Pulmonary delivery of antibodies

Abstract

This invention relates to the lung delivery of antibodies or antibody derivatives.

Description

Antibody lung delivery This invention relates to the lung delivery of antibodies or antibody derivatives. Attention to therapeutic antibodies has increased dramatically year by year because their highly specific targeting of antigens can provide very effective treatments for a wide range of diseases. Lung delivery of antibodies (such as monoclonal antibodies) represents an attractive, non-invasive alternative to parental delivery. The pulmonary delivery route has proven effective for the local and systemic delivery of various drugs and biologics for the treatment of both pulmonary and non-pulmonary diseases. However, administering proteins (such as antibodies) to the lungs is associated with numerous challenges, including the need for appropriate antibody formulations to overcome strong intermolecular / particle interactions and physicochemical degradation, which can lead to aggregation and potentially loss of biological / therapeutic activity and / or safety issues. For example, proteins may be sensitive to aerosol-related shear stress and / or temperature elevation, and / or may exhibit reduced stability at the air-liquid interface in aerosols. Therefore, one object of the present invention is to identify formulation systems that are suitable for pulmonary delivery of antibodies and help maintain the stability and activity of antibodies during aerosolization / nebulization. In one embodiment, the present invention relates to an aerosol comprising droplets, the droplets comprising a liquid formulation, wherein the liquid formulation comprises (i) an antibody or antibody derivative, (ii) a buffer selected from acetates, histidines, and combinations thereof, and (iii) an aqueous medium; and wherein the liquid formulation has a pH equal to or lower than about 5.5. In one embodiment, the antibody or antibody derivative is an IgG1 antibody or antibody derivative. In one embodiment, the antibody is a monoclonal antibody. In one embodiment, the liquid formulation does not contain citrate. In one embodiment, the liquid formulation has a pH in the range of about 3.5 to about 5.5. In one embodiment, the buffer is an acetate, and the liquid formulation has a pH below about 5.0 or below about 4.5. In one embodiment, the buffer is an acetate, and the liquid formulation has a pH in the range of about 3.5 to below about 4.5, or between about 3.7 and about 4.3, or between about 3.8 and about 4.2, or between about 3.9 and about 4.1. In one embodiment, the liquid formulation has a pH of about 4.0. In one embodiment, the liquid formulation further comprises a surfactant. In one embodiment, the surfactant is selected from polysorbates, poloxamers, polyoxyethylene alkyl ethers, alkylphenol polyoxyethylene, and sodium dodecyl sulfate. In one embodiment, the concentration of the surfactant in the liquid formulation is equal to or less than about 0.1% (w / v) or equal to or less than about 0.05% (w / v). In one embodiment, the liquid formulation does not contain any surfactants. In one embodiment, the liquid formulation does not contain NaCl. In one embodiment, the liquid formulation does not contain any non-buffered salts. In one embodiment, the droplet has an average diameter ranging from about 0.5 μm to about 5 μm, from about 0.5 μm to about 4.5 μm, from about 0.5 μm to about 4 μm, from about 0.5 μm to about 3.5 μm, or from about 0.5 μm to about 3 μm. In one embodiment, the droplet has an average diameter of less than 5 μm. In one embodiment, the droplet has an average diameter of less than 4.5 μm. In one embodiment, the droplet has an average diameter of less than 4.0 μm. In one embodiment, the droplet has an average diameter of less than 3.5 μm. In one embodiment, the droplet has an average diameter of less than 3.0 μm. In another embodiment, the present invention relates to a method for preparing an aerosol comprising droplets containing a liquid formulation, the method comprising the steps of: (i) providing a liquid formulation as defined above, and (ii) atomizing the liquid formulation provided in step (i) by means of an atomizer, thereby preparing the aerosol. In one embodiment, the atomizer is a mesh atomizer. In one embodiment, the method further includes the following steps between steps (i) and (ii): (ia) lyophilizing the liquid formulation provided in step (i) to provide lyophilized powder, and (ib) reconstituted the lyophilized powder provided in step (ia) by adding an appropriate amount of aqueous medium. In another embodiment, the invention relates to an aerosol comprising droplets containing a liquid formulation, wherein the aerosol can be obtained by the methods defined above. In one embodiment, the droplets have an average diameter ranging from about 0.5 μm to about 5 μm or from about 0.5 μm to about 3 μm. In another respect, the present invention relates to a method of delivering an antibody or antibody derivative to the lungs of a subject using a liquid formulation or aerosol as defined above, wherein the aerosol is administered to the subject by inhalation, or the liquid formulation is administered to the subject by inhalation via a nebulizer. In one embodiment, the antibody or antibody derivative is an IgG1 antibody or antibody derivative. In one embodiment, the atomizer is a mesh atomizer. In another respect, the present invention relates to a method of using a liquid formulation as defined above for treating or preventing a disease in a subject, wherein the aerosol is administered to the subject by inhalation, or the liquid formulation is administered to the subject by inhalation via a nebulizer. In one embodiment, the disease is a lung disease. In one embodiment, the atomizer is a mesh atomizer. In another embodiment, the present invention relates to a method for delivering an antibody or antibody derivative to the lungs of a subject, the method comprising administering to the subject an effective amount of an aerosol as defined above by inhalation or an effective amount of a