL, anhydrous dibasic sodium phosphate at a concentration of about 0.05 mM to about 5 mM, monobasic sodium phosphate monohydrate at a concentration of about 5 mM to about 20 mM, polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is Pembrolizumab.

[066] In one embodiment, the present invention provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, α,α-trehalose dihydrate at a concentration of about 50 mg / mL to about 100 mg / mL, sodium acetate trihydrate at a concentration of about 2 mM to about 20 mM, glacial acetic acid at a concentration of about 0.5 mM to about 10 mM, polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is pembrolizumab.

[067] In one embodiment, the present invention provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, α,α-trehalose dihydrate at a concentration of about 50 mg / mL to about 100 mg / mL, succinic acid at a concentration of about 1 mM to about 10 mM, sodium succinate hexahydrate at a concentration of about 2 mM to about 20 mM, Petition 870260076824, dated 07 / 31 / 2026, p. 23 / 108 16 / 50 polysorbate 80 at a concentration in the range of about 0.05 mg / ml to about 2.0 mg / ml, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is pembrolizumab.

[068] Another embodiment of the present invention is to provide an anti-PD-1 antibody composition wherein the composition can be administered by intravenous administration or by subcutaneous administration, or a combination thereof.

[069] In one embodiment, the composition and methods of the invention include high concentrations of an anti-PD1 antibody, or antigen-binding moieties thereof, and (a) a sugar, for example, a non-reducing sugar; (b) a buffer; and (c) a non-ionic surfactant.

[070] A stable anti-PD-1 antibody composition of the present invention can be used for the prophylaxis or treatment of a PD-1-mediated disease or disorder, wherein the disease or disorder is preferably cancer; more preferably cancer expressing PD-L1; wherein the disease or disorder is especially preferably breast cancer, lung cancer, stomach cancer, intestinal cancer, kidney cancer, melanoma; especially preferably non-small cell lung cancer, melanoma and kidney cancer. DESCRIPTION OF THE INVENTION

[071] It should be understood that the terminology used in this document is for the purpose of describing embodiments only and is not intended to be limiting. Unless defined otherwise, all technical and scientific terms used in this document have the same meaning commonly understood by a person skilled in the art to which this invention pertains.

[072] Although any similar or equivalent methods and materials Petition 870260076824, dated 07 / 31 / 2026, p. 24 / 108 17 / 50 of the materials and methods described in this document can be used in practice for testing the present invention; exemplary materials and methods are described in this document. In describing and claiming the present invention, the following terminology will be used.

[073] As used in this descriptive report and the accompanying claims, the singular forms a, an and the include plural references, unless the content clearly indicates otherwise. Thus, for example, a reference to a cell includes a combination of two or more cells and the like.

[074] The transitional terms comprising, “essentially consisting of”, and consisting of are intended to denote their generally accepted meanings in the patent vernacular; namely, (i) “comprising”, which is synonymous with “including”, “containing”, or “characterized by”, is inclusive or open-ended and does not exclude unmentioned elements or additional method steps; (ii) “consisting of” excludes any element, step, or ingredient not specified in the claim; and (iii) essentially consisting of limits the scope of a claim to the materials or steps specified and those that do not materially affect the basic and novel features of the claimed invention. The embodiments described in terms of the phrase comprising (or their equivalents) also provide as embodiments those independently described in terms of consisting of and essentially consisting of.

[075] The pharmaceutical composition of the present invention may comprise a human antibody, or an antigen-binding fragment thereof, that binds specifically to human PD-1. As used in this document, the term PD-1 means human programmed death protein-1. An example of a human PD-1 antibody is Keytruda® from Merck. However, the composition as described in this document may be used for other PD-1 antibodies.

[076] The term antibody, as used in this document, is generally intended to refer to immunoglobulin molecules comprising four chains Petition 870260076824, dated 07 / 31 / 2026, page 25 / 108 18 / 50 polypeptides, two heavy chains (H) and two light chains (L) interconnected by disulfide bonds, as well as multimers thereof (e.g., IgM); however, immunoglobulin molecules consisting only of heavy chains (i.e., absent light chains) are also encompassed within the definition of the term antibody. Each heavy chain comprises a variable heavy chain region (abbreviated in this document as HCVR or VH) and a constant heavy chain region. The constant heavy chain region comprises three domains, CHI, CH2, and CH3. Each light chain comprises a variable light chain region (abbreviated in this document as LCVR or VL) and a constant light chain region. The constant light chain region comprises one domain (CL1).The VH and VL regions can be further subdivided into regions of hypervariability, called complementarity-determining regions (CDRs), interspersed with more conserved regions, called framework regions (FRs). Each VH and VL region is composed of three CDRs and four FRs, arranged from the amino terminal to the carboxy terminal in the following order: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4.

[077] Unless otherwise indicated, the term antibody, as used in this document, should be understood to encompass complete antibody molecules as well as antigen-binding fragments thereof. The term antigen-binding portion or antigen-binding fragment of an antibody (or simply antibody portion or antibody fragment), as used in this document, refers to one or more fragments of an antibody that retain the ability to bind specifically to human PD-1 or an epitope thereof.

[078] The high antibody composition and methods of the invention not only overcome a number of known challenges for pharmaceutical compounding, including high concentrations in a stable composition.

[079] The term Reference Listed Drug (RLD), as used in this Petition 870260076824, dated 07 / 31 / 2026, page 26 / 108 The 19 / 50 document is an approved drug to which new generic versions are compared to show that they are bioequivalent. A pharmaceutical company seeking approval to market a generic equivalent must consult the listed reference drug in an Abbreviated New Drug Application (ANDA). By designating a single listed reference drug as the standard to which all generic versions must be shown to be bioequivalent, the FDA hopes to avoid potential significant variations between generic drugs and their brand-name counterparts.

[080] Reference will now be made in detail to the exemplary embodiments of the present disclosure, examples of which are illustrated in the attached figures. Wherever possible, the same reference numbers are used in the drawings and description to refer to identical or similar parts.

[081] One objective of the present invention is to provide a stable anti-PD-1 antibody composition.

[082] Another objective of the present invention is to provide a stable liquid pharmaceutical composition comprising: (a) a human anti-PD1 antibody; (b) a sugar, for example, a non-reducing sugar; (c) a buffer; and (d) a non-ionic surfactant.

[083] In one embodiment, the present invention provides a stable anti-PD-1 antibody composition in which the anti-PD1 antibody is present at a concentration in the range of about 5 mg / mL to about 30 mg / mL.

[084] In one embodiment, the present invention provides a stable anti-PD-1 antibody composition in which the non-reducing sugar is sucrose, trehalose or mannitol, preferably trehalose, more preferably α,α-trehalose dihydrate.

[085] In one embodiment, the present invention provides a composition Petition 870260076824, dated 07 / 31 / 2026, page 27 / 108 A stable 20 / 50 anti-PD-1 antibody composition wherein the buffer comprises a citrate, L-Histidine, Disodium Succinate Hexahydrate, Succinic Acid, Sodium Citrate, Glacial Acetic Acid, Citric Acid Monohydrate and / or Adipic Acid, preferably L-Histidine, L-Histidine HCl Monohydrate and / or Succinic Acid. An object of the present invention is to provide a stable anti-PD-1 antibody composition wherein the non-ionic surfactant is Sodium Chloride, Disodium Edetate Dehydrate, Polysorbate 20, Polysorbate 80 or Poloxamer 188, preferably Disodium Edetate Dihydrate or Polysorbate 80.

[086] In one embodiment, the present invention provides a stable anti-PD-1 antibody composition in which the anti-PD-1 antibody is Nivolumab or Pembrolizumab, preferably Pembrolizumab.

[087] In one embodiment, the present invention provides a stable liquid pharmaceutical composition in which sugar is present at a concentration of about 50 mg / ml to about 150 mg / ml.

[088] Yet another embodiment of the present invention is to provide a stable anti-PD-1 antibody composition in which the buffer is present at a concentration of about 0.05 mM to about 50 mM, preferably 0.05 mM to 25 mM.

[089] Yet another embodiment of the present invention is to provide a stable anti-PD-1 antibody composition in which the nonionic surfactant is present at a concentration in the range of about 0.01 mg / ml to about 2.0 mg / ml.

[090] In one embodiment, the present invention provides a stable anti-PD-1 antibody composition in which the composition has a pH of about 5.2 to about 6.5.

[091] In one embodiment, the present invention provides a stable liquid pharmaceutical composition comprising: (a) a human anti-PD1 antibody; Petition 870260076824, dated 07 / 31 / 2026, page 28 / 108 21 / 50 (b) a sugar, for example, a non-reducing sugar; (c) a buffer; and (d) a nonionic surfactant, wherein: the non-reducing sugar is sucrose or trehalose or mannitol; the buffer comprises a citrate, L-Histidine, sodium succinate hexahydrate, succinic acid, sodium citrate, citric acid monohydrate or adipic acid; and the nonionic surfactant is disodium edetate dehydrate, polysorbate 20, polysorbate 80 or poloxamer 188.

