Antibody formulation and use thereof

Abstract

A liquid formulation, comprising an anti-IgE antibody, a buffer, a stabilizer and a surfactant, wherein the buffer is selected from a histidine / histidine hydrochloric acid buffer, an acetic acid / sodium acetate buffer and / or a histidine / sodium acetate buffer, the stabilizer is selected from sorbitol and / or sucrose, and the surfactant is selected from polysorbate 20 and / or polysorbate 80. Further provided are a freeze-dried formulation comprising the liquid formulation, and the use of the liquid formulation or freeze-dried reagent in the prevention, diagnosis and / or treatment of diseases.

Description

An antibody preparation and its uses Technical Field

[0001] This application relates to the field of biomedicine, specifically to an antibody preparation and its uses. Background Technology

[0002] Allergies and other allergic reactions are inappropriate or excessive immune responses to foreign antigens. Inappropriate immune responses include those that are misdirected against the body's own components, leading to autoimmune diseases. Allergic diseases (also known as atopic dermatitis) are the sixth leading cause of chronic disease worldwide, affecting a variety of organs and tissues. Once they flare up, they cause a range of uncomfortable symptoms, severely reducing quality of life and even endangering life. Examples include allergic reactions, allergic rhinitis, asthma, hereditary atopic dermatitis, food allergies, and rubella. Allergic diseases are broadly classified into IgE-mediated and IgE-non-mediated, with immunoglobulin E (IgE)-mediated hypersensitivity reactions being the most common. Because IgE plays a crucial role in mediating most allergic reactions, developing treatment strategies that target IgE levels in allergic diseases is essential.

[0003] Currently, antibodies developed targeting IgE may suffer from protein aggregation, degradation, denaturation, or chemical modification during manufacturing, storage, transportation, or use, resulting in a loss of biological activity. Furthermore, antibody molecules may form soluble or insoluble protein aggregates, potentially triggering undesirable immune responses after administration. Therefore, to better treat related diseases, there is an urgent need to develop new formulations of stable anti-IgE antibodies to address these issues. Summary of the Invention

[0004] This application provides a formulation. In this application, the formulation has one or more of the following properties: (1) high purity; (2) good thermal stability; (3) good long-term stability; (4) good photostability.

[0005] On one hand, this application provides a liquid formulation comprising:

[0006] (1) An antibody, wherein the antibody comprises three complementarity-determining regions HCDR1, HCDR2 and HCDR3 of the antibody heavy chain variable region, and three complementarity-determining regions LCDR1, LCDR2 and LCDR3 of the antibody light chain variable region, wherein the amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:51, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:52, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:53;

[0007] (2) Buffer solution, wherein the buffer solution is selected from histidine / histidine hydrochloride buffer (His / His-HCl), acetate / sodium acetate buffer (HAc / NaAc) and / or histidine / sodium acetate buffer (His / NaAc);

[0008] (3) a stabilizer, wherein the stabilizer is selected from sorbitol and / or sucrose; and

[0009] (4) A surfactant, wherein the surfactant is selected from polysorbate 20 (PS20) and / or polysorbate 80 (PS80).

[0010] In some embodiments, the buffer solution is His / His-HCl.

[0011] In some embodiments, the concentration of the buffer solution is about 0-100 mM.

[0012] In some embodiments, the concentration of the buffer solution is about 5-20 mM.

[0013] In some embodiments, the concentration of the buffer solution is about 8-12 mM.

[0014] In some implementations, the buffer solution is provided with a pH of 5-7.

[0015] In some implementations, the buffer solution is provided with a pH of 5.3-6.4.

[0016] In some embodiments, the buffer solution is provided with a pH of 5.4-6.4.

[0017] In some embodiments, the stabilizer is sorbitol.

[0018] In some embodiments, the stabilizer content is about 2-10% (w / v).

[0019] In some embodiments, the stabilizer content is about 3%-5.5% (w / v).

[0020] In some embodiments, the stabilizer content is about 4.5%-5.5% (w / v).

[0021] In some embodiments, the surfactant is PS80.

[0022] In some embodiments, the surfactant content is about 0-0.1% (w / v).

[0023] In some embodiments, the surfactant content is about 0.005%-0.02% (w / v).

[0024] In some embodiments, the surfactant content is about 0.01%-0.02% (w / v).

[0025] In some embodiments, the antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are selected from any of the following combinations:

[0026] 1) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:10, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:11.

[0027] 2) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:26, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30; and

[0028] 3) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30.

[0029] In some embodiments, the antibody comprises a heavy chain variable region VH and a light chain variable region VL, wherein the amino acid sequence of VH is shown in SEQ ID NO:8, SEQ ID NO:21, SEQ ID NO:28, SEQ ID NO:37 or SEQ ID NO:41, and the amino acid sequence of VL is shown in SEQ ID NO:16, SEQ ID NO:25, SEQ ID NO:35 or SEQ ID NO:40.

[0030] In some embodiments, the antibody comprises VH and VL, the amino acid sequences of which are selected from any combination of the following:

[0031] 1) The amino acid sequence of VH is shown in SEQ ID NO:8, and the amino acid sequence of VL is shown in SEQ ID NO:16;

[0032] 2) The amino acid sequence of VH is shown in SEQ ID NO:21, and the amino acid sequence of VL is shown in SEQ ID NO:25;

[0033] 3) The amino acid sequence of VH is shown in SEQ ID NO:28, and the amino acid sequence of VL is shown in SEQ ID NO:35;

[0034] 4) The amino acid sequence of VH is shown in SEQ ID NO:37, and the amino acid sequence of VL is shown in SEQ ID NO:40; and

[0035] 5) The amino acid sequence of VH is shown in SEQ ID NO:41, and the amino acid sequence of VL is shown in SEQ ID NO:40.

[0036] In some embodiments, the antibody comprises a heavy chain and a light chain, the amino acid sequence of the heavy chain being as shown in SEQ ID NO:45, SEQ ID NO:47 or SEQ ID NO:49, and the amino acid sequence of the light chain being as shown in SEQ ID NO:46 or SEQ ID NO:48.

[0037] In some embodiments, the antibody comprises a heavy chain and a light chain, the amino acid sequences of which are selected from any combination of the following:

[0038] 1) The amino acid sequence of the heavy chain is shown in SEQ ID NO:45, and the amino acid sequence of the light chain is shown in SEQ ID NO:46;

[0039] 2) The amino acid sequence of the heavy chain is shown in SEQ ID NO:47, and the amino acid sequence of the light chain is shown in SEQ ID NO:48; and

[0040] 3) The amino acid sequence of the heavy chain is shown in SEQ ID NO:49, and the amino acid sequence of the light chain is shown in SEQ ID NO:48.

[0041] In some embodiments, the concentration of the antibody is about 10-200 mg / mL.

[0042] In some embodiments, the concentration of the antibody is about 50-150 mg / mL.

[0043] In some embodiments, the concentration of the antibody is about 90-110 mg / mL.

[0044] In some embodiments, the antibody is an anti-IgE antibody.

[0045] In some embodiments, the formulation also includes an antioxidant.

[0046] In some embodiments, the antioxidant is methionine.

[0047] In some embodiments, the concentration of the antioxidant is about 0-20 mM.

[0048] In some embodiments, the concentration of the antioxidant is about 0-10 mM.

[0049] On the other hand, this application provides a unit dosage form containing:

[0050] (1) 10-200 mg / mL anti-IgE antibody;

[0051] (2) His / His-HCl, which provides a pH of 5-7;

[0052] (3) 2-10% (w / v) sorbitol; and

[0053] (4) 0-0.1% (w / v) PS80,

[0054] The anti-IgE antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3. The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:51, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:52, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:53.

[0055] On the other hand, this application provides a unit dosage form containing:

[0056] (1) 50-150 mg / mL anti-IgE antibody;

[0057] (2) His / His-HCl, which provides a pH of 5.3-6.4;

[0058] (3) 3%-5.5% (w / v) sorbitol; and

[0059] (4)0.005%-0.02%(w / v)PS80,

[0060] The anti-IgE antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are selected from any of the following combinations:

[0061] 1) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:10, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:11.

[0062] 2) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:26, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30; and

[0063] 3) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30.

[0064] On the other hand, this application provides a unit dosage form containing:

[0065] (1) 10-200 mg / mL anti-IgE antibody;

[0066] (2) 0-100mM His / His-HCl, which provides a pH of 5-7;

[0067] (3) 2-10% (w / v) sorbitol;

[0068] (4) 0-0.1% (w / v) PS80; and

[0069] (5) 0-20mM methionine,

[0070] The anti-IgE antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3. The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:51, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:52, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:53.

[0071] On the other hand, this application provides a unit dosage form containing:

[0072] (1) 50-150 mg / mL anti-IgE antibody;

[0073] (2) 5-20 mM His / His-HCl, which provides a pH of 5.3-6.4;

[0074] (3) 3%-5.5% (w / v) sorbitol;

[0075] (4) 0.005%-0.02% (w / v) PS80; and

[0076] (5) 0-10mM methionine,

[0077] The anti-IgE antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are selected from any of the following combinations:

[0078] 1) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:10, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:11.

[0079] 2) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:26, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30; and

[0080] 3) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30.

[0081] On the other hand, this application provides a lyophilized formulation comprising the liquid formulation and a lyophilization protectant.

[0082] On the other hand, this application provides a kit comprising the liquid formulation and / or the lyophilized formulation, and a container for holding the liquid formulation and / or the lyophilized formulation.

[0083] On the other hand, this application provides methods for preparing the liquid formulation, the lyophilized formulation, and / or the kit.

[0084] In some embodiments, the liquid or lyophilized formulation is intended for intraperitoneal, intraspinal, intra-articular, intrasynovial, intrathecal, oral, topical, inhalation, subcutaneous, intramuscular, or intravenous administration.

[0085] On the other hand, this application provides the use of the liquid formulation or the lyophilized formulation in the preparation of a medicament for the prevention, diagnosis and / or treatment of a disease.

[0086] In some implementations, the disease is an IgE-related disease.

[0087] In some implementations, the disease is asthma, chronic urticaria, food allergy, nasal polyps, and / or allergic rhinitis.

[0088] On the other hand, this application provides a method for preventing, diagnosing and / or treating diseases, which includes administering the liquid formulation or the lyophilized formulation to a subject in need.

[0089] In some implementations, the disease is an IgE-related disease.

[0090] In some implementations, the disease is asthma, chronic urticaria, food allergy, nasal polyps, and / or allergic rhinitis.

[0091] On the other hand, this application provides the liquid formulation or the lyophilized formulation for the prevention, diagnosis and / or treatment of diseases.

[0092] In some implementations, the disease is an IgE-related disease.

[0093] In some implementations, the disease is asthma, chronic urticaria, food allergy, nasal polyps, and / or allergic rhinitis.

[0094] Other aspects and advantages of this application will readily be apparent to those skilled in the art from the detailed description below. Only exemplary embodiments of this application are shown and described in the following detailed description. As will be appreciated by those skilled in the art, the content of this application enables them to make modifications to the disclosed specific embodiments without departing from the spirit and scope of the invention to which this application pertains. Accordingly, the descriptions in the accompanying drawings and specification of this application are merely exemplary and not restrictive. Attached Figure Description

[0095] The specific features of the invention involved in this application are shown in the appended claims. The features and advantages of the invention can be better understood by referring to the exemplary embodiments and drawings described in detail below. A brief description of the drawings is as follows:

[0096] Figure 1 shows the SE-HPLC purity detection results of the formulations described in this application under different pH buffers.

[0097] Figure 2 shows the purity test results of the nrCE-SDS formulations under different pH buffers described in this application.

[0098] Figure 3 shows the results of rCE-SDS purity testing for the formulations described in this application under different pH buffers.

[0099] Figure 4A shows the SE-HPLC main peak percentage of the formulation described in this application as a function of pH and buffer system; Figure 4B shows the SE-HPLC HMWS percentage of the formulation described in this application as a function of pH and buffer system.

[0100] Figure 5A shows the results of the change of nrCE-SDS main peak % of the formulation described in this application with pH and buffer system; Figure 5B shows the results of the change of nrCE-SDS HMWS% of the formulation described in this application with pH and buffer system.

[0101] Figure 6 shows the results of the rCE-SDS(LC+HC)% of the formulation described in this application as a function of pH and buffer system.

[0102] Figure 7A shows the change of the icIEF main peak % of the formulation described in this application with pH and buffer system; Figure 7B shows the change of the icIEF acidic peak % of the formulation described in this application with pH and buffer system; Figure 7C shows the change of the icIEF alkaline peak % of the formulation described in this application with pH and buffer system.

[0103] Figure 8A shows the SE-HPLC main peak % of the formulation described in this application as a function of excipients; Figure 8B shows the SE-HPLC HMWS% of the formulation described in this application as a function of excipients; Figure 8C shows the SE-HPLC LMWS% of the formulation described in this application as a function of excipients.

[0104] Figure 9A shows the change of the % of the main peak of icIEF in the formulation described in this application with the excipients; Figure 9B shows the change of the % of the acidic peak of icIEF in the formulation described in this application with the excipients; Figure 9C shows the change of the % of the basic peak of icIEF in the formulation described in this application with the excipients.

[0105] Figure 10A shows the detection results of insoluble particulate matter at different PS20 concentrations as described in this application; Figure 10B shows the detection results of insoluble particulate matter at different PS80 concentrations as described in this application.

[0106] Figure 11 shows the SE-HPLC results of the formulation described in this application under different light conditions, with the change of the percentage of the main peak as a function of the surfactant.

[0107] Figure 12 shows the detection results of insoluble microparticles in the formulation described in this application under different light conditions.

[0108] Figure 13A shows the SE-HPLC protein purity detection results of the formulation described in this application under different light conditions; Figure 13B shows the SE-HPLC polymer detection results of the formulation described in this application under different light conditions.

[0109] Figure 14A shows the results of the change of nrCE-SDS main peak % with antioxidant under different light conditions of the formulation described in this application; Figure 14B shows the results of the change of nrCE-SDS HMWS% with antioxidant under different light conditions of the formulation described in this application.

[0110] Figure 15 shows the results of the rCE-SDS main peak % of the formulation described in this application changing with antioxidants under different light conditions.

[0111] Figure 16A shows the change of the % of the main peak of icIEF in the formulation described in this application with antioxidants under different light conditions; Figure 16B shows the change of the % of the acidic peak of icIEF in the formulation described in this application with antioxidants under different light conditions; Figure 16C shows the change of the % of the basic peak of icIEF in the formulation described in this application with antioxidants under different light conditions.

[0112] Figure 17A shows the SE-HPLC main peak percentage of the formulation described in this application as a function of antioxidants under different temperature conditions; Figure 17B shows the SE-HPLC HMWS percentage of the formulation described in this application as a function of antioxidants under different temperature conditions.

[0113] Figure 18A shows the results of the change of nrCE-SDS main peak % with antioxidant under different temperature conditions of the formulation described in this application; Figure 18B shows the results of the change of nrCE-SDS HMWS% with antioxidant under different temperature conditions of the formulation described in this application.

[0114] Figure 19A shows the results of the rCE-SDS main peak % of the formulation described in this application changing with antioxidants under different temperature conditions; Figure 19B shows the results of the rCE-SDS HMWS% of the formulation described in this application changing with antioxidants under different temperature conditions.

[0115] Figure 20A shows the variation of the icIEF main peak % with antioxidants under different temperature conditions of the formulation described in this application; Figure 20B shows the variation of the icIEF acidic peak % with antioxidants under different temperature conditions of the formulation described in this application; Figure 20C shows the variation of the icIEF basic peak % with antioxidants under different temperature conditions of the formulation described in this application.

[0116] Figure 21A shows the SE-HPLC main peak percentage of the formulation described in this application as a function of protein concentration under different temperature conditions; Figure 21B shows the SE-HPLC HMWS percentage of the formulation described in this application as a function of protein concentration under different temperature conditions.

[0117] Figure 22A shows the results of the change of nrCE-SDS main peak % with protein concentration under different temperature conditions of the formulation described in this application; Figure 22B shows the results of the change of nrCE-SDS HMWS% with protein concentration of the formulation described in this application under different temperature conditions.

[0118] Figure 23 shows the results of the rCE-SDS main peak % change with protein concentration under different temperature conditions for the formulation described in this application.

[0119] Figure 24A shows the change of icIEF main peak % with protein concentration under different temperature conditions of the formulation described in this application; Figure 24B shows the change of icIEF acidic peak % with protein concentration under different temperature conditions of the formulation described in this application.

[0120] Figure 25 shows the SE-HPLC results of the formulation described in this application under different temperature conditions, where the percentage of the main peak changes with the concentration of sorbitol.

[0121] Figure 26 shows the results of the change of the nrCE-SDS main peak % with sorbitol concentration under different temperature conditions for the formulation described in this application.

[0122] Figure 27 shows the results of the rCE-SDS main peak % change with sorbitol concentration under different temperature conditions for the formulation described in this application.