liquid preparation as defined above by inhalation via a nebulizer. In one embodiment, the antibody or antibody derivative is an IgG1 antibody or antibody derivative. In one embodiment, the atomizer is a mesh atomizer. In another respect, the present invention relates to a method for treating or preventing a disease in a subject, the method comprising administering to the subject an effective amount of an aerosol as defined above by inhalation, or administering to the subject an effective amount of a liquid preparation as defined above by inhalation via a nebulizer. In one embodiment, the disease is a lung disease. In one embodiment, the atomizer is a mesh atomizer. In one embodiment, the lung diseases mentioned above are selected from asthma, chronic obstructive pulmonary disease (COPD), lung cancer, cystic fibrosis (CF), interstitial lung disease (ILD) (such as idiopathic pulmonary fibrosis, hypersensitivity pneumonia, sarcoidosis and asbestosis), bacterial infection, viral infection, acute respiratory distress syndrome (ARDS), pulmonary alveolar proteinosis (PAP), acute bronchitis, bronchiolitis obliterans and pulmonary hypertension. In another embodiment, the present invention relates to an atomizer comprising a liquid formulation as defined above. In one embodiment, the atomizer is a mesh atomizer. In another embodiment, the invention relates to a kit comprising (i) a container containing a liquid formulation as defined above or a powder obtained by lyophilizing a liquid formulation, and (ii) an atomizer. In one embodiment, the atomizer is a mesh atomizer. In another respect, the present invention relates to the use of the liquid formulation as defined above for preparing an aerosol by means of an atomizer through atomization. In one embodiment, the atomizer is a mesh atomizer. In another respect, the present invention relates to the use of a buffer selected from acetates, histidines, and combinations thereof for increasing the stability of a liquid formulation containing an antibody or antibody derivative by means of a nebulizer, wherein the buffer is contained in the liquid formulation prior to nebulization. In one embodiment, the antibody or antibody derivative is an IgG1 antibody or antibody derivative. In one embodiment, the atomizer is a mesh atomizer. In one embodiment, the liquid formulation has a pH equal to or lower than about 5.5. In one embodiment, the antibody is a monoclonal antibody. In one embodiment, the liquid formulation does not contain citrate. In one embodiment, the liquid formulation has a pH in the range of about 3.5 to about 5.5. In one embodiment, the buffer is an acetate, and the liquid formulation has a pH below about 5.0 or below about 4.5. In one embodiment, the buffer is an acetate, and the liquid formulation has a pH in the range of about 3.5 to below about 4.5, or between about 3.7 and about 4.3, or between about 3.8 and about 4.2, or between about 3.9 and about 4.1. In one embodiment, the liquid formulation has a pH of about 4.0. In one embodiment, the liquid formulation further comprises a surfactant. In one embodiment, the surfactant is selected from polysorbate, poloxamer, polyoxyethylene alkyl ether, alkylphenol polyoxyethylene, and sodium dodecyl sulfate. In one embodiment, the concentration of the surfactant in the liquid formulation is equal to or less than about 0.1% (w / v) or equal to or less than about 0.05% (w / v). In one embodiment, the liquid formulation does not contain any surfactants. In one embodiment, the liquid formulation does not contain NaCl. In one embodiment, the liquid formulation does not contain any non-buffered salts. Before describing the invention in detail below, it should be understood that the invention is not limited to the specific methods, schemes, and reagents described herein, as they can vary. It should also be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of the invention, which will be limited only by the scope of the appended claims. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which they pertain. Preferably, the terms used herein are as defined in "A multilingual glossary of biotechnological terms: (IUPAC Recommendations)," edited by Leuenberger, HGW, Nagel, B., and Kolb, H. (1995), Helvetica Chimica Acta, CH-4010 Basel, Switzerland. Throughout this specification, certain documents have been referenced. Every reference cited herein (including all patents, patent applications, scientific publications, manufacturer's specifications, instructions, etc.) is incorporated herein by reference in its entirety. Nothing herein should be construed as an admission that the invention is based on a prior art and is not entitled to any work prior to these disclosures. The elements of the invention will be described below. These elements are set forth with specific embodiments; however, it should be understood that these specific embodiments can be combined in any manner and in any number to produce other embodiments. The examples and preferred / specific embodiments described differently should not be construed as limiting the invention to only the embodiments explicitly described. This specification should be understood to support and cover embodiments combining the explicitly described embodiments with any number of the disclosed and / or preferred elements. Furthermore, unless the context otherwise indicates, any permutation and combination of all the elements disclosed in this application should be considered. Throughout this specification and the following claims, unless the context otherwise requires, the word "comprise" and its variations such as "comprises" or "comprising" should be understood to imply inclusion of the stated whole or step or group of wholes or steps, but not to exclude any other whole or step or group of wholes or steps. As used in this specification and the appended claims, the singular forms "a," "an," and "described" include the plural meanings, unless the context expressly specifies otherwise. In one embodiment, the present invention relates to an aerosol comprising droplets, the droplets comprising a liquid