[092] In one embodiment, the present invention provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, α,α-trehalose dihydrate at a concentration of about 50 mg / mL to about 100 mg / mL, L-histidine at a concentration of about 0.5 mM to about 5 mM, L-Histidine HCl monohydrate at a concentration of about 5 mM to about 15 mM, polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, and a pH of about 5.2 to about 6.5, wherein the anti-PD-1 antibody is Pembrolizumab.

[093] In one embodiment, the present invention provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, sucrose at a concentration of about 50 mg / mL to about 100 mg / mL, succinic acid at a concentration of about 5 mM to about 25 mM, disodium edetate dihydrate at a concentration of about 0.01 mg / mL to about 1.0 mg / mL, polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is pembrolizumab.

[094] In one embodiment, the present invention provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, Sucrose in a Petition 870260076824, dated 07 / 31 / 2026, page 29 / 108 22 / 50 concentration of about 50 mg / ml to about 100 mg / ml, Succinic Acid at a concentration of about 0.05 mM to about 2 mM, Disodium Succinate Hexahydrate at a concentration of about 0.5 mM to about 10 mM, Polysorbate 80 at a concentration in the range of about 0.05 mg / ml to about 2.0 mg / ml, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is Pembrolizumab.

[095] In one embodiment, the present invention provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, sucrose at a concentration of about 50 mg / mL to about 100 mg / mL, glacial acetic acid at a concentration of about 5 mM to about 20 mM, polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is Pembrolizumab.

[096] In one embodiment, the present invention provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, Mannitol at a concentration of about 5 mg / mL to about 15 mg / mL, Sodium Chloride at a concentration of about 5 mg / mL to about 10 mg / mL, Citric Acid Monohydrate at a concentration of about 0.5 mM to about 5 mM, Adipic Acid at a concentration of about 5 mM to about 50 mM, Polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is Pembrolizumab.

[097] In one embodiment, the present invention provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, Mannitol at a concentration of about 5 mg / mL to about 15 mg / mL, Sodium Chloride at a concentration of about 5 mg / mL to about 10 mg / mL, Sodium Citrate at a concentration of about 0.1 mM to about 5 mM, Citric Acid Monohydrate in Petition 870260076824, dated 07 / 31 / 2026, page 30 / 108 23 / 50 at a concentration of about 3 mM to about 15 mM, polysorbate 80 at a concentration in the range of about 0.05 mg / ml to about 2.0 mg / ml, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is pembrolizumab.

[098] In one embodiment, the present invention provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, L-Histidine at a concentration of about 5 mM to about 15 mM, sodium chloride at a concentration of about 5 mg / mL to about 10 mg / mL, polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is Pembrolizumab.

[099] In one embodiment, the present invention provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, sucrose at a concentration of about 50 mg / mL to about 100 mg / mL, L-histidine at a concentration of about 0.5 mM to about 5 mM, L-histidine HCl monohydrate at a concentration of about 5 mM to about 20 mM, polysorbate 20 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is pembrolizumab.

[0100] In one embodiment, the present invention provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, sucrose at a concentration of about 50 mg / mL to about 100 mg / mL, L-histidine at a concentration of about 0.5 mM to about 5 mM, L-histidine HCl monohydrate at a concentration of about 5 mM to about 20 mM, poloxamer 188 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is pembrolizumab.

[0101] In one embodiment, the present invention provides a composition Petition 870260076824, dated 07 / 31 / 2026, p. 31 / 108 24 / 50 stable liquid pharmaceutical comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, sucrose at a concentration of about 50 mg / mL to about 100 mg / mL, glacial acetic acid at a concentration of about 0.5 mM to about 10 mM, sodium acetate trihydrate at a concentration of about 2 mM to about 20 mM, polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is pembrolizumab.

[0102] In one embodiment, the present invention provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, sucrose at a concentration of about 50 mg / mL to about 100 mg / mL, anhydrous dibasic sodium phosphate at a concentration of about 0.05 mM to 5 mM, monobasic sodium phosphate monohydrate at a concentration of about 5 mM to about 20 mM, polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is pembrolizumab.

[0103] In one embodiment, the present invention provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, sucrose at a concentration of about 50 mg / mL to about 100 mg / mL, succinic acid at a concentration of about 1 mM to about 10 mM, sodium succinate hexahydrate at a concentration of about 2 mM to about 20 mM, polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is pembrolizumab.

[0104] In one embodiment, the present invention provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, α,α-trehalose di Petition 870260076824, dated 07 / 31 / 2026, page 32 / 108 25 / 50 hydrated at a concentration of about 50 mg / ml to about 100 mg / ml, anhydrous dibasic sodium phosphate at a concentration of about 0.05 mM to about 5 mM, monobasic sodium phosphate monohydrate at a concentration of about 5 mM to about 20 mM, polysorbate 80 at a concentration in the range of about 0.05 mg / ml to about 2.0 mg / ml, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is pembrolizumab.

[0105] In one embodiment, the present invention provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, α,α-trehalose dihydrate at a concentration of about 50 mg / mL to about 100 mg / mL, sodium acetate trihydrate at a concentration of about 2 mM to about 20 mM, glacial acetic acid at a concentration of about 0.5 mM to about 10 mM, polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is pembrolizumab.

[0106] In one embodiment, the present invention provides a stable liquid pharmaceutical composition comprising an anti-PD-1 antibody at a concentration in the range of about 5 mg / mL to about 30 mg / mL, α,α-trehalose dihydrate at a concentration of about 50 mg / mL to about 100 mg / mL, succinic acid at a concentration of about 1 mM to about 10 mM, sodium succinate hexahydrate at a concentration of about 2 mM to about 20 mM, polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, a pH of about 5.2 to about 6.5, and wherein the anti-PD-1 antibody is pembrolizumab.

[0107] Another embodiment of the present invention is to provide an anti-PD-1 antibody composition wherein the composition can be administered by intravenous administration or by subcutaneous administration, or a Petition 870260076824, dated 07 / 31 / 2026, p. 33 / 108 26 / 50 combination of them.

[0108] In one embodiment, the composition and methods of the invention include high concentrations of an anti-PD1 antibody, or antigen-binding moieties thereof, and (a) a sugar, for example, a non-reducing sugar; (b) a buffer; and (c) a non-ionic surfactant.

[0109] A stable anti-PD-1 antibody composition of the present invention can be used for the prophylaxis or treatment of a PD-1-mediated disease or disorder, wherein the disease or disorder is preferably cancer; more preferably cancer expressing PD-L1; wherein the disease or disorder is especially preferably breast cancer, lung cancer, stomach cancer, intestinal cancer, kidney cancer, melanoma; especially preferably non-small cell lung cancer, melanoma and kidney cancer. EXAMPLES

[0110] The following examples are presented so as to provide those skilled in the art with a disclosure and description of how to produce and use the methods and compositions of the invention and are not intended to limit the scope of what the inventors consider their invention. Efforts have been made to ensure accuracy with respect to the numbers used (e.g., quantities, temperature, etc.), but as is known to those skilled in the art, some experimental errors and deviations must be accounted for. Unless otherwise indicated, parts are parts per mole, molecular weight is the average molecular weight, temperature is in degrees Celsius, and pressure is at or close to atmospheric pressure. Development of stable anti-PD-1 antibody compositions Screening of different compositions.

[0111] For screening, different compositions were exposed to conditions of Petition 870260076824, dated 07 / 31 / 2026, page 34 / 108 27 / 50 stress as follows. Photographic tension 1 cycle (Exposure to light) Phototension 1 cycle + 50 °C for 6 days (Exposure to light followed by heat) Photostress 3 cycles (Exposure to excessive light) The stress conditions considered above were listed based on previous degradation studies conducted with RLD.