[0123] Figure 28A shows the change of icIEF main peak % with sorbitol concentration under different temperature conditions of the formulation described in this application; Figure 28B shows the change of icIEF acid peak % with sorbitol concentration of the formulation described in this application under different temperature conditions.

[0124] Figure 29 shows the SE-HPLC results of the formulation described in this application under different temperature conditions, where the percentage of the main peak changes with the concentration of Met.

[0125] Figure 30 shows the results of the change of nrCE-SDS main peak % with Met concentration under different temperature conditions of the formulation described in this application.

[0126] Figure 31 shows the results of the rCE-SDS main peak % change with Met concentration under different temperature conditions of the formulation described in this application.

[0127] Figure 32A shows the change of icIEF main peak % with Met concentration under different temperature conditions of the formulation described in this application; Figure 32B shows the change of icIEF acid peak % with Met concentration of the formulation described in this application under different temperature conditions.

[0128] Figure 33 shows the SE-HPLC results of the main peak percentage of the formulation described in this application changing with pH under different temperature conditions.

[0129] Figure 34 shows the results of the change of nrCE-SDS main peak % with pH under different temperature conditions for the formulation described in this application.

[0130] Figure 35 shows the results of the rCE-SDS main peak % change with pH under different temperature conditions for the formulation described in this application.

[0131] Figure 36A shows the change of icIEF main peak % with pH under different temperature conditions for the formulation described in this application; Figure 36B shows the change of icIEF acidic peak % with pH under different temperature conditions for the formulation described in this application.

[0132] Figure 37 shows the changes in the percentage of the main peak of nrCE-SDS in the formulation described in this application under different temperature conditions.

[0133] Figure 38 shows the changes in the % of the main peak of rCE-SDS in the formulation described in this application under different temperature conditions.

[0134] Figure 39 shows the SE-HPLC results of the main peak % change of the formulation described in this application under different temperature conditions.

[0135] Figure 40 shows the changes in the % of the main peak of icIEF in the formulation described in this application under different temperature conditions. Detailed Implementation

[0136] The following specific embodiments illustrate the implementation of the invention. Those skilled in the art can easily understand other advantages and effects of the invention from the content disclosed in this specification.

[0137] Terminology Definition

[0138] In this application, the terms "IgE," "IgE immunoglobulin," and "immunoglobulin E" are generally used interchangeably and typically refer to a class of antibodies (or immunoglobulins (Ig)) produced by plasma cells in mammals. IgE monomers consist of two heavy chains (ε chains) and two light chains, with the ε chains containing four Ig-like constant regions (Cε1-Cε4). The primary functions of IgE are known to include immunity against parasites (e.g., worms such as Schistosoma mansoni, Plasmodium falciparum, Trichinella spiralis, or Fasciola hepatica). IgE may also be involved in defense against venom (e.g., bee and snake bites). IgE also plays an important role in type I hypersensitivity reactions, such as allergic asthma, most types of sinusitis, allergic rhinitis, food allergies, and certain types of chronic urticaria and atopic dermatitis. IgE also plays a crucial role in responses to allergens, such as allergic reactions to drugs. In humans, IgE belongs to the class of antibodies that are essentially encoded by the well-known immunoglobulin epsilon gene. IgE can include membrane-anchored (mIgE) or non-membrane-anchored, also known as circulating IgE.

[0139] In this application, the term "IgE-related disease" refers to any disorder or condition mediated by or related to IgE. This typically includes excessive production of immunoglobulin IgE and / or hypersensitivity to IgE. For example, said IgE-related disease could be asthma, chronic urticaria, food allergies, nasal polyps, and / or allergic rhinitis.

[0140] In this application, the term "antibody" generally refers to an immunoglobulin or fragment thereof that can specifically bind to a corresponding antigen. In this application, the antibody may comprise a protein, or an antigen-binding fragment thereof, consisting of at least two heavy chains and two light chains interconnected by disulfide bonds. In this application, the antibody may be a single-domain antibody. For example, in this application, the heavy chain may comprise a heavy chain variable region (VH) and a heavy chain constant region (CH). The heavy chain constant region comprises three domains: CH1, CH2, and CH3. In this application, the light chain may comprise a light chain variable region (VL) and a light chain constant region (CL). The light chain constant region comprises one domain. In this application, the VH and VL regions may comprise hypervariable regions and more conserved regions, the hypervariable regions being called complementarity-determining regions (CDR) or hypervariable regions (HVR), which alternate with more conserved regions called framework regions (FR). In this application, the VH and VL each contain three CDRs and four FRs, arranged in the following order from the amino terminus to the carboxyl terminus: FR1, CDR1, FR2, CDR2, FR3, CDR3, and FR4. For example, the variable structural domains of the heavy and light chains each contain four FR regions (H-FR1, H-FR2, H-FR3, H-FR4, L-FR1, L-FR2, L-FR3, L-FR4). In this application, the CDRs can be determined by various coding systems. For example, the CDRs can be determined by CCG, Kabat, Chothia, IMGT, AbM, or a combination of Kabat / Chothia. In this application, the CDRs encompass CDR sequences partitioned according to any CDR partitioning method. For example, the CDRs encompass variants. For example, the amino acid sequence of the CDR may be substituted, deleted, and / or added with one or more amino acids, such as 1-30, 1-20, or 1-10, or for example, 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acids. For example, the CDR encompasses homologs. For example, the homolog can be an amino acid sequence having at least about 85% (e.g., having at least about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or higher) sequence homology with the amino acid sequence of the CDR. In this application, the antibody may be wild-type or synthetically produced. For example, the antibody may be secreted by immune cells (e.g., effector B cells). For example, the antibody may be derived from plasma, hybridoma, or recombinant cell lines. In this application, the antibody may be animal-derived or non-animal-derived. For example, the antibody may be mouse-derived. For example, the antibody may be human-derived. In this application, the antibody may be wild-type or synthetically produced. In this application, the antibody may be a monoclonal antibody, polyclonal antibody, bispecific antibody, or multispecific antibody.In this application, the antibody may be a chimeric antibody, a humanized antibody, or a fully human antibody. In this application, the antibody may be a recombinant, hybrid, mutated, or transplanted antibody.

[0141] In this application, the term "antigen-binding fragment" generally refers to a portion of a complete antibody and includes the variable region of the complete antibody. For example, the antigen-binding fragment may include Fab, (Fab)2, F(ab')2, scFv, di-scFv, Fv, VHH, or dAb fragments. In this application, the antigen-binding fragment is obtained using conventional techniques known to those skilled in the art, and its function is evaluated in the same manner as that of the complete antibody. For example, the antigen-binding fragment may be obtained using in vitro display techniques.

[0142] The protein and / or amino acid sequences involved in this application should also be understood to include at least the following range: variants or homologs having the same or similar functions as the protein. In this application, the variant can be a protein or polypeptide that has undergone substitution, deletion, or addition of one or more amino acids in the amino acid sequence of the protein (e.g., the antibody described in this application). For example, the functional variant may comprise a protein or polypeptide that has undergone amino acid alterations through substitution, deletion, and / or insertion of at least one, such as 1-30, 1-20, or 1-10, or even 1, 2, 3, 4, or 5 amino acids. The functional variant may substantially retain the biological properties of the protein or polypeptide before the alteration (e.g., substitution, deletion, or addition). For example, the functional variant may retain at least 60%, 70%, 80%, 90%, or 100% of the biological activity (e.g., antigen-binding capacity) of the protein or polypeptide before the alteration. For example, the substitution may be a conserved substitution.

[0143] In this application, a portion of the amino acid sequence of the antibody may be homologous to the corresponding amino acid sequence in an antibody from a specific species, or belong to a specific category. For example, both the variable region and the constant region of the antibody may originate from the variable region and the constant region of an antibody from an animal species (such as a human).

[0144] In this application, the homolog can be a protein or polypeptide having at least about 85% (e.g., having at least about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or higher) sequence homology with the amino acid sequence of the protein and / or the polypeptide (e.g., the antibody described in this application).

[0145] In this application, the terms "stability" and "stable" generally refer to the fact that the active molecules in an antibody formulation do not aggregate, or only minimally aggregate, degrade, or fragment under given manufacturing, preparation, transportation, and / or storage conditions. A "stable" liquid formulation maintains biological activity under given manufacturing, preparation, transportation, and / or storage conditions. The stability of the antibody can be assessed by measuring the degree of aggregation, degradation, or fragmentation of the formulation, for example, using size exclusion high-performance liquid chromatography (SE-HPLC), reductive capillary electrophoresis (rCE-SDS), non-reductive capillary electrophoresis (nrCE-SDS), whole-column imaging capillary isoelectric focusing electrophoresis (icIEF), and / or particle size (PM) detection techniques. In this application, the long-term stability of the antibody can be assessed by measuring the Tm, Tagg, KD (diffusion interaction index), B22, or G22 of the formulation, for example, using differential scanning calorimetry (DSC) and / or differential scanning full-spectrum fluorescence (DSF).

[0146] In this application, the term "w / v" generally refers to "mass-volume ratio", which is the ratio of the mass of a component to the volume of a formulation.

[0147] In this application, the term "device" generally refers to a device that contains a formulation. For example, the device may contain the formulation and a container holding the formulation. For example, the device may be a storage and / or administration device. For example, the device may be a device for storing the formulation. For example, the device may be a device for delivering the formulation.

[0148] In this application, the term "prevention, diagnosis, and / or treatment" generally refers to the prevention, diagnosis, and / or treatment of diseases and / or conditions. For example, prevention, diagnosis, and / or treatment may include preventing the onset of the disease, slowing or reversing the disease progression, preventing or slowing the onset of one or more symptoms associated with the disease, reducing or alleviating one or more symptoms associated with the disease, reducing the severity and duration of the disease and any related symptoms, preventing further increase in the severity of the disease and any related symptoms, or diagnosing the presence and severity of the disease. In this application, the disease may be an immune-related disease. For example, the disease may be asthma, chronic urticaria, food allergy, nasal polyps, and / or allergic rhinitis. In this application, the disease may be a tumor disease. For example, preventing or alleviating the onset of one or more tumor-related symptoms, reducing the severity and duration of the tumor and related symptoms.

[0149] In this application, the term "about" generally refers to a variation within a range of 0.5% to 10% above or below a specified value, such as a variation within a range of 0.5%, 1%, 1.5%, 2%, 2.5%, 3%, 3.5%, 4%, 4.5%, 5%, 5.5%, 6%, 6.5%, 7%, 7.5%, 8%, 8.5%, 9%, 9.5%, or 10% above or below a specified value.

[0150] Invention Details

[0151] preparation

[0152] On one hand, this application provides a liquid formulation comprising an anti-IgE antibody. In this application, the formulation has one or more of the following properties: (1) high purity; (2) good thermal stability; (3) good long-term stability; (4) good photostability. In this application, the anti-IgE antibody may comprise three complementary determinant regions HCDR1, HCDR2, and HCDR3 of the antibody heavy chain variable region, and three complementary determinant regions LCDR1, LCDR2, and LCDR3 of the antibody light chain variable region. The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:51, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:52, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:53. In this application, the CDR encompasses a CDR sequence partitioned according to any CDR partitioning method; it also encompasses variants thereof, which include substitutions, deletions, and / or additions of one or more amino acids to the amino acid sequence of the CDR. For example, 1-30, 1-20, or 1-10 amino acids, or, for example, 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acid substitutions, deletions, and / or insertions; it also encompasses homologs thereof, which can be amino acid sequences having at least about 85% (e.g., having at least about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or higher) sequence homology to the amino acid sequence of the CDR. For example, the CDR of the anti-IgE antibody described in this application can be determined using Kabat.

[0153] In this application, the liquid formulation, by selecting appropriate buffer systems, stabilizers and / or surfactants, can effectively suppress the increase of acid peaks, aggregates, fragments and insoluble particles due to long-term storage, temperature changes and light changes, so that the active ingredients can be preserved stably for a long time.

[0154] In this application, the liquid formulation may be stable and contain low levels of protein aggregates or fragments. For example, the liquid formulation may have thermal stability, light stability, and / or long-term stability. In this application, the stability of the liquid formulation can be evaluated by appearance, turbidity, the content of protein fragments, the content of protein aggregates, and / or the content of insoluble particles.

[0155] In this application, the stability of the antibody can be assessed by measuring the degree of aggregation, degradation, or fragmentation of the formulation using, for example, size exclusion high-performance liquid chromatography (SE-HPLC), reducing capillary electrophoresis (rCE-SDS), non-reducing capillary electrophoresis (nrCE-SDS), whole-column imaging capillary isoelectric focusing electrophoresis (icIEF), and / or particle size (PM) detection techniques. In this application, the long-term stability of the antibody can be assessed by measuring the Tm, Tagg, KD (diffusion interaction index), B22, or G22 of the formulation using, for example, differential scanning calorimetry (DSC) and / or differential scanning full-spectrum fluorescence (DSF).

[0156] In this application, the concentration of the anti-IgE antibody can be about 10 mg / mL-200 mg / mL, about 10 mg / mL-150 mg / mL, about 50 mg / mL-200 mg / mL, about 50 mg / mL-150 mg / mL, about 90 mg / mL-150 mg / mL, about 90 mg / mL-110 mg / mL, about 100 mg / mL-200 mg / mL, or about 100 mg / mL-150 mg / mL. For example, the concentration of the anti-IgE antibody can be about 10 mg / mL-200 mg / mL. For example, the concentration of the anti-IgE antibody can be about 50 mg / mL-150 mg / mL. For example, the concentration of the anti-IgE antibody may be about 10 mg / mL, about 20 mg / mL, about 30 mg / mL, about 40 mg / mL, about 50 mg / mL, about 60 mg / mL, about 70 mg / mL, about 80 mg / mL, about 90 mg / mL, about 95 mg / mL, about 96 mg / mL, about 97 mg / mL, about 98 mg / mL, about 99 mg / mL, about 100 mg / mL, about 101 mg / mL, about 102 mg / mL, about 103 mg / mL, about 104 mg / mL, about 105 mg / mL, about 110 mg / mL, about 120 mg / mL, about 130 mg / mL, about 140 mg / mL, about 150 mg / mL, about 160 mg / mL, about 170 mg / mL, about 180 mg / mL, about 190 mg / mL, or about 200 mg / mL.

[0157] In this application, the formulation may further comprise one or more buffer solutions, which may be organic and / or inorganic. In this application, the buffer solution may comprise organic and inorganic acids and / or salts of said acids. In this application, the buffer solution may comprise a cross-buffer consisting of two or more buffer solutions. For example, the buffer solution may be selected from one or more of the following: citrate buffer, acetate buffer, histidine buffer, phosphate (PB) buffer, Tris buffer, histidine / histidine hydrochloride buffer (His / His-HCl), acetate / sodium acetate buffer (HAc / NaAc), and histidine / sodium acetate buffer (His / NaAc). For example, the buffer solution may be selected from His / His-HCl, acetate / sodium acetate buffer (HAc / NaAc), and / or histidine / sodium acetate buffer (His / NaAc). In this application, the concentration of the buffer solution can be about 0 mM-100 mM, about 0 mM-50 mM, about 1 mM-50 mM, about 1 mM-45 mM, about 1 mM-40 mM, about 1 mM-35 mM, about 1 mM-30 mM, about 1 mM-25 mM, about 1 mM-20 mM, about 1 mM-15 mM, about 2 mM-15 mM, about 2 mM-20 mM, about 5 mM-20 mM, or about 8 mM-12 mM. For example, the concentration of the buffer solution can be about 5 mM-20 mM. For example, the concentration of the buffer solution may be about 5 mM, about 6 mM, about 7 mM, about 8 mM, about 9 mM, about 9.5 mM, about 9.6 mM, about 9.7 mM, about 9.8 mM, about 9.9 mM, about 10 mM, about 10.1 mM, about 10.2 mM, about 10.3 mM, about 10.4 mM, about 10.5 mM, about 11 mM, about 12 mM, about 13 mM, about 14 mM, about 15 mM, about 16 mM, about 17 mM, about 18 mM, about 19 mM, about 20 mM, about 30 mM, about 40 mM, or about 50 mM.

[0158] In this application, the buffer solution can provide different pH values. For example, the buffer solution can provide a pH of about 3.5-8.0, about 3.5-7.5, about 3.5-7.0, about 3.5-6.5, about 3.5-6.1, about 4.0-8.0, about 4.5-8.0, about 5.0-8.0, about 5.3-8.0, about 4.0-7.5, about 4.5-7.5, about 4.0-7.0, about 4.5-7.0, about 5.0-7.0, about 4.5-6.5, about 5.0-6.5, about 5.3-6.5, about 5.3-6.4, about 5.4-6.4, about 5.0-6.1, or about 5.3-6.1. For example, the buffer solution can provide a pH of about 5.3-6.4. For example, the buffer solution may provide a pH of about 3.5, about 4.0, about 4.5, about 5.0, about 5.3, about 5.4, about 5.5, about 5.6, about 5.7, about 5.8, about 5.9, about 6.0, about 6.1, about 6.2, about 6.3, about 6.4, about 6.5, about 7.0, about 7.5, or about 8.0.