formulation, wherein the liquid formulation comprises (i) an antibody or antibody derivative, (ii) a buffer selected from acetates, histidines, and combinations thereof, and (iii) an aqueous medium; and wherein the liquid formulation has a pH equal to or lower than about 5.5. In one embodiment, the antibody or antibody derivative is an IgG1 antibody or antibody derivative. The term "antibody" (or "immunoglobulin") generally refers to a glycoprotein comprising at least two heavy (H) chains and two light (L) chains linked together by disulfide bonds. The term "antibody" includes monoclonal antibodies, recombinant antibodies, human antibodies, humanized antibodies, chimeric antibodies, and any combination of the foregoing. Each heavy chain consists of a heavy chain variable region (VH) and a heavy chain constant region (CH). Each light chain consists of a light chain variable region (VL) and a light chain constant region (CL). The variable and constant regions are also referred to herein as variable domains and constant domains, respectively. The VH and VL regions can be further subdivided into highly variable regions called complementarity-determining regions (CDRs), which are scattered within more conserved regions called framework regions (FRs). Each VH and VL consists of three CDRs and four FRs, arranged in the following order from the amino terminus to the carboxyl terminus: FR1, CDR1, FR2, CDR2, FR3, CDR3, FR4. The CDRs of VH are called HCDR1, HCDR2, and HCDR3, and the CDRs of VL are called LCDR1, LCDR2, and LCDR3. The variable regions of the heavy and light chains contain binding domains that interact with the antigen. The constant regions of an antibody include a heavy chain constant region (CH) and a light chain constant region (CL), where CH can be further subdivided into constant domain CH1, a hinge region, and constant domains CH2 and CH3 (arranged in the following order from the amino terminus to the carboxyl terminus: CH1, CH2, CH3). The constant regions of an antibody can mediate the binding of immunoglobulins to host tissues or factors, including various cells of the immune system (e.g., effector cells) and the first component (Clq) of the conventional complement system. Antibodies can be derived from different species, including, but not limited to, mice, rats, rabbits, guinea pigs, and humans. Antibodies described herein include antibodies of the isotype / type of IgA, such as IgA1 or IgA2, IgG1, IgG2, IgG3, IgG4, IgE, IgM, and IgD. In various embodiments, the antibody is an IgG1 antibody, more particularly IgG1κ or IGg1 λ isoform (i.e., IGg1, κ, λ), IgG2a antibodies (e.g., IgG2a, κ, λ), IgG2b antibodies (e.g., IgG2b, κ, λ), IgG3 antibodies (e.g., IgG3, κ, λ), or IgG4 antibodies (e.g., IgG4, κ, λ). In one embodiment, the antibody is an IgG1 antibody. The term "antibody derivative" as used herein refers to a molecule that comprises at least the domain of its specified inclusion but does not have the overall structure of an antibody (such as IgA, IgD, IgE, IgG, IgM, IgY, or IgW, especially IgG1), despite being able to bind the molecule of interest. The derivatives may be, but are not limited to, functional (i.e., target-binding, especially specific target-binding) antibody fragments thereof, such as Fab2, or combinations of such derivatives, such as bivalent Fab. It also involves antibodies to which other antibody domains (such as other variable domains) have been added. In one embodiment, the term "antibody derivative" refers to a single-chain antibody, e.g., as in Spiess et al. (J Mol Imm. 2015, 67:95-106), WO 2017, 9:182-212) and Fitzgerald et al. (Mol Cancer Ther. 2013, 13:410-25). Other non-limiting examples of antibody derivatives include nanoantibodies, dual antibody microantibodies, and other forms as described, for example, in Spiess et al. (J Mol Imm. 2015 , 67:95–106). The term “IgG1 antibody derivative” refers to an antibody derivative that can be identified as derived from an IgG1 antibody, for example due to the presence of one or more IgG1 specific (sequence) elements. In one embodiment, the antibody is a monoclonal antibody. As used herein, the term "single strain antibody" refers to a product of an antibody molecule composed of a single molecule. The monoclonal antibody exhibits single binding specificity and affinity. In one embodiment, the monoclonal antibody is produced by a hybridoma comprising a B cell obtained from a non-human animal (e.g., a mouse) fused to an immortalized cell. Generally, the terms “antibody” and “antibody derivative” as used herein include both monospecific and multispecific (e.g., bispecific, trispecific, or tetraspecific) antibodies and antibody derivatives. In one embodiment, the antibody or antibody derivative is a pharmaceutically active antibody or antibody derivative. As used herein, the term "pharmaceutically active antibody or antibody derivative" refers to an antibody or antibody derivative suitable for therapeutic purposes (i.e., that can be used to treat a disease or disorder). In one embodiment, the pharmaceutically active antibody or antibody derivative binds to a treatment-related antigen. Exemplary antibodies that can be used according to the present invention include, but are not limited to, anti-respiratory fusion virus (RSV) antibodies, anti-IL-4 antibodies, anti-IL-4 receptor antibodies, anti-IFN-β antibodies, anti-IL-13 antibodies, anti-thymocyte stromal lymphopoietin (TSLP) antibodies, anti-IL-1 receptor antibodies, anti-IL-2 antibodies, and anti-TNF antibodies. In one embodiment, the antibody concentration ranges from about 150 mg / ml to 1 mg / ml; or from about 150 mg / ml to about 5 mg / ml; or from about 150 mg / ml to about 10 mg / ml; or from about 150 mg / ml to about 20 mg / ml; or from about 150 mg / ml to about 50 mg / ml. In one embodiment, the antibody concentration ranges from about 120 mg / ml to 1 mg / ml; or from about 120 mg / ml to about 5 mg / ml; or from about 120 mg / ml to about 10 mg / ml; or from about 120 mg / ml to about 20 mg / ml; or from about 120 mg / ml to about 50 mg / ml. In one embodiment, the antibody