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KR-102962504-B1 - Pharmaceutical composition containing antibody against IL-5 and use thereof

KR102962504B1KR 102962504 B1KR102962504 B1KR 102962504B1KR-102962504-B1

Abstract

The present application discloses a pharmaceutical composition containing an antibody against IL-5 and the use thereof. In particular, the present application discloses a pharmaceutical composition containing an IL-5 antibody or an antigen-binding fragment thereof in a buffer solution. Furthermore, the pharmaceutical composition additionally contains a saccharide and a nonionic surfactant.

Inventors

  • 우, 팅팅
  • 리, 하오
  • 리우, 쉰
  • 타오, 웨이캉

Assignees

  • 지앙수 헨그루이 파마슈티컬스 컴퍼니 리미티드
  • 샹하이 헨그루이 파마수티컬 컴퍼니 리미티드

Dates

Publication Date
20260507
Application Date
20200327
Priority Date
20190329

Claims (20)

  1. As a pharmaceutical composition, (a) anti-IL-5 antibody or its antigen-binding fragment; (b) a buffer, wherein the buffer is an acetate-sodium acetate or succinate-sodium succinate buffer, the pH of the buffer is 5.0 to 6.5, and the concentration of the buffer is 10 mM to 40 mM; (c) a surfactant, wherein the surfactant is polysorbate 80, and the concentration of polysorbate 80 is 0.1 mg/ml to 0.6 mg/ml; and (d) Stabilizer, wherein the stabilizer is sucrose, and the sucrose concentration is 50 mg/ml to 80 mg/ml. Including; The anti-IL-5 antibody or its antigen-binding fragment is A heavy chain variable region comprising HCDR1, HCDR2, and HCDR3 as indicated by amino acid sequence SEQ ID NOs: 16, 17, and 18, respectively, and A pharmaceutical composition comprising a light chain variable region including LCDR1, LCDR2, and LCDR3 as indicated by amino acid sequence SEQ ID NO: 19, 20, and 21, respectively.
  2. A pharmaceutical composition according to claim 1, wherein the pH of the buffer is 5.0 to 5.8.
  3. A pharmaceutical composition according to paragraph 2, wherein the pH of the buffer is 5.5.
  4. A pharmaceutical composition according to claim 1, wherein the concentration of the buffer is 20 mM to 30 mM.
  5. A pharmaceutical composition according to claim 1, wherein the concentration of the buffer is 30 mM or 32 mM.
  6. A pharmaceutical composition according to claim 1, wherein the concentration of the anti-IL-5 antibody or its antigen-binding fragment is 1 mg/ml to 120 mg/ml.
  7. A pharmaceutical composition according to claim 6, wherein the concentration of the anti-IL-5 antibody or its antigen-binding fragment is 80 mg/ml to 120 mg/ml.
  8. A pharmaceutical composition according to claim 7, wherein the concentration of the anti-IL-5 antibody or its antigen-binding fragment is 100 mg/ml.
  9. A pharmaceutical composition according to claim 1, wherein the concentration of polysorbate 80 is 0.2 mg/ml to 0.6 mg/ml.
  10. A pharmaceutical composition according to claim 9, wherein the concentration of polysorbate 80 is 0.4 mg/ml to 0.6 mg/ml.
  11. A pharmaceutical composition according to claim 1, wherein the concentration of sucrose is 70 mg/ml to 75 mg/ml.
  12. A pharmaceutical composition according to claim 11, wherein the concentration of sucrose is 72 mg/ml.
  13. In paragraph 1, 80 mg/ml to 120 mg/ml of anti-IL-5 antibody or its antigen-binding fragment, As a sodium acetate buffer of 10 mM to 30 mM, having a pH of 5.0 to 5.8, a sodium acetate buffer, Polysorbate 80 at 0.2 mg/ml to 0.6 mg/ml, and 70 mg/ml to 80 mg/ml of sucrose A pharmaceutical composition comprising
  14. A pharmaceutical composition according to claim 1, wherein the anti-IL-5 antibody or its antigen-binding fragment is a murine antibody, a chimeric antibody, or a humanized antibody.
  15. In paragraph 14, the humanized anti-IL-5 antibody is A heavy chain variable region that is the same as indicated by any one of SEQ ID NO: 49, 50, and 51, or has 95% sequence identity with any one of SEQ ID NO: 49, 50, and 51; and A light chain variable region that is the same as indicated by any one of SEQ ID NO: 46, 47, and 48, or has 95% sequence identity with any one of SEQ ID NO: 46, 47, and 48. A pharmaceutical composition comprising
  16. In paragraph 15, the humanized anti-IL-5 antibody is Heavy chain variable region as indicated by SEQ ID NO: 51 and light chain variable region as indicated by SEQ ID NO: 47 A pharmaceutical composition comprising
  17. A pharmaceutical composition according to claim 1, wherein the anti-IL-5 antibody comprises human antibody constant region(s).
  18. A pharmaceutical composition according to claim 1, wherein the anti-IL-5 antibody comprises a human antibody heavy chain constant region as indicated by SEQ ID NO: 52 and a human antibody light chain constant region as indicated by SEQ ID NO: 53.
  19. In paragraph 17, the anti-IL-5 antibody is Heavy chain as indicated by SEQ ID NO: 83 and light chain as indicated by SEQ ID NO: 84 A pharmaceutical composition comprising
  20. A method for preparing a pharmaceutical composition according to claim 1, comprising the step of replacing a stock solution of an anti-IL-5 antibody or an antigen-binding fragment thereof with a buffer, wherein the buffer is a sodium acetate buffer.

