High-concentration and high-stability antibody preparation and preparation method therefor

Abstract

The present invention belongs to the field of antibody preparations. Disclosed are a high-concentration and high-stability antibody preparation and a preparation method therefor. The antibody preparation comprises an anti-C5 antibody having a light chain sequence of SEQ ID NO. 1, and a heavy chain sequence of SEQ ID NO. 2 or a long-acting modified sequence thereof; and further comprises a buffer system of: 20-50 mM histidine-histidine hydrochloride, 70-110 mM arginine, 25-50 mM sodium chloride, and 0.03% PS80. The concentration of a conventional antibody preparation is generally 100 mg / mL or lower, and the antibody concentration of the buffer system reaches about 200 mg / mL. In addition, the antibody preparation shows good long-term stability, affinity and bioavailability.

Description

A high-concentration and high-stability antibody preparation and its preparation method Technical Field

[0001] The present invention belongs to the field of antibody preparations, and particularly relates to a high-concentration and high-stability antibody preparation and a preparation method thereof. Background Art

[0002] With the development of biological antibody drug treatment, the active ingredient needs to be highly concentrated (about 20 mg / mL to about 100-150 mg / mL, or even 200 mg / mL or higher) for intravenous or subcutaneous high-concentration administration. In the treatment of chronic diseases with large single-dose doses, such as PNH (paroxysmal nocturnal hemoglobinuria, manifested as chronic intravascular hemolysis), in order to achieve patient self-medication and improve the convenience and treatment compliance of patients, it is necessary to develop antibody preparations with small dosage volume and high concentration. However, during the high-concentration concentration process, antibody drugs will produce problems such as increased viscosity, protein aggregation and charge heterogeneity changes, which will cause risks such as decreased activity of active antibodies and enhanced immunogenicity. Therefore, it is necessary to improve the formulation of antibody drugs to increase the solubility of antibodies, reduce viscosity, and solve the problems of protein aggregation and charge heterogeneity changes.

[0003] Improvements to antibody drug preparations mainly include the following aspects:

[0004] I. Antibodies in the formulation;

[0005] II. Calcium and Acetate or Buffer:

[0006] Reducing the viscosity of the antibody formulation by adding calcium salt and / or acetate (and / or buffer) to the formulation: Determination method The viscosity of the protein formulation is measured before and after the addition of calcium salt and / or acetate (and / or buffer);

[0007] III. Excipients in the formulation:

[0008] Excipients can impart or enhance the stability of protein formulations and, to a certain extent, affect the efficacy and immunogenicity of drugs. Therefore, it is necessary to develop protein formulations with excipients that are stable and safe. Excipients can be buffers, stabilizers, or surfactants.

[0009] EA5 monoclonal antibody is a humanized monoclonal antibody that specifically targets complement C5. After enzymatic cleavage, complement C5 is converted into C5a and C5b. C5a is a key proinflammatory molecule, while C5b can further form C5b-9, the membrane attack complex (MAC), which causes cell puncture or lysis. Deposition of the MAC on the red blood cell surface of patients with paronychia nodosum (PNH) can cause erythrocyte lysis, the primary clinical manifestation of PNH. EA5 monoclonal antibody blocks C5 cleavage and prevents the formation of C5a and C5b-9, making it an effective treatment for PNH. It also has a positive therapeutic effect on diseases caused by complement terminal activation, such as aHUS and gMG.