concentration ranges from about 100 mg / ml to 1 mg / ml; or from about 100 mg / ml to about 5 mg / ml; or from about 100 mg / ml to about 10 mg / ml; or from about 100 mg / ml to about 20 mg / ml; or from about 100 mg / ml to about 50 mg / ml. In one embodiment, the antibody concentration ranges from about 80 mg / ml to 1 mg / ml; or from about 80 mg / ml to about 5 mg / ml; or from about 80 mg / ml to about 10 mg / ml; or from about 80 mg / ml to about 20 mg / ml; or from about 80 mg / ml to about 50 mg / ml. In one embodiment, the antibody concentration ranges from about 50 mg / ml to 5 mg / ml; or from about 40 mg / ml to about 5 mg / ml; or from about 30 mg / ml to about 5 mg / ml; or from about 20 mg / ml to about 5 mg / ml; or from about 10 mg / ml to about 5 mg / ml. In one embodiment, the antibody concentration ranges from about 50 mg / ml to 1 mg / ml; or from about 40 mg / ml to about 1 mg / ml; or from about 30 mg / ml to about 1 mg / ml; or from about 20 mg / ml to about 1 mg / ml; or from about 10 mg / ml to about 1 mg / ml. In one preferred embodiment, the antibody concentration is about 150 mg / ml. In another preferred embodiment, the antibody concentration is about 140 mg / ml. In another preferred embodiment, the antibody concentration is about 130 mg / ml. In another preferred embodiment, the antibody concentration is about 120 mg / ml. In another preferred embodiment, the antibody concentration is about 110 mg / ml. In one preferred embodiment, the antibody concentration is about 100 mg / ml. In another preferred embodiment, the antibody concentration is about 90 mg / ml. In another preferred embodiment, the antibody concentration is about 80 mg / ml. In another preferred embodiment, the antibody concentration is about 70 mg / ml. In another preferred embodiment, the antibody concentration is about 60 mg / ml. In one preferred embodiment, the antibody concentration is about 50 mg / ml. In another preferred embodiment, the antibody concentration is about 40 mg / ml. In another preferred embodiment, the antibody concentration is about 30 mg / ml. In another preferred embodiment, the antibody concentration is about 20 mg / ml. In another preferred embodiment, the antibody concentration is about 10 mg / ml. In another preferred embodiment, the antibody concentration is about 5 mg / ml. In another preferred embodiment, the antibody concentration is about 1 mg / ml. In one embodiment, the concentration of the buffer in the liquid formulation is in the range of about 1 mM to about 200 mM, for example, from about 5 mM to about 150 mM, or from about 5 mM to about 100 mM, or from about 5 mM to about 50 mM. In one embodiment, the concentration of the buffer in the liquid formulation is in the range of about 5 mM to about 25 mM, for example, from about 5 mM to about 20 mM, or from about 5 mM to about 15 mM, or from about 7.5 mM to about 12.5 mM. In one embodiment, the concentration of the buffer in the liquid formulation is about 10 mM. In one embodiment, the buffer is an acetate, and the concentration of the acetate in the liquid formulation is in the range of about 1 mM to about 200 mM, for example, from about 5 mM to about 150 mM, or from about 5 mM to about 100 mM, or from about 5 mM to about 50 mM. In one embodiment, the concentration of acetate in the liquid formulation is in the range of about 5 mM to about 25 mM, for example, from about 5 mM to about 20 mM, or from about 5 mM to about 15 mM, or from about 7.5 mM to about 12.5 mM. In one embodiment, the concentration of acetate in the liquid formulation is about 10 mM. In one embodiment, the buffer is histidine, and the concentration of histidine in the liquid formulation is in the range of about 1 mM to about 200 mM, for example, from about 5 mM to about 150 mM, or from about 5 mM to about 100 mM, or from about 5 mM to about 50 mM. In one embodiment, the concentration of histidine in the liquid formulation is in the range of about 5 mM to about 25 mM, for example, from about 5 mM to about 20 mM, or from about 5 mM to about 15 mM, or from about 7.5 mM to about 12.5 mM. In one embodiment, the concentration of histidine in the liquid formulation is about 10 mM. In one embodiment, the concentration of histidine in the liquid formulation is about 20 mM. In one embodiment, the acetate acting as a buffer is sodium acetate (or another suitable acetate, such as potassium acetate), for example, combined with acetic acid (i.e., in the form of an acetate buffer). Methods for preparing suitable acetate buffers are well known to those skilled in the art. In one embodiment, the histidine acting as a buffer is sodium L-histidine (or another suitable histidine salt), for example, in the form of a histidine buffer. Methods for preparing suitable histidine buffers are well known to those skilled in the art. In one embodiment, the liquid formulation does not contain citrate. As used herein, the term "aqueous medium" (or "aqueous solution") refers to a liquid medium or solution in which water is a solvent. In one embodiment, the aqueous medium is water or composed of water, particularly purified water or water for injection (WFI). In one embodiment, the aqueous medium is sterile. In one embodiment, the liquid formulation is sterile. In one embodiment, the liquid formulation has a pH in the range of about 3.5 to about 5.5. In one embodiment, the buffer is an acetate, and the liquid formulation has a pH below about 5.0 or below about 4.5. In one embodiment, the buffer is an acetate, and the liquid formulation has a pH in the range of about 3.5 to below about 4.5, or between about 3.7 and about 4.3, or between about 3.8 and about 4.2, or between about 3.9 and about 4.1. In one embodiment, the liquid formulation has a pH of about 4.0. In one embodiment, the buffer is a 10 mM acetate, and the liquid formulation has a pH below about 5.0 or below about 4.5. In another embodiment, the buffer is a 10 mM acetate, and the liquid formulation has a pH in the range of about 3.5 to below about 4.5, or between about 3.7 and about 4.3, or between about 3.8 and about 4.2, or between about 3.9 and