[0112] The compositions of the present invention (1-15 set forth below) were exposed to the stress conditions described above and then subjected to analysis by size exclusion chromatography (SEC)-HPLC, Monomer, hydrophobic interaction chromatography (HIC), ion exchange chromatography (IEX) and protein A HPLC. The results of which are set forth in studies AJ below. TABLE 1: PD1 Compositions (1-6) Name of ingredients Compositions 1 2 3 4 5 6 mg / ml mg / ml mg / ml mg / ml mg / ml mg / ml Pembrolizumab 25 25 25 25 25 25 Polysorbate 80 0.2 0.2 0.2 0.2 0.2 0.2 L-Histidine 9.99 mM Sucrose 70 70 70 - - - Disodium Succinate Hexahydrate 4.48 mM Succinic Acid 19.98 mM 0.51 mM Sodium Chloride 6.16 6.16 9 Mannitol 12.0 12.0 Sodium Citrate Dihydrate 1.02 mM Citric Acid Monohydrate 1.22 mM 6.19 mM Disodium Edetate Dihydrate 0.05 - - - - - Petition 870260076824, dated 07 / 31 / 2026, page 35 / 108 28 / 50 Glacial Acetic Acid 9.99 mM Adipic Acid - - - 22.99 mM - - Sodium Hydroxide to pH to pH to pH to pH to pH to pH to pH Hydrochloric Acid to pH to pH to pH to pH to pH to pH to pH WFI qs to 1 ml Final / Target pH of the Composition pH 5.5 pH 5.5 pH 5.5 pH 5.5 pH 5.5 pH 5.5 TABLE 2: PD1 Compositions (7-15) Name of ingredients Compositions 7 8 9 10 11 12 13 14 15 mg / ml mg / ml mg / ml mg / ml mg / ml mg / ml mg / ml mg / ml mg / ml Pembrolizumab 25 25 25 25 25 25 25 25 25 Polysorbate 80 0.2 0.2 0.2 0.2 0.2 0.2 0.2 Polysorbate 20 - 0.4 - - - - - - - Poloxamer 188 0.5 Sucrose - 70 70 70 70 71 - - - α,α-trehalose dihydrate 79 76 76 76 L-Histidine 1.93 mM 1.93 mM 1.93 mM L-Histidine HCl monohydrate 8.11 mM 8.11 mM 8.11 mM Dibasic sodium phosphate anhydrous 0.58 mM 0.58 mM Monobasic sodium phosphate monohydrate 10.15 mM 10.15 mM Succinic acid 2.63 mM 2.63 mM Sodium succinate hexahydrate 6.11 mM 6.11 mM Glacial acetic acid 1.83 mM 1.83 mM Sodium acetate trihydrate 8.82 mM 8.82 mM WFI qs to 1 ml Final / Target pH of Composition 5.5 5.5 5.5 5.5 6.0 5.5 6.0 5.5 5.5

[0113] The proposed compositions (1-15) showed less change from Initial value compared to the RLD composition, thus suggesting that Petition 870260076824, dated 07 / 31 / 2026, page 36 / 108 29 / 50 The proposed compositions may be more stable than the RLD composition. The proposed compositions (1-15) demonstrated comparable or smaller differences from baseline values ​​for all four CQAs for all three stress conditions compared to RLD, as mentioned in the studies.

[0114] All compositions (1-15) reached pH 5.5 + 0.4 with a target of 5.5 except for Composition 11 and 13 with a target pH of 6.0.

[0115] The osmolality of all compositions was in the range between 220 330 mOsm / kg.

[0116] All compositions 1-15 achieved a Protein Concentration of ~ 25.00 + 1.2 mg / ml. Screening of compositions 1-15 compared to RLD TABLE 3.A: Screening of compositions 1 to 3 in comparison with RLD Petition 870260076824, dated 07 / 31 / 2026, page 37 / 108 No. SN° B. / No. NIF RLD 1 2 3 Initial Test Parameters / Conditions Photostability of 1 cycle Photo 0 of 1 cycle 0 + 6D 50 °C Photostability of 3 cycles Initial Photostability of 1 cycle Photo 0 of 1 cycle 0 + 6D 50 °C Photostability of 3 cycles Initial Photostability of 1 cycle Photo 0 of 1 cycle 0 + 6D 50 °C Photostability of 3 cycles Initial Photostability of 1 cycle Photo 0 of 1 cycle 0 + 6D 50 °C Photostability of 3 cycles 1 Description * * * * * * * * * * * * * * * * 2 pH 5.5 7 NA NA NA 5.5 1 NA NA NA 5.8 NA NA NA 5.8 7 NA NA NA 3 Osmolality (mOsm) 25 3 NA NA NA 28 1 NA NA NA 27 4 NA NA NA 24 7 NA NA NA 4 Protein Concentration (mg / mL) 24.89 NA NA NA 24.93 NA NA NA 25.2 NA NA NA 24.91 NA NA NA 5 Purity by SEC HPLC (%) 5.1 HMW 0.1 4 1.33 3.3 2 5.37 0.1 3 1.65 3.1 2 4.21 0.1 4 1.90 3.8 9 3.46 0.1 5 2.89 3.9 4 5.19 5.2 Monomer 99, 86 98.5 96, 37 94.24 99, 87 98.25 96.67 95.58 99.86 97.98 95.91 96.34 99.86 96.97 95.77 94.56 5.3 LMW 0 0.16 0.3 1 0.38 0 0.10 0.2 1 0.21 0 0.11 0.2 1 0.2 0 0.14 0.2 9 0.25 6 Exchange Chromatography. 30 / 50 Petition 870260076824, dated 07 / 31 / 2026, page 38 / 108 Cationic (%) 6.1 Acidic Variants 13.25 21.58 31.64 32.23 13.4 18.39 29.67 18.77 13.65 21.12 31.14 20.59 14.23 23.42 31.41 23.98 6.2 Main Peak 67.58 52.1 44.83 34.94 68.26 52.58 41.63 33.06 67.82 48.65 38.18 34.29 67.15 48.7 46.56 33.22 6.3 Basic Variants 18.89 26.33 23.52 32.84 18.34 29.02 28.7 48.18 18.55 30.22 30.67 45.11 18.61 27.89 22.03 42.79 7 Purity - by HIC (%) 7.1 Pre-peak 18.72 55.02 65.73 93.85 18.74 50.97 51.41 77.42 18.94 55.29 55.93 74.44 18.88 51.79 52.29 72.49 7.2 Main peak 70.61 38.75 29.85 4.94 70.71 42.52 42.72 18.71 70.3 38.9 38.72 21.44 70.31 41.83 41.71 22.97 7.3 Post-peak 1 10.68 6.22 4.4 2 1.2 10.56 6.52 5.8 6 3.87 10.76 5.81 5.3 6 4.12 10.81 6.4 6.0 0 4.52 * Clear, colorless solution, NA - not analyzed TABLE 3.B: Screening of compositions 4 to 6 compared to RLD NS. No. B. / No. NIF RLD 4 5 6 Initial Test Parameters / Conditions 1-cycle photostability 1-cycle photo + 6D 50°C 3-cycle photostability Initial 1-cycle photo 1-cycle photo + 3-cycle photostability Initial 1-cycle photo 1-cycle photo + 6D 50°C 3-cycle photostability Initial 1-cycle photo 1-cycle photo + 3-cycle photostability 31 / 50 Petition 870260076824, dated 07 / 31 / 2026, p. 39 / 108 6D 50 °C 6D 50 °C 1 Description Precipitated sample, not analyzed Sample not retained Precipitated sample, not analyzed 2 pH 5.57 NA NA NA 5.64 NA NA 5.76 NA NA 5.75 NA NA 3 Osmolality (mOsm) 253 NA NA NA 326 NA NA 315 NA NA 312 NA NA 4 Protein Concentration (mg / mL) 24.89 NA NA NA 25.11 NA NA 25.52 NA NA 25.16 NA NA 5 Purity by SEC HPLC (%) 5.1 HMW 0.14 1.33 3.32 5.37 0.16 5.06 9.79 0.19 4.04 3.9 0.14 2.07 8.02 5.2 Monomer 99.86 98.5 96.37 94.24 99.84 94.71 89.75 99.81 95.77 95.86 99.86 97.73 91.5 5.3 LMW 0.16 0.31 0.38 0 0.22 0.46 0 0.18 0.24 0 0.19 0.47 6 Electron Exchange Chromatography 32 / 50 Petition 870260076824, dated 07 / 31 / 2026, page 40 / 108 Cationic (%) 6.1 Acidic Variants 13.25 21.58 31.64 32.23 13.78 24.56 31.44 13.63 26.09 35.91 13.41 22.56 32.43 6.2 Main Peak 67.58 52.1 44.83 34.94 67.55 49.61 33.76 67.88 46.49 42.6 67.83 52.18 34.28 6.3 Basic Variants 18.89 26.33 23.52 32.84 18.66 25.85 34.78 18.49 27.42 21.5 18.77 25.27 33.28 7 Purity - by HIC (%) 7.1 Pre-peak 18.72 55.02 65.73 93.85 18.98 67.33 89.35 18.88 73.39 76.23 19.19 55.35 95.38 7.2 Main peak 70.61 38.75 29.85 4.94 70.34 27.66 9.16 70.45 22.78 20.82 70.2 38.37 4.00 7.3 Post-peak 10.68 6.22 4.42 1.2 10.68 5.01 1.49 10.68 3.84 2.96 10.61 6.27 0.62 * Clear, colorless solution, NA - not analyzed 33 / 50 TABLE 3.C: Screening of compositions 7 to 9 compared to RLD N.° S. N,° B,ZN,° NIF RLD 7 8 9 Photo Photo Photo Photo stab Photo Photo Photo Photo Photo Photo Photo Photo Photo Photo Parameters / Conditions stability of 1 stability Initial stability of 1 stability Initial stability of 1 stability Initial stability cycle + stability stability cycle + stability Initial stability cycle + stability Initial stability cycle + stability Test 1 6D of 3 I and of 1 cycle 6D of 3 I of of 1 cycle 6D of 3 of 1 6D of 3 cycle 50°C cycles 50°C cycles 50°C cycles cycle 50°C cycles 1 Description * * * * * * * * * * * * * * * * 2 pH 5.5 NA NA NA 5.5 NA NA NA 5.48 NA NA NA 5.5 NA NA NA Petition 870260076824, dated 07 / 31 / 2026, page 41 / 108 3. Osmolality (mOsm) 249 NA NA NA 265 NA NA NA 252 NA NA NA 255 NA NA NA 4. Protein Concentration (mg / mL) 24.11 NA NA NA 24.22 NA NA NA 26.11 NA NA NA 24.69 NA NA NA 5. Purity by SEC HPLC (%) 5.1 HMW 0.17 2.11 4.23 6.44 0.14 1.56 3.05 5.36 0.14 1.70 4.23 6 0.13 1.2 2.63 4.75 5.2 Monomer 99.83 97.79 95.54 93.24 99.86 98.37 96.8 94.35 99.86 98.22 95.58 93.67 99.86 98.75 97.18 94.98 6 Cation Exchange Chromatography (%) 6.1 Acid Variants 15.93 23.38 32.2 28.59 13.18 18.74 27.02 22.99 14.44 22.29 31.79 26.08 14.77 18.98 26.75 23.72 6.2 Main Peak 57.84 37.99 36.06 25.14 51.85 38.55 35.97 26.67 51.71 32.9 33.86 20.61 51.35 38 36.13 25.07 6.3 Basic variants 26.22 38.63 31.74 46.27 34.98 42.72 37.02 50.33 33.84 44.82 34.36 53.32 33.88 43.03 37.12 51.21 7 Purity - by HIC (%) 7.1 Pre-peak 20.08 62.52 55.23 93.35 35.85 61.82 61.44 93.46 35.87 71.67 63.22 97.67 35.77 62.25 55.96 95.21 7.2 Main Peak 69.7 31.8 38.97 6.64 58.69 34.85 35.54 6.56 58.73 25.72 33.66 2.31 59.07 34.68 40.14 4.81 7.3 Post-peak 10.22 5.69 5.79 NA 5.46 3.34 3.04 NA 5.4 2.61 3.12 NA 5.16 3.05 3.90 NA 8 Content - (HPLC of Protein A) (%) 8.1 Total oxidized impurities 3.45 41.01 33.82 77.57 2.8 32.8 28.95 72.71 2.86 45.18 33.95 86.53 2.75 34.14 28.08 76.28 8.2 Main Peak 96.55 58.99 66.18 22.43 97.2 67.2 71.05 27.29 97.14 54.82 66.05 13.47 97.25 65.86 71.92 23.72 9 % of SPR test (% of Relative Bonding) 115.7 NA NA 13.1 87.7 NA NA 22.2 83.2 NA NA 9.2 89.8 NA NA 29.4. * Clear, colorless solution, NA - not analyzed 34 / 50 Petition 870260076824, dated 07 / 31 / 2026, page 42 / 108 TABLE 3.D: Screening of compositions 10 to 12 compared to RLD N.° S. N,° B, / N,° NIF RLD 10 11 12 Test Parameters / Conditions Initial Photostability of 1 cycle Photo 0 of 1 cycle 0 + 6D 50° C Photostability of 3 cycles Initial Photostability of 1 cycle Photo 0 of 1 cycle 0 + 6D 50° C Photostability of 3 cycles Initial Photostability of 1 cycle Photo 0 of 1 cycle 0 + 6D 50° C Photostability of 3 cycles Initial Photostability of 1 cycle Photo 0 of 1 cycle 0 + 6D 50° C Photostability of 3 cycles 1 Description * * * * * * * * * * * * * * * * 2 pH 5.5 NA NA NA 5.5 3 NA NA NA 5.8 NA NA NA 5.4 6 NA NA NA 3 Osmolality (mOsm) 249 NA NA NA 252 NA NA NA 259 NA NA NA 253 NA NA NA 4 Protein Concentration (mg / mL) 24.11 NA NA NA 25.72 NA NA NA 26.25 NA NA NA 25.31 NA NA NA 5 Purity by SEC HPLC (%) 5.1 HMW 0.1 7 2.11 4.2 3 6.44 0.1 5 1.78 2.4 4 3.92 0.1 6 4.53 2.8 9 5.36 0.1 5 1.51 2.2 7 3.83 5.2 Monomer 99.83 97.79 95.54 93.24 99.86 98.16 97.4 95.87 99.84 95.33 96.88 94.32 99.86 98.43 97.59 95.95 6 Cation Exchange Chromatography (%) 6.1 Acid Variants 15.93 23.38 32.2 28.59 13.76 16.3 23.34 19.85 13.67 21.57 28.75 21.85 13.9 15.99 26.27 15.88. 35 / 50 Petition 870260076824, dated 07 / 31 / 2026, page 43 / 108 6.2 Main Peak 57.84 37.99 36.06 25.14 51.61 34.49 36.9 25.61 51.8 33.07 35.33 26.69 51.42 35.68 35.32 26.68 6.3 Basic Variants 26.22 38.63 31.74 46.27 34.63 49.2 39.77 54.52 34.54 45.36 35.92 51.46 34.69 48.33 38.43 57.44 7 Purity - by HIC (%) 7.1 Pre-peak 20.08 62.52 55.23 93.35 35.73 64.53 55.74 82.06 35.65 65.53 54.71 79.79 36.05 65.31 54.26 82.46 7.2 Main Peak 69.7 31.8 38.97 6.64 58.79 32.15 40.44 15.63 58.89 31.49 42.08 17.86 58.46 31.67 42.12 15.53 7.3 Post-Peak 10.22 5.69 5.79 NA 5.49 3.33 3.8 3 2.3 5.4 7 2.97 3.2 2 2.34 5.4 8 3.03 3.6 2 2.01 8 Content - (HPLC of Protein A) (%) 8.1 Total oxidized impurities 3.4 5 41.01 33.82 77.57 2.8 4 44.25 29.08 65.44 2.8 45.24 29.54 61.9 2.8 2 41.2 27.11 64.69 8.2 Main Peak 96.55 58.99 66.18 22.43 97.16 55.75 70.92 34.56 97.2 54.76 70.46 38.1 97.18 58.8 72.89 35.31 9% of the SPR test (% of Relative Bonding) 115.7 NA NA 13.1 111.9 NA NA 41.8 88.8 NA NA 69.3 92.3 NA NA 88.2 * Clear, colorless solution, NA - not analyzed 36 / 50 TABLE 3.E: Screening of compositions 13 to 15 compared to RLD No. SN° B. / No. NIF RLD 13 14 15 Initial Test Parameters / Conditions 1-cycle Photostability 3-cycle Photostability Initial 1-cycle Photostability 3-cycle Photostability Initial 1-cycle Photostability 3-cycle Photostability Initial 1-cycle Photostability 3-cycle Photostability Petition 870260076824, dated 07 / 31 / 2026, page 44 / 108 1 cycle 0 + 6D 50 °C cycles 1 cycle 0 + 6D 50 °C cycles 1 cycle 0 + 6D 50 °C cycles 1 cycle 0 + 6D 50 °C cycles 1 Description * * * * * * * * NA * NA * NA * 5, 2 5.5 0 5.51 5.5 2 5.50 5.4 2 5.42 5.4 1 5.44 3 Osmolality (mOsm) 24 9 NA 25 3 NA 26 0 NA NO 25, 16 AND 24, 77 AND 24, 66 AND 5 Purity by SEC HPLC (%) 5.1 HMW 0.3 3 2.35 2.1 8 2.73 5.2 Monomer 99,83 97.79 95, 54 93.24 99, 84 97.65 98, 13 95.29 99, 97.65 97, 83 97.28 6 Chromatography a by Cationic Moiety (%) 6.1 Acidic variants 15.93 23.38 32.2 28.59 14.13 17.35 25.34 13.9 19.82 15.84 14.17 17.28 26.45 15.26 6.2 Main Peak 57.84 37.99 36.06 25.14 51.44 38.04 39.81 62.16 45.08 43.48 39.64 6.3 Basic Variants 26, 22 38,63 31, 74 46,27 34, 43 44,6 35, 85 51,1 23, 16 33,74 29, 07 44,20 23, 65 37,64 30, 08 45,11 7 Purity - by HIC (%). 37 / 50 Petition 870260076824, dated 07 / 31 / 2026, page 45 / 108 7.1 Pre-peak K 08 62.52 55.23 93.35 35.48 57.77 47.88 74.99 20.97 41.08 38.70 60.90 21.05 49.92 39.30 61.39 7.2 Main peak 69.7 31.8 38.97 6.64 59.15 38.14 48.07 22.29 72.70 53.98 55.77 35.16 72.73 45.39 55.41 35.18 7.3 Post-peak 10.22 5.69 5.79 NA 5.3 7 4.09 4.0 4 2.71 6.3 3 4.94 5.5 3 3.93 6.2 2 4.71 5.2 9 3.43 8 Content - (HPLC of Protein A) (%) 8.1 Total oxidized impurities 3.4 5 41.01 33.82 77.57 2.8 4 34.26 21.53 55.27 97.42 73.83 79.05 53.91 97.40 65.03 76.93 52.53 8.2 Main Peak 96.55 58.99 66.18 22.43 97.16 65.74 78.47 44.73 2.5 9 26.17 20.95 46.09 2.5 9 34.97 23.06 47.46 9% of the SPR test (% of Relative Bonding) 11 5.7 NA NA 13.1 89.5 NA NA 110.5 10 1 NA NA 77 87 NA NA 89 * Clear, colorless solution, NA - not analyzed 38 / 50 TABLE 3.F: Stability data for composition 7 to 8 compared to RLD N.° S. N,° B, / N,° NIF Keytruda RLD_U029039 7 8 Initial Test Parameters / Conditions 1-cycle photostability 1-cycle photo + 6D 50°C 3-cycle photostability 6M, 28°C 6M, 25°C / 60% RH initial 1-cycle photostability 1-cycle photo + 6D 50°C 3-cycle photostability 6M, 28°C 6M, 25°C / 60% RH initial 1-cycle photostability 1-cycle photo + 6D 50°C 3-cycle photostability 6M, 200°C 6M, 25°C / 60% RH 1 Description * * * * * * * * * * * * * * * * * * 2 pH 5.5 5 NA NA NA 5.4 1 5.56 5 NA NA NA 5.4 9 5.79 5 NA NA NA 5.5 5.55 Petition 870260076824, dated 07 / 31 / 2026, p. 46 / 108 5 4 8 3 Osmolalid 24 Q NA NA NA 25 5 259 2 6 NA NA NA 27 288 2 5 NA NA NA 25 Q 262 of (mOsm) 5 □ 2 2 2 Protein Concentration 24, 11 4 6 4 NA NA NA NA NA 2 NA NA NA NA NA 1 NA NA NA NA NA NA (mg / mL) 2 1 5 Purity by SEC HPLC (%) 0.1 7 0.1 5 0 0.1 2 0 0.1 2 5.1 2.11 4.23 6.44 0.52 1 1.56 3.05 5.36 0.33 1 1.70 4.23 6 0.34 HMW 4 4 9 9 99, 83 99 85 9 99 88 9 99 88 5.2 97.79 95.54 93.24 99.48 , 8 98.37 96.8 94.35 99.67 , 8 98.22 95.58 93.67 99.66 Monomer 6 6 6 Cation Exchange Chromatography (%) 1 1 15.93 16.02 3 14.07 4 14.13 6.1 Variants 23.38 32.2 28.59 27.04 1 18.74 27.02 22.99 23.79 , 4 22.29 31.79 26.08 23.18 acidic 8 4 5 5 57, 84 59, 42 1 53, 78 1 53, 73 6.2 Peak 37.99 36.06 25.14 51.53, 8 38.55 35.97 26.67 47.51, 7 32.9 33.86 20.61 47.8 Main 5 1 6.3 Variants 26, 38.63 31.74 46.27 24, 21.42 3 42.72 37.02 50.33 32, 28.69 3 44.82 34.36 53.32 32, 29.01 39 / 50 Petition 870260076824, dated 07 / 31 / 2026, page 47 / 108 Basic 22 57 4 9 8 16 3 8 4 15 7 Purity - by HIC (%) 7.1 Pre-peak 20.08 62.52 55.23 93.35 21.75 26.66 35.85 61.82 61.44 93.46 36.95 39.01 35.87 71.67 63.22 97.67 36.76 37.54 7.2 Main peak 69.7 31.8 38.97 6.64 67.83 63.76 58.69 34.85 35.54 6.56 57.61 55.70 5 8, 7 3 25.72 33.66 2.31 57.75 57.08 7.3 Post-peak 10.22 5.69 5.79 NA 10.41 9.57 5 6 3.34 3.04 NA 5.4 3 5.28 5, 4 2.61 3.12 NA 5.4 9 5.38 8 Content - (HPLC of Protein A) (%) 8.1 Total oxidized impurities 3.4 5 41.01 33.82 77.57 3.9 6 6.06 2, 8 32.8 28.95 72.71 2.9 8 4.3 2 6 45.18 33.95 86.53 3.1 6 4.14 8.2 Main Peak 96.55 58.99 66.18 22.43 96.04 93.94 97.2 67.2 71.05 27.29 97.02 95.7 97.14 54.82 66.05 13.47 96.84 95.86 9% of SPR assay (% of Binding) 11 5.7 NA NA 13.1 10 6 NA 8 7 NA NA 22.2 11 2 NA 8 3 NA NA 92 92 NA 40 / 50 Petition 870260076824, dated 07 / 31 / 2026, page 48 / 108 I Relative) | |_______|_________|__________|_|______7_________I_________I__________l_l______2 * Clear, colorless solution, NA - not analyzed TABLE 3.G: Stability data for composition 9 to 10 compared to RLD N.° S. N,° B, / N,° NIF Keytruda RLDJJ029039 9 10 Test Parameters / Conditions Initial I 1-cycle photostability 1-cycle photo 1° + 6D 50°C 3-cycle photostability 6 M, 28°C 6M, 25°C / 60% RH Initial I 1-cycle photostability 1-cycle photo 1° + 6D 50°C 3-cycle photostability 6 M, 2-8°C 6M, 25°C / 60% RH Initial I 1-cycle photostability 1-cycle photo 1° + 6D 50°C 3-cycle photostability M, 28°C 6M, 25°C / 60% RH 1 Description * * * * * * * * * * * * * * * * * * 2 pH 5.55 NA NA NA 5.41 5.56 5.5 NA NA NA 5.51 5.52 5.53 NA NA NA 5.51 5.53 3 Osmolality (mOsm) 24 9 NA NA NA 25 5 259 25 5 NA NA NA 26 2 269 25 2 NA NA NA 26 0 265 4 Protein Concentration (mg / mL) 24.1 NA N NA N NA 24.6 NA N NA N NA 25.7 NA N NA N NA 1 AA 9 AA 2 AA 5 Purity by SEC HPLC (%) 5.1 HMW 0.211 6.44 0.52 0.12 2.475 0.35 0, 1.78 2, 3.92 0, 0.49 17 23 15 13 63 11 15 44 12 99 95 99 99.4 0 99 97 99 99.6 99 97 ,4 99 99.5 1 5.2 Monomer ,8 97.79 ,5 93.24 ,8 98.75 ,1 94.98 ,8 98.16 95.87 ,8 3 4 5 □ 3 8 9 O 6 8 6 Cation Exchange Chromatography (%). 41 / 50 Petition 870260076824, dated 07 / 31 / 2026, page 49 / 108 15 32 ,2 16 27,0 4 14 26 16 22,8 1 13 23 14 23,5 5 6.1 Acid Variants ,9 23,38 28,59 ,0 ,7 18,98 ,7 23,72 ,1 ,7 16,3 ,3 19,85 ,7 3 2 7 5 2 6 4 2 57 36 59 51,5 O 51 36 51 48,3 O 51 36 53 47,9 8 6.2 Main Peak ,8 37,99 ,0 25,14 ,4 ,3 38 ,1 25,07 ,9 ,6 34,49 ,9 25,61 ,0 4 6 2 □ 5 3 1 o 1 9 26 31 24 21.4 2 33 37 31 28.8 9 34 39 32 ,2 28.4 8 6.3 Basic Variants ,2 2 38.63 ,7 4 46.27 ,5 7 ,8 8 43.03 ,1 2 51.21 ,9 ,6 3 49.2 ,7 7 54.52 7 Purity - by HIC (%) 20 55 21 26.6 6 35 55 36 36.8 9 35 55 37.8 8 7.1 Pre-peak ,0 8 62.52 ,2 3 93.35 ,7 5 ,7 7 62.25 ,9 6 95.21 ,6 9 ,7 3 64.53 ,7 4 82.06 □I ,7 38 67 63.7 59 40 57 57.6 Q 58 40 57 56.3 7 7.2 Main Peak 69 ,7 31.8 ,9 6.64 .8 ,0 34.68 ,1 4.81 ,7 32.15 ,4 15.63 ,8 7 3 □ 7 4 2 9 4 5 Post-peak 10 5.79 10 5.16 3.90 5.48 5.49 3.83 5.45 7.3 ,2 2 5.69 NA ,4 1 9.57 3.05 NA 5.41 3.33 2.3 5.75 8 Content - (HPLC of Protein A) (%) 8.1 Oxidized impurities 3, 41.01 33.8 77.57 3- 6.06 2, 34.14 28.0 76.28 3, 3.93 44.25 29.0 65.44 3, 4.18 Totals 45 2 96 75 8 03 84 8 12 96 66 96 93.9 4 97 71 96 96.0 O 97 70 96 95.8 9 8.2 Main Peak ,5 58.99 ,1 22.43 ,0 ,2 65.86 ,9 23.72 ,9 ,1 55.75 ,9 34.56 ,8 5 8 4 5 2 6 □ 6 2 8 9 % of the SPR test (% 11 5, 7 NA N 13,1 10 NA 89 NA N 29,4 10 NA 11 1, 9 NA N 41,8 98 NA of Relative Bonding) A 6 ,8 A 4 A. 42 / 50 Petition 870260076824, dated 07 / 31 / 2026, page 50 / 108 * Clear colorless solution, NA - not analyzed TABLE 3.H: Stability data for composition 11 to 12 compared to RLD N° S. N° B / N° NIF Keytruda R LD_U029039 11 12 Initial Test Parameters / Conditions 1-Cycle Photostatability F ot 0 1-Cycle 0 + 6 D 50 °C 3-Cycle Photostatability 6 M, 2- 8o C 6M, 25° C / 6 0% RH Initial Photoes tability of 1 cycle F ot 0 of 1 cycle 0 + 6 D 50 °C Photos tabilities of 3 cycles 6 M, 2- 8o C 6M, 25° C / 6 0% RH Initial Photos tabilities of 1 cycle F ot 0 of 1 cycle 0 + 6 D 50 °C Photos tabilities 3 cycles 6 M, 28°C 6M, 25°C / 6 0% RH 1 Description * * * * * * * * * * * * * * * * * * 2 pH 5.55 NA NA NA 5.41 5.56 5.8 NA NA NA 5.73 5.77 5.46 NA NA NA 5.42 5.42 3 Osmolality (mOsm) 24 9 NA NA NA 25 5 259 25 9 NA NA NA 27 1 271 25 3 NA NA NA 26 2 263 4 Protein Concentration (mg / mL) 24.1 1 NA NA NA NA NA 26.2 5 NA NA NA NA NA 25.3 1 NA NA NA NA NA 5 Purity by SEC HPLC (%) 5.1 HMW 0.17 2.11 4.23 6.44 0.15 0.52 0.16 4.53 2.89 5.36 0.14 0.57 0.15 1.51 2.27 3.83 0.12 0.53 5.2 Monomer 99.8 3 97.79 95.5 4 93.24 99.8 5 99.4 8 99.8 4 95.33 96.8 8 94.32 99.8 5 99.4 3 99.8 6 98.43 97.5 9 95.95 99.8 8 99.4 7. 43 / 50 Petition 870260076824, dated 07 / 31 / 2026, page 51 / 108 Cation Exchange Chromatography (%) 6. 1 Acidic variants 15 .9 3 23.38 32 .2 28.59 16 .0 2 27.0 4 13 .6 7 21.57 28 .7 5 21.85 14 .4 6 24.0 9 13 .9 15.99 26 .2 7 15.88 14.0 5 25.3 9 6. 2 Main Peak 57.8 4 37.99 36.0 6 25.14 59.4 2 51.5 3 51.8 33.07 35.3 3 26.69 53.7 1 47.1 5 51 .4 2 35.68 35 ,3 2 26.68 53.7 4 45.8 7 6.3 Basic Variants 26.2 2 38.63 31.7 4 46.27 24.5 7 21.4 2 34.5 4 45.36 35.9 2 51.46 31.8 3 27.9 6 34.6 9 48.33 38.4 3 57.44 32.2 2 28.7 3 7 Purity - by HIC (%) 7.1 Pre-peak 20.0 8 62.52 55.2 3 93.35 21.7 5 26.6 6 35.6 5 65.53 54.7 1 79.79 36.4 4 39.4 36.0 5 65.31 54.2 6 82.46 36.6 4 39.1 9 7.2 Main Peak 69.7 31.8 38.9 7 6.64 67.8 3 63.7 6 58.8 9 31.49 42.0 8 17.86 58.1 55.3 4 58.4 6 31.67 42.1 2 15.53 57.8 9 55.4 1 7.3 Post-Peak 10.2 2 5.69 5.79 NA 10.4 1 9.57 5.47 2.97 3.22 2.34 5.47 5.25 5.48 3.03 3.62 2.01 5.46 5.39 8 Protein A Content (HPLC) (%) 8.1 Total oxidized impurities 3.45 41.01 33.8 2 77.57 3.96 6.06 2.8 45.24 29.5 4 61.9 3.17 4.63 2.82 41.2 27.1 1 64.69 2.81 4 8. 2 Main Peak 96 .5 5 58.99 66 .1 8 22.43 96 .0 4 93.9 4 97 .2 54.76 70 .4 6 38.1 96 .8 2 95.3 7 97 .1 8 58.8 72 .8 9 35.31 97 .1 9 96 9% of the SPR assay (% Relative Binding) 11 5, 7 NA NA 13.1 10 6 NA 88.8 NA NA 69.3 10 2 NA 92.3 NA NA 88.2 88 NA. * Clear, colorless solution, NA - not analyzed 44 / 50 Petition 870260076824, dated 07 / 31 / 2026, page 52 / 108 TABLE 3.I: Stability data of composition 13 compared to RLD N.° S. N,° B, / N,° NIF Key truda RLD_U029039 13 Initial Test Parameters / Conditions 1-cycle Photostability 0 of 1 cycle 0 + 6D 50°C 3-cycle Photostability 6M, 2-8°C 6M, 25°C / 6 0% RH Initial 1-cycle Photostability 0 of 1 cycle 0 + 6D 50°C 3-cycle Photostability 6M, 28°C 6M, 25°C / 6 0% RH 1 Description * * * * * * * * * * * * 2 pH 5.5 5 NA NA NA 5.4 1 5.56 5.7 2 NA NA NA 5.6 7 5.71 3 Osmolality (mOsm) 249 NA NA NA 255 259 253 NA NA NA 262 266 4 Protein Concentration (mg / mL) 24.11 NA NA NA NA NA 25.16 NA NA NA NA NA 5 Purity by SEC HPLC (%) 5.1 HMW 0.1 7 2.11 4.2 3 6.44 0.1 5 0.52 0.1 6 2.3 1.7 7 4.55 0.1 5 0.59 5.2 Monomer 99.83 97.79 95.54 93.24 99.85 99.48 99.84 97.65 98.13 95.29 99.85 99.41 6 Cation Exchange Chromatography (%) 6.1 Acidic variants 15.93 23.38 32.2 28.59 16.02 27.04 14.13 17.35 25.34 19.4 14.19 24.11 6.2 Main Peak 57.84 37.99 36.06 25.14 59, 42 51.53 51, 44 38.04 38, 81 29.5 53, 72 47.33 6.3 Basic Variants 26, 38, 63 31, 46, 27 24, 21, 42 34, 44, 6 35, 51, 1 32, 28, 56. 45 / 50 Petition 870260076824, dated 07 / 31 / 2026, page 53 / 108 b2 I 74 I 57 | 43 I 85 | 07 I 7 Purity - by HIC (%) 7.1 Pre-peak 20.08 62.52 55.23 93.35 21.75 26.66 35.48 57.77 47.88 74.99 36.5 38.19 7.2 Main peak 69.7 31.8 38.97 6.64 67.83 63.76 59.15 38.14 48.07 22.29 58.02 56.44 7.3 Post-peak 10.22 5.69 5.79 NA 10.41 9.57 5.37 4.09 4.04 2.71 5.5 5.38 8 Content - (HPLC of Protein A) (%) 8.1 Total oxidized impurities 3.4 5 41.01 33.82 77.57 3.9 6 6.06 2.8 4 34.26 21.53 55.27 2.8 5 4.13 8.2 Main Peak 96.55 58.99 66.18 22.43 96.04 93.94 97.16 65.74 78.47 44.73 97.14 95.87 9 % of SPR assay (% of 115 NA NA 13.1 106 NA 89 NA NA 110.5 91 NA Relative Binding) ,7 5 * Clear, colorless solution, NA - not analyzed TABLE 3.J: Stability data for compositions 14 and 15 compared to RLD No. SN° B. / No. NIF Keytruda RLD U029039 14 15 Test Parameters / Conditions Initial I 1-cycle photostability 1-cycle photo 1°C + 6D 50°C 3-cycle photostability 6 M, 28°C 6 M, 25°C / 60% RH Initial I 1-cycle photostability 1-cycle photo 1°C + 6D 50°C 3-cycle photostability 6 M, 2-8°C 6 M, 25°C / 60% RH Initial I 1-cycle photostability 1-cycle photo 1°C + 6D 50°C 3-cycle photostability M, 28°C 6 M, 25°C / 60% RH 1 Description * * * * * * * * * * * * * * * * * * 2 pH 5, NA N NA 5, 5.56 5, 5.51 5, 5.50 5, 5.61 5, 5.42 5, 5.44 5, 5.51 46 / 50 Petition 870260076824, dated 07 / 31 / 2026, p. 54 / 108 55 A 41 50 52 56 42 41 54 3 Osmolality (mOsm) 24 9 NA NA NA 25 5 259 26 0 NA NA NA 26 4 268 25 9 NA NA NA 25 9 261 4 Protein Concentration (mg / mL) 24 ,1 NA N NA N NA 24 ,7 NA N NA N NA 24 ,6 NA N NA N NA 1 AA 7 AA 6 AA 5 Purity by SEC HPLC (%) 5.1 HMW 0.17 2.11 4.23 6.44 o.15 0.52 0.36 1.33 2.24 3.06 o. 68 0.77 0.33 2.35 2.18 2.73 0.69 0.88 99 95 99 99.4 O 99 97 99 99.2 O 99 97 99 99.1 9 5.2 Monomer 0.8 97.79 0.5 93.24 0.8 0.6 98.67 0.7 96.95 0.3 0.6 97.65 0.8 97.28 0.3 3 4 5 o 4 6 2 o 7 3 1 6 Cation Exchange Chromatography (%) 15 32 0.2 16 27.0 4 12 23 11 20.6 4 14 26 11 22.6 1 6.1 Acid Variants ,9 23.38 28.59 ,0 ,8 15.49 ,1 15.84 ,8 ,1 17.28 ,4 15.26 ,7 3 2 2 6 4 7 5 9 57 36 59 51.5 O 64 47 62 55.7 1 62 43 63 54.5 A 6.2 Main Peak ,8 37.99 ,0 25.14 ,4 ,0 50.75 ,7 39.95 ,9 ,1 45.08 ,4 39.64 ,1 4 6 2 □ 4 9 9 6 8 5 H- 26 31 24 21.4 23 29 25 23.6 c 23 30 25 82.8 5 6.3 Basic Variants ,2 38.63 ,7 46.27 ,5 ,1 33.74 ,0 44.20 ,1 ,6 37.64 ,0 45.11 ,0 2 4 7 2 6 7 7 O 5 8 6 7 Purity - by HIC (%) 20 55 21 26.6 O 20 38 21 21.0 4 21 39 21 20.2 9 7.1 Pre-peak ,0 62.52 ,2 93.35 ,7 ,9 41.08 ,7 60.90 ,7 ,0 49.92 ,3 61.39 ,8 8 3 5 □ 7 0 5 0 2 38 67 63.7 72 55 71 72.4 72 55 71 73.3 0 7.2 Main peak 69.7 31.8 9 6.64 8.7 53.98 7 35.16 >7.7 45.39 4 35.18 6 7 3 □ 0 7 2 O 3 1 6 Post-peak 10 5.79 10 6.33 5.53 6.51 6.22 5.29 6.52 7.3 2 5.69 NA 4 1 9.57 4.94 3.93 6.50 4.71 3.43 6.41 2. 47 / 50 Petition 870260076824, dated 07 / 31 / 2026, page 55 / 108 8. Protein A Content (HPLC) (%) 8.1 Total Oxidized Impurities 45 41.01 33.8 2 77.57 3 96 6.06 2.59 26.17 20.9 5 46.09 NA NA 2.59 34.97 23.0 6 47.46 NA NA 8.2 Main Peak 96.5 5 58.99 66.1 8 22.43 96.0 4 93.9 4 97.4 2 73.83 79.0 5 53.91 NA NA 97.4 0 65.03 76.9 3 52.53 NA NA 9 % of SPR assay (% of Binding) Relative) 11 5, 7 NA NA 13.1 10 6 NA 10 1 NA NA 77 97 NA 87 NA NA 89 10 1 NA 48 / 50 Petition 870260076824, dated 07 / 31 / 2026, page 56 / 108 49 / 50 * Clear, colorless solution, NA - not analyzed Determining the expiration date

[0117] The shelf life of any of the compositions described in 7-15 of the invention was measured by the stability of the active protein in the pharmaceutical composition that is stored under specified storage conditions, for example, 2-8 °C.

[0118] Each batch was stored at temperatures, for example, 2° to 8°C (refrigerator) and also subjected to an accelerated condition of 25+2) °C 60% RH (room temperature) to understand any impact on stability. The shelf life of the protein in the formulation was determined by the storage period during which the active protein undergoes minimal degradation when stored at 2-8°C. Protein degradation in a pharmaceutical composition can be detected using accelerated tests (also called stress tests) under exaggerated storage conditions designed to increase the rate of chemical or physical degradation of the pharmaceutical substance.

[0119] Samples from each batch of compositions 7-15 were then analyzed at different time points (e.g., time zero, 6 months) for the amount of therapeutic protein still present in the formulation compared to aggregates, fragments, or unfolded or misfolded protein. Samples stored under accelerated conditions, such as higher temperatures (25 ± 2 °C), were typically tested for degradation over time up to 6 months. For comparison, the same protein in compositions 7-15 containing osmolyte and stabilizer was monitored to determine the stability impact of such excipients on shelf life.

[0120] All compositions (7-15) reached pH 5.5 + 0.4 with a target of 5.5 except for compositions 11 and 13 which had a target pH of 6.0. The osmolality of all compositions 7-15 was in the range of 220-330 mOsm / kg. The data of Petition 870260076824, dated 07 / 31 / 2026, page 57 / 108 50 / 50 stability over 6 months suggests that HMW for all compositions was comparable to the reference product. Therapeutic protein analysis in the formulation was performed by a variety of detection methods: SEC-HPLC to understand HMM, Monomer, and LMW proteins; Cation-exchange chromatography to understand the impact of acidic and basic impurities; Hydrophobic interaction chromatography to understand any impact on the pre-peak and post-peak to the main peak; SPR assay in some cases; Protein A HPLC to understand oxidized impurities in some cases; or a combination of any of these methods, as mentioned in Tables 3.F-3.J.

[0121] Cation Exchange Chromatography (%) and Purity - by HIC (%) data suggest that compositions 7-15 do not show significantly different impurity trends. Total oxidized impurities were evaluated for NIF 7 to NIF 13, the data were comparable to those of the reference product. The % of the SPR assay (i.e., % of the Relative Bonding assay) was comparable to that of the reference product for all compositions. In general, similar results were observed for all compositions of the present invention (1-15) during different screening and stability studies. Generally, compositions 7-15 were comparable to the data of the reference product, except for compositions 4 and 6, where the sample precipitated during 1 exposure cycle Foto + 6D 50 °C. Petition 870260076824, dated 07 / 31 / 2026, page 58 / 108

Claims

1 / 9 CLAIMS 1. Stable liquid pharmaceutical composition CHARACTERIZED in that it comprises: (a) an anti-human PD1 antibody; (b) a sugar; (c) a buffer; and (d) a non-ionic surfactant.

2. Stable liquid pharmaceutical composition, according to claim 1, CHARACTERIZED in that the anti-PD1 antibody in the composition is at a concentration in the range of about 5 mg / mL to about 30 mg / mL.

3. Stable liquid pharmaceutical composition, according to claim 1, CHARACTERIZED in that the sugar in the composition is a non-reducing sugar selected from the group comprising sucrose, trehalose, α, α-trehalose dihydrate or mannitol.

4. Stable liquid pharmaceutical composition, according to claim 1, CHARACTERIZED in that the buffer in the composition is selected from the group comprising: citrate, L-Histidine, disodium succinate hexahydrate, succinic acid, sodium citrate, glacial acetic acid, citric acid monohydrate, citric adipic acid, L-Histidine, L-Histidine monohydrate HCl and / or succinic acid.

5. Stable liquid pharmaceutical composition according to claim 1, CHARACTERIZED in that the anti-PD-1 antibody is Nivolumab or Pembrolizumab.

6. Stable liquid pharmaceutical composition according to claim 1, CHARACTERIZED in that the anti-PD-1 antibody is Pembrolizumab.

7. Stable liquid pharmaceutical composition, according to claim 1, CHARACTERIZED in that the non-ionic surfactant in the composition is selected from the group comprising: Sodium Chloride, Disodium Edetate Petition 870250071943, dated 08 / 14 / 2025, page 58 / 70 2 / 9 dehydrated, Polysorbate 20, Polysorbate 80, Poloxamer 188, Disodium Edetate dihydrate or Polysorbate 80.

8. Stable liquid pharmaceutical composition, according to claim 1, CHARACTERIZED in that the sugar in the composition is present in a concentration of about 50 mg / ml to about 150 mg / ml.

9. Stable liquid pharmaceutical composition, according to claim 1, CHARACTERIZED in that the buffer in the composition is present in a concentration of about 0.05 mM to about 50 mM.

10. Stable liquid pharmaceutical composition, according to claim 1, CHARACTERIZED in that the buffer in the composition is present in a concentration of about 0.05 mM to 25 mM.

11. Stable liquid pharmaceutical composition, according to claim 1, CHARACTERIZED in that a non-ionic surfactant in the composition is present in a concentration in the range of about 0.01 mg / ml to about 2.0 mg / ml.

12. Stable liquid pharmaceutical composition, according to claim 1, CHARACTERIZED in that the composition has a pH of about 5.2 to about 6.

5.

13. Stable liquid pharmaceutical composition CHARACTERIZED in that it comprises: Pembrolizumab at a concentration in the range of about 5 mg / mL to about 30 mg / mL; α,α-trehalose dihydrate at a concentration of about 50 mg / mL to about 100 mg / mL; L-histidine at a concentration of about 0.5 mM to about 5 mM; L-Histidine HCl monohydrate at a concentration of about 5 mM to about 15 mM; and polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL; wherein said composition has a pH of about 5.2 to about 6.

5.

14. Stable liquid pharmaceutical composition CHARACTERIZED in that it comprises: Pembrolizumab in a concentration in the range of about 5 mg / mL to about 30 mg / mL; sucrose in a concentration of about 50 mg / mL to about 100 mg / mL; succinic acid in a concentration of about 5 mM to about 25 mM; disodium edetate dihydrate in a concentration of about 0.01 mg / mL to about 1.0 mg / mL; and polysorbate 80 in a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL; wherein said composition has a pH of about 5.2 to about 6.

5.

15. Stable liquid pharmaceutical composition CHARACTERIZED in that it comprises: Pembrolizumab in a concentration in the range of about 5 mg / mL to about 30 mg / mL; sucrose in a concentration of about 50 mg / mL to about 100 mg / mL; succinic acid in a concentration of about 0.05 mM to about 2 mM; disodium succinate hexahydrate in a concentration of about 0.5 mM to about 10 mM; and polysorbate 80 in a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL; wherein said composition has a pH of about 5.2 to about 6.

5.

16. Stable liquid pharmaceutical composition CHARACTERIZED in that it comprises: Pembrolizumab at a concentration in the range of about 5 mg / mL to about 30 mg / mL; sucrose at a concentration of about 50 mg / mL to about 100 mg / mL; glacial acetic acid at a concentration of about 5 mM to about 20 mM; and polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL; wherein said composition has a pH of about 5.2 to about 6.

5.

17. Stable liquid pharmaceutical composition CHARACTERIZED in that it comprises: Pembrolizumab in a concentration in the range of about 5 mg / mL to about 30 mg / mL; Mannitol in a concentration of about 5 mg / mL to about 15 mg / mL; Sodium Chloride in a concentration of about 5 mg / mL to about 10 mg / mL; Citric acid monohydrate in a concentration of about 0.5 mM to about 5 mM; Adipic acid in a concentration of about 5 mM to about 50 mM; and Polysorbate 80 in a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL; wherein said composition has a pH of about 5.2 to about 6.

5.

18. Stable liquid pharmaceutical composition CHARACTERIZED in that it comprises: Pembrolizumab at a concentration in the range of about 5 mg / mL to about 30 mg / mL; mannitol at a concentration of about 5 mg / mL to about 15 mg / mL; sodium chloride at a concentration of about 5 mg / mL to about 10 mg / mL; sodium citrate at a concentration of about 0.1 mM to about 5 mM; citric acid monohydrate at a concentration of about 3 mM to about 15 mM; and polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL; Petition 870250071943, dated 08 / 14 / 2025, p. 61 / 70 5 / 9 in which the aforementioned composition has a pH of approximately 5.2 to approximately 6.

5.

19. Stable liquid pharmaceutical composition CHARACTERIZED in that it comprises: Pembrolizumab in a concentration in the range of about 5 mg / mL to about 30 mg / mL; L-Histidine in a concentration of about 5 mM to about 15 mM; sodium chloride in a concentration of about 5 mg / mL to about 10 mg / mL; and polysorbate 80 in a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL: wherein said composition has a pH of about 5.2 to about 6.

5.

20. Stable liquid pharmaceutical composition CHARACTERIZED in that it comprises: Pembrolizumab in a concentration in the range of about 5 mg / mL to about 30 mg / mL; Sucrose in a concentration of about 50 mg / mL to about 100 mg / mL; L-Histidine in a concentration of about 0.5 mM to about 5 mM; L-Histidine HCl monohydrate in a concentration of about 5 mM to about 20 mM; and polysorbate 20 in a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL; wherein said composition has a pH of about 5.2 to about 6.

5.

21. Stable liquid pharmaceutical composition CHARACTERIZED in that it comprises: Pembrolizumab at a concentration in the range of about 5 mg / mL to about 30 mg / mL; Sucrose at a concentration of about 50 mg / mL to about 100 mg / mL; L-Histidine at a concentration of about 0.5 mM to about 5 mM; L-Histidine HCl monohydrate at a concentration of about 5 mM to about 20 mM; and Poloxamer 188 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL; wherein said composition has a pH of about 5.2 to about 6.

5.

22. Stable liquid pharmaceutical composition CHARACTERIZED in that it comprises: Pembrolizumab at a concentration in the range of about 5 mg / mL to about 30 mg / mL; Sucrose at a concentration of about 50 mg / mL to about 100 mg / mL; Glacial acetic acid at a concentration of about 0.5 mM to about 10 mM; Sodium acetate trihydrate at a concentration of about 2 mM to about 20 mM; and polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, wherein said composition has a pH of about 5.2 to about 6.

5.

23. Stable liquid pharmaceutical composition CHARACTERIZED in that it comprises: Pembrolizumab at a concentration in the range of about 5 mg / mL to about 30 mg / mL; sucrose at a concentration of about 50 mg / mL to about 100 mg / mL; anhydrous dibasic sodium phosphate at a concentration of about 0.05 mM to 5 mM; monobasic sodium phosphate monohydrate at a concentration of about 5 mM to about 20 mM; and polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL; wherein said composition has a pH of about 5.2 to about 6.

5.

24. Stable liquid pharmaceutical composition CHARACTERIZED in that it comprises: Pembrolizumab at a concentration in the range of about 5 mg / mL to about 30 mg / mL; Sucrose at a concentration of about 50 mg / mL to about 100 mg / mL; Succinic acid at a concentration of about 1 mM to about 10 mM; Sodium succinate hexahydrate at a concentration of about 2 mM to about 20 mM; and polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL; wherein said composition has a pH of about 5.2 to about 6.

5.

25. Stable liquid pharmaceutical composition CHARACTERIZED in that it comprises: Pembrolizumab at a concentration in the range of about 5 mg / mL to about 30 mg / mL; α,α-trehalose dihydrate at a concentration of about 50 mg / mL to about 100 mg / mL; anhydrous dibasic sodium phosphate at a concentration of about 0.05 mM to about 5 mM; monobasic sodium phosphate monohydrate at a concentration of about 5 mM to about 20 mM; and polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL; wherein said composition has a pH of about 5.2 to about 6.

5.

26. Stable liquid pharmaceutical composition CHARACTERIZED in that it comprises: Pembrolizumab at a concentration in the range of about 5 mg / mL to about 30 mg / mL; α,α-trehalose dihydrate at a concentration of about 50 mg / mL to about 100 mg / mL; Sodium acetate trihydrate at a concentration of about 2 mM to about 20 mM; Glacial acetic acid at a concentration of about 0.5 mM to about 10 mM; and polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL, wherein said composition has a pH of about 5.2 to about 6.

5.

27. Stable liquid pharmaceutical composition CHARACTERIZED in that it comprises: Pembrolizumab at a concentration in the range of about 5 mg / mL to about 30 mg / mL; α,α-trehalose dihydrate at a concentration of about 50 mg / mL to about 100 mg / mL; Succinic acid at a concentration of about 1 mM to about 10 mM; Sodium succinate hexahydrate at a concentration of about 2 mM to about 20 mM; and polysorbate 80 at a concentration in the range of about 0.05 mg / mL to about 2.0 mg / mL; wherein said composition has a pH of about 5.2 to about 6.

5.

28. Stable liquid pharmaceutical composition according to claim 1, CHARACTERIZED in that the composition is administered by intravenous administration, by subcutaneous administration or a combination thereof.

29. Stable liquid pharmaceutical composition according to claim 1, CHARACTERIZED in that the composition includes high concentrations of anti-PD1 antibody, or antigen-binding moieties thereof, and (a) a sugar; (b) a buffer; and (c) a nonionic surfactant.

30. Stable liquid pharmaceutical composition, according to claim Petition 870250071943, dated 08 / 14 / 2025, pp. 65 / 70 9 / 9 1, CHARACTERIZED in that the composition is used for the prophylaxis or treatment of a disease or disorder mediated by PD-1.

31. Stable liquid pharmaceutical composition, according to claim 1, CHARACTERIZED in that the composition is used for the prophylaxis or treatment of cancer.

32. Stable liquid pharmaceutical composition, according to claim 1, CHARACTERIZED in that the composition is used for the prophylaxis or treatment of a cancer that expresses PD-L1.

33. Stable liquid pharmaceutical composition, according to claim 1, CHARACTERIZED in that the composition is used for the prophylaxis or treatment of breast cancer, lung cancer, stomach cancer, intestinal cancer, kidney cancer and melanoma.

34. Stable liquid pharmaceutical composition, according to claim 1, CHARACTERIZED in that the composition is used for the prophylaxis or treatment of non-small cell lung cancer, melanoma and renal cancer. Petition 870250071943, dated 08 / 14 / 2025, pp. 66 / 70