CN115518151A - Human immunodeficiency virus neutralizing antibody preparation and application thereof - Google Patents

Abstract

The present invention provides a human immunodeficiency virus neutralizing antibody formulation and uses thereof, specifically, the formulation comprises (a) a therapeutically effective amount of HIV neutralizing antibodies; (b) a buffer solution with the concentration of 10-30 mmol/L; (c) a stabilizer; and (d) a surfactant, wherein the liquid formulation has a pH of 5.5 to 6.5. The preparation of the invention not only can effectively reduce the chemical degradation reaction rate of the neutralizing antibody of the human immunodeficiency virus, improve the physical and chemical stability of the antibody, prolong the shelf life of the product, reduce the number of medicine bottles, but also can eliminate or lighten the side reaction of the injection part of a patient and improve the medicine comfort of the patient.

Description

Human immunodeficiency virus neutralizing antibody preparation and application thereof

Technical Field

The invention relates to the technical field of biology, in particular to a human immunodeficiency virus neutralizing antibody preparation and application thereof.

Background

AIDS, collectively called Acquired Immunodeficiency Syndrome (AIDS), is a malignant infectious disease with a very high fatality rate caused by HIV virus, i.e., human Immunodeficiency virus. The HIV virus invades the human body and can destroy the immune system of the human body, so that infected persons gradually lose the resistance to various diseases and finally die. There is currently no effective drug or method for preventing or curing such diseases with vaccines

The number of AIDS attacks in China in 1-8 months in 2020 is 39349, and the number of deaths is 11595. In 2019, the number of the Chinese AIDS is 71204, the number of the dead people is 20999, and a new AIDS treatment scheme and the updating iteration of medicines are imperative to ensure that 95 percent of HIV infected people in China are effectively treated.

The number of people in China and the world with drug therapy is large. At present, anti-HIV therapeutic drugs and a plurality of compound preparations are on the market globally, and most of the anti-HIV therapeutic drugs and the compound preparations are oral drugs. The free HIV antiviral treatment program variety of the government of China is extremely short, and the medicines and treatment schemes which can be selected by patients are extremely limited. The development of the medicine which has independent intellectual property, a new action mechanism, long acting and effective to drug-resistant virus can increase the selection of drugs for treating AIDS on the whole and improve the treatment level of AIDS in China, and is the focus and key point of the current anti-HIV medicine research in China.

The HIV-treating neutralizing antibodies of the present invention were developed by the team of the famous immunologist Nussenzweig, university of Rockfeler, originally from 44-year-old Hispanic male HIV patients whose sera had significant HIV-neutralizing activity. It is one of the most active broad-spectrum HIV neutralizing antibodies in the world at present, and is also the only AIDS treating new drug inducing HIV immune recognition globally, and the large-scale production is realized through gene clone transduction and cell expression purification technology. It has different molecular action mechanism from that of HIV resisting medicine, and may be used in combination with other compound preparation.

The antibody has the same tendency of instability at high concentration as other protein medicines, and the dosage of the antibody is generally larger, so the development of a preparation of the HIV neutralizing antibody with high concentration can better meet the clinical requirement and improve the compliance of patients.

Disclosure of Invention

The invention aims to provide a human immunodeficiency virus neutralizing antibody preparation and application thereof.

In a first aspect of the invention, there is provided a liquid preparation of an antibody, the preparation comprising:

(a) A therapeutically effective amount of an HIV neutralizing antibody;

(b) A buffer solution with the concentration of 10-30 mmol/L;

(c) A stabilizer; and

(d) A surface-active agent, which is a surfactant,

wherein the concentration of the HIV neutralizing antibody is 90-140mg/mL;

the buffer solution is histidine buffer solution;

the stabilizer is one or the combination of more than two of sodium chloride, amino acid and polyhydric alcohol, the amino acid is selected from arginine or histidine, the polyhydric alcohol is one or the combination of more than two of sucrose, sorbitol and mannitol, and the concentration of the sodium chloride is 20-80mmol/L; the concentration of the amino acid is 10-100mmol/L; the concentration of the polyol is 1 wt% to 15 wt%, based on the total weight of the liquid formulation;

the surfactant is tween 80 or tween 20, and the concentration of the surfactant is 0.01 to 0.08 percent by weight based on the total weight of the liquid preparation;

and the pH of the liquid formulation is 5.5-6.5.