about 4.1. In yet another embodiment, the liquid formulation has a pH of about 4.0, and the buffer is a 10 mM acetate. In one embodiment, the buffer is histidine, and the liquid formulation has a pH equal to or lower than about 5.5. In one embodiment, the buffer is histidine, and the liquid formulation has a pH lower than about 5.0 or lower than about 4.5. In one embodiment, the buffer is histidine, and the liquid formulation has a pH in the range of about 3.5 to below about 4.5, or between about 3.7 and about 4.3, or between about 3.8 and about 4.2, or between about 3.9 and about 4.1. In one embodiment, the liquid formulation has a pH of about 4.0. In one embodiment, the buffer is 10 mM histidine, and the liquid formulation has a pH equal to or lower than about 5.5. In one embodiment, the buffer is 10 mM histidine, and the liquid formulation has a pH lower than about 5.0 or lower than about 4.5. In one embodiment, the buffer is 10 mM histidine, and the liquid formulation has a pH in the range of about 3.5 to below about 4.5, or between about 3.7 and about 4.3, or between about 3.8 and about 4.2, or between about 3.9 and about 4.1. In one embodiment, the liquid formulation has a pH of about 4.0, and the buffer is 10 mM histidine. In one embodiment, the buffer is 20 mM histidine, and the liquid formulation has a pH equal to or lower than about 5.5. In one embodiment, the buffer is 20 mM histidine, and the liquid formulation has a pH lower than about 5.0 or lower than about 4.5. In one embodiment, the buffer is 20 mM histidine, and the liquid formulation has a pH in the range of about 3.5 to below about 4.5, or between about 3.7 and about 4.3, or between about 3.8 and about 4.2, or between about 3.9 and about 4.1. In one embodiment, the liquid formulation has a pH of about 4.0, and the buffer is 20 mM histidine. The liquid formulation may contain one or more other excipients, provided they are pharmaceutically acceptable and do not impair the suitability of the liquid formulation for administration by inhalation, particularly via a nebulizer. Suitable excipients are listed in pharmacopoeias or, for example, in REMINGTON'S PHARMACEUTICAL SCIENCES (18th edition, edited by AR Gennaro, Mack Publishing Company 1990), and subsequent editions. As used herein, the term "pharmaceuticalally acceptable" means that the material is non-toxic and, in one embodiment, does not interact with the active agent of the liquid formulation. In one embodiment, the liquid formulation further comprises a surfactant. As used herein, the term "surfactant" (or "surface active agent") refers to a compound that reduces the surface tension (or interfacial tension) between two liquids, between a gas and a liquid, or between a liquid and a solid. In one embodiment, the compound reduces the surface tension (or interfacial tension) between a gas (e.g., air) and a liquid. In one embodiment, the surfactant is a nonionic surfactant. In one embodiment, the surfactant is selected from polysorbates (e.g., polysorbate 20 or polysorbate 80), poloxamer (e.g., poloxamer 188, as Pluronic...). ® F68 is commercially available; or Poloxamer 407, as Pluronic ® F127 is commercially available), polyoxyethylene alkyl ethers (e.g., Brij TM surfactants), alkylphenol polyoxyethylene (e.g., Triton) ® X100) and sodium dodecyl sulfate (SDS). In one embodiment, the surfactant is polysorbate 80 (PS80). In one embodiment, the concentration of the surfactant in the liquid formulation is equal to or less than about 0.1% (w / v) or equal to or less than about 0.05% (w / v), for example, equal to or less than about 0.04% (w / v), equal to or less than about 0.03% (w / v), equal to or less than about 0.02% (w / v), or equal to or less than about 0.01% (w / v). In another embodiment, the concentration of the surfactant in the liquid formulation is less than about 0.01% (w / v). In one embodiment, the concentration of polysorbate in the liquid formulation is equal to or less than about 0.1% (w / v) or equal to or less than about 0.05% (w / v), for example, equal to or less than about 0.04% (w / v), equal to or less than about 0.03% (w / v), equal to or less than about 0.02% (w / v), or equal to or less than about 0.01% (w / v). In another embodiment, the concentration of polysorbate in the liquid formulation is less than about 0.01% (w / v). In one embodiment, the concentration of PS80 in the liquid formulation is equal to or less than about 0.1% (w / v) or equal to or less than about 0.05% (w / v), for example, equal to or less than about 0.04% (w / v), equal to or less than about 0.03% (w / v), equal to or less than about 0.02% (w / v), or equal to or less than about 0.01% (w / v). In another embodiment, the concentration of PS80 in the liquid formulation is less than about 0.01% (w / v). In one embodiment, the liquid formulation contains only one surfactant. In one embodiment, this surfactant is PS80. In one embodiment, the liquid formulation does not contain any surfactants, such as those defined above. In one embodiment, the liquid formulation does not contain NaCl. In one embodiment, the liquid formulation does not contain any non-buffered salts. As used herein, the term "non-buffered salt" refers to a salt that does not, or substantially does not, contribute to maintaining the pH of the liquid formulation when an acid or base is added. In one embodiment, the non-buffered salt is a halogen salt (e.g., containing Cl-). - or Br - In one embodiment, the non-buffered salt is sodium (Na₂O₃). + ), potassium (K) + ), calcium (Ca 2+ ) or magnesium (Mg 2+ A halogen salt containing one or more cations from the group consisting of sodium (Na). In one embodiment, the unbuffered salt is a halogen salt containing sodium (Na) + ) or potassium (K + The unbuffered salt is a halide salt of one or more cations selected from NaCl, KCl, and CaCl₂. In yet another embodiment, the unbuffered salt is selected from NaCl, KCl, and CaCl₂. 