[0159] In this application, the formulation may further comprise one or more stabilizers. In this application, the stabilizer may be an excipient that protects the active ingredient from chemical and / or physical degradation during manufacturing, storage, and / or use. In this application, the stabilizer may be a sugar, amino acid, polyol, and / or its derivatives. For example, the stabilizer may be selected from one or more of the following: sorbitol, sucrose, sodium chloride, and arginine hydrochloride. For example, the stabilizer may be selected from one or more of the following: sorbitol and sucrose. In this application, the concentration of the stabilizer may be expressed as a mass-volume ratio. In this application, the concentration of the stabilizer can be about 0%-50%, about 0%-45%, about 0%-40%, about 0%-35%, about 0%-30%, about 0%-25%, about 0%-20%, about 0%-15%, about 0%-10%, about 0%-5%, about 1%-50%, about 2%-50%, about 2%-45%, about 2%-40%, about 2%-35%, about 2%-30%, about 2%-25%, about 2%-20%, about 2%-15%, about 2%-10%, about 3%-10%, about 3%-5.5%, about 3%-5.5%, or about 4.5-5.5%. For example, the concentration of the stabilizer can be about 3%-5.5%. For example, the concentration of the stabilizer may be about 1%, about 2%, about 3%, about 4%, about 4.5%, about 4.6%, about 4.7%, about 4.8%, about 4.9%, about 5%, about 5.1%, about 5.2%, about 5.3%, about 5.4%, about 5.5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 20%, about 30%, about 40%, or about 50%.

[0160] In this application, the formulation may further comprise a surfactant. In this application, the surfactant may be an excipient used to protect proteins from various fortifying conditions, such as stirring, shearing, or high temperature. In this application, the surfactant may be polysorbate 20 (PS20) and / or polysorbate 80 (PS80). In this application, the concentration of the surfactant may be expressed as a mass-volume ratio. In this application, the concentration of the surfactant can be about 0%-0.1%, about 0.0001%-0.1%, about 0.0005%-0.1%, about 0.0005%-0.1%, about 0.001%-0.1%, about 0.001%-0.09%, about 0.001%-0.08%, about 0.001%-0.07%, about 0.001%-0.06%, about 0.001%-0.05%, about 0.001%-0.04%, or about 0.001%. The concentrations are approximately 0.03%, 0.001%-0.02%, 0.005%-0.09%, 0.005%-0.08%, 0.005%-0.07%, 0.005%-0.06%, 0.005%-0.05%, 0.005%-0.04%, 0.005%-0.03%, 0.005%-0.02%, 0.01%-0.02%, 0.01%-0.015%, or 0.015%-0.02%. For example, the concentration of the surfactant may be approximately 0.005%-0.02%. For example, the concentration of the surfactant may be about 0.0001%, about 0.0005%, about 0.001%, about 0.005%, about 0.01%, about 0.011%, about 0.012%, about 0.013%, about 0.014%, about 0.015%, about 0.016%, about 0.017%, about 0.018%, about 0.019%, about 0.02%, about 0.03%, about 0.04%, about 0.05%, about 0.06%, about 0.07%, about 0.08%, or about 0.09%.

[0161] In this application, the formulation may further comprise an antioxidant. In this application, the antioxidant may be methionine and / or EDTA. In this application, the concentration of the antioxidant may be about 0 mM-50 mM, about 0 mM-45 mM, about 0 mM-40 mM, about 0 mM-35 mM, about 0 mM-30 mM, about 0 mM-25 mM, about 0 mM-20 mM, about 0 mM-15 mM, about 0 mM-10 mM, about 1 mM-20 mM, or about 1 mM-10 mM. For example, the concentration of the antioxidant may be about 0 mM-10 mM. For example, the concentration of the antioxidant may be about 1 mM, about 2 mM, about 3 mM, about 4 mM, about 4.5 mM, about 4.6 mM, about 4.7 mM, about 4.8 mM, about 4.9 mM, about 5 mM, about 5.1 mM, about 5.2 mM, about 5.3 mM, about 5.4 mM, about 5.5 mM, about 6 mM, about 7 mM, about 8 mM, about 9 mM, or about 10 mM.

[0162] In this application, the anti-IgE antibody has one or more of the following properties: (1) it can bind to IgE and has good binding activity; (2) it has good stability; (3) it can inhibit the binding of IgE to its receptor.

[0163] In this application, the anti-IgE antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3. The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2 or SEQ ID NO:26, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:10 or SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:11 or SEQ ID NO:30.

[0164] In this application, the anti-IgE antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are selected from any of the following combinations:

[0165] 1) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:10, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:11.

[0166] 2) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:26, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30; and

[0167] 3) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30.

[0168] In this application, the anti-IgE antibody may further comprise FR. For example, the anti-IgE antibody comprises a heavy chain variable region VH, which may comprise H-FR1, H-FR2, H-FR3, and / or H-FR4. For example, the anti-IgE antibody comprises a light chain variable region VL, which may comprise L-FR1, L-FR2, L-FR3, and / or L-FR4. For example, the anti-IgE antibody may comprise both VH and VL, where VH may comprise H-FR1, H-FR2, H-FR3, and H-FR4, and VL may comprise L-FR1, L-FR2, L-FR3, and L-FR4. In this application, the C-terminus of H-FR1 can be directly or indirectly connected to the N-terminus of HCDR1; H-FR2 can be located between HCDR1 and HCDR2; H-FR3 can be located between HCDR2 and HCDR3; and the N-terminus of H-FR4 can be directly or indirectly connected to the C-terminus of HCDR3. In this application, the C-terminus of L-FR1 can be directly or indirectly connected to the N-terminus of LCDR1; L-FR2 can be located between LCDR1 and LCDR2; L-FR3 can be located between LCDR2 and LCDR3; and the N-terminus of L-FR4 can be directly or indirectly connected to the C-terminus of LCDR3.

[0169] In this application, the amino acid sequence of H-FR1 may be as shown in SEQ ID NO:4 or SEQ ID NO:17. In this application, the amino acid sequence of H-FR2 may be as shown in SEQ ID NO:5, SEQ ID NO:18, SEQ ID NO:27, or SEQ ID NO:36. In this application, the amino acid sequence of H-FR3 may be as shown in SEQ ID NO:6 or SEQ ID NO:19. In this application, the amino acid sequence of H-FR4 may be as shown in SEQ ID NO:7 or SEQ ID NO:20. In this application, the amino acid sequence of L-FR1 may be as shown in SEQ ID NO:12, SEQ ID NO:22, SEQ ID NO:31, or SEQ ID NO:38. In this application, the amino acid sequence of L-FR2 may be as shown in SEQ ID NO:13, SEQ ID NO:23, or SEQ ID NO:32. In this application, the amino acid sequence of L-FR3 may be as shown in SEQ ID NO:14, SEQ ID NO:24, SEQ ID NO:33, or SEQ ID NO:39. In this application, the amino acid sequence of L-FR4 may be as shown in SEQ ID NO:15 or SEQ ID NO:34.

[0170] In this application, the anti-IgE antibody may comprise VH and VL, wherein VH may comprise H-FR1, H-FR2, H-FR3, and H-FR4, and VL may comprise L-FR1, L-FR2, L-FR3, and L-FR4. The amino acid sequences of H-FR1, H-FR2, H-FR3, H-FR4, L-FR1, L-FR2, L-FR3, and L-FR4 may be selected from any of the following combinations:

[0171] 1) The amino acid sequence of H-FR1 is shown in SEQ ID NO:4, the amino acid sequence of H-FR2 is shown in SEQ ID NO:5, the amino acid sequence of H-FR3 is shown in SEQ ID NO:6, the amino acid sequence of H-FR4 is shown in SEQ ID NO:7, the amino acid sequence of L-FR1 is shown in SEQ ID NO:12, the amino acid sequence of L-FR2 is shown in SEQ ID NO:13, the amino acid sequence of L-FR3 is shown in SEQ ID NO:14, and the amino acid sequence of L-FR4 is shown in SEQ ID NO:15;

[0172] 2) The amino acid sequence of H-FR1 is shown in SEQ ID NO:17, the amino acid sequence of H-FR2 is shown in SEQ ID NO:18, the amino acid sequence of H-FR3 is shown in SEQ ID NO:19, the amino acid sequence of H-FR4 is shown in SEQ ID NO:20, the amino acid sequence of L-FR1 is shown in SEQ ID NO:22, the amino acid sequence of L-FR2 is shown in SEQ ID NO:23, the amino acid sequence of L-FR3 is shown in SEQ ID NO:24, and the amino acid sequence of L-FR4 is shown in SEQ ID NO:15;

[0173] 3) The amino acid sequence of H-FR1 is shown in SEQ ID NO:4, the amino acid sequence of H-FR2 is shown in SEQ ID NO:27, the amino acid sequence of H-FR3 is shown in SEQ ID NO:6, the amino acid sequence of H-FR4 is shown in SEQ ID NO:7, the amino acid sequence of L-FR1 is shown in SEQ ID NO:31, the amino acid sequence of L-FR2 is shown in SEQ ID NO:32, the amino acid sequence of L-FR3 is shown in SEQ ID NO:33, and the amino acid sequence of L-FR4 is shown in SEQ ID NO:34; and

[0174] 4) The amino acid sequence of H-FR1 is shown in SEQ ID NO:17, the amino acid sequence of H-FR2 is shown in SEQ ID NO:36, the amino acid sequence of H-FR3 is shown in SEQ ID NO:19, the amino acid sequence of H-FR4 is shown in SEQ ID NO:20, the amino acid sequence of L-FR1 is shown in SEQ ID NO:38, the amino acid sequence of L-FR2 is shown in SEQ ID NO:23, the amino acid sequence of L-FR3 is shown in SEQ ID NO:39, and the amino acid sequence of L-FR4 is shown in SEQ ID NO:15.

[0175] In this application, the anti-IgE antibody may comprise HCDR1, HCDR2, HCDR3, H-FR1, H-FR2, H-FR3 and / or H-FR4, wherein the C-terminus of H-FR1 is directly or indirectly connected to the N-terminus of HCDR1, H-FR2 is located between HCDR1 and HCDR2, H-FR3 is located between HCDR2 and HCDR3, and the N-terminus of H-FR4 is directly or indirectly connected to the C-terminus of HCDR3. In this application, the anti-IgE antibody may comprise LCDR1, LCDR2, LCDR3, L-FR1, L-FR2, L-FR3 and / or L-FR4, wherein the C-terminus of L-FR1 is directly or indirectly connected to the N-terminus of LCDR1, L-FR2 is located between LCDR1 and LCDR2, L-FR3 is located between LCDR2 and LCDR3, and the N-terminus of L-FR4 is directly or indirectly connected to the C-terminus of LCDR3.

[0176] In this application, the FR can be of any species origin. For example, the FR can be of mouse, rabbit, goat, alpaca, or human origin.

[0177] In this application, the amino acid sequence of FR can be adjusted as needed. For example, FR can be a wild-type sequence. For example, the amino acid sequence of FR can be changed without reducing the binding activity / affinity of the anti-IgE antibody. For example, one or more amino acid sequences in FR can be mutated or optimized without reducing the binding activity / affinity of the anti-IgE antibody. For example, FR can be a variant thereof, which includes the substitution, deletion, and / or addition of one or more amino acids in the amino acid sequence of FR. For example, 1-30, 1-20, or 1-10 amino acids, or for example, 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acid substitutions, deletions, and / or insertions. For example, the FR can be a homolog, which can be an amino acid sequence having at least about 85% (e.g., having at least about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or higher) sequence homology with the amino acid sequence of the FR.

[0178] In this application, the anti-IgE antibody comprises an antibody heavy chain variable region VH, the amino acid sequence of which is shown in SEQ ID NO:8, SEQ ID NO:21, SEQ ID NO:28, SEQ ID NO:37, or SEQ ID NO:41. In this application, the anti-IgE antibody comprises an antibody light chain variable region VL, the amino acid sequence of which is shown in SEQ ID NO:16, SEQ ID NO:25, SEQ ID NO:35, or SEQ ID NO:40. In this application, the anti-IgE antibody comprises VH and VL, the amino acid sequence of which is shown in SEQ ID NO:8, SEQ ID NO:21, SEQ ID NO:28, SEQ ID NO:37, or SEQ ID NO:41, and the amino acid sequence of which is shown in SEQ ID NO:16, SEQ ID NO:25, SEQ ID NO:35, or SEQ ID NO:40.

[0179] In this application, the amino acid sequences of VH and VL are selected from any of the following combinations:

[0180] 1) The amino acid sequence of VH is shown in SEQ ID NO:8, and the amino acid sequence of VL is shown in SEQ ID NO:16;

[0181] 2) The amino acid sequence of VH is shown in SEQ ID NO:21, and the amino acid sequence of VL is shown in SEQ ID NO:25;

[0182] 3) The amino acid sequence of VH is shown in SEQ ID NO:28, and the amino acid sequence of VL is shown in SEQ ID NO:35;

[0183] 4) The amino acid sequence of VH is shown in SEQ ID NO:37, and the amino acid sequence of VL is shown in SEQ ID NO:40; and

[0184] 5) The amino acid sequence of VH is shown in SEQ ID NO:41, and the amino acid sequence of VL is shown in SEQ ID NO:40.

[0185] In this application, the amino acid sequences of VH and / or VL can be adjusted as needed. For example, VH and / or VL can be wild-type sequences. For example, the amino acid sequences of VH and / or VL can be altered without reducing the binding activity / affinity of the anti-IgE antibody. For example, one or more amino acid sequences in VH and / or VL can be mutated or optimized without reducing the binding activity / affinity of the anti-IgE antibody. For example, VH and / or VL can be variants thereof, which include substitutions, deletions, and / or additions of one or more amino acids in the amino acid sequences of VH and / or VL. For example, 1-30, 1-20, or 1-10 amino acids, or, for example, 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acid substitutions, deletions, and / or insertions. For example, the VH and / or VL can be homologs, which can be amino acid sequences having at least about 85% (e.g., having at least about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or higher) sequence homology with the amino acid sequences of the VH and / or VL.

[0186] In this application, the anti-IgE antibody may further comprise an immunoglobulin constant region. For example, the immunoglobulin constant region may be a mouse immunoglobulin constant region. For example, the immunoglobulin constant region may be a human immunoglobulin constant region.

[0187] In this application, the immunoglobulin constant region can be the heavy chain constant region of IgG and / or the light chain constant region of an antibody. For example, the immunoglobulin constant region can be the heavy chain constant region of human IgG and / or the light chain constant region of a human antibody. In this application, the heavy chain constant region of IgG can be the heavy chain constant region of IgG1, IgG2, IgG3, or IgG4. For example, the heavy chain constant region of IgG can be the heavy chain constant region of human IgG1, IgG2, IgG3, or IgG4. In this application, the light chain constant region of the human antibody can be the Kappa or Lambda light chain constant region. For example, the light chain constant region of the antibody can be the human Kappa or Lambda light chain constant region.

[0188] In this application, the anti-IgE antibody may further comprise its antigen-binding fragment. In this application, the anti-IgE antibody may include, but is not limited to, recombinant antibodies, monoclonal antibodies, human antibodies, murine antibodies, chimeric antibodies, humanized antibodies, fully human antibodies, single-chain antibodies, monospecific antibodies, bispecific antibodies, multispecific antibodies, Fv fragments, scFv fragments, Fab fragments, Fab' fragments, and F(ab')2 fragments.

[0189] In this application, the anti-IgE antibody may comprise a heavy chain and / or a light chain. The amino acid sequence of the heavy chain and / or light chain may be adjusted as needed. For example, the heavy chain and / or light chain may be wild-type sequences. For example, one or more amino acid sequences in the heavy chain and / or light chain may be mutated or optimized without reducing the binding activity / affinity of the anti-IgE antibody. For example, the heavy chain and / or light chain may be variants thereof, which include substitutions, deletions, and / or additions of one or more amino acids in the amino acid sequence of the heavy chain and / or light chain. Examples include 1-30, 1-20, or 1-10 amino acids, or, for example, 1, 2, 3, 4, 5, 6, 7, 8, or 9 amino acid substitutions, deletions, and / or insertions. For example, the heavy chain and / or light chain can be homologs, which can be amino acid sequences having at least about 85% (e.g., having at least about 85%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99% or higher) sequence homology with the amino acid sequence of the heavy chain and / or light chain.

[0190] In this application, the anti-IgE antibody may be wild-type. In this application, the anti-IgE antibody may be recombinant. For example, the anti-IgE antibody may contain a wild-type sequence. For example, the anti-IgE antibody may be mutated or optimized.