Description

Pharmaceutical composition containing antibody against IL-5 and use thereof The present disclosure belongs to the field of pharmaceutical formulations and, in particular, relates to pharmaceutical compositions comprising an anti-IL-5 antibody or an antigen-binding fragment thereof, and to the use thereof as diagnostic agents and therapeutic drugs for IL-5-related disease(s). The description herein provides only background information related to the present disclosure and does not necessarily constitute prior art. Interleukin-5 (IL-5) is one of the important members of the interleukin family, also known as T cell replacing factor (TRF), B cell growth factor-II (BCGF-II), IgA-enhancing factor (IgA-EF), or eosinophil differentiation factor (EDF), and is a homo-dimeric glycoprotein primarily secreted by helper T cell 2 (Th2). Human IL-5 consists of 134 amino acid residues, including a signal peptide composed of 22 amino acids and two glycosylation sites. Active IL-5 exists in the form of an oligo-dimer, where the two peptide chains are connected by disulfide bonds and exist in an antiparallel configuration; IL-5 monomers do not have biological activity (Reference [Adv Immunol. 1994; 57: 145-90]). Eosinophils (EOS) are associated with various inflammatory diseases of the lungs, including allergic diseases related to allergic reactions. Asthma is a chronic inflammatory respiratory disease. Globally, there are approximately 300 million patients, with an incidence rate of 10%. The pathogenesis of asthma is associated with various cytokines. IL-5 and its receptor, IL-5R, play a significant role in the pathogenesis of asthma. Currently, the most effective way to treat asthma is to reduce lung inflammation by administering sterols via nasal or oral routes to inhibit the expression of several key mediators (including IL-5) involved in asthma. However, the long-term use of steroid drugs carries many side effects. Therefore, it is necessary to find novel pharmacological targets for the treatment of asthma. Studies show that the administration of anti-IL-5 antibodies inhibits the binding of IL-5 to its receptor; significantly reduces the accumulation of eosinophils in the lungs; and decreases the levels of eosinophils in blood, tissues, and sputum; It is confirmed to reduce eosinophil-mediated inflammatory responses; improve lung function; and have excellent effects on severe eosinophilic asthma and recurrent asthma (Drugs. 2017 May; 77(7):777-784). Antibody drugs possess large molecular weights and complex structures. During production, transport, and storage, antibodies often face problems caused by denaturation, aggregation, contamination, and particle formation. To effectively maintain antibodies, their biological activity must be preserved during production, purification, transport, and storage. Currently, new technologies for production and purification have been developed to mass-produce highly purified monoclonal antibodies. However, methods to stabilize these antibodies for transport and storage and provide them in dosage forms suitable for administration have always been a challenge. Currently, the only anti-IL-5 antibodies available on the market are Mepolizumab from GSK and Reslizumab from Teva Pharma. Relevant patents include WO2018119016, WO2017033121, WO2014141149, WO2016040007, WO2015095539, WO2012138958, and WO9535375. The present disclosure provides a pharmaceutical composition comprising an IL-5 antibody or an antigen-binding fragment thereof, a buffer, and a surfactant, wherein the buffer is any one selected from the group consisting of sodium acetate, sodium succinate, histidine hydrochloride, and sodium citrate buffers, preferably sodium acetate or sodium succinate buffers; and the anti-IL-5 antibody or the antigen-binding fragment thereof comprises a heavy chain variable region and a light chain variable region, wherein: (i) The heavy chain variable region comprises HCDR1, HCDR2, and HCDR3 as indicated by amino acid sequence SEQ ID NO: 16, 17, and 18, respectively, and The light chain variable region comprises LCDR1, LCDR2, and LCDR3 as indicated by amino acid sequence SEQ ID NO: 19, 20, and 21, respectively; (ii) The heavy chain variable region comprises HCDR1, HCDR2, and HCDR3 as indicated by amino acid sequence SEQ ID NO: 22, 23, and 24, respectively, and The light chain variable region comprises LCDR1, LCDR2, and LCDR3 as indicated by amino acid sequence SEQ ID NO: 25, 26, and 27, respectively; (iii) The heavy chain variable region comprises HCDR1, HCDR2, and HCDR3 as indicated by amino acid sequence SEQ ID NO: 28, 29, and 30, respectively, and The light chain variable region comprises LCDR1, LCDR2, and LCDR3 as indicated by amino acid sequence SEQ ID NO: 31, 32, and 33, respectively; (iv) The heavy chain variable region comprises HCDR1, HCDR2, and HCDR3 as indicated by amino acid sequence SEQ ID NO: 34, 35, and 36, respectively, and The light chain variable region comprises LCDR1, LCDR2, and LC