2 and MgCl 2. Typically, aerosols are suspensions of fine solid particles or droplets in air or another gas. According to the present invention, the term "aerosol" refers to a suspension of liquid formulations in a gas (e.g., air) as defined above. In one embodiment, the droplet has an average diameter of less than 5 μm. In one embodiment, the droplet has an average diameter of less than 4.5 μm. In one embodiment, the droplet has an average diameter of less than 4.0 μm. In one embodiment, the droplet has an average diameter of less than 3.5 μm. In one embodiment, the droplet has an average diameter of less than 3.0 μm. In one embodiment, the droplet has an average diameter ranging from about 0.5 μm to about 5 μm. In one embodiment, the droplet has an average diameter ranging from about 0.5 μm to about 4.5 μm. In one embodiment, the droplet has an average diameter ranging from about 0.5 μm to about 4 μm. In one embodiment, the droplet has an average diameter ranging from about 0.5 μm to about 3.5 μm. In one embodiment, the droplet has an average diameter ranging from about 0.5 μm to about 3 μm. In one embodiment, the average diameter is the volume median diameter (VMD; also known as the Dv50 value). In one embodiment, the VMD is determined by laser diffraction, for example, as described in United States Pharmacopeia (USP) 429. The droplet size can also be measured by, for example, interferometric laser imaging. The results may vary depending on the measurement method used. In one embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH of about 5.0 or below about 4.5, and comprises droplets having an average diameter of less than 5.0 μm. In another embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH of about 5.0 or below about 4.5, and comprises droplets having an average diameter ranging from about 0.5 μm to about 5 μm. In yet another embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH ranging from about 3.5 to below about 4.5, and comprises droplets having an average diameter of less than 5 μm. In yet another embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH ranging from about 3.5 to below about 4.5, and comprises droplets having an average diameter ranging from about 0.5 μm to about 5 μm. In yet another embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH that is or is between about 3.7 and about 4.3, and comprises droplets having an average diameter of less than 5 μm. In one embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH between about 3.7 and about 4.3, and comprises droplets having an average diameter ranging from about 0.5 μm to about 5 μm. In one embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH between about 3.8 and about 4.2, and comprises droplets having an average diameter of less than 5 μm. In one embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH between about 3.8 and about 4.2, and comprises droplets having an average diameter ranging from about 0.5 μm to about 5 μm. In one embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH between about 3.9 and about 4.1, and comprises droplets having an average diameter of less than 5 μm. In one embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH between about 3.9 and about 4.1, and comprises droplets having an average diameter ranging from about 0.5 μm to about 5 μm. In another embodiment, the liquid formulation comprises only one surfactant. In one embodiment, this surfactant is PS80. In one embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH of about 5.0 or below about 4.5, and comprises droplets having an average diameter of less than 4.5 μm. In another embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH of about 5.0 or below about 4.5, and comprises droplets having an average diameter ranging from about 0.5 μm to about 4.5 μm. In yet another embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH ranging from about 3.5 to below about 4.5, and comprises droplets having an average diameter of less than 4.5 μm. In yet another embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH ranging from about 3.5 to below about 4.5, and comprises droplets having an average diameter ranging from about 0.5 μm to about 4.5 μm. In one embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH between about 3.7 and about 4.3, and comprises droplets having an average diameter of less than 4.5 μm. In another embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH between about 3.7 and about 4.3, and comprises droplets having an average diameter ranging from about 0.5 μm to about 4.5 μm. In yet another embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH between about 3.8 and about 4.2, and comprises droplets having an average diameter of less than 4.5 μm. In yet another embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH between about 3.8 and about 4.2, and comprises droplets having an average diameter ranging from about 0.5 μm to about 4.5 μm. In one embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH between about 3.9 and about 4.1, and comprises droplets having an average diameter of less than 4.5 μm. In another embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH between about 3.9 and about 4.1, and comprises droplets having an average diameter ranging from about 0.5 μm to about 4.5 μm. In yet another embodiment, the liquid formulation comprises only one surfactant. In one embodiment, this surfactant is PS80. In one embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH of about 5.0 or below about 4.5, and comprises droplets with an average diameter of less than 4 μm. In another embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH of about 5.0 or below about 4.5, and comprises droplets with an average diameter ranging from about 0.5 μm to about 4 μm. In yet another embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH ranging from about 3.5 to below about 4.5, and comprises droplets with an average diameter of less than 4 μm. In yet another embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH ranging from about 3.5 to below about 4.5, and comprises droplets with an average diameter ranging from about 0.5 μm to about 4 μm. In yet another embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH between about 3.7 and about 4.3, and