[0010] PNH (paroxysmal nocturnal hemoglobinuria) is a rare and life-threatening clonal disorder of hematopoietic stem cells with a prevalence of approximately 13 per million. Clinical manifestations include hemolytic anemia, hemoglobinuria, venous thrombosis, bone marrow failure, and smooth muscle dysfunction. Intravascular hemolysis caused by the complement system attacking red blood cells is a core factor in the morbidity and mortality of PNH. CD59 is the most important inhibitor of the complement membrane attack complex (MAC) on the red blood cell surface. PNH patients have acquired somatic mutations in the phosphatidylinositol glycan (PIG-A) gene located on the X chromosome (Xp22.1). This results in CD59 being unable to bind to the red blood cell membrane due to defects in glycosylphosphatidylinositol (GPI) synthesis, ultimately leading to the loss of its ability to inhibit complement pathway activation. The main treatments for PNH include complement inhibitors, glucocorticoids, and allogeneic hematopoietic stem cell transplantation. The complement C5 inhibitors Soliris (Eculizumab) and Ultomiris (Ravulizumab) are standard treatments for PNH, effectively controlling intravascular hemolysis, reducing thrombosis, and improving long-term survival. However, these drugs are expensive and require intravenous administration, requiring regular hospitalization for infusions, which can be quite inconvenient for patients. Therefore, the development of safe and effective subcutaneous complement C5 inhibitors for the treatment of PNH patients is of great significance.

[0011] PNH is a typical disease caused by complement activation. EA5 antibody also has great therapeutic potential for other diseases caused by complement activation, such as rheumatoid arthritis, antiphospholipid antibody syndrome, lupus nephritis, ischemia-reperfusion injury, atypical hemolytic uremic syndrome (aHUS), typical hemolytic uremic syndrome, paroxysmal nocturnal hemoglobinuria (PNH), dense deposit disease, neuromyelitis optica, multifocal motor neuropathy, multiple sclerosis, macular degeneration, HELLP syndrome, spontaneous abortion, thrombotic thrombocytopenic purpura, pauciimmune vasculitis, epidermolysis bullosa, recurrent abortion, traumatic brain injury, myocarditis, cerebrovascular diseases, peripheral vascular diseases, renal vascular diseases, mesenteric / intestinal vascular diseases, vasculitis, and allergic Purpura nephritis, systemic lupus erythematosus-associated vasculitis, rheumatoid arthritis-associated vasculitis, immune complex vasculitis, Takayasu's disease, dilated cardiomyopathy, diabetic angiopathy, Kawasaki disease, venous air embolism, stent implantation, rotational atherectomy, restenosis after percutaneous transluminal coronary angioplasty, myasthenia gravis, cold agglutinin disease, dermatomyositis, paroxysmal cold hemoglobinuria, antiphospholipid syndrome, Graves' disease, atherosclerosis, Alzheimer's disease, systemic inflammatory response sepsis, septic shock, spinal cord injury, glomerulonephritis, transplant rejection, Hashimoto's thyroiditis, type 1 diabetes mellitus, psoriasis, pemphigus, autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, Goodpasture's syndrome, Digges' disease, and catastrophic antiphospholipid syndrome.

[0012] Summary of the Invention

[0013] In order to solve the above problems, the present invention provides an anti-C5 antibody and a preparation thereof, which optimizes the molecular design of the antibody and the buffer system of the preparation, with the aim of improving the overall stability of the antibody preparation.

[0014] In the present invention, "PS80" refers to polysorbate 80, also known as Tween 80.

[0015] In the present invention, "histidine-histidine hydrochloride" refers to sodium histidine + histidine hydrochloride buffer.

[0016] In one aspect, the present invention provides an anti-C5 antibody.

[0017] The anti-C5 antibody is a modified antibody with a light chain sequence of SEQ ID NO. 1 and a heavy chain sequence of SEQ ID NO. 2 or a long-acting modified sequence thereof. This antibody molecule improves its solubility and stability through engineering of the Fc region; raises its isoelectric point to prevent loss during downstream processing; and enhances its affinity for FcRn to achieve a longer in vivo half-life.

[0018] Preferably, the long-acting modified sequence of the heavy chain sequence is SEQ ID NO.3.

[0019] In another aspect, the present invention provides an antibody preparation comprising the aforementioned anti-C5 antibody.

[0020] The content of the anti-C5 antibody is 0-200 mg / L, preferably 160-200 mg / mL, and more preferably 180 mg / mL.

[0021] The antibody preparation also includes a buffer system.

[0022] The buffer system comprises: 20-50 mM histidine-histidine hydrochloride, 70-110 mM arginine, 25-50 mM sodium chloride and 0.03% PS80.

[0023] The content of the histidine-histidine hydrochloride can be selected from: 20-30mM, 30-40mM, 40-50mM, 25-35mM, 25-45mM.

[0024] The arginine content can be selected from: 70-80mM, 80-90mM, 90-100mM, 100-110mM, 70-90mM, 80-100mM, 90-110mM, 100-110mM.

[0025] The content of sodium chloride can be selected from: 25-30mM, 25-35mM, 30-50mM, 40-50mM, 35-40mM, 25-45mM, 30-45mM.

[0026] Preferably, the buffer system comprises: 20 mM histidine-histidine hydrochloride, 70-110 mM arginine, 25-50 mM sodium chloride and 0.03% PS80.

[0027] More preferably, the buffer system comprises: 20 mM histidine-histidine hydrochloride, 80 mM arginine, 25-50 mM sodium chloride and 0.03% PS80.

[0028] More preferably, the buffer system comprises: 20 mM histidine-histidine hydrochloride, 80 mM arginine, 50 mM sodium chloride and 0.03% PS80.

[0029] The pH of the buffer system is 6.0-6.5.

[0030] Preferably, the pH of the buffer system is 6.0-6.3.

[0031] More preferably, the pH of the buffer system is 6.3.

[0032] The present invention also provides a buffer system used in antibody preparations.

[0033] In another aspect, the present invention provides use of the aforementioned anti-C5 antibody or antibody preparation in the preparation of a medicament.

[0034] The drug indications are selected from: rheumatoid arthritis, antiphospholipid antibody syndrome, lupus nephritis, ischemia-reperfusion injury, atypical hemolytic uremic syndrome (aHUS), typical hemolytic uremic syndrome, PNH, dense deposit disease, neuromyelitis optica, multifocal motor neuropathy, multiple sclerosis, macular degeneration, HELLP syndrome, spontaneous abortion, thrombotic thrombocytopenic purpura, pauciimmune vasculitis, epidermolysis bullosa, recurrent abortion, traumatic brain injury, myocarditis, cerebrovascular diseases, peripheral vascular diseases, renal vascular diseases, mesenteric / intestinal vascular diseases, vasculitis, Henoch-Schonlein purpura nephritis, systemic lupus erythematosus-associated vasculitis, rheumatoid arthritis-associated vasculitis, immune complex vasculitis, Takayasu's disease, dilated cardiomyopathy, diabetic angiopathy, Kawasaki disease, venous air embolism, restenosis after stent implantation, rotational atherectomy, percutaneous transluminal coronary angioplasty, myasthenia gravis, cold agglutinin disease, dermatomyositis, paroxysmal cold hemoglobinuria, antiphospholipid syndrome, Graves' disease, atherosclerosis, Alzheimer's disease, systemic inflammatory response sepsis, septic shock, spinal cord injury, glomerulonephritis, transplant rejection, Hashimoto's thyroiditis, type 1 diabetes mellitus, psoriasis, pemphigus, autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, Goodpasture's syndrome, Digges' disease, or catastrophic antiphospholipid syndrome.

[0035] Preferably, the drug is indicated for PNH.

[0036] In another aspect, the present invention provides a medicament comprising the aforementioned anti-C5 antibody or antibody preparation.

[0037] Preferably, the medicament is used to treat PNH.

[0038] Preferably, the dosage form of the drug is an injection.

[0039] In another aspect, the present invention provides use of the aforementioned buffer system in the preservation of antibody drugs.

[0040] Preferably, the antibody drug is an anti-C5 antibody-related drug, such as the aforementioned anti-C5 antibody preservation.

[0041] Beneficial effects of the present invention:

[0042] Compared to existing technologies, this invention improves the stability of anti-C5 antibodies and the buffer systems associated with antibody preparations, addressing issues such as high viscosity, aggregation, and charge heterogeneity in antibody preparations, and enhancing the stability of high-concentration liquid preparations of the corresponding antibodies. While conventional antibody preparations typically have concentrations below 100 mg / mL, this buffer system achieves antibody concentrations of approximately 200 mg / mL. Furthermore, the antibody preparations of the present invention exhibit excellent long-term stability, affinity, and bioavailability. BRIEF DESCRIPTION OF THE DRAWINGS

[0043] FIG1 shows the inhibitory activity of EA5 antibody at different concentrations on complement-dependent cytotoxicity (CDC).

[0044] FIG2 is a drug-dose curve of EA5 antibody after single intravenous and subcutaneous injection of 30 mg / kg in ICR mice. DETAILED DESCRIPTION

[0045] The present invention will be further described in detail below with reference to specific examples. The following examples are not intended to limit the present invention but are merely intended to illustrate the present invention. The experimental methods used in the following examples are generally based on conventional conditions unless otherwise specified. The materials and reagents used in the following examples are all commercially available unless otherwise specified.

[0046] Example 1 Preparation Method of an Anti-C5 Antibody Preparation

[0047] (1) Antibody preparation

[0048] A highly stable anti-C5 antibody, whose heavy chain sequence is SEQ ID NO. 2 and light chain sequence is SEQ ID NO. 1. A long-acting modification is performed to increase the half-life. The modified antibody has a heavy chain sequence of SEQ ID NO. 3 and a light chain sequence of SEQ ID NO. 1.

[0049] The preparation method of the antibody in this example is a conventional preparation method in the art. An expression vector is constructed and stably transferred into the host cell CHO to construct a high-expression stable cell line. The seed cells are batch-fed cultured to express the anti-C5 antibody. After harvest, the anti-C5 antibody is obtained after affinity chromatography and ion exchange chromatography.

[0050] (2) Preparation of buffer solution

[0051] Prepare the buffer solution according to the specific recipe and adjust the pH of the buffer solution to 6.3.

[0052] (3) Preparation of antibody preparations

[0053] A high-concentration antibody preparation was prepared using the modified antibody from step (1) and the buffer from step (2) at a concentration of 180 mg / mL. The preparation process was as follows:

[0054] The centrifuge speed was set to 3500 rcf, and the protein was concentrated using an ultrafiltration centrifuge tube and the solution was exchanged into the formulation formula. The solution was exchanged 155 times in total, and the protein concentration was adjusted to the target concentration of 180 mg / mL. Then, each formulation sample was filtered and dispensed into 2R vials and 5 mL storage bags in an ultra-clean bench, and the vials were stoppered and capped.

[0055] Prescription 1 Buffer: 50 mM histidine-histidine hydrochloride, 80 mM arginine hydrochloride, 25 mM sodium chloride, 0.03% (w / v) PS80. Adjust the buffer pH to 6.3.

[0056] Recipe 2 Buffer: 20 mM histidine-histidine hydrochloride, 80 mM arginine hydrochloride, 25 mM sodium chloride, 0.03% (w / v) PS80.

[0057] Recipe 3 buffer: 20 mM histidine-histidine hydrochloride, 110 mM arginine hydrochloride, 25 mM sodium chloride, 0.03% (w / v) PS80.

[0058] Prescription 4 buffer: 20 mM citric acid-sodium citrate + 70 mM arginine hydrochloride + 50 mM sodium chloride + 0.03% PS80 pH 6.3.

[0059] Experimental Example 1 Study on the Quality Attributes of Antibody Preparations

[0060] Taking prescription 1 as an example, the antibody preparation was tested for appearance, protein concentration, osmotic pressure, viscosity, SEC-HPLC detection, CEX-HPLC, nrCE-SDS, binding activity, affinity with C5, and CDC effect.

[0061] (1) Protein concentration was determined by ultraviolet spectrophotometry (Shimadzu, model: UV-1900). The protein extinction coefficient was 1.531 (mg / mL). -1 cm -1 Rinse the microcuvettes 2-3 times with ultrapure water. Add 200 μL of ultrapure water to each of the two microcuvettes for blank correction. Then add 200 μL of sample to each cuvette and read the sample three times. Calculate the sample concentration using the extinction coefficient, dilution factor, and OD value.

[0062] (2) The osmotic pressure detection method is as follows: place the sample on the osmotic pressure meter probe, the instrument automatically starts measuring, and displays and prints the test results after 1 minute.

[0063] (3) The viscosity test method is: use the microVISC pipettes syringe to draw a certain volume of sample, press the syringe needle against the injection port, and after the sample is loaded, the instrument automatically starts measuring.

[0064] (4) SEC-HPLC detection column manufacturer: Agilent, model AdvanceBio SEC 300A, specification 2.7 μm.

[0065] High performance liquid phase HPLC manufacturer: Thermo, UltiMate 3000.

[0066] The mobile phase composition was 20 mM PB + 200 mM NaCl + 100 mM Arg, pH 6.8.

[0067] The main peak, aggregate peak and fragment peak after monomer were calculated by area normalization method.

[0068] The SEC-HPLC purity test conditions are as follows:

[0069] (5) CEX-HPLC purity

[0070] Chromatographic column: Sepax, model proteomix SCX-NP5, dimensions 4.6×250 mm; HPLC: Thermo, model UltiMate 3000. Mobile phase A: 20 mM MES, pH 6.5; mobile phase B: 20 ​​mM MES + 500 mM NaCl, pH 6.5. Peak area normalization was used for quantitative analysis of the results, and the content of acidic components (sum of the area percentages of all peaks before the main peak), main component content (sum of the area percentages of the main peak), and basic component content (sum of the area percentages of all peaks after the main peak) were calculated. Details are shown in the table below:

[0071] CEX-HPLC purity detection method

[0072] (6) nrCE-SDS purity

[0073] Capillary electrophoresis instrument: SCIEX, model PA800 Plus. Capillary electrophoresis chromatograph: Aglient, model G7100A. The sample was first desalted, and pH 6.5 citric acid-phosphate buffer was added to the centrifugal concentrator to a volume of 400 μL. The sample was centrifuged at 13,000 rpm for 15 minutes. The centrifugal concentrator column was then inverted and transferred to a new centrifuge tube. The protein was recovered by centrifugation at 6,000 rpm for 3 minutes. 250 mM NEM solution was added, mixed, heated at 70°C for 10 minutes, cooled, and centrifuged at 10,000 rpm for 3 minutes before injection. A PDA detector with a detection window of 100 × 800 μm was used. Samples were injected from the left end of the capillary, with an effective separation length of 20 cm. Voltage injection was performed at 5 kV for 20 seconds. Constant voltage separation was performed at a separation voltage of 15 kV. The samples were rinsed with an alkaline rinse solution at 70 psi for 3 minutes, an acidic rinse solution at 70 psi for 1 minute, pure water at 70 psi for 1 minute, and SDS gel buffer at 70 psi for 10 minutes. The peak area normalization method was used to calculate the content of high-molecular-weight components (the sum of the area percentages of all peaks before the main peak), the content of the main component (the area percentage of the main peak), and the content of the low-molecular-weight components (the sum of the area percentages of all peaks after the main peak).

[0074] (7) Binding activity detection method (ELISA):

[0075] Use 1×PBS coating buffer to dilute 250μg / mL C5 antigen (purchased from Acro Bio, product number CO5-H52Ha) to 0.5μg / mL, and coat 96-well enzyme-labeled plates at 100μL / well at 4°C overnight. Wash the plate 4 times, add 250μL / well of blocking solution, and incubate at room temperature for 2 hours. Wash the plate 4 times, transfer 100μL / well of the gradient diluted sample to a 96-well enzyme-labeled plate, and incubate at room temperature for 1h. Wash the plate 4 times, add 100μL / well of secondary antibody working solution (1:20000 dilution), and incubate at room temperature for 1h. Wash the plate 4 times, add 100μL / well of TMB colorimetric solution, react at room temperature for 10min, and add stop solution. Read the absorbance value at 450nm on the enzyme reader with 630nm as the reference wavelength. With concentration as the horizontal axis, OD 450-630nm As the vertical coordinate, four-parameter curve fitting can be performed to directly obtain EC 50 and R 2 Calculate the relative binding activity of the sample to be tested. Relative binding activity = EC of the reference (or working reference) 50 / Test sample EC 50 ×100%.

[0076] The main quality attributes tested are as follows:

[0077] Experimental Example 2 Antibody Preparation Affinity Detection

[0078] (1) Detect the affinity of anti-C5 antibodies to C5. The detection method is as follows:

[0079] Biotinylated C5 was diluted to 5 μg / mL in SD buffer (0.1% BSA, 0.01% Tween 20, 1× PBS). The test sample was then diluted to 50 μg / mL. Three replicates were prepared. The diluted test sample, FcRn, and SD buffer were added to a black 96-well plate. The SA Sensor and black 96-well plate were placed in the instrument. The program was set up for curve fitting and data analysis. The test results for the formulation shown in Prescription 1 are as follows:

[0080] The results showed that the anti-C5 antibody of the present invention has good affinity with C5.

[0081] (2) Detect the affinity of the antibody to FcRn. The detection method is as follows:

[0082] Before the experiment, adjust the pH of the SD buffer to 6.0. Dilute the biotinylated FcRn to 5 μg / mL in SD buffer, then dilute the test article to 50 μg / mL. Prepare triplicates. Add the diluted test article, FcRn, and buffer to a black 96-well plate. Place the SA Sensor and black 96-well plate in the instrument. Set up the program for curve fitting and data analysis. Eculizumab (see US 6355245, expression plasmid constructed, transiently transfected with PEI US5736137A in 293T cells, and stored in buffer after one-step affinity chromatography) was used as a positive control.

[0083] The test results are as follows:

[0084] The test results show that the antibody in the antibody preparation of the present invention has a better ability to bind to FcRn than the positive control.

[0085] (3) Detect the CDC effect of different concentrations of antibodies. The detection method is:

[0086] An appropriate amount of target cells (human Burkitt's lymphoma cells, ATCC CCL-213) were added with 10 μg / mL Rituximab (see US5736137A, expression plasmid constructed, transiently transfected with PEI in 293t cells, and subjected to one-step affinity chromatography followed by buffer storage). The cells were incubated for half an hour. The antibody drug was then added at concentrations ranging from 216 ng / mL to 12500 ng / mL and incubated for 3 hours. The cells were then removed and equilibrated to room temperature. Cell titer detection reagent (Promega, Cat. No. G7572) was added and the cells were shaken in the dark before reading. A four-parameter curve was fitted using antibody drug concentration as the horizontal axis and RLU value as the vertical axis. The RLU value was positively correlated with the cell lysis rate. The results are shown in Figure 1. Figure 1 shows that as the antibody concentration decreases, the cell lysis rate increases, and the complement-induced CDC effect caused by Rituximab is enhanced. However, high concentrations of anti-C5 antibody can inhibit the CDC effect caused by Rituximab.

[0087] Experimental Example 3 Accelerated Stability Test

[0088] The antibody formulations of Formulations 1-4 were placed at 40°C for 14 days, and their initial parameters (T0) and 14-day parameters were tested according to Experimental Example 1 to evaluate the stability of the formulations. The results are as follows:

[0089] Experimental Example 4 Subcutaneous injection bioavailability

[0090] Taking prescription 1 as an example, the bioavailability of the antibody preparation was studied. The specific method was as follows: This experiment observed the changes in the blood concentration of the antibody in CD-1 mice over time after subcutaneous and intravenous injection of the antibody preparation, obtained the basic pharmacokinetic parameters of the drug, and understood the basic kinetic characteristics of the test substance.

[0091] The specific method is as follows:

[0092] The mice were randomly divided into groups of 6 (half male and half female) according to body weight. ICR mice (8 weeks old, weighing 30 g) were injected with the antibody preparations via tail vein or subcutaneous neck injection at a dose of 10 mL / kg.

[0093] Sampling times: immediately after dosing (within 1 minute), 1 hour ± 5 minutes, 6 hours ± 5 minutes, 24 hours ± 5 minutes, 48 ​​hours ± 5 minutes, 72 hours ± 5 minutes, 96 hours ± 5 minutes, 120 hours ± 5 minutes, 168 hours ± 5 minutes, 240 hours ± 5 minutes, 336 hours ± 5 minutes, 504 hours ± 5 minutes, and 672 hours ± 5 minutes after dosing; blood volume: approximately 0.2 mL / animal / time; animals: 3 animals / time point / sex / group; blood collection method: orbital vein. Antibody concentrations in plasma samples were analyzed using a validated ELISA assay. All samples were assayed in duplicate. The plasma antibody concentration and time profiles were analyzed using a non-compartmental model.

[0094] ELISA method to determine the content of antibodies in plasma:

[0095] A goat anti-human polyclonal antibody (purchased from Abcam, catalog number Ab6858) was coated onto a hydrophobic ELISA plate, and the plasma EA5 content was measured using a double antibody sandwich assay. The results are shown in Figure 2, which demonstrates that, compared to intravenous injection, subcutaneous injection is primarily absorbed via the lymphatic system, with peak drug absorption occurring after 24 hours, an average Cmax of 240 μg / mL, and a bioavailability of approximately 70%.

Claims

1. An antibody preparation, characterized in that It is composed of anti-C5 antibody and buffer system; The anti-C5 antibody light chain sequence is SEQ ID NO.1, and the heavy chain sequence is SEQ ID NO.3; The buffer system consists of 20-50 mM histidine-histidine hydrochloride, 70-110 mM arginine, 25-50 mM sodium chloride, and 0.03% PS80; The anti-C5 antibody content is 160-200 mg / mL.

2. The antibody preparation according to claim 1, characterized in that The buffer system consists of 20 mM histidine-histidine hydrochloride, 70-110 mM arginine, 25-50 mM sodium chloride and 0.03% PS80.

3. The antibody preparation according to claim 2, characterized in that The buffer system consisted of 20 mM histidine-histidine hydrochloride, 80 mM arginine, 25-50 mM sodium chloride and 0.03% PS80.

4. The antibody preparation according to claim 3, characterized in that The buffer system consisted of 20 mM histidine-histidine hydrochloride, 80 mM arginine, 50 mM sodium chloride and 0.03% PS80.

5. The antibody preparation according to claim 4, characterized in that The pH of the buffer system is 6.0-6.

5.

6. The antibody preparation according to claim 5, characterized in that The pH of the buffer system is 6.0-6.

3.

7. Use of the antibody preparation according to any one of claims 1 to 6 in the preparation of a drug, characterized in that: The drug is used to treat rheumatoid arthritis, antiphospholipid antibody syndrome, lupus nephritis, ischemia-reperfusion injury, atypical hemolytic uremic syndrome, typical hemolytic uremic syndrome, PNH, dense deposit disease, neuromyelitis optica, multifocal motor neuropathy, multiple sclerosis, macular degeneration, HELLP syndrome, spontaneous abortion, thrombotic thrombocytopenic purpura, oligoimmune vasculitis, bullous epidermolysis, recurrent abortion, traumatic brain injury, myocarditis, cerebrovascular disease, peripheral vascular disease, renal vascular disease, mesenteric / intestinal vascular disease, vasculitis, Henoch-Schönlein purpura nephritis, systemic lupus erythematosus-associated vasculitis, rheumatoid arthritis-associated vasculitis, One or more of immune complex vasculitis, Takayasu's disease, dilated cardiomyopathy, diabetic vasculopathy, Kawasaki disease, venous air embolism, restenosis after stenting, rotational atherectomy, percutaneous transluminal coronary angioplasty, myasthenia gravis, cold agglutinin disease, dermatomyositis, paroxysmal cold hemoglobinuria, antiphospholipid syndrome, Graves' disease, atherosclerosis, Alzheimer's disease, systemic inflammatory response sepsis, septic shock, spinal cord injury, glomerulonephritis, transplant rejection, Hashimoto's thyroiditis, type I diabetes mellitus, psoriasis, pemphigus, autoimmune hemolytic anemia, idiopathic thrombocytopenic purpura, Goodpasture's syndrome, Diego's disease, or catastrophic antiphospholipid syndrome.

8. The use according to claim 7, characterized in that: For subcutaneous injection of medication.

9. A subcutaneous injection drug comprising the antibody preparation according to any one of claims 1 to 6.

Images