In another preferred embodiment, the heavy chain amino acid sequence of the HIV neutralizing antibody is as set forth in SEQ ID NO:1 is shown in the specification; the light chain amino acid sequence of the HIV neutralizing antibody is shown as SEQ ID NO:2, respectively.

In another preferred embodiment, the concentration of said HIV neutralizing antibody is 100-130mg/mL.

In another preferred embodiment, the stabilizer is one or a combination of more than two of amino acid and polyhydric alcohol.

In another preferred embodiment, the concentration of sodium chloride is 30-70mmol/L, preferably 40-60mmol/L, more preferably 45-55mmol/L.

In another preferred embodiment, the concentration of histidine in the histidine buffer is 15-25mmol/L.

In another preferred embodiment, the amino acid is arginine, the concentration of the amino acid is 5-50mmol/L, and preferably, the concentration of the amino acid is 15-25mmol/L.

In another preferred embodiment, the polyol is sucrose, and the concentration of the sucrose is 3 wt% to 10 wt%, preferably, the concentration of the sucrose is 4.5 wt% to 6.5 wt%.

In another preferred embodiment, the pH of the liquid formulation is 5.8 to 6.2.

In another preferred embodiment, the surfactant is tween 80, and the concentration of the surfactant is 0.04 wt% to 0.07 wt%.

In another preferred embodiment, the buffer is a histidine buffer;

the amino acid is arginine;

the polyol is sucrose;

the surfactant is tween 80.

In another preferred embodiment, the formulation comprises:

(a) 100-130mg/mL of HIV neutralizing antibody;

(b) 15-25mmol/L histidine buffer solution;

(c) 4.5-6.5% by weight sucrose;

(d) 45-55mmol/L sodium chloride;

(e) 15-25mmol/L arginine; and

(f) 0.04 to 0.07% by weight of tween 80.

In a second aspect of the present invention, there is provided a kit comprising:

a liquid preparation of the antibody according to the first aspect of the invention; and

a container for holding the liquid formulation.

In another preferred embodiment, the kit further comprises instructions for use.

It is to be understood that within the scope of the present invention, the above-described features of the present invention and those specifically described below (e.g., in the examples) may be combined with each other to form new or preferred embodiments. Not to be repeated herein, depending on the space.

Detailed Description

The inventor of the present invention has found through extensive and intensive studies that a liquid preparation comprising a high concentration of neutralizing antibody against human immunodeficiency virus (HIV neutralizing antibody), a specific concentration of buffer system containing histidine, a stabilizer (such as sucrose, arginine, sodium chloride), and a surfactant (such as tween) maintains excellent stability in terms of appearance, protein concentration, turbidity, purity, etc., and the chemical stability of the preparation is significantly improved, the generation rate of charge isomers in the preparation is significantly reduced, and the storage time of the preparation is effectively prolonged under the condition of pH 5.5-6.5. The present invention has been completed on the basis of this finding.

As used herein, the term "liquid formulation" refers to a preparation in a form that allows the biological activity of the active ingredient to be effective without additional ingredients that would be unacceptably toxic to a subject to which the formulation would be administered. The subject includes a mammal, preferably a human.

As used herein, the term "antibody stability" refers to an antibody that substantially retains its physical and/or chemical stability and/or biological activity upon storage. The shelf life is generally selected based on the intended shelf life of the formulation. A variety of analytical techniques for measuring antibody stability are known in the art.