comprises droplets with an average diameter of less than 4 μm. In one embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH between about 3.7 and about 4.3, and comprises droplets having an average diameter ranging from about 0.5 μm to about 4 μm. In one embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH between about 3.8 and about 4.2, and comprises droplets having an average diameter of less than 4 μm. In one embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH between about 3.8 and about 4.2, and comprises droplets having an average diameter ranging from about 0.5 μm to about 4 μm. In one embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH between about 3.9 and about 4.1, and comprises droplets having an average diameter of less than 4 μm. In one embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH between about 3.9 and about 4.1, and comprises droplets having an average diameter ranging from about 0.5 μm to about 4 μm. In another embodiment, the liquid formulation comprises only one surfactant. In one embodiment, this surfactant is PS80. In one embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH of about 5.0 or below about 4.5, and comprises droplets having an average diameter of less than 3.5 μm. In another embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH of about 5.0 or below about 4.5, and comprises droplets having an average diameter ranging from about 0.5 μm to about 3.5 μm. In yet another embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH ranging from about 3.5 to below about 4.5, and comprises droplets having an average diameter of less than 3.5 μm. In yet another embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH ranging from about 3.5 to below about 4.5, and comprises droplets having an average diameter ranging from about 0.5 μm to about 3.5 μm. In one embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH between about 3.7 and about 4.3, and comprises droplets having an average diameter of less than 3.5 μm. In another embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH between about 3.7 and about 4.3, and comprises droplets having an average diameter in the range of about 0.5 μm to about 3.5 μm. In yet another embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH between about 3.8 and about 4.2, and comprises droplets having an average diameter of less than 3.5 μm. In yet another embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH between about 3.8 and about 4.2, and comprises droplets having an average diameter in the range of about 0.5 μm to about 3.5 μm. In one embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH between about 3.9 and about 4.1, and comprises droplets having an average diameter of less than 3.5 μm. In another embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH between about 3.9 and about 4.1, and comprises droplets having an average diameter ranging from about 0.5 μm to about 3.5 μm. In yet another embodiment, the liquid formulation comprises only one surfactant. In one embodiment, this surfactant is PS80. In one embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH of about 5.0 or below about 4.5, and comprises droplets having an average diameter of less than 3 μm. In another embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH of about 5.0 or below about 4.5, and comprises droplets having an average diameter ranging from about 0.5 μm to about 3 μm. In yet another embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH ranging from about 3.5 to below about 4.5, and comprises droplets having an average diameter of less than 3 μm. In yet another embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH ranging from about 3.5 to below about 4.5, and comprises droplets having an average diameter ranging from about 0.5 μm to about 3 μm. In yet another embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH that is or is between about 3.7 and about 4.3, and comprises droplets having an average diameter of less than 3 μm. In one embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH between about 3.7 and about 4.3, and comprises droplets having an average diameter ranging from about 0.5 μm to about 3 μm. In one embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH between about 3.8 and about 4.2, and comprises droplets having an average diameter of less than 3 μm. In one embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH between about 3.8 and about 4.2, and comprises droplets having an average diameter ranging from about 0.5 μm to about 3 μm. In one embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH between about 3.9 and about 4.1, and comprises droplets having an average diameter of less than 3 μm. In one embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH between about 3.9 and about 4.1, and comprises droplets having an average diameter ranging from about 0.5 μm to about 3 μm. In another embodiment, the liquid formulation comprises only one surfactant. In one embodiment, this surfactant is PS80. In one embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH of about 5.0 or below about 4.5, and comprises droplets having an average diameter of less than 5 μm. In another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH of about 5.0 or below about 4.5, and comprises droplets having an average diameter ranging from about 0.5 μm to about 5 μm. In yet another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH ranging from about 3.5 to below about 4.5, and comprises droplets having an average diameter of less than 5 μm. In yet another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH ranging from about 3.5 to below about 4.5, and comprises droplets having an average diameter ranging from about 0.5 μm to about 5 μm. In one embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH between about 3.7 and about 4.3, and comprises droplets having an average diameter of less than 5 μm. In another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH between about 3.7 and about 4.3, and comprises droplets having an average diameter ranging from about 0.5 μm to about 5 