CN-121987776-A - Anti-IL-23 p19 antibody formulations

Abstract

The present invention provides a liquid pharmaceutical formulation of an anti-IL-23 p19 antibody comprising a) 150 mg/ml of an anti-IL-23 p19 antibody, wherein the antibody comprises a light chain amino acid sequence according to SEQ ID No. 1 and a heavy chain amino acid sequence according to SEQ ID No. 2, b) a polyol, and c) a surfactant. The high concentration formulations disclosed herein advantageously have storage stability and are suitable for subcutaneous administration.

Inventors

• P. Garidel
• SCHULTZ-FADEMRECHT TORSTEN

Assignees

• 勃林格殷格翰国际有限公司

Dates

Publication Date

20260508

Application Date

20200909

Priority Date

20190909

Claims (10)

1. 1. A liquid pharmaceutical formulation comprising A) 150 mg/ml of an anti-IL-23 p19 antibody, wherein the antibody comprises a light chain amino acid sequence according to SEQ ID No. 1 and a heavy chain amino acid sequence according to SEQ ID No. 2; b) Polyhydric alcohol C) And (3) a surfactant.
2. 2. The formulation of claim 1, comprising D) A buffer.
3. 3. The formulation of claim 1 or 2, wherein the antibody is rituximab (risankizumab).
4. 4. A formulation as in any of claims 1-3, wherein the polyol is selected from the group consisting of sugar, sugar alcohol, and combinations thereof.
5. 5. The formulation of claim 4, wherein the polyol is selected from the group consisting of trehalose, sucrose, sorbitol, mannitol, and combinations thereof, optionally wherein the polyol is trehalose.
6. 6. The formulation according to one or more of claims 1 to 5, wherein the concentration of the polyol in the formulation is at least 95 mM, optionally in the range of 125 mM to 250 mM or 145 mM to 225 mM.
7. 7. The formulation of any one of claims 1 to 6, wherein the surfactant is a nonionic surfactant, optionally a polysorbate.
8. 8. The formulation according to one or more of claims 1 to 7, wherein the concentration of surfactant in the formulation is in the range of 0.05 mg/ml to 0.5 mg/ml, optionally in the range of 0.075 mg/ml to 0.4 mg/ml or 0.1 mg/ml to 0.3 mg/ml.
9. 9. The formulation of one or more of claims 1 to 8, wherein the pH of the liquid pharmaceutical formulation is in the range of pH 5.0 to 7.5, pH 5.0 to 7.0, or pH 5.2 to 6.5.
10. 10. The formulation of one or more of claims 1 to 9, wherein the pH of the liquid pharmaceutical formulation is in the range of 5.2 to 6.2, 5.5 to 5.9 or 5.6 to 5.8, optionally wherein the pH is 5.7.

Description

Anti-IL-23 p19 antibody formulations The application is a divisional application of Chinese patent application with the application date of 2020, 9 months and 9 days, chinese application number of 202080062754.3 and the application name of 'anti-IL-23 p19 antibody preparation'. Cross Reference to Related Applications The present application claims priority from U.S. provisional application No. 62/897,930 filed on 9/2019, which is incorporated herein in its entirety. Technical Field The present invention relates generally to formulations of anti-IL-23 p19 antibodies, such as rev Sha Zhu mab (risankizumab), comprising a p19 subunit that binds human IL-23. More particularly, pharmaceutical formulations comprising a high concentration of anti-IL-23 p19 antibody, rev Sha Zhu mab, and related products and uses for treating various diseases and disorders are disclosed. Disclosed herein are stable liquid pharmaceutical formulations comprising 150 mg/ml of the antibody rituximab. Background Human IL-23 is composed of a common subunit (p 40) with IL-12 and a unique p19 subunit. Although sharing the p40 subunit, the roles of IL-23 and IL-12 are quite different. IL-12 is critical for Th1 response by promoting differentiation, proliferation and activation of Th1 cells. In contrast, IL-23 supports the development and maintenance of the CD4 + T helper cell group, known as Th17 cells, because of the ability of the cells to produce IL-17 and related cytokines. IL-23 is involved in chronic autoimmune inflammation and modulation of IL-23 activity provides an effective therapy for autoimmune diseases. One of the autoimmune diseases in which IL-23 plays a major role is psoriasis, a chronic immune-mediated inflammatory disease characterized by excessive proliferation of keratinocytes and skin-infiltrating T lymphocytes that overexpress pro-inflammatory mediators. The disease is chronic painful immune-mediated inflammatory skin disease and has a life-long remitting and recurrent process with a triggering predisposing individual to worsening, thus making treatment a challenging variable. Uncontrolled inflammation of psoriasis may cause common co-occurrence disorders including Cardiovascular (CV) diseases (including hypertension and increased risk of myocardial infarction, stroke, and CV death), obesity, type 2 diabetes, arthritis, and chronic kidney disease. Psoriasis is also associated with severe psychotropic disorders including depression, anxiety and suicidal tendencies, and drug abuse. A highly potent and specific inhibitor of IL-23 is the antibody Rayleigh Sha Zhushan. The Rayleigh Sha Zhu mab is a humanized immunoglobulin G1 (IgG 1) monoclonal antibody directed against the p19 subunit of IL-23. Binding of anti-rayleigh Sha Zhushan to IL-23 p19 inhibits IL-23 induction and maintains the effects of T helper (Th) 17 cells, congenital lymphocytes, γδ T cells, and Natural Killer (NK) cells, which cause tissue inflammation, destruction, and abnormal tissue repair. Rayleigh Sha Zhushan is particularly effective in the treatment of autoimmune and inflammatory diseases, in particular psoriasis. Clinical studies reveal the excellent safety and efficacy of rui Sha Zhushan against plaque psoriasis in the treatment. The recommended dose approved for the treatment of psoriasis is 150 mg, which is administered subcutaneously with two 75 mg injections at weeks 0, 4 and every 12 weeks thereafter. The injection requirements of larger medicament volumes present challenges, especially in patients suffering from chronic conditions where the drug compliance and persistence ratio are significantly lower than in patients suffering from acute conditions. The subcutaneous route of administration is preferred for therapeutic indications requiring home (self) medication, for example for chronic diseases such as psoriasis. However, the subcutaneous route of administration is limited by the injection volume, which can be attributed to tissue backpressure and injection pain. This is also the case depending on the formulation injected. Most drugs such as rev Sha Zhu mab administered by subcutaneous injection are often used in unit doses not exceeding 1 ml in volume. Thus, for higher volumes such as greater than 2ml, multiple injections are typically used, but this approach may increase the rate of depletion or reduce patient compliance. Thus, to allow administration of high doses of antibodies such as rituximab with a single injection, pharmaceutical formulations with increased antibody concentrations are needed. However, increasing the concentration of antibodies in an antibody formulation may cause stability problems, such as aggregation and increased viscosity resulting in the formation of High Molecular Weight Species (HMWS). Thus, it is a great challenge to provide stable high concentration liquid antibody formulations suitable for parenteral administration, such as subcutaneous injection. Disclosure of Invention The present invention provides a liq