Stability can be measured at a selected temperature for a selected time. Preferably, the formulation is stable for at least 1 month at room temperature or 30 ℃ to 40 ℃ and/or for at least 2 years at about 2-8 ℃.

The antibody in the formulation retains its physical stability if it exhibits substantially no evidence of significant aggregation, precipitation and/or denaturation as determined by visual inspection for color and/or clarity, or by UV light scattering or by size exclusion chromatography.

An antibody retains its chemical stability in a formulation if it is chemically stable at a specified time such that the antibody is said to still retain the biological activity defined below. Chemical stability can be assessed by detecting and quantifying chemically altered forms of the antibodies. Chemical changes may involve size changes (e.g., shearing), for example, as may be assessed by using size exclusion chromatography, SDS-PAGE and/or matrix-assisted laser-resolved ionization/time-of-flight mass spectrometry (MALDI/TOF MS). Other types of chemical changes include charge changes (e.g., changes due to deamidation), which can be assessed, for example, by ion exchange chromatography.

An antibody in a formulation retains its biological activity in the formulation if the antibody has biological activity for its intended use. For example, an antibody in the formulation is considered to retain its biological activity (e.g., as determined by an antigen binding assay) if its biological activity is within about 70% to 130% (within the error of the assay) of the biological activity exhibited when the formulation was prepared.

As used herein, the "therapeutically effective amount" or "effective amount" means an effective amount in the pharmacological sense, within the scope of the present invention, in the prevention or treatment of a disease. The antibodies are effective for the treatment of the disease. "treatment" means both therapeutic treatment and prophylactic or defensive measures. Subjects in need of treatment include subjects already suffering from the relevant condition, as well as subjects in need of prevention of the relevant disease.

As used herein, "human immunodeficiency virus neutralizing antibody of the invention," "human immunodeficiency virus neutralizing antibody," "HIV neutralizing antibody of the invention," "HIV neutralizing antibody" are used interchangeably and all refer to a polypeptide comprising SEQ ID NO:1 and 2.

The heavy chain and light chain sequences of the HIV neutralizing antibody of the invention are as follows:

heavy chain (SEQ ID NO: 1):

QVQLLQSGAAVTKPGASVRVSCEASGYNIRDYFIHWWRQAPGQGLQWVGWINPKTGQPNNPRQFQGRVSLTRHASWDFDTFSFYMDLKALRSDDTAVYFCARQRSDYWDFDVWGSGTQVTVSSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK

light chain (SEQ ID NO: 2):

DIQMTQSPSSLSASVGDTVTITCQANGYLNWYQQRRGKAPKLLIYDGSKLERGVPSRFSGRRWGQEYNLTINNLQPEDIATYFCQVYEFVVPGTRLDLKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

liquid preparation of antibodies

The antibody liquid preparation mainly comprises:

(a) A therapeutically effective amount of an HIV neutralizing antibody;

(b) A buffer solution with the concentration of 10-30 mmol/L;

(c) A stabilizer;

(d) A surfactant.

The therapeutically effective amount of antibody present in the formulations of the invention is determined by taking into account the required dosage volume and mode of administration. In the present invention, the concentration of the antibody is 90 to 150mg/mL, preferably 100 to 130mg/mL. The present invention includes ranges of values that use any combination of the above values as the upper and/or lower limits.

The buffer system used in the formulation of the present invention is a buffer system comprising histidine, and histidine may be present alone or in the form of, for example, histidine hydrochloride, histidine acetate, histidine phosphate, histidine sulfate, etc. In a preferred embodiment, histidine is present in the buffer system alone or as histidine hydrochloride.

The stabilizer in the formulation of the present invention may be one or a combination of two or more selected from sodium chloride, amino acids, and polyhydric alcohols. Wherein the amino acid is selected from arginine or histidine. Preferably, the amino acid is arginine, and the concentration of the arginine is 5-50mmol/L, preferably 15-25mmol/L.

The osmotic pressure regulator of the present invention is mainly composed of a polyhydric alcohol and sodium chloride, wherein the "polyhydric alcohol" is a substance having a plurality of hydroxyl groups and includes sugars (reducing sugars and non-reducing sugars), sugar alcohols and sugar acids. "reducing sugars" are sugars that include hemiacetal groups that are capable of reducing metal ions or covalently reacting with lysine and other amino groups in proteins, while "non-reducing sugars" are sugars that do not have the above-described characteristics of reducing sugars. Examples of reducing sugars include fructose, mannose, maltose, lactose, arabinose, xylose. Non-reducing sugars include sucrose, trehalose, sorbose, melezitose and raffinose. Examples of sugar alcohols include mannitol, xylitol, erythritol, threitol, sorbitol, and glycerol. As sugar acids, L-gluconic acid and its metal salts are included. If it is desired that the formulation be freeze-thaw stable, the polyol is preferably non-crystallizing at freezing temperatures (e.g., -20 ℃) so that it destabilizes the antibodies in the formulation.

The amount of polyol used may vary depending on the desired isotonicity of the formulation. The formulations of the present invention are preferably isotonic. The amount of polyol added may also vary depending on the molecular weight of the polyol. Preferred polyols of the present invention are sugar alcohols. In a preferred embodiment of the invention, the polyol is sucrose, the concentration of sucrose is from 1 wt% to 15 wt%, more preferably from 3 wt% to 10 wt%, more preferably from 4.5 wt% to 6.5 wt%, and the invention includes ranges using combinations of any of the above values as upper and/or lower values.

The concentration of sodium chloride is 30-70mmol/L, preferably 40-60mmol/L, more preferably 45-55mmol/L.

The surfactant in the formulations of the present invention is preferably a nonionic surfactant, such as a sorbitan polyoxyethylene ether fatty acid ester (e.g. sorbitan polyoxyethylene (20) ether laurate, sorbitan polyoxyethylene (20) ether oleate, etc.) or a poloxamer (e.g. poloxamer 188). The amount of surfactant added is such that it reduces aggregation of the antibody in the formulation and/or reduces formation of particles in the formulation and/or reduces adsorption. A preferred surfactant in the present invention is a tween, such as tween 80. In a preferred embodiment, the concentration of tween is 0.01% to 0.08% by weight, preferably 0.04% to 0.07% by weight. The present invention includes ranges of values that use any combination of the above values as the upper and/or lower limits.

The present invention includes ranges of values using combinations of any of the above as upper and/or lower limits, by adjusting the pH of the formulation via a buffer system to control the pH within the range of 5.5-6.5, and in certain embodiments between 5.5 and 6.4, 5.6 and 6.3, 5.7 and 6.2, 5.8 and 6.1, and 5.9 and 6.0. In some preferred embodiments, the formulation pH is 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, or 6.5.

It will be appreciated that the buffer system of the present invention may further comprise one or more other buffer components in addition to histidine, the pH of the formulation being controlled within the above ranges by combination with the other buffer components. Suitable additional buffer components include citrate, phosphate, acetate (e.g., sodium acetate), succinate (e.g., sodium succinate), and the like.

In a preferred embodiment of the invention, the buffer system is a histidine buffer system, wherein the histidine concentration is in the range of from 10 to 30mmol/L, preferably from 15 to 25mmol/L. The present invention includes ranges of values that use any combination of the above values as the upper and/or lower limits. In another embodiment, the pH of the formulation is adjusted with a mineral acid such as citric acid, acetic acid or phosphoric acid.

Through extensive experiments and data screening, the inventor finds that when the concentration of histidine in the preparation of the invention is lower than 15mg/ml, the buffering capacity of a buffering system is obviously limited, and when the concentration of histidine is higher than 25mg/ml, the stability of the preparation is not improved, and adverse reactions can be caused.

In addition, through repeated experiments, the inventor screens a large number of components and contents of various buffer systems, and finally screens a histidine system of the invention from a large number of buffer systems, and finds that the stability of the antibody protein in the system is obviously improved.

One or more other pharmaceutically acceptable carriers, excipients or stabilizers, such as those described in Remington's pharmaceutical 1 Sciences 1uth edition, osol, A.Ed. (1980), may be included in the formulations of the invention so long as they do not adversely affect the desired characteristics of the formulation. Acceptable carriers, excipients, or stabilizers are nontoxic to recipients at the dosages and concentrations employed, and include other co-solvents; antioxidants, including ascorbic acid and methionine; integrins such as EDTA; metal complexes (e.g., zn-protein complexes); biodegradable polymers such as polyvinyl acetate; and/or salt-forming counterions.

The formulations of the present invention may be prepared by combining the various components at certain concentrations using methods well known in the art.

One preferred class of methods generally comprises the steps of:

the HIV neutralizing antibody of the invention is concentrated and changed into different preparation buffers by centrifugation (4500 rpm,4-10 ℃) by using an Ultracel-30K ultrafiltration centrifugal tube, and the protein concentration is adjusted to the required concentration by using the preparation buffers. The preparations were filter sterilized using a 0.22 μm Millex needle filter. The prepared preparation is packaged for convenient use, and the selected packaging material can be a glass bottle, a pre-filled syringe or a pen-type syringe.

The features mentioned above with reference to the invention, or the features mentioned with reference to the embodiments, can be combined arbitrarily. All the features disclosed in this specification may be combined in any combination, and each feature disclosed in this specification may be replaced by alternative features serving the same, equivalent or similar purpose. Thus, unless expressly stated otherwise, the features disclosed are merely generic examples of equivalent or similar features.

Compared with the prior art, the invention has the following beneficial effects:

1. the preparation of the invention can effectively reduce the chemical degradation reaction rate of the HIV neutralizing antibody and the formation of polymer, improve the physical and chemical stability of the antibody and prolong the shelf life of the product.

2. By controlling the pH value of the preparation and removing potential components (such as citric acid) causing adverse reactions, the adverse reactions at the injection part of a patient can be eliminated or lightened, and the medication comfort of the patient is improved.

The invention is further illustrated by the following examples. It should be understood that these examples are for illustrative purposes only and are not intended to limit the scope of the present invention. Experimental procedures without specifying the detailed conditions in the following examples, generally followed by conventional conditions such as Sambrook et al, molecular cloning: the conditions described in the Laboratory Manual (New York: cold Spring Harbor Laboratory Press, 1989), or according to the manufacturer's recommendations. Unless otherwise indicated, percentages and parts are by weight.

Size exclusion chromatography (SEC-HPLC) was used to determine the purity, aggregation and degradant content of the HIV neutralizing antibodies of the invention. The method adopts Tosoh Bioscience TSK-Gel 3000SW _XL SEC chromatography column as stationary phase. A mobile phase consisting of 100mM sodium phosphate, 50mM sodium chloride, 10% acetonitrile, pH7.0 was prepared. A test sample and a reference substance for HIV neutralizing antibodies were prepared by diluting to a target protein concentration of 1mg/mL with a preparation buffer, and after a series of known gel filtration standards (670 kDa-1.35 kDa) were injected, the test sample and the reference substance were injected into a chromatographic column. The peak areas and elution times of the reference material and the test article were determined. Purity results are reported, expressed as the percentage of HIV neutralizing antibody monomer peaks relative to all other peaks (i.e. high and low molecular weight species).