[0191] In this application, the liquid formulation may comprise:

[0192] (1) An anti-IgE antibody, wherein the anti-IgE antibody comprises three complementary determinant regions HCDR1, HCDR2 and HCDR3 of the antibody heavy chain variable region, and three complementary determinant regions LCDR1, LCDR2 and LCDR3 of the antibody light chain variable region, wherein the amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:51, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:52, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:53;

[0193] (2) Buffer solution, wherein the buffer solution is selected from histidine / histidine hydrochloride buffer (His / His-HCl), acetate / sodium acetate buffer (HAc / NaAc) and / or histidine / sodium acetate buffer (His / NaAc);

[0194] (3) a stabilizer, wherein the stabilizer is selected from sorbitol and / or sucrose; and

[0195] (4) A surfactant, wherein the surfactant is selected from polysorbate 20 (PS20) and / or polysorbate 80 (PS80).

[0196] In this application, the concentration of the anti-IgE antibody can be about 10 mg / mL-200 mg / mL, about 10 mg / mL-150 mg / mL, about 50 mg / mL-200 mg / mL, about 50 mg / mL-150 mg / mL, about 90 mg / mL-150 mg / mL, about 90 mg / mL-110 mg / mL, about 100 mg / mL-200 mg / mL, about 100 mg / mL-150 mg / mL, or about 100 mg / mL-110 mg / mL. For example, the concentration of the anti-IgE antibody can be about 50 mg / mL-150 mg / mL. For example, the concentration of the anti-IgE antibody may be about 10 mg / mL, about 20 mg / mL, about 30 mg / mL, about 40 mg / mL, about 50 mg / mL, about 60 mg / mL, about 70 mg / mL, about 80 mg / mL, about 90 mg / mL, about 95 mg / mL, about 96 mg / mL, about 97 mg / mL, about 98 mg / mL, about 99 mg / mL, about 100 mg / mL, about 101 mg / mL, about 102 mg / mL, about 103 mg / mL, about 104 mg / mL, about 105 mg / mL, about 110 mg / mL, about 120 mg / mL, about 130 mg / mL, about 140 mg / mL, about 150 mg / mL, about 160 mg / mL, about 170 mg / mL, about 180 mg / mL, about 190 mg / mL, or about 200 mg / mL.

[0197] In this application, the buffer solution can be histidine / histidine hydrochloride buffer (His / His-HCl). In this application, the buffer solution can be acetate / sodium acetate buffer (HAc / NaAc). In this application, the buffer solution can be histidine / sodium acetate buffer (His / NaAc). In this application, the buffer solution can be a mixture selected from two or more of histidine / histidine hydrochloride buffer (His / His-HCl), acetate / sodium acetate buffer (HAc / NaAc), and histidine / sodium acetate buffer (His / NaAc).

[0198] In this application, the buffer solution may be a histidine / histidine hydrochloride buffer (His / His-HCl) with a concentration of approximately 0 mM-100 mM, approximately 0 mM-50 mM, approximately 1 mM-50 mM, approximately 1 mM-45 mM, approximately 1 mM-40 mM, approximately 1 mM-35 mM, approximately 1 mM-30 mM, approximately 1 mM-25 mM, approximately 1 mM-20 mM, approximately 1 mM-15 mM, approximately 2 mM-15 mM, approximately 2 mM-20 mM, approximately 5 mM-20 mM, or 8-12 mM. For example, the concentration of the histidine / histidine hydrochloride buffer solution may be approximately 5 mM-20 mM. For example, the concentration of the histidine / histidine hydrochloride buffer may be about 5 mM, about 6 mM, about 7 mM, about 8 mM, about 9 mM, about 9.5 mM, about 9.6 mM, about 9.7 mM, about 9.8 mM, about 9.9 mM, about 10 mM, about 10.1 mM, about 10.2 mM, about 10.3 mM, about 10.4 mM, about 10.5 mM, about 11 mM, about 12 mM, about 13 mM, about 14 mM, about 15 mM, about 16 mM, about 17 mM, about 18 mM, about 19 mM, about 20 mM, about 30 mM, about 40 mM, or about 50 mM.

[0199] In this application, the buffer solution may be a histidine / histidine hydrochloride buffer solution, which can provide different pH values. For example, the pH value provided by the histidine / histidine hydrochloride buffer solution may be about 3.5-8.0, about 3.5-7.5, about 3.5-7.0, about 3.5-6.5, about 3.5-6.1, about 4.0-8.0, about 4.5-8.0, about 5.0-8.0, about 5.3-8.0, about 4.0-7.5, about 4.5-7.5, about 4.0-7.0, about 4.5-7.0, about 5.0-7.0, about 4.5-7.0, about 5.0-7.0, about 4.5-6.5, about 5.0-6.5, about 5.3-6.5, about 5.3-6.4, about 5.4-6.4, about 5.0-6.1, or about 5.3-6.1. For example, the histidine / histidine hydrochloride buffer solution may provide a pH of about 5.3-6.4. For example, the histidine / histidine hydrochloride buffer solution may provide a pH of about 3.5, about 4.0, about 4.5, about 5.0, about 5.3, about 5.4, about 5.5, about 5.6, about 5.7, about 5.8, about 5.9, about 6.0, about 6.1, about 6.2, about 6.3, about 6.5, about 7.0, about 7.5, or about 8.0.

[0200] In this application, the stabilizer may be sorbitol. In this application, the stabilizer may be sucrose. In this application, the stabilizer may be a mixture. For example, the stabilizer may be sorbitol and sucrose. In this application, the stabilizer may be a derivative thereof.

[0201] In this application, the stabilizer may be sorbitol, and the concentration of sorbitol may be about 0%-50%, about 0%-45%, about 0%-40%, about 0%-35%, about 0%-30%, about 0%-25%, about 0%-20%, about 0%-15%, about 0%-10%, about 0%-5%, about 1%-50%, about 2%-50%, about 2%-45%, about 2%-40%, about 2%-35%, about 2%-30%, about 2%-25%, about 2%-20%, about 2%-15%, about 2%-10%, about 3%-10%, about 3%-5.5%, about 3%-5.5%, or about 4.5-5.5%. For example, the concentration of sorbitol may be about 3%-5.5%. For example, the concentration of sorbitol may be about 1%, about 2%, about 3%, about 4%, about 4.5%, about 4.6%, about 4.7%, about 4.8%, about 4.9%, about 5%, about 5.1%, about 5.2%, about 5.3%, about 5.4%, about 5.5%, about 6%, about 7%, about 8%, about 9%, about 10%, about 20%, about 30%, about 40%, or about 50%.

[0202] In this application, the surfactant may be polysorbate 80 (PS80). In this application, the surfactant may be polysorbate 20 (PS20). In this application, the surfactant may be a mixture. For example, the surfactant may be PS80 and PS20. In this application, the surfactant may be a derivative thereof.

[0203] In this application, the surfactant may be PS80, and the concentration of PS80 may be about 0%-0.1%, about 0.0001%-0.1%, about 0.0005%-0.1%, about 0.0005%-0.1%, about 0.001%-0.1%, about 0.001%-0.09%, about 0.001%-0.08%, about 0.001%-0.07%, about 0.001%-0.06%, about 0.001%-0.05%, or about 0.001%-0.04%. Approximately 0.001%-0.03%, approximately 0.001%-0.02%, approximately 0.005%-0.09%, approximately 0.005%-0.08%, approximately 0.005%-0.07%, approximately 0.005%-0.06%, approximately 0.005%-0.05%, approximately 0.005%-0.04%, approximately 0.005%-0.03%, approximately 0.005%-0.02%, approximately 0.01%-0.02%, approximately 0.01%-0.015%, or approximately 0.015%-0.02%. For example, the concentration of PS80 can be approximately 0.005%-0.02%. For example, the concentration of PS80 can be about 0.0001%, about 0.0005%, about 0.001%, about 0.005%, about 0.01%, about 0.011%, about 0.012%, about 0.013%, about 0.014%, about 0.015%, about 0.016%, about 0.017%, about 0.018%, about 0.019%, about 0.02%, about 0.03%, about 0.04%, about 0.05%, about 0.06%, about 0.07%, about 0.08%, or about 0.09%.

[0204] In this application, the formulation may further comprise an antioxidant, which may be methionine and / or EDTA. In this application, the antioxidant may be methionine. In this application, the antioxidant may be EDTA. In this application, the antioxidant may be a mixture. For example, the antioxidant may be methionine and EDTA.

[0205] In this application, the antioxidant can be methionine, and the concentration of methionine can be about 0mM-50mM, about 0mM-45mM, about 0mM-40mM, about 0mM-35mM, about 0mM-30mM, about 0mM-25mM, about 0mM-20mM, about 0mM-15mM, about 0mM-10mM, about 1mM-20mM, or about 1mM-10mM. For example, the concentration of methionine can be about 0mM-10mM. For example, the concentration of the methionine may be about 1 mM, about 2 mM, about 3 mM, about 4 mM, about 4.5 mM, about 4.6 mM, about 4.7 mM, about 4.8 mM, about 4.9 mM, about 5 mM, about 5.1 mM, about 5.2 mM, about 5.3 mM, about 5.4 mM, about 5.5 mM, about 6 mM, about 7 mM, about 8 mM, about 9 mM, or about 10 mM.

[0206] In this application, the liquid formulation may comprise: 10-200 mg / mL anti-IgE antibody, wherein the anti-IgE antibody comprises three complementary determinant regions HCDR1, HCDR2, and HCDR3 of the antibody heavy chain variable region, and three complementary determinant regions LCDR1, LCDR2, and LCDR3 of the antibody light chain variable region, wherein the amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:51, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:52, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:53; His / His-HCl, which provides a pH of 5-7; 2-10% (w / v) sorbitol; and 0-0.1% (w / v) PS80.

[0207] In this application, the liquid formulation may comprise: 50-150 mg / mL anti-IgE antibody, wherein the anti-IgE antibody comprises three complementary determinant regions HCDR1, HCDR2, and HCDR3 of the antibody heavy chain variable region, and three complementary determinant regions LCDR1, LCDR2, and LCDR3 of the antibody light chain variable region, wherein the amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:51, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:52, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:53; His / His-HCl, which provides a pH of 5.3-6.4; 3%-5.5% (w / v) sorbitol; and 0.005%-0.02% (w / v) PS80.

[0208] In this application, the liquid formulation may comprise: 90-110 mg / mL anti-IgE antibody, wherein the anti-IgE antibody comprises three complementary determinant regions HCDR1, HCDR2, and HCDR3 of the antibody heavy chain variable region, and three complementary determinant regions LCDR1, LCDR2, and LCDR3 of the antibody light chain variable region, wherein the amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:51, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:52, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:53; His / His-HCl, which provides a pH of 5.4-6.4; 4.5%-5.5% (w / v) sorbitol; and 0.01%-0.02% (w / v) PS80.

[0209] In this application, the liquid formulation may comprise: 10-200 mg / mL anti-IgE antibody; His / His-HCl, providing a pH of 5-7; 2-10% (w / v) sorbitol; and 0-0.1% (w / v) PS80, wherein the anti-IgE antibody comprises three complementarity-determining regions HCDR1, HCDR2, and HCDR3 of the antibody heavy chain variable region, and three complementarity-determining regions LCDR1, LCDR2, and LCDR3 of the antibody light chain variable region, wherein the amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are selected from any group of the following combinations:

[0210] 1) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:10, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:11.

[0211] 2) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:26, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30; and

[0212] 3) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30.

[0213] In this application, the liquid formulation may comprise: 50-150 mg / mL anti-IgE antibody; His / His-HCl, providing a pH of 5.3-6.4; 3%-5.5% (w / v) sorbitol; 0.005%-0.02% (w / v) PS80, wherein the anti-IgE antibody comprises three complementarity-determining regions HCDR1, HCDR2, and HCDR3 of the antibody heavy chain variable region, and three complementarity-determining regions LCDR1, LCDR2, and LCDR3 of the antibody light chain variable region, wherein the amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are selected from any of the following combinations:

[0214] 1) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:10, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:11.

[0215] 2) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:26, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30; and

[0216] 3) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30.

[0217] In this application, the liquid formulation may comprise: 90-110 mg / mL anti-IgE antibody; His / His-HCl, providing a pH of 5.4-6.4; 4.5%-5.5% (w / v) sorbitol; and 0.01%-0.02% (w / v) PS80, wherein the anti-IgE antibody comprises three complementarity-determining regions HCDR1, HCDR2, and HCDR3 of the antibody heavy chain variable region, and three complementarity-determining regions LCDR1, LCDR2, and LCDR3 of the antibody light chain variable region, wherein the amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are selected from any group of the following combinations:

[0218] 1) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:10, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:11.

[0219] 2) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:26, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30; and

[0220] 3) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30.

[0221] In this application, the liquid formulation may comprise: 10-200 mg / mL anti-IgE antibody, wherein the anti-IgE antibody comprises three complementary determinant regions HCDR1, HCDR2, and HCDR3 of the antibody heavy chain variable region, and three complementary determinant regions LCDR1, LCDR2, and LCDR3 of the antibody light chain variable region, wherein the amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:51, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:52, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:53; 0-100 mM His / His-HCl, which provides a pH of 5-7; 2-10% (w / v) sorbitol; and 0-0.1% (w / v) PS80.

[0222] In this application, the liquid formulation may comprise: 50-150 mg / mL anti-IgE antibody, wherein the anti-IgE antibody comprises three complementary determinant regions HCDR1, HCDR2, and HCDR3 of the antibody heavy chain variable region, and three complementary determinant regions LCDR1, LCDR2, and LCDR3 of the antibody light chain variable region, wherein the amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:51, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:52, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:53; 5-20 mM His / His-HCl, providing a pH of 5.3-6.4; 3%-5.5% (w / v) sorbitol; and 0.005%-0.02% (w / v) PS80.

[0223] In this application, the liquid formulation may comprise: 90-110 mg / mL anti-IgE antibody, wherein the anti-IgE antibody comprises three complementary determinant regions HCDR1, HCDR2, and HCDR3 of the antibody heavy chain variable region, and three complementary determinant regions LCDR1, LCDR2, and LCDR3 of the antibody light chain variable region, wherein the amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:51, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:52, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:53; 8-12 mM His / His-HCl, providing a pH of 5.4-6.4; 4.5%-5.5% (w / v) sorbitol; and 0.01%-0.02% (w / v) PS80.

[0224] In this application, the liquid formulation may comprise: 10-200 mg / mL anti-IgE antibody; 0-100 mM His / His-HCl, providing a pH of 5-7; 2-10% (w / v) sorbitol; and 0-0.1% (w / v) PS80, wherein the anti-IgE antibody comprises three complementarity-determining regions HCDR1, HCDR2, and HCDR3 of the antibody heavy chain variable region, and three complementarity-determining regions LCDR1, LCDR2, and LCDR3 of the antibody light chain variable region, wherein the amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are selected from any group of the following combinations:

[0225] (1) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:10, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:11.

[0226] (2) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:26, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30; and

[0227] (3) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30.

[0228] In this application, the liquid formulation may comprise: 50-150 mg / mL anti-IgE antibody; 5-20 mM His / His-HCl, providing a pH of 5.3-6.4; 3%-5.5% (w / v) sorbitol; 0.005%-0.02% (w / v) PS80, wherein the anti-IgE antibody comprises three complementary determinant regions HCDR1, HCDR2, and HCDR3 of the antibody heavy chain variable region, and three complementary determinant regions LCDR1, LCDR2, and LCDR3 of the antibody light chain variable region, wherein the amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are selected from any group of the following combinations:

[0229] (1) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:10, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:11.

[0230] (2) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:26, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30; and

[0231] (3) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30.

[0232] In this application, the liquid formulation may comprise: 90-110 mg / mL anti-IgE antibody; 8-12 mM His / His-HCl, providing a pH of 5.4-6.4; 4.5%-5.5% (w / v) sorbitol; and 0.01%-0.02% (w / v) PS80, wherein the anti-IgE antibody comprises three complementarity-determining regions HCDR1, HCDR2, and HCDR3 of the antibody heavy chain variable region, and three complementarity-determining regions LCDR1, LCDR2, and LCDR3 of the antibody light chain variable region, wherein the amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are selected from any group of the following combinations:

[0233] (1) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:10, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:11.

[0234] (2) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:26, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30; and

[0235] (3) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30.

[0236] In this application, the liquid formulation may comprise: 10-200 mg / mL anti-IgE antibody, wherein the anti-IgE antibody comprises three complementary determinant regions HCDR1, HCDR2, and HCDR3 of the antibody heavy chain variable region, and three complementary determinant regions LCDR1, LCDR2, and LCDR3 of the antibody light chain variable region, wherein the amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:51, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:52, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:53; His / His-HCl, which provides a pH of 5-7; 2-10% (w / v) sorbitol; 0-0.1% (w / v) PS80; and 0-20 mM methionine.