μm. In yet another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH between about 3.8 and about 4.2, and comprises droplets having an average diameter of less than 5 μm. In yet another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH between about 3.8 and about 4.2, and comprises droplets having an average diameter ranging from about 0.5 μm to about 5 μm. In yet another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH between about 3.9 and about 4.1, and comprises droplets having an average diameter of less than 5 μm. In one embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH between about 3.9 and about 4.1, and comprises droplets having an average diameter ranging from about 0.5 μm to about 5 μm. In another embodiment, the liquid formulation comprises only one surfactant. In one embodiment, this surfactant is PS80. In one embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH of about 5.0 or below about 4.5, and comprises droplets having an average diameter of less than 4.5 μm. In another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH of about 5.0 or below about 4.5, and comprises droplets having an average diameter ranging from about 0.5 μm to about 4.5 μm. In yet another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH ranging from about 3.5 to below about 4.5, and comprises droplets having an average diameter of less than 4.5 μm. In yet another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH ranging from about 3.5 to below about 4.5, and comprises droplets having an average diameter ranging from about 0.5 μm to about 4.5 μm. In one embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH between about 3.7 and about 4.3, and comprises droplets having an average diameter of less than 4.5 μm. In another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH between about 3.7 and about 4.3, and comprises droplets having an average diameter ranging from about 0.5 μm to about 4.5 μm. In another embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH between about 3.8 and about 4.2, and comprises droplets having an average diameter of less than 4.5 μm. In yet another embodiment, the liquid formulation comprises an acetate buffer as a buffer, has a pH between about 3.8 and about 4.2, and comprises droplets having an average diameter ranging from about 0.5 μm to about 4.5 μm. In one embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH that is or is between about 3.9 and about 4.1, and comprises droplets having an average diameter of less than 4.5 μm. In another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH that is or is between about 3.9 and about 4.1, and comprises droplets having an average diameter in the range of about 0.5 μm to about 4.5 μm. In yet another embodiment, the liquid formulation comprises only one surfactant. In one embodiment, this surfactant is PS80. In one embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH of about 5.0 or below about 4.5, and comprises droplets having an average diameter of less than 4 μm. In another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH of about 5.0 or below about 4.5, and comprises droplets having an average diameter ranging from about 0.5 μm to about 4 μm. In yet another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH ranging from about 3.5 to below about 4.5, and comprises droplets having an average diameter of less than 4 μm. In yet another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH ranging from about 3.5 to below about 4.5, and comprises droplets having an average diameter ranging from about 0.5 μm to about 4 μm. In one embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH between about 3.7 and about 4.3, and comprises droplets having an average diameter of less than 4 μm. In another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH between about 3.7 and about 4.3, and comprises droplets having an average diameter ranging from about 0.5 μm to about 4 μm. In yet another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH between about 3.8 and about 4.2, and comprises droplets having an average diameter of less than 4 μm. In yet another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH between about 3.8 and about 4.2, and comprises droplets having an average diameter ranging from about 0.5 μm to about 4 μm. In yet another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH between about 3.9 and about 4.1, and comprises droplets having an average diameter of less than 4 μm. In one embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH between about 3.9 and about 4.1, and comprises droplets having an average diameter ranging from about 0.5 μm to about 4 μm. In another embodiment, the liquid formulation comprises only one surfactant. In one embodiment, this surfactant is PS80. In one embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH of about 5.0 or below about 4.5, and comprises droplets with an average diameter of less than 3.5 μm. In another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH of about 5.0 or below about 4.5, and comprises droplets with an average diameter ranging from about 0.5 μm to about 3.5 μm. In yet another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH ranging from about 3.5 to below about 4.5, and comprises droplets with an average diameter of less than 3.5 μm. In yet another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH ranging from about 3.5 to below about 4.5, and comprises droplets with an average diameter ranging from about 0.5 μm to about 3.5 μm. In one embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH that is or is between about 3.7 and about 4.3, and comprises droplets having an average diameter of less than 3.5 μm. In another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH that is or is between about 3.7 and about 4.3, and comprises droplets having an average diameter in the range of about 0.5 μm to about 3.5 μm. In yet another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH that is or is between about 3.8 and about 4.2, and comprises droplets having an average diameter of less than 3.5 μm. In yