JPWO2019217927A5 - - Google Patents

Claims (24)

Aqueous pharmaceutical product:
A VEGF receptor fusion protein at a concentration of at least about 100 mg / ml, each containing an immunoglobulin-like (Ig) domain 2 of VEGFR1, an Ig domain 3 of VEGFR2, and two polypeptides containing a multimerizing component;
About 5% sucrose;
L-Arginine;
Histidine buffer; and approximately 0.03% surfactant;
Including
The formulation has a pH of about 5.0 to about 6.8.
The above formulation. The preparation according to claim 1, which is suitable for intravitreal administration. The preparation according to claim 1, further comprising sodium sulfate, sodium thiocyanate, glycine, NaCl, sodium aspartate, and / or sodium glutamate. The preparation according to claim 1, wherein the VEGF receptor fusion protein comprises amino acids 27 to 457 of SEQ ID NO: 2. The preparation according to claim 1, wherein the VEGF receptor fusion protein is Convercept. The preparation according to claim 1, wherein the VEGF receptor fusion protein is aflibercept. Aflibercept has the following concentrations:
-Approximately 100 mg / ml;
-Approximately 111.5 mg / ml;
Approximately 112.0 mg / ml;
-Approximately 113.3 mg / ml;
-Approximately 114.3 mg / ml;
-Approximately 115.6 mg / ml;
-Approximately 116.3 mg / ml;
-Approximately 120 mg / ml;
-Approximately 133 mg / ml;
・ Approximately 140 mg / ml;
・ Approximately 150 mg / ml;
-Approximately 200 mg / ml;
・ Approximately 250 mg / ml;
-Contains about 4 mg of aflibercept in less than about 40 μl;
-Contains about 6 mg of aflibercept in less than about 60 μl;
-Contains about 8 mg of aflibercept in about 80 μl or less; or-contains about 10 mg of aflibercept in about 100 μl or less;
The preparation according to claim 6. (I) 17. pharmaceutical formulation. The preparation according to claim 1, wherein the pH is 5.8 to 6.5. The preparation according to claim 9, wherein the pH is about 5.8. The preparation according to claim 1, wherein the surfactant is a nonionic surfactant. The preparation according to claim 11, wherein the nonionic surfactant is selected from the group consisting of polysorbate 20, polysorbate 80, poloxamer 188, polyethylene glycol 3350 and a mixture thereof. The preparation according to claim 1, wherein the histidine-based buffer solution contains histidine hydrochloride. The preparation according to claim 13, which comprises a histidine-based buffer solution of about 10 mM to 20 mM. The preparation according to claim 1, wherein L-arginine is L-arginine monohydrochloride. Claimed that the VEGF receptor fusion protein has a high molecular weight species of less than about 3.5% immediately after production and purification and / or a high molecular weight species of about 6% or less after storage at about 2-8 ° C. for about 24 months. Item 1. The preparation according to Item 1. Aqueous pharmaceutical product:
A VEGF receptor fusion protein at a concentration of at least about 100 mg / ml, each containing an immunoglobulin-like (Ig) domain 2 of VEGFR1, an Ig domain 3 of VEGFR2, and two polypeptides containing a multimerizing component;
About 10-100 mM L-arginine;
sucrose;
Histidine buffer; and surfactant;
Including
The formulation has a pH of about 5.0 to about 6.8;
The VEGF receptor fusion protein has a high molecular weight species of less than about 3.5% immediately after production and purification and / or a high molecular weight species of about 6% or less after storage at about 2-8 ° C. for about 24 months.
The above formulation. The preparation according to claim 17, wherein the VEGF receptor fusion protein is aflibercept. The preparation according to claim 17, wherein the VEGF receptor fusion protein is Convercept. A container or injection device comprising the pharmaceutical product according to claim 17. The container or injection device according to claim 20, wherein the injection device is a prefilled syringe. The method for preparing the pharmaceutical product according to claim 17, wherein the VEGF receptor fusion protein, L-arginine, sucrose, histidine buffer, and detergent are mixed to form a single aqueous composition. The above method comprising the steps. 22. The method of claim 22, further comprising loading a syringe with a volume of pharmaceutical product. A pharmaceutical product, which is a product of the method according to claim 22.