Whole column imaging ceif performs capillary isoelectric focusing (ceif) for determining charge isomerism of the HIV neutralizing antibodies of the invention. Samples and standards were prepared using 0.35% methylcellulose and 10% glycerol additives in a pH 8-10.5 carrier ampholyte. Quantification was performed using pI markers pI 7.55 and pI 10.10. Samples, HIV neutralizing antibody reference and pI markers were injected into fluorocarbon-coated fused silica capillaries. Focused at 1.5kV for 1 minute and 3.0kV for 12 minutes. The focused protein region was photographed using a Charge Coupled Device (CCD) camera that can detect at 280 nm. Chromatographic peaks for HIV neutralizing antibody subtypes were integrated and pI values were quantified based on pixel position relative to internal pI markers.

EXAMPLE 1 formulation

(1) The following 2 buffers were prepared:

buffer 1:20mM histidine, 50mM sodium chloride, 20mM arginine, 5% sucrose, pH6.0

Buffer 2:20mM histidine, 50mM sodium chloride, 20mM arginine, 5% sucrose, 10% Tween 80, pH6.0

(2) And replacing the buffer solution of the intermediate of the HIV neutralizing antibody to be changed with buffer solution 1 by a dialysis mode, and controlling the concentration of the HIV neutralizing antibody to be about 100mg/mL to obtain the intermediate of the HIV neutralizing antibody after the change of the solution.

(3) Adding buffer solution 2 according to the proportion of 5g/kg of the total amount of the intermediate to obtain the formulated bulk drug. The ingredients are 20mM histidine, 50mM sodium chloride, 20mM arginine, 5% sucrose, 0.05% Tween 80, and pH6.0. The concentration of HIV neutralizing antibodies was about 100mg/mL.

Example 2 formulation comparison

Drug stability evaluations were completed at different concentrations for the following two formulations.

The preparation formula A:8.06mM sodium phosphate, 1.47mM potassium phosphate, 136.9mM sodium chloride, 2.68mM potassium chloride, tween 80, pH7.0.

Preparation formula B:20mM histidine, 50mM sodium chloride, 20mM arginine, 5% sucrose, tween 80, pH6.0.

As shown in table 1, formulation a corresponds to formulations 1, 2, 3, 4 according to different tween 80; formulation formula B corresponds to formulations 5, 6.

TABLE 1 formulation ingredients

(1) Appearance of the solution: the appearance of the formulation may change negatively upon storage at elevated temperatures or for prolonged periods of time, such as: darkening, turbidity, etc.

After the formulation was completed, visual inspection was performed. As shown in table 2, formulation B exhibited better clarity and solubility at high concentrations (> 70 mg/mL).

TABLE 2 formulation appearance test

Meanwhile, as shown in table 3, the appearance of formulation formula B was more stable at both 5 ℃ and 40 ℃.

TABLE 3 formulation appearance test at different temperatures

(2) Particle size: the particle size of the drug molecules in the formulation tends to increase after high temperature or long time storage.

As shown in table 4, the molecular particle size in the solution of formulation a at 70mg/mL varied greatly over time at 5 ℃ and 40 ℃, while formulation B can keep the particle size relatively stable at higher concentrations. In repeated freeze-thaw experiments, the particle sizes of formulation 5 and formulation 6 were substantially consistent before and after freeze-thawing, while the particle size of formulation 2 was significantly increased.

TABLE 4 detection of particle size of formulations at different temperatures

(3) Purity: after high temperature or long time storage, the purity of the antibody tends to decrease and the high polymer (HMW) content tends to increase.

As shown in Table 5, the purity of each preparation did not change in a tendency within 8 weeks at 5 ℃ but the purity of preparation A decreased drastically and high-molecular impurities increased after 8 weeks at 40 ℃. Particularly when the concentration was increased to 70mg/mL, the acidic component was increased by 187%. Meanwhile, the purity of the preparation B at the concentration of 100mg/mL has a slow change trend, and the acidic component is only increased by 87%.

TABLE 5 detection of the purity of the preparations at different temperatures

(4) Charge isomers: after high temperature or long time storage, the acidic component of the antibody tends to increase and the main peak decreases.

As shown in table 6, although the charge isomeric composition of each formulation did not change significantly at 5 ℃, formulations 1 and 2 both exhibited significant trend changes with 73% and 75% reduction in the main peak components, respectively, after 8 weeks at 40 ℃. While the charge isomers of formulations 5 and 6 were relatively insignificant, the main peak components were reduced by only 55% and 49%.

TABLE 6 detection of charge isomers of formulations at different temperatures

In summary, when the concentration is increased to 70mg/mL, the stability of formulation A in terms of particle size, purity, charge isomer composition, etc. is poor. Meanwhile, the stability of the preparation B is obviously better than that of the preparation A when the concentration is not less than 100mg/mL.

All documents referred to herein are incorporated by reference into this application as if each were individually incorporated by reference. Furthermore, it should be understood that various changes and modifications of the present invention can be made by those skilled in the art after reading the above teachings of the present invention, and these equivalents also fall within the scope of the present invention as defined by the appended claims.

Sequence listing

<110> leading edge biopharmaceutical industry (Nanjing) GmbH

<120> HIV neutralizing antibody preparation and use thereof

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Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val

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Claims (10)

1. A liquid formulation of a antibody, wherein the formulation comprises:

(a) A therapeutically effective amount of an HIV neutralizing antibody;

(b) A buffer solution with the concentration of 10-30 mmol/L;

(c) A stabilizer; and

(d) A surfactant, a water-soluble surfactant and a water-soluble surfactant,

wherein the concentration of the HIV neutralizing antibody is 90-140mg/mL;

the buffer solution is histidine buffer solution;

the stabilizer is one or the combination of more than two of sodium chloride, amino acid and polyhydric alcohol, the amino acid is selected from arginine or histidine, the polyhydric alcohol is one or the combination of more than two of sucrose, sorbitol and mannitol, and the concentration of the sodium chloride is 20-80mmol/L; the concentration of the amino acid is 10-100mmol/L; the concentration of the polyol is 1 wt% to 15 wt%, based on the total weight of the liquid formulation;

the surfactant is tween 80 or tween 20, and the concentration of the surfactant is 0.01 to 0.08 percent by weight based on the total weight of the liquid preparation;

and the pH of the liquid formulation is 5.5-6.5.

2. The liquid formulation of claim 1, wherein the heavy chain amino acid sequence of the HIV neutralizing antibody is as set forth in SEQ ID NO:1 is shown in the specification; the light chain amino acid sequence of the HIV neutralizing antibody is shown as SEQ ID NO:2, respectively.

3. The liquid formulation of claim 1, wherein the concentration of HIV neutralizing antibodies is 100-130mg/mL.

4. The liquid formulation of claim 1, wherein the concentration of sodium chloride is 30-70mmol/L, preferably 40-60mmol/L, more preferably 45-55mmol/L.

5. The liquid formulation of claim 1, wherein the concentration of histidine in the histidine buffer is 15-25mmol/L.

6. The liquid formulation of claim 1, wherein the amino acid is arginine, and the concentration of the amino acid is 5 to 50mmol/L, preferably 15 to 25mmol/L.

7. The liquid formulation of claim 1, wherein the polyol is sucrose, and the concentration of sucrose is 3 wt% to 10 wt%, preferably the concentration of sucrose is 4.5 wt% to 6.5 wt%.

8. The liquid formulation of claim 1, wherein the liquid formulation has a pH of 5.8 to 6.2.

9. The liquid formulation of claim 1, wherein the formulation comprises:

(a) 100-130mg/mL HIV neutralizing antibody;

(b) 15-25mmol/L histidine buffer;

(c) 4.5-6.5% by weight sucrose;

(d) 45-55mmol/L sodium chloride;

(e) 15-25mmol/L arginine; and

(f) 0.04 to 0.07% by weight of tween 80.

10. A kit, comprising:

the antibody liquid formulation of any one of claims 1-9; and

a container for holding the liquid formulation.