[0237] In this application, the liquid formulation may comprise: 50-150 mg / mL anti-IgE antibody, wherein the anti-IgE antibody comprises three complementary determinant regions HCDR1, HCDR2, and HCDR3 of the antibody heavy chain variable region, and three complementary determinant regions LCDR1, LCDR2, and LCDR3 of the antibody light chain variable region, wherein the amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:51, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:52, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:53; His / His-HCl, providing a pH of 5.3-6.4; 3%-5.5% (w / v) sorbitol; 0.005%-0.02% (w / v) PS80; and 0-10 mM methionine.

[0238] In this application, the liquid formulation may comprise: 90-110 mg / mL anti-IgE antibody, wherein the anti-IgE antibody comprises three complementary determinant regions HCDR1, HCDR2, and HCDR3 of the antibody heavy chain variable region, and three complementary determinant regions LCDR1, LCDR2, and LCDR3 of the antibody light chain variable region, wherein the amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:51, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:52, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:53; His / His-HCl, providing a pH of 5.4-6.4; 4.5%-5.5% (w / v) sorbitol; 0.01%-0.02% (w / v) PS80; and 0-10 mM methionine.

[0239] In this application, the liquid formulation may comprise: 10-200 mg / mL anti-IgE antibody; His / His-HCl, providing a pH of 5-7; 2-10% (w / v) sorbitol; 0-0.1% (w / v) PS80; and 0-20 mM methionine, wherein the anti-IgE antibody comprises three complementarity-determining regions HCDR1, HCDR2, and HCDR3 of the antibody heavy chain variable region, and three complementarity-determining regions LCDR1, LCDR2, and LCDR3 of the antibody light chain variable region, wherein the amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are selected from any of the following combinations:

[0240] (1) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:10, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:11.

[0241] (2) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:26, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30; and

[0242] (3) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30.

[0243] In this application, the liquid formulation may comprise: 50-150 mg / mL anti-IgE antibody; His / His-HCl, providing a pH of 5.3-6.4; 3%-5.5% (w / v) sorbitol; 0.005%-0.02% (w / v) PS80; and 0-10 mM methionine, wherein the anti-IgE antibody comprises three complementarity-determining regions HCDR1, HCDR2, and HCDR3 of the antibody heavy chain variable region, and three complementarity-determining regions LCDR1, LCDR2, and LCDR3 of the antibody light chain variable region, wherein the amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are selected from any one of the following combinations:

[0244] (1) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:10, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:11.

[0245] (2) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:26, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30; and

[0246] (3) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30.

[0247] In this application, the liquid formulation may comprise: 90-110 mg / mL anti-IgE antibody; His / His-HCl, providing a pH of 5.4-6.4; 4.5%-5.5% (w / v) sorbitol; 0.01%-0.02% (w / v) PS80; and 0-10 mM methionine, wherein the anti-IgE antibody comprises three complementarity-determining regions HCDR1, HCDR2, and HCDR3 of the antibody heavy chain variable region, and three complementarity-determining regions LCDR1, LCDR2, and LCDR3 of the antibody light chain variable region, wherein the amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are selected from any of the following combinations:

[0248] (1) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:10, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:11.

[0249] (2) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:26, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30; and

[0250] (3) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30.

[0251] In this application, the liquid formulation may comprise: 10-200 mg / mL anti-IgE antibody, wherein the anti-IgE antibody comprises three complementary determinant regions HCDR1, HCDR2, and HCDR3 of the antibody heavy chain variable region, and three complementary determinant regions LCDR1, LCDR2, and LCDR3 of the antibody light chain variable region, wherein the amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:51, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:52, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:53; 0-100 mM His / His-HCl, which provides a pH of 5-7; 2-10% (w / v) sorbitol; and 0-0.1% (w / v) PS80.

[0252] In this application, the liquid formulation may comprise: 50-150 mg / mL anti-IgE antibody, wherein the anti-IgE antibody comprises three complementary determinant regions HCDR1, HCDR2, and HCDR3 of the antibody heavy chain variable region, and three complementary determinant regions LCDR1, LCDR2, and LCDR3 of the antibody light chain variable region, wherein the amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:51, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:52, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:53; 5-20 mM His / His-HCl, providing a pH of 5.3-6.4; 3%-5.5% (w / v) sorbitol; and 0.005%-0.02% (w / v) PS80.

[0253] In this application, the liquid formulation may comprise: 90-110 mg / mL anti-IgE antibody, wherein the anti-IgE antibody comprises three complementary determinant regions HCDR1, HCDR2, and HCDR3 of the antibody heavy chain variable region, and three complementary determinant regions LCDR1, LCDR2, and LCDR3 of the antibody light chain variable region, wherein the amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:51, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:52, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:53; 8-12 mM His / His-HCl, providing a pH of 5.4-6.4; 4.5%-5.5% (w / v) sorbitol; and 0.01%-0.02% (w / v) PS80.

[0254] In this application, the liquid formulation may comprise: 10-200 mg / mL anti-IgE antibody; 0-100 mM His / His-HCl, providing a pH of 5-7; 2-10% (w / v) sorbitol; and 0-0.1% (w / v) PS80, wherein the anti-IgE antibody comprises three complementarity-determining regions HCDR1, HCDR2, and HCDR3 of the antibody heavy chain variable region, and three complementarity-determining regions LCDR1, LCDR2, and LCDR3 of the antibody light chain variable region, wherein the amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are selected from any group of the following combinations:

[0255] (1) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:10, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:11.

[0256] (2) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:26, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30; and

[0257] (3) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30.

[0258] In this application, the liquid formulation may comprise: 50-150 mg / mL anti-IgE antibody; 5-20 mM His / His-HCl, providing a pH of 5.3-6.4; 3%-5.5% (w / v) sorbitol; 0.005%-0.02% (w / v) PS80, wherein the anti-IgE antibody comprises three complementary determinant regions HCDR1, HCDR2, and HCDR3 of the antibody heavy chain variable region, and three complementary determinant regions LCDR1, LCDR2, and LCDR3 of the antibody light chain variable region, wherein the amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are selected from any group of the following combinations:

[0259] (1) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:10, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:11.

[0260] (2) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:26, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30; and

[0261] (3) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30.

[0262] In this application, the liquid formulation may comprise: 90-110 mg / mL anti-IgE antibody; 8-12 mM His / His-HCl, providing a pH of 5.4-6.4; 4.5%-5.5% (w / v) sorbitol; and 0.01%-0.02% (w / v) PS80, wherein the anti-IgE antibody comprises three complementarity-determining regions HCDR1, HCDR2, and HCDR3 of the antibody heavy chain variable region, and three complementarity-determining regions LCDR1, LCDR2, and LCDR3 of the antibody light chain variable region, wherein the amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are selected from any group of the following combinations:

[0263] (1) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:10, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:11.

[0264] (2) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:26, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30; and

[0265] (3) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30.

[0266] In this application, the liquid formulation may comprise: 10-200 mg / mL anti-IgE antibody, wherein the anti-IgE antibody comprises three complementary determinant regions HCDR1, HCDR2, and HCDR3 of the antibody heavy chain variable region, and three complementary determinant regions LCDR1, LCDR2, and LCDR3 of the antibody light chain variable region, wherein the amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:51, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:52, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:53; 0-100 mM His / His-HCl, which provides a pH of 5-7; 2-10% (w / v) sorbitol; 0-0.1% (w / v) PS80; and 0-20 mM methionine.

[0267] In this application, the liquid formulation may comprise: 50-150 mg / mL anti-IgE antibody, wherein the anti-IgE antibody comprises three complementary determinant regions HCDR1, HCDR2, and HCDR3 of the antibody heavy chain variable region, and three complementary determinant regions LCDR1, LCDR2, and LCDR3 of the antibody light chain variable region, wherein the amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:51, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:52, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:53; 5-20 mM His / His-HCl, providing a pH of 5.3-6.4; 3%-5.5% (w / v) sorbitol; 0.005%-0.02% (w / v) PS80; and 0-10 mM methionine.

[0268] In this application, the liquid formulation may comprise: 90-110 mg / mL anti-IgE antibody, wherein the anti-IgE antibody comprises three complementary determinant regions HCDR1, HCDR2, and HCDR3 of the antibody heavy chain variable region, and three complementary determinant regions LCDR1, LCDR2, and LCDR3 of the antibody light chain variable region, wherein the amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:51, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:52, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:53; 8-12 mM His / His-HCl, providing a pH of 5.4-6.4; 4.5%-5.5% (w / v) sorbitol; 0.01%-0.02% (w / v) PS80; and 0-10 mM methionine.

[0269] In this application, the liquid formulation may comprise: 10-200 mg / mL anti-IgE antibody; 0-100 mM His / His-HCl, providing a pH of 5-7; 2-10% (w / v) sorbitol; 0-0.1% (w / v) PS80; and 0-20 mM methionine, wherein the anti-IgE antibody comprises three complementarity-determining regions HCDR1, HCDR2, and HCDR3 of the antibody heavy chain variable region, and three complementarity-determining regions LCDR1, LCDR2, and LCDR3 of the antibody light chain variable region, wherein the amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are selected from any group of the following combinations:

[0270] (1) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:10, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:11.

[0271] (2) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:26, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30; and

[0272] (3) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30.

[0273] In this application, the liquid formulation may comprise: 50-150 mg / mL anti-IgE antibody; 5-20 mM His / His-HCl, providing a pH of 5.3-6.4; 3%-5.5% (w / v) sorbitol; 0.005%-0.02% (w / v) PS80; and 0-10 mM methionine, wherein the anti-IgE antibody comprises three complementarity-determining regions HCDR1, HCDR2, and HCDR3 of the antibody heavy chain variable region, and three complementarity-determining regions LCDR1, LCDR2, and LCDR3 of the antibody light chain variable region, wherein the amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are selected from any group of the following combinations:

[0274] (1) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:10, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:11.

[0275] (2) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:26, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30; and

[0276] (3) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30.

[0277] In this application, the liquid formulation may comprise: 90-110 mg / mL anti-IgE antibody; 8-12 mM His / His-HCl providing a pH of 5.4-6.4; 4.5%-5.5% (w / v) sorbitol; 0.01%-0.02% (w / v) PS80; and 0-10 mM methionine, wherein the anti-IgE antibody comprises three complementarity-determining regions HCDR1, HCDR2, and HCDR3 of the antibody heavy chain variable region, and three complementarity-determining regions LCDR1, LCDR2, and LCDR3 of the antibody light chain variable region, wherein the amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are selected from any group of the following combinations:

[0278] (1) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:10, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:11.

[0279] (2) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:26, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30; and

[0280] (3) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30.

[0281] In this application, the liquid formulation may comprise: 10-200 mg / mL anti-IgE antibody, wherein the anti-IgE antibody comprises an antibody heavy chain variable region VH and an antibody light chain variable region VL, the amino acid sequence of the VH being as shown in SEQ ID NO:8, SEQ ID NO:21, SEQ ID NO:28, SEQ ID NO:37 or SEQ ID NO:41, and the amino acid sequence of the VL being as shown in SEQ ID NO:16, SEQ ID NO:25, SEQ ID NO:35 or SEQ ID NO:40; His / His-HCl, providing a pH of 5-7; 2-10% (w / v) sorbitol; and 0-0.1% (w / v) PS80.

[0282] In this application, the liquid formulation may comprise: 50-150 mg / mL anti-IgE antibody, wherein the anti-IgE antibody comprises an antibody heavy chain variable region VH and an antibody light chain variable region VL, the amino acid sequence of the VH being as shown in SEQ ID NO:8, SEQ ID NO:21, SEQ ID NO:28, SEQ ID NO:37 or SEQ ID NO:41, and the amino acid sequence of the VL being as shown in SEQ ID NO:16, SEQ ID NO:25, SEQ ID NO:35 or SEQ ID NO:40; His / His-HCl, providing a pH of 5.3-6.4; 3%-5.5% (w / v) sorbitol; and 0.005%-0.02% (w / v) PS80.

[0283] In this application, the liquid formulation may comprise: 90-110 mg / mL anti-IgE antibody, wherein the anti-IgE antibody comprises an antibody heavy chain variable region VH and an antibody light chain variable region VL, the amino acid sequence of the VH being as shown in SEQ ID NO:8, SEQ ID NO:21, SEQ ID NO:28, SEQ ID NO:37 or SEQ ID NO:41, and the amino acid sequence of the VL being as shown in SEQ ID NO:16, SEQ ID NO:25, SEQ ID NO:35 or SEQ ID NO:40; His / His-HCl, providing a pH of 5.4-6.4; 4.5%-5.5% (w / v) sorbitol; and 0.01%-0.02% (w / v) PS80.

[0284] In this application, the liquid formulation may comprise: 10-200 mg / mL anti-IgE antibody, wherein the anti-IgE antibody comprises an antibody heavy chain variable region VH and an antibody light chain variable region VL, the amino acid sequence of the VH being as shown in SEQ ID NO:8, SEQ ID NO:21, SEQ ID NO:28, SEQ ID NO:37 or SEQ ID NO:41, and the amino acid sequence of the VL being as shown in SEQ ID NO:16, SEQ ID NO:25, SEQ ID NO:35 or SEQ ID NO:40; 0-100 mM His / His-HCl, providing a pH of 5-7; 2-10% (w / v) sorbitol; and 0-0.1% (w / v) PS80.

[0285] In this application, the liquid formulation may comprise: 50-150 mg / mL anti-IgE antibody, wherein the anti-IgE antibody comprises an antibody heavy chain variable region VH and an antibody light chain variable region VL, the amino acid sequence of the VH being as shown in SEQ ID NO:8, SEQ ID NO:21, SEQ ID NO:28, SEQ ID NO:37 or SEQ ID NO:41, and the amino acid sequence of the VL being as shown in SEQ ID NO:16, SEQ ID NO:25, SEQ ID NO:35 or SEQ ID NO:40; 5-20 mM His / His-HCl, providing a pH of 5.3-6.4; 3%-5.5% (w / v) sorbitol; and 0.005%-0.02% (w / v) PS80.

[0286] In this application, the liquid formulation may comprise: 90-110 mg / mL anti-IgE antibody, wherein the anti-IgE antibody comprises an antibody heavy chain variable region VH and an antibody light chain variable region VL, the amino acid sequence of the VH being as shown in SEQ ID NO:8, SEQ ID NO:21, SEQ ID NO:28, SEQ ID NO:37 or SEQ ID NO:41, and the amino acid sequence of the VL being as shown in SEQ ID NO:16, SEQ ID NO:25, SEQ ID NO:35 or SEQ ID NO:40; 8-12 mM His / His-HCl, providing a pH of 5.4-6.4; 4.5%-5.5% (w / v) sorbitol; and 0.01%-0.02% (w / v) PS80.

[0287] In this application, the liquid formulation may comprise: 10-200 mg / mL anti-IgE antibody, wherein the anti-IgE antibody comprises an antibody heavy chain variable region VH and an antibody light chain variable region VL, the amino acid sequence of the VH being as shown in SEQ ID NO:8, SEQ ID NO:21, SEQ ID NO:28, SEQ ID NO:37 or SEQ ID NO:41, and the amino acid sequence of the VL being as shown in SEQ ID NO:16, SEQ ID NO:25, SEQ ID NO:35 or SEQ ID NO:40; His / His-HCl, providing a pH of 5-7; 2-10% (w / v) sorbitol; 0-0.1% (w / v) PS80; and 0-20 mM methionine.

[0288] In this application, the liquid formulation may comprise: 50-150 mg / mL anti-IgE antibody, wherein the anti-IgE antibody comprises an antibody heavy chain variable region VH and an antibody light chain variable region VL, the amino acid sequence of the VH being as shown in SEQ ID NO:8, SEQ ID NO:21, SEQ ID NO:28, SEQ ID NO:37 or SEQ ID NO:41, and the amino acid sequence of the VL being as shown in SEQ ID NO:16, SEQ ID NO:25, SEQ ID NO:35 or SEQ ID NO:40; His / His-HCl, providing a pH of 5.3-6.4; 3%-5.5% (w / v) sorbitol; 0.005%-0.02% (w / v) PS80; and 0-10 mM methionine.

[0289] In this application, the liquid formulation may comprise: 90-110 mg / mL anti-IgE antibody, wherein the anti-IgE antibody comprises an antibody heavy chain variable region VH and an antibody light chain variable region VL, the amino acid sequence of the VH being as shown in SEQ ID NO:8, SEQ ID NO:21, SEQ ID NO:28, SEQ ID NO:37 or SEQ ID NO:41, and the amino acid sequence of the VL being as shown in SEQ ID NO:16, SEQ ID NO:25, SEQ ID NO:35 or SEQ ID NO:40; His / His-HCl, providing a pH of 5.4-6.4; 4.5%-5.5% (w / v) sorbitol; 0.01%-0.02% (w / v) PS80; and 0-10 mM methionine.

[0290] On the other hand, this application provides a unit dosage form that may contain:

[0291] (1) 10-200 mg / mL anti-IgE antibody;

[0292] (2) His / His-HCl, which provides a pH of 5-7;

[0293] (3) 2-10% (w / v) sorbitol; and

[0294] (4) 0-0.1% (w / v) PS80,

[0295] The anti-IgE antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3. The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:51, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, and the amino acid sequence of LCDR2 is shown in SEQ ID NO:52.

[0296] The amino acid sequence of LCDR3 is shown in SEQ ID NO:53.

[0297] On the other hand, this application provides a unit dosage form that may contain:

[0298] (1) 50-150 mg / mL anti-IgE antibody;

[0299] (2) His / His-HCl, which provides a pH of 5.3-6.4;

[0300] (3) 3%-5.5% (w / v) sorbitol; and

[0301] (4)0.005%-0.02%(w / v)PS80,

[0302] The anti-IgE antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3. The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:51, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, and the amino acid sequence of LCDR2 is shown in SEQ ID NO:52.

[0303] The amino acid sequence of LCDR3 is shown in SEQ ID NO:53.

[0304] On the other hand, this application provides a unit dosage form that may contain:

[0305] (1) 90-110 mg / mL anti-IgE antibody;

[0306] (2) His / His-HCl, which provides a pH of 5.4-6.4;

[0307] (3) 4.5%-5.5% (w / v) sorbitol; and

[0308] (4)0.01%-0.02%(w / v)PS80,

[0309] The anti-IgE antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3. The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:51, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:52, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:53.

[0310] On the other hand, this application provides a unit dosage form that may contain:

[0311] (1) 10-200 mg / mL anti-IgE antibody;

[0312] (2) His / His-HCl, which provides a pH of 5-7;

[0313] (3) 2-10% (w / v) sorbitol; and

[0314] (4) 0-0.1% (w / v) PS80,

[0315] The anti-IgE antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are selected from any of the following combinations:

[0316] 1) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:10, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:11.

[0317] 2) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:26, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30; and

[0318] 3) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30.

[0319] On the other hand, this application provides a unit dosage form that may contain:

[0320] (1) 50-150 mg / mL anti-IgE antibody;

[0321] (2) His / His-HCl, which provides a pH of 5.3-6.4;

[0322] (3) 3%-5.5% (w / v) sorbitol; and

[0323] (4)0.005%-0.02%(w / v)PS80,

[0324] The anti-IgE antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are selected from any of the following combinations:

[0325] (1) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:10, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:11.

[0326] (2) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:26, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30; and

[0327] (3) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30.

[0328] On the other hand, this application provides a unit dosage form that may contain:

[0329] (1) 90-110 mg / mL anti-IgE antibody;

[0330] (2) His / His-HCl, which provides a pH of 5.4-6.4;

[0331] (3) 4.5%-5.5% (w / v) sorbitol; and

[0332] (4)0.01%-0.02%(w / v)PS80,

[0333] The anti-IgE antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are selected from any of the following combinations:

[0334] (1) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:10, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:11.

[0335] (2) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:26, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30; and

[0336] (3) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30.

[0337] On the other hand, this application provides a unit dosage form that may contain:

[0338] (1) 10-200 mg / mL anti-IgE antibody;

[0339] (2) His / His-HCl, which provides a pH of 5-7;

[0340] (3) 2-10% (w / v) sorbitol;

[0341] (4) 0-0.1% (w / v) PS80; and

[0342] (5) 0-20mM methionine,

[0343] The anti-IgE antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3. The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:51, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:52, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:53.

[0344] On the other hand, this application provides a unit dosage form that may contain:

[0345] (1) 50-150 mg / mL anti-IgE antibody;

[0346] (2) His / His-HCl, which provides a pH of 5.3-6.4;

[0347] (3) 3%-5.5% (w / v) sorbitol;

[0348] (4) 0.005%-0.02% (w / v) PS80; and

[0349] (5) 0-10mM methionine,

[0350] The anti-IgE antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3. The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:51, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:52, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:53.

[0351] On the other hand, this application provides a unit dosage form that may contain:

[0352] (1) 90-110 mg / mL anti-IgE antibody;

[0353] (2) His / His-HCl, which provides a pH of 5.4-6.4;

[0354] (3) 4.5%-5.5% (w / v) sorbitol;

[0355] (4) 0.01%-0.02% (w / v) PS80; and

[0356] (5) 0-10mM methionine,

[0357] The anti-IgE antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3. The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:51, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:52, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:53.

[0358] On the other hand, this application provides a unit dosage form that may contain:

[0359] (1) 10-200 mg / mL anti-IgE antibody;

[0360] (2) His / His-HCl, which provides a pH of 5-7;

[0361] (3) 2-10% (w / v) sorbitol;

[0362] (4) 0-0.1% (w / v) PS80; and

[0363] (5) 0-20mM methionine,

[0364] The anti-IgE antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are selected from any of the following combinations:

[0365] (1) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:10, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:11.

[0366] (2) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:26, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30; and

[0367] (3) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30.

[0368] On the other hand, this application provides a unit dosage form that may contain:

[0369] (1) 50-150 mg / mL anti-IgE antibody;

[0370] (2) His / His-HCl, which provides a pH of 5.3-6.4;

[0371] (3) 3%-5.5% (w / v) sorbitol;

[0372] (4) 0.005%-0.02% (w / v) PS80; and

[0373] (5) 0-10 mM methionine, wherein the anti-IgE antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, and the amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are selected from any of the following combinations:

[0374] (1) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:10, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:11.

[0375] (2) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:26, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30; and

[0376] (3) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30.

[0377] On the other hand, this application provides a unit dosage form that may contain:

[0378] (1) 90-110 mg / mL anti-IgE antibody;

[0379] (2) His / His-HCl, which provides a pH of 5.4-6.4;

[0380] (3) 4.5%-5.5% (w / v) sorbitol;

[0381] (4) 0.01%-0.02% (w / v) PS80; and

[0382] (5) 0-10mM methionine,

[0383] The anti-IgE antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are selected from any of the following combinations:

[0384] (1) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:10, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:11.

[0385] (2) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:26, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30; and

[0386] (3) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30.

[0387] On the other hand, this application provides a lyophilized formulation comprising the liquid formulation and a lyophilization protectant. In this application, the lyophilization protectant can be a low-molecular-weight compound or a high-molecular-weight compound. For example, the low-molecular-weight compound can be an acidic, neutral, or basic substance. For example, the high-molecular-weight compound can be gelatin, albumin, gum arabic, serum, or pectin. In this application, the lyophilization protectant can be a protectant, a filler, an antioxidant, or a pH adjuster. For example, the protectant can be glycerol, dimethyl sulfoxide, trehalose, sucrose, or polyvinylpyrrolidone. For example, the filler can be mannitol, lactose, or gelatin. For example, the antioxidant can be vitamin D, vitamin E, protein hydrolysate, or sodium thiosulfate. For example, the pH adjuster can be phosphoric acid, sorbitol, EDTA, or an amino acid. In this application, the lyophilization protectant can be a sugar, alcohol, amino acid, salt, or a derivative thereof.

[0388] In this application, the liquid or lyophilized formulation can be administered via intraperitoneal, intraspinal, intra-articular, intrasynovial, intrathecal, oral, topical, inhalation, subcutaneous, intramuscular, or intravenous routes. For example, the formulation can be administered to a subject in need by continuous infusion over a period of time. In this application, the administration can be performed by injecting the formulation using an injection device. In this application, the injection device can be a syringe, injection pen, automatic injection device, patch pump, etc.

[0389] In this application, the formulation can be used in combination with one or more other active ingredients. For example, the formulation can be used in combination with one or more other therapeutic agents. In this application, the formulation and active ingredient can be administered separately, simultaneously, or sequentially. In this application, the formulation and active ingredient can be administered at the same or different doses or routes of administration. For example, the formulation and active ingredient in this application can be administered to a patient as separate entities at the same / different doses or routes of administration. In this application, the formulation and active ingredient can be administered to a patient simultaneously as a single entity or dose. For example, the formulation and active ingredient can be administered to a patient simultaneously, jointly, or sequentially as separate entities. In this application, the specific route of administration can be determined according to the category of the active ingredient, and the specific dosage can be adjusted according to the severity of the subject's condition, the subject's physical condition, etc.

[0390] On the other hand, this application provides a kit and / or device comprising the liquid formulation and / or the lyophilized formulation, and a container holding the liquid formulation and / or the lyophilized formulation. In this application, the container may be a bottle, vial, syringe, test tube, or other container component into which the liquid formulation or lyophilized formulation can be placed. For example, the vial may be a dual-chamber vial. For example, the syringe may be a single-chamber or dual-chamber syringe. In this application, the container may be made of various materials. For example, the material may be glass or plastic. In this application, the container may be reusable or repeatedly administered. In this application, the kit and / or device may further include a second container containing a suitable diluent. In this application, a reconstituted formulation with a suitable anti-IgE antibody concentration can be obtained by mixing the diluent and the lyophilized formulation.

[0391] On the other hand, this application provides methods for preparing the liquid formulation, the lyophilized formulation, and / or the kit and / or device.

[0392] use

[0393] On the other hand, this application provides the use of the liquid formulation or the lyophilized formulation in the preparation of a medicament for the prevention, diagnosis and / or treatment of diseases and / or conditions.

[0394] On the other hand, this application provides a method for preventing, diagnosing and / or treating diseases and / or conditions, comprising administering the liquid formulation or the lyophilized formulation to a subject in need.

[0395] On the other hand, this application provides the liquid formulation or the lyophilized formulation for the prevention, diagnosis and / or treatment of diseases and / or conditions.

[0396] In this application, the prevention, diagnosis, and / or treatment may be to prevent the onset of the disease, slow down or reverse the disease progression, prevent or slow down the onset of one or more symptoms associated with the disease, reduce or alleviate one or more symptoms associated with the disease, reduce the severity and duration of the disease and any symptoms associated therewith, prevent further increase in the severity of the disease and any symptoms associated therewith, or diagnose the presence and severity of the disease.

[0397] In this application, the disease can be an IgE-related disease. In this application, the disease can be an IgE-mediated disease.

[0398] In this application, the disease may be asthma, chronic urticaria, food allergy, nasal polyps, and / or allergic rhinitis.

[0399] The embodiments described below are not intended to be limited by any theory, but are merely for illustrating the formulations, preparation methods and uses of this application, and are not intended to limit the scope of the invention.

[0400] Example

[0401] Detection method:

[0402] Appearance inspection: The appearance of the solution was examined in accordance with the Chinese Pharmacopoeia 2020 edition, namely "0901 Solution Color Inspection Method" and "0902 Clarity Inspection Method".

[0403] Turbidity detection: Utilizing the scattering of light by particles, the difference in ultraviolet absorbance is reflected in the absorbance at 340 / 320 nm using an ultraviolet spectrophotometer.

[0404] SE-HPLC detection: The SE-HPLC column was packed with a chromatographic gel suitable for separating proteins with molecular weights of 10–500 kD. The mobile phase was 50 mM acetate / sodium acetate buffer, 0.2 M arginine hydrochloride, pH 5.0, and the detection wavelength was 280 nm. The test sample was diluted to the analytical concentration with sample buffer to prepare the test solution, which was then injected into the HPLC system. The monomer purity was calculated using the area normalization method to investigate the formation of aggregates or degradation products.

[0405] CE-SDS (nr&r) detection: The purity of monoclonal antibody products was quantitatively determined by capillary electrophoresis (CE-SDS) under both reducing and non-reducing conditions, based on molecular weight, using capillary electrophoresis. A diode array detector was used. Acquisition wavelength: 220 nm. The purity of the main peak was calculated using the area normalization method, as the percentage of the area of ​​the main peak's correction peak relative to the sum of the areas of all correction peaks.

[0406] icIEF detection: Whole-column imaging capillary isoelectric focusing electrophoresis (icIEF) separates different charge variants based on their isoelectric point (pI) characteristics, according to capillary electrophoresis (Chinese Pharmacopoeia 2020 General Chapter 0542). The isoelectric point of each charge variant in the monoclonal antibody product is determined, and its relative percentage content is calculated. A whole-column imaging capillary isoelectric focusing electrophoresis system is used, employing an ultraviolet detector at a wavelength of 280 nm, and a capillary-coated quartz capillary as the separation medium.

[0407] kD & B22 assays: The Uncle (Unchinedlabs) multi-functional protein stability analyzer was used to examine the interactions between protein colloids. Kd (diffusion interaction parameter) is determined by observing the diffusion coefficient as concentration increases. If protein interactions increase with concentration (mutual attraction), the proteins behave as if they have increased in size, and the diffusion coefficient decreases (negative slope). If protein interactions decrease with concentration (mutual repulsion), the proteins behave as if they have decreased in size, and the diffusion coefficient increases (positive slope). B22 is the second virial coefficient, similar to kD, but it excludes some protein solvent effects, precipitation effects, and thermodynamic phenomena. Changes in salt, pH, and temperature affect these interactions, which are influenced by the apparent molecular weight of the protein.

[0408] Tm & Tagg assay: The prepared samples were subjected to thermal stability studies using the Uncle (Unchinedlabs) multifunctional protein stability analyzer. The heating range was 20-95℃, and the heating rate was 0.5℃ / min. The Tm & Tagg parameters reflecting the thermal stability of protein structure were measured.

[0409] Osmotic pressure measurement: The freezing point depression of a solution is proportional to the molar concentration of the solute. The osmotic pressure of the solution is calculated by measuring the freezing point depression.

[0410] Activity (ELISA method): The prepared sample aims to treat related diseases by inhibiting or blocking the binding of IgE to its receptor (FcεRI). The activity of the sample is evaluated at the ELISA level by the effect of the sample on inhibiting or blocking the binding of IgE to its receptor (FcεRI).

[0411] Example 1: Screening and confirming the pH range

[0412] Different pH gradient buffer solutions were prepared as shown in Table 1.

[0413] Table 1 Information on buffer solutions for each pH gradient

[0414] The experimental steps are as follows:

[0415] 1) Concentrate the anti-IgE antibody (SE5ss, heavy chain amino acid sequence as shown in SEQ ID NO:49, light chain amino acid sequence as shown in SEQ ID NO:48) and change the solution to a 10mM His / His HCl system at pH 6.0, and control the protein concentration at approximately 10mg / mL.

[0416] 2) Mix with the 8 buffer solutions in Table 1 at a ratio of 1:9 (volume ratio) to prepare 8 formulations with a concentration of 1.0 mg / mL and a pH range of 3.5-8.3. Dispense into 1.0 mL vials and store at 37°C for 14 days.

[0417] 3) Samples were subjected to appearance inspection, turbidity detection, SE-HPLC detection, nrCE-SDS purity detection, and rCE-SDS purity detection at 37℃ / 14d.

[0418] The experimental results are as follows:

[0419] The appearance test results are shown in Table 2. The experimental results show that there is no significant difference in appearance among the formulations at pH 3.5-4.9, and trace amounts of white granular / flocculated precipitate can be seen in all of them. When the pH is 6.3, the protein solution changes from colorless to light yellow.

[0420] Table 2 Appearance Inspection Results

[0421] The turbidity test results are shown in Table 3. The experimental results show that, except for the formation of more particles at pH 6.3, there is no significant difference in turbidity at pH 3.5-5.6 and pH 7.0-8.3.

[0422] Table 3 Turbidity Detection Results

[0423] The SE-HPLC purity test results are shown in Figure 1. In the pH range of 3.5-4.9, the content of the main peak is low due to the formation of a large number of aggregates. In the pH range of 5.6-8.3, the content of the main peak is high, which is suitable for formulation screening.

[0424] The purity test results of nrCE-SDS are shown in Figure 2. At pH 3.5-4.9 and pH 8.3, the main peak content is low due to the formation of a large number of fragments and a small number of aggregates. In the pH range of 5.6-7.7, the main peak content is high, which is suitable for formulation screening.

[0425] The purity test results of rCE-SDS are shown in Figure 3. In the pH range of 3.5-4.9, the main peak content is low due to the formation of a large number of fragments. In the pH range of 5.6-8.3, the fragment content is low, which is suitable for formulation screening.

[0426] The above experimental results show that formulations with pH 3.5-4.9 form a large number of aggregates and fragments, and those with pH 8.3 form a large number of fragments, making them unsuitable for subsequent formulations. Therefore, further research will be conducted on buffer systems with pH 5.6-7.7 in the next stage of formulation development.

[0427] Example 2: Narrowing and confirming the pH range

[0428] Different pH gradient buffer solutions were prepared as shown in Table 4.

[0429] Table 4 Information on buffer solutions for each pH gradient

[0430] The experimental steps are as follows:

[0431] 1) Take the anti-IgE antibody (SE5ss) sample, concentrate it, and change the solution into the 9 formulations in Table 4. The protein concentration should be controlled at about 20 mg / mL.

[0432] 2) Fill 1mL / vial into vials and store at 5℃ and 37℃ for 13 days respectively.

[0433] 3) After 13 days, the samples were subjected to appearance testing, turbidity testing, Tm & Tagg testing, KD & B22 testing, SE-HPLC testing, icIEF protein charge heterogeneity testing, nrCE-SDS purity testing, and rCE-SDS purity testing.

[0434] The experimental results are as follows:

[0435] The appearance and turbidity test results are shown in Table 5. The experimental results show that after being placed at 37℃ for 13 days, there is no significant difference in appearance and turbidity among the buffer system formulations with pH 5.5-6.5. The buffer system formulation with pH 7.0 has an opalescent appearance.

[0436] Table 5. Results of Appearance and Turbidity Tests

[0437] The Tm & Tagg test results are shown in Table 6. The experimental results show that Ac5.5, H-HCl5.5, H-NaAc5.5, H-HCl6.0, and CA6.0 have higher Tagg 266 values, are less likely to form aggregates, are more stable, and are suitable for formulation. CA5.5, H-NaAc6.0, PB6.5, and PB7.0 have lower Tagg 266 values, are more likely to form aggregates, and are not conducive to subsequent formulation development.

[0438] Table 6. Detection results of predictive parameters Tm & Tagg.

[0439] The KD (diffusion interaction index) and B22 results are shown in Table 7. The experimental results indicate that AC5.5, H-HCl5.5, H-NaAc5.5, H-HCl6.0, and H-NaAc6.0 have positive KD and B22 values, indicating repulsive intermolecular forces and long-term stability of the formulation system. CA5.5, CA6.0, PB6.5, and PB7 have negative KD and B22 values, indicating attractive intermolecular forces and an unstable state.

[0440] Table 7. Detection results of the predictive parameter KD&B22

[0441] The SE-HPLC purity detection results are shown in Figures 4A and 4B. All nine formulations showed high main peak percentages and high purity. Among them, the four formulations at pH 5.5 (93.5%–94.4%) showed little difference from the three formulations at pH 6.0 (93.4%–94.3%), and were slightly better than the two formulations at pH 6.5 and pH 7.0 (92.0%–92.9%). Among the formulations at pH 5.5 and pH 6.0, the CA5.5 and CA6.0 formulations (93.5%, 93.4%) were worse than the other formulations at the same pH. This suggests that the acetate buffer system (AC) and histidine buffer system (H-HCl and H-NaAc) are more conducive to protein stability than the citrate buffer system (CA). Within the pH range of pH 5.5–pH 6.0 of the former buffer system, the protein stability is higher.

[0442] The nrCE-SDS purity test results are shown in Figures 5A and 5B. Similar to the SE-HPLC results, the main peak results of the pH 5.5 and pH 6.0 formulations are similar, slightly better than those of pH 6.5 and pH 7.0. Among the formulations at pH 5.5 and pH 6.0, the results of the CA 5.5 and CA 6.0 formulations (88.5%, 86.1%) are worse than those of other formulations at the same pH. This suggests that the acetate buffer system (AC) and histidine buffer system (H-HCl and H-NaAc) are more conducive to protein stability than the citrate buffer system (CA). The protein stability is higher in the pH range of pH 5.5-pH 6.0 of the former buffer system.

[0443] The rCE-SDS purity test results are shown in Figure 6. After being placed at 37°C for 13 days, no significant change was observed in the content of the main peak (LC+HC) in the nine formulations, and there was no significant difference between the formulations.

[0444] The icIEF protein charge heterogeneity detection results are shown in Figures 7A-7C. Similar to the results of SE-HPLC and nrCE-SDS, the pH 5.5 and pH 6.0 formulations showed similar results, outperforming those at pH 6.5 and pH 7.0. Among the pH 5.5 and pH 6.0 formulations, the acid peaks (42.5% and 41.1%) of the CA 5.5 and CA 6.0 formulations were higher than those of other formulations at the same pH, suggesting that the citrate buffer (CA) system is unfavorable for protein stability and easily forms acid peaks. Protein stability is higher within the pH range of 5.5-6.0 using the acetate buffer (AC) system and histidine buffer systems (H-HCl and H-NaAc).

[0445] In summary, proteins exhibit good stability, high purity, and low charge heterogeneity in His / His-HCl and His / NaAc buffer systems. Buffer systems at pH 5.5-7.0 demonstrate some stability, with pH 5.5-6.0 showing slightly better stability than others. The types and pH values ​​of the buffers mentioned are suitable for formulation.

[0446] Example 3: Screening and Confirmation of Excipients

[0447] The anti-IgE antibody (SE5ss) protein concentration of 100 mg / mL was selected and further studied by adding different excipients to His / His-HCl buffer system and His / NaAc buffer system at pH 5.8. The different excipient formulations are shown in Table 8.

[0448] Table 8. Excipient Formulation Information

[0449] The experimental steps are as follows:

[0450] 1) Excipient selection: Pharmaceutical excipients that can inhibit aggregate formation and regulate osmotic pressure include polysorbate (Sorbitol), sucrose, sodium chloride (NaCl), and arginine hydrochloride (Arg HCl). The anti-IgE antibody sample was concentrated and the buffer was changed to pH 5.8. Eight formulations of His / His-HCl and His / His-NaAc buffer systems containing 0.01% Tween 20 (PS20) and different excipients were prepared, with the protein concentration controlled at approximately 100 mg / mL. Details are shown in Table 8.

[0451] 2) Fill 1mL / vial into vials and store at 5℃ and 37℃ for 12 days respectively.

[0452] 3) After 12 days, the samples were subjected to appearance inspection, turbidity inspection, Tm & Tagg inspection, KD & B22 inspection, SE-HPLC inspection and icIEF protein charge heterogeneity inspection.

[0453] The experimental results are as follows:

[0454] The appearance and turbidity test results are shown in Table 9. The 320nm test results show that after 12 days at 37℃, no significant changes in appearance were observed, but the turbidity of each formulation increased slightly compared to the control. The A320 value of the His / His-HCl formulation containing sorbitol or sucrose was slightly lower than the other six formulations, indicating the lowest particle formation and low turbidity, making it superior to the other formulations.

[0455] Table 9. Results of Appearance and Turbidity Tests

[0456] The Tm and Tagg test results are shown in Table 10. The Tagg results show that the His / His-HCl formulations containing sorbitol or sucrose have higher Tagg values, indicating that they are less prone to aggregate formation and are more stable, making them suitable for pharmaceutical formulations. The Tm results show that the addition of NaCl and Arg HCl slightly increases the Tm1 value compared to the addition of sorbitol and sucrose, meaning that the thermal stability of the samples in this formulation is increased, which is superior to that of sorbitol and sucrose.

[0457] Table 10: Detection results of predictive parameters Tm & Tagg

[0458] KD & B22 assays can be used to test the colloidal stability of proteins. Described through protein-protein interactions, they test the attraction and repulsion between proteins and predict their aggregation tendency. When KD or B22 > 0, it indicates repulsive forces between proteins, suggesting a stable state. When KD or B22 < 0, it indicates attractive forces between proteins, suggesting an unstable state where aggregates are easily formed.

[0459] The KD&B22 test results are shown in Table 11. In the same buffer system, the KD&B22 values ​​of the groups with the excipients sorbitol and sucrose were all positive, indicating intermolecular repulsion, which is beneficial for long-term protein storage. The KD&B22 values ​​of the groups with the excipients NaCl and Arg HCl were negative, indicating intermolecular attraction, which is an unstable state. Among the buffer system formulations with the same excipients, the KD&B22 value of the His / His-HCl buffer system was higher than that of the His / NaAc buffer system, indicating that the protein has higher long-term stability in the His / His-HCl buffer system.

[0460] Table 11 KD&B22 Test Results

[0461] The SE-HPLC results are shown in Figures 8A-8C. After 12 days of storage at 37℃, all formulations formed aggregates and fragments of varying amounts. The main peak contents of the two buffer systems containing sorbitol or sucrose were similar (94.4% vs 94.1%; 93.5% vs 93.7%), with no significant difference. The main peak contents of the His / His HCl buffer system containing NaCl or Arg HCl were superior to those of the His / NaAc buffer system (92.5% vs 91.3%, 93.0% vs 91.3%), indicating that the His / His HCl buffer system was generally superior to the His / NaAc buffer system. Furthermore, sorbitol exhibited the strongest ability to inhibit aggregate and fragment formation, superior to the other three excipients.

[0462] The results of the icIEF protein charge heterogeneity assay are shown in Figures 9A-9C. After being stored at 37℃ for 12 days, the content of the main peak of the anti-IgE antibody decreased (4.5%–6.3%) due to the increase in the acidic peak content, with no significant difference between the formulations. This indicates that the excipients have no significant difference in their effect on the charge isomers of the anti-IgE antibody.

[0463] In conclusion, the formulation of 10mM His / His-HCl + 5% sorbitol + 0.01% PS20 at pH 5.8 is superior to other formulations, indicating that sorbitol is suitable as an excipient for pharmaceutical formulations.

[0464] Example 4: Screening and Confirmation of Surfactant Types and Concentrations

[0465] The study investigated the types and concentrations of surfactants. Using an anti-IgE antibody (SE5ss) protein concentration of approximately 100 mg / mL, different types (Tween 20:PS20; Tween 80:PS80) and different concentrations (0%–0.06%) of surfactants were added to a His / His-HCl + 5% Sorbitol pH 5.8 formulation for further investigation.

[0466] Different surfactant formulations are shown in Table 12.

[0467] Table 12 Surfactant Screening

[0468] The experimental steps are as follows:

[0469] 1) Take the concentrated anti-IgE antibody and replace the solution with one of the 10 formulations in Table 12. The protein concentration should be controlled at about 100 mg / mL. Fill 1 mL / vial into a vial.

[0470] 2) The prepared samples were shaken at room temperature (200 rpm) and left to stand for 7 days.

[0471] 3) The appearance and purity (SE-HPLC) and insoluble particulate matter of the sample were tested (with standing / 7 days as a shaken control).

[0472] The experimental results are as follows:

[0473] The appearance and turbidity test results are shown in Table 13. For each formulation without Tween, after 200 rpm for 7 days, a large number of particles were formed, and the appearance changed from slightly opalescent to white turbidity. After adding different concentrations of PS20 or PS80, particle formation was significantly inhibited. After shaking at 200 rpm for 7 days, there was no obvious change in appearance. Moreover, the A320 value of this formulation was higher than that of other formulations, indicating higher turbidity.

[0474] Table 13 Results of Appearance and Turbidity Tests

[0475] The results of insoluble particulate matter detection are shown in Figures 10A and 10B. The results show that compared to the formulation without Tween, the addition of PS20 or PS80 significantly reduced the number of insoluble particulate matter, indicating that particle formation was significantly inhibited. When PS80 was added as a surfactant and allowed to stand for 7 days, the formation of insoluble particulate matter was partially inhibited at a PS80 concentration of 0.040%, but a considerable number of particles still remained. The group that was shaken for 7 days had a lower number of insoluble particulate matter. Compared to the corresponding formulations that were allowed to stand for 7 days, no significant increase in particles was observed after 7 days of shaking in formulations with PS20 or PS80 content higher than 0.005%. In formulations with 0.005% PS20 or PS80, a slight increase in particles was observed after 7 days of shaking. The results for insoluble particulate matter in all formulations met regulatory requirements (≥10μm, <6000 particles / bottle; ≥25μm, <600 particles / bottle).

[0476] The SE-HPLC purity test results are shown in Figure 11. After shaking (SK) for 7 days, except for the formulation without PS which had a 0.5% decrease in main peak content due to the formation of aggregates, the main peak content of the other formulations with different concentrations of PS20 or PS80 showed no significant difference, and there was no significant change compared with the control after standing for 7 days.

[0477] In summary, adding 0.005%–0.06% PS20 or PS80 to a formulation of 10mM His / His-HCl + 5% sorbitol at pH 5.8 can reduce the number of insoluble particles and is suitable for pharmaceutical formulations.

[0478] Example 5: Screening and Validation of Antioxidants

[0479] To investigate the types of antioxidants, anti-IgE antibody (SE5ss) was concentrated and diluted in a formulation containing 5 mM Met or 1 mM EDTA, with a formulation without added antioxidants serving as a control. The protein concentration was controlled at approximately 100 mg / mL, and 1 mL was filled into vials. Detailed formulations are shown in Table 14. The prepared samples were then placed at 25°C under light for 14 days, at 25°C in the dark for 14 days (as a control of 25°C under light for 14 days), at 37°C for 14 days, and at 5°C for 14 days. Simultaneously, the prepared sample buffers were placed at 25°C under light for 14 days and at 25°C in the dark for 14 days (as a control of 25°C under light for 14 days) for photostable and temperature stability tests.

[0480] The samples underwent appearance inspection, insoluble particulate matter detection, SE-HPLC detection, CE-SDS detection, and icIEF detection.

[0481] Different antioxidant formulations are shown in Table 14.

[0482] Table 14 Screening of Antioxidant Formulations

[0483] The experimental results are as follows:

[0484] 1. Light stability test

[0485] Appearance and turbidity tests showed that after 14 days of light exposure at 25°C, the solution's color changed, becoming darker. No significant color change was observed in the concurrently tested formulation buffer. Insoluble particle detection results are shown in Figure 12. w / o indicates no antioxidant added, ML indicates Meta+ light exposure, MD indicates Meta+ light protection, EL indicates EDTA+ light exposure, ED indicates EDTA+ light protection, 20 indicates PS20, and 80 indicates PS80. Under both light and light protection conditions at 25°C, only the addition of Meta to PS20 resulted in an increase in particle size; other formulations showed no significant difference. This indicates that the addition of antioxidants did not inhibit particle formation, and the combination of PS80 and Meta was superior to the combination of PS20 and Meta. Insoluble particle detection results for all groups met regulatory requirements (10μm, ≤6000 particles / mL; 25μm, ≤6000 particles / mL).

[0486] The SE-HPLC purity test results are shown in Figures 13A and 13B. After 14 days of exposure to light at 25°C, aggregates of each formulation formed, ranging from 11.3% to 17.0%. The addition of Met partially inhibited aggregate formation (PS20 inhibited by 2.9%, PS80 by 5.7%). In the formulation containing polysorbate 20, the addition of EDTA also partially inhibited aggregate formation (inhibition by 4.5%), while in the formulation containing polysorbate 80, the addition of EDTA had no significant effect on aggregate formation.

[0487] The nrCE-SDS test results are shown in Figures 14A and 14B. Under light conditions, 7.6%-12.0% of aggregates were observed to form in each formulation of nrCE-SDS. The addition of antioxidants Met and EDTA can partially inhibit the formation of aggregates, and the inhibition effect of Met (inhibition of 4.1%-4.7%) is better than that of EDTA (inhibition of 2.5%-2.7%).

[0488] The rCE-SDS detection results are shown in Figure 15. Compared with the control (light-protected), no significant differences were observed in the rCE-SDS of each formulation under different light conditions, and the purity of the main peak was 93.4%–95.0%.

[0489] The purity test results of icIEF are shown in Figures 16A-16C. Compared with the control (protected from light), the charge isomers of each formulation changed significantly under light irradiation. The content of the acidic peak increased by 11.0%–16.3%, accompanied by a decrease in the content of the main peak of 8.8%–12.7% and a decrease in the content of the basic peak of 2.2%–3.6%. The addition of Met partially inhibited the increase of the acidic peak, while the addition of EDTA had no significant inhibitory effect on the increase of the acidic peak content.

[0490] In summary, the addition of the antioxidant Met is beneficial in inhibiting the formation of aggregates and acidic charge isomers. PS80 is suitable for the formulation of this application.

[0491] 2. Temperature stability test

[0492] Appearance test results showed that after being placed in the dark at 4℃, 25℃, and 37℃ for 14 days, no color change was observed in any of the formulations.

[0493] The SE-HPLC purity detection results are shown in Figures 17A and 17B. Increased temperature led to an increase in aggregates, resulting in a decrease in the main peak content. Compared to the control (4℃ / 14 days), the main peak content of each formulation decreased by 0.4%–0.6% at 25℃ / 14 days and by 0.7%–2.1% at 37℃ / 14 days, with only a small number of fragments (0%–0.2%) forming. Except for the formulation without antioxidants containing PS20, where the aggregate increase (↑1.9%) was higher than other formulations (↑0.7%–1.2%), and the formulation with Met containing PS20, where the aggregate increase (↑0.7%) was slightly lower than the other four formulations (↑1.1%–1.2%), there were no significant differences among the other four formulations.

[0494] The nrCE-SDS detection results are shown in Figures 18A and 18B. As the temperature increases from 5℃ to 37℃, the main peak content of nrCE-SDS in each formulation gradually decreases. The main peak content at 25℃ decreases by 0.2%–0.7% compared to 5℃, and the main peak content at 37℃ decreases by 0.3%–1.6% compared to 5℃. In the formulation containing PS80, the stability of the formulation slightly decreases after the addition of antioxidants (Met and EDTA). In the formulation containing PS20, the stability of the formulation slightly increases after the addition of antioxidants (Met and EDTA).

[0495] The rCE-SDS test results are shown in Figures 19A and 19B, with no significant differences among the formulations.

[0496] The purity test results of icIEF are shown in Figures 20A-20C. After being placed at 25℃ for 14 days, the purity of icIEF in each formulation showed no significant change compared to the control (5℃ / 14 days). After being placed at 37℃ for 14 days, compared to the control, the acidic peak content of icIEF in each formulation increased, leading to a decrease in the main peak content. The basic peak showed no significant change, while the acidic peak content increased by 3.6%–4.9%. The experimental results indicate that the addition of antioxidants Met or EDTA had no significant effect on temperature-induced charge isomerism changes, and PS20 and PS80 also had no significant effect on temperature-induced charge isomerism changes.

[0497] In summary, similar to the results of light-induced detection, temperature affects the formation of aggregates and acidic charge isomers of anti-IgE antibody preparations, but the amount formed is lower than under light-induced conditions (37℃ / 14d).

[0498] Example 6: Confirmation of excipients and pH range

[0499] Take the anti-IgE antibody (SE5ss), concentrate it, and add it to the formula in Table 15. Place the prepared samples at 37℃ and 5℃ for 14 days respectively, with 5℃ / 14 days as a control. Analyze the appearance, SE-HPLC, nrCE-SDS, rCE-SDS, and icIEF of each sample.

[0500] Table 15 Formulations of Anti-IgE Agents

[0501] 6.1 Confirmation of protein concentration range

[0502] Appearance testing results showed that the solution color gradually darkened as the protein concentration increased, but no significant color change was observed after 5℃ / 14 days or 37℃ / 14 days.

[0503] The purity detection results of SE-HPLC and nrCE-SDS are shown in Figures 21A-21B and 22A-22B, respectively. Increased protein concentration led to an increase in aggregates, resulting in a slight decrease in the main peak content. At different protein concentrations at 5℃ / 14 days and 37℃ / 14 days, the difference in the main peak was small, indicating high stability of the formulation. The purity detection results of rCE-SDS are shown in Figure 23. At different protein concentrations at 5℃ / 14 days and 37℃ / 14 days, the difference in the main peak was small, indicating that no significant changes were observed with increasing protein concentration.

[0504] The icIEF detection results are shown in Figures 24A-24B. At different protein concentrations at 5℃ / 14 days and 37℃ / 14 days, the content of the main peak and the acid peak were almost the same.

[0505] Experimental results show that there are no significant differences in the detection results among different protein concentration formulations in the antibody formulation described in this application, and the formulation of this application exhibits high stability within the protein concentration range.

[0506] 6.2 Confirmation of Sorbitol Concentration Range

[0507] Appearance testing results showed that there was no significant difference in solution color among the various formulations containing 3%-5% sorbitol, and no significant color change was observed after 5℃ / 14 days or 37℃ / 14 days.

[0508] The purity detection results of SE-HPLC, nrCE-SDS, and rCE-SDS are shown in Figures 25-27. At different sorbitol concentrations at 5℃ / 14 days and 37℃ / 14 days, the main peak content showed little difference, indicating high stability of the formulation.

[0509] The icIEF test results are shown in Figures 28A-28B. At different sorbitol concentrations at 5℃ / 14 days and 37℃ / 14 days, the contents of the main peak and acid peak were almost identical. There were no significant differences in the test results among different concentration formulations, indicating no significant differences between the formulations.

[0510] Experimental results show that there are no significant differences in the test results among different sorbitol concentration formulations in the antibody formulation described in this application, and the formulation of this application exhibits high stability within the range of stabilizer concentration.

[0511] 6.3 Confirmation of Methionine Concentration Range

[0512] Appearance testing results showed that there was no significant difference in solution color among the various formulations containing 0-10mM methionine, and no significant color change was observed after 5℃ / 14 days or 37℃ / 14 days.

[0513] The purity detection results of SE-HPLC, nrCE-SDS, and rCE-SDS are shown in Figures 29-31. At different methionine concentrations at 5℃ / 14 days and 37℃ / 14 days, the contents of the main peak and acidic peak were almost the same, indicating that the formulation has high stability.

[0514] The icIEF detection results are shown in Figures 32A-32B. At different methionine concentrations at 5℃ / 14 days and 37℃ / 14 days, the contents of the main peak and acidic peak were almost identical. There were no significant differences in the detection results among different concentration formulations, indicating no significant differences between the formulations.

[0515] Experimental results show that there are no significant differences in the test results among different methionine concentration formulations in the antibody formulation described in this application, and the formulation of this application exhibits high stability within the range of antioxidant concentrations.

[0516] 6.4 pH Range Confirmation

[0517] The pH of each buffer formulation was studied for pH 5.3-6.1 (after adding 100 mg / mL of protein, the pH of each formulation will shift towards alkalinity by approximately 0.3 pH).

[0518] The appearance test results showed that the solution color did not differ significantly within this pH range, and no significant color change was observed after 5℃ / 14 days or 37℃ / 14 days.

[0519] The purity detection results of SE-HPLC, nrCE-SDS, and rCE-SDS are shown in Figures 33-35. At different pH buffer concentrations at 5℃ / 14 days and 37℃ / 14 days, the main peak content showed little difference, indicating high stability of the formulation.

[0520] The icIEF detection results are shown in Figures 36A-36B. At 5℃ / 14 days and 37℃ / 14 days, the differences in the content of the main peak and the acidic peak were small at different pH buffer concentrations. There were no significant differences in the detection results among different pH buffer formulations, indicating no significant differences between the formulations.

[0521] Experimental results show that there are no significant differences in the detection results of different pH range formulations of the antibody formulation described in this application, and the formulation of this application has high stability within the pH range.

[0522] Example 7: Validation of anti-IgE antibody

[0523] Anti-IgE antibody preparations were prepared using different anti-IgE antibodies (SE2, SE5, SE5ss), and each sample was tested.

[0524] Take the anti-IgE antibody, concentrate it and change the solution to the formula in Table 16. Place the prepared samples at 5℃ and 37℃ respectively (two weeks (2W)). Perform SE-HPLC, nrCE-SDS, rCE-SDS and icIEF detection on each sample.

[0525] Table 16 Formulations of Anti-IgE Agents

[0526] The nrCE-SDS detection results are shown in Figure 37. The differences in the main peak content between different antibodies and different formulations at different protein concentrations are small, indicating high stability.

[0527] The rCE-SDS detection results are shown in Figure 38. The differences in the main peak content among different antibodies and formulations at different protein concentrations are small, indicating high stability.

[0528] The SEC-HPLC results are shown in Figure 39. The main peak content of different antibodies at different protein concentrations and different formulations showed little difference, indicating high stability.

[0529] The icIEF detection results are shown in Figure 40. Under the same formulation conditions, even with different protein concentrations, the main peaks of the three antibodies showed little difference, indicating high stability.

[0530] In summary, the formulations described in this application involve SE2, SE5, and SE5ss antibodies. Under different formulation conditions, there are no significant differences in the detection results. Even at higher protein concentrations, the properties can still be maintained. Experimental results show that the formulations described in this application are effective within the stated range and have high formulation stability.

Claims

1. A liquid formulation comprising: (1) An antibody, wherein the antibody comprises three complementarity-determining regions HCDR1, HCDR2 and HCDR3 of the antibody heavy chain variable region, and three complementarity-determining regions LCDR1, LCDR2 and LCDR3 of the antibody light chain variable region, wherein the amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:51, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:52, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:53; (2) Buffer solution, wherein the buffer solution is selected from histidine / histidine hydrochloride buffer (His / His-HCl), acetate / sodium acetate buffer (HAc / NaAc) and / or histidine / sodium acetate buffer (His / NaAc); (3) a stabilizer, wherein the stabilizer is selected from sorbitol and / or sucrose; and (4) A surfactant, wherein the surfactant is selected from polysorbate 20 (PS20) and / or polysorbate 80 (PS80).

2. The liquid formulation according to claim 2, wherein the buffer solution is His / His-HCl.

3. The liquid formulation according to any one of claims 1-2, wherein the concentration of the buffer solution is about 0-100 mM.

4. The liquid formulation according to any one of claims 1-3, wherein the concentration of the buffer solution is about 5-20 mM.

5. The liquid formulation according to any one of claims 1-4, wherein the concentration of the buffer solution is about 8-12 mM.

6. The liquid formulation according to any one of claims 1-5, wherein the buffer solution provides a pH of 5-7.

7. The liquid formulation according to any one of claims 1-6, wherein the buffer solution provides a pH of 5.3-6.

4.

8. The liquid formulation according to any one of claims 1-7, wherein the buffer solution provides a pH of 5.4-6.

4.

9. The liquid formulation according to any one of claims 1-8, wherein the stabilizer is sorbitol.

10. The liquid formulation according to any one of claims 1-9, wherein the stabilizer content is about 2-10% (w / v).

11. The liquid formulation according to any one of claims 1-10, wherein the stabilizer content is about 3%-5.5% (w / v).

12. The liquid formulation according to any one of claims 1-11, wherein the stabilizer content is about 4.5%-5.5% (w / v).

13. The liquid formulation according to any one of claims 1-12, wherein the surfactant is PS80.

14. The liquid formulation according to any one of claims 1-13, wherein the surfactant content is about 0-0.1% (w / v).

15. The liquid formulation according to any one of claims 1-14, wherein the surfactant content is about 0.005%-0.02% (w / v).

16. The liquid formulation according to any one of claims 1-15, wherein the surfactant content is about 0.01%-0.02% (w / v).

17. The liquid formulation according to any one of claims 1-16, wherein the antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, and the amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are selected from any group of the following combinations: 1) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:10, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:

11. 2) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:26, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30; and 3) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:

30.

18. The liquid formulation according to any one of claims 1-17, wherein the antibody comprises an antibody heavy chain variable region VH and an antibody light chain variable region VL, wherein the amino acid sequence of the VH is as shown in SEQ ID NO:8, SEQ ID NO:21, SEQ ID NO:28, SEQ ID NO:37 or SEQ ID NO:41, and the amino acid sequence of the VL is as shown in SEQ ID NO:16, SEQ ID NO:25, SEQ ID NO:35 or SEQ ID NO:

40.

19. The liquid formulation according to any one of claims 1-18, wherein the antibody comprises VH and VL, the amino acid sequences of said VH and VL being selected from any group of the following combinations: 1) The amino acid sequence of VH is shown in SEQ ID NO:8, and the amino acid sequence of VL is shown in SEQ ID NO:16; 2) The amino acid sequence of VH is shown in SEQ ID NO:21, and the amino acid sequence of VL is shown in SEQ ID NO:25; 3) The amino acid sequence of VH is shown in SEQ ID NO:28, and the amino acid sequence of VL is shown in SEQ ID NO:35; 4) The amino acid sequence of VH is shown in SEQ ID NO:37, and the amino acid sequence of VL is shown in SEQ ID NO:40; and 5) The amino acid sequence of VH is shown in SEQ ID NO:41, and the amino acid sequence of VL is shown in SEQ ID NO:

40.

20. The liquid formulation according to any one of claims 1-19, wherein the antibody comprises a heavy chain and a light chain, the amino acid sequence of the heavy chain being as shown in SEQ ID NO:45, SEQ ID NO:47 or SEQ ID NO:49, and the amino acid sequence of the light chain being as shown in SEQ ID NO:46 or SEQ ID NO:

48.

21. The liquid formulation according to any one of claims 1-20, wherein the antibody comprises a heavy chain and a light chain, the amino acid sequences of said heavy chain and light chain being selected from any group of the following combinations: 1) The amino acid sequence of the heavy chain is shown in SEQ ID NO:45, and the amino acid sequence of the light chain is shown in SEQ ID NO:46; 2) The amino acid sequence of the heavy chain is shown in SEQ ID NO:47, and the amino acid sequence of the light chain is shown in SEQ ID NO:48; and 3) The amino acid sequence of the heavy chain is shown in SEQ ID NO:49, and the amino acid sequence of the light chain is shown in SEQ ID NO:

48.

22. The liquid formulation according to any one of claims 1-21, wherein the concentration of said antibody is about 10-200 mg / mL.

23. The liquid formulation according to any one of claims 1-22, wherein the concentration of said antibody is about 50-150 mg / mL.

24. The liquid formulation according to any one of claims 1-23, wherein the concentration of said antibody is about 90-110 mg / mL.

25. The liquid formulation according to any one of claims 1-24, wherein the antibody is an anti-IgE antibody.

26. The liquid formulation according to any one of claims 1-25, wherein the formulation further comprises an antioxidant.

27. The liquid formulation according to claim 26, wherein the antioxidant is methionine.

28. The liquid formulation according to any one of claims 26-27, wherein the concentration of the antioxidant is about 0-20 mM.

29. The liquid formulation according to any one of claims 26-28, wherein the concentration of the antioxidant is about 0-10 mM.

30. A unit dosage form comprising: (1) 10-200 mg / mL anti-IgE antibody; (2) His / His-HCl, which provides a pH of 5-7; (3) 2-10% (w / v) sorbitol; and (4) 0-0.1% (w / v) PS80, The anti-IgE antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3. The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:51, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:52, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:

53.

31. A unit dosage form comprising: (1) 50-150 mg / mL anti-IgE antibody; (2) His / His-HCl, which provides a pH of 5.3-6.4; (3) 3%-5.5% (w / v) sorbitol; and (4)0.005%-0.02%(w / v)PS80, The anti-IgE antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are selected from any of the following combinations: 1) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:10, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:

11. 2) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:26, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30; and 3) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:

30.

32. A unit dosage form comprising: (1) 10-200 mg / mL anti-IgE antibody; (2) 0-100mM His / His-HCl, which provides a pH of 5-7; (3) 2-10% (w / v) sorbitol; (4) 0-0.1% (w / v) PS80; and (5) 0-20mM methionine, The anti-IgE antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3. The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:51, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:52, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:

53.

33. A unit dosage form comprising: (1) 50-150 mg / mL anti-IgE antibody; (2) 5-20 mM His / His-HCl, which provides a pH of 5.3-6.4; (3) 3%-5.5% (w / v) sorbitol; (4) 0.005%-0.02% (w / v) PS80; and (5) 0-10mM methionine, The anti-IgE antibody comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, wherein the amino acid sequences of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 are selected from any of the following combinations: 1) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:10, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:

11. 2) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:26, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:30; and 3) The amino acid sequence of HCDR1 is shown in SEQ ID NO:1, the amino acid sequence of HCDR2 is shown in SEQ ID NO:2, the amino acid sequence of HCDR3 is shown in SEQ ID NO:3, the amino acid sequence of LCDR1 is shown in SEQ ID NO:9, the amino acid sequence of LCDR2 is shown in SEQ ID NO:29, and the amino acid sequence of LCDR3 is shown in SEQ ID NO:

30.

34. A lyophilized formulation comprising the liquid formulation of any one of claims 1-29, and a lyophilization protectant.

35. An apparatus comprising a liquid formulation according to any one of claims 1-29 and / or a lyophilized formulation according to claim 34, and a container holding the liquid formulation and / or the lyophilized formulation.

36. A method for preparing the liquid formulation of any one of claims 1-29, the lyophilized formulation of claim 34, and / or the kit of claim 35.

37. The liquid formulation according to any one of claims 1-29 or the lyophilized formulation according to claim 34, wherein the liquid formulation or lyophilized formulation is for intraperitoneal, intraspinal, intra-articular, intrasynovial, intrathecal, oral, topical, inhalation, subcutaneous, intramuscular or intravenous administration.

38. Use of the liquid formulation of any one of claims 1-29 or the lyophilized formulation of claim 34 in the preparation of a medicament for the prevention, diagnosis and / or treatment of a disease.

39. The use according to claim 38, wherein the disease is an IgE-related disease.

40. The use according to any one of claims 38-39, wherein the disease is asthma, chronic urticaria, food allergy, nasal polyps and / or allergic rhinitis.

41. A method for preventing, diagnosing and / or treating a disease, comprising administering to a subject in need the liquid formulation of any one of claims 1-29 and / or the lyophilized formulation of claim 34.

42. The method of claim 41, wherein the disease is an IgE-related disease.

43. The method according to any one of claims 41-42, wherein the disease is asthma, chronic urticaria, food allergy, nasal polyps and / or allergic rhinitis.

44. The liquid formulation of any one of claims 1-29 or the lyophilized formulation of claim 34, for the prevention, diagnosis and / or treatment of disease.

45. The liquid or lyophilized formulation according to claim 44, wherein the disease is an IgE-related disease.

46. ​​The liquid or lyophilized formulation according to any one of claims 44-45, wherein the disease is asthma, chronic urticaria, food allergy, nasal polyps and / or allergic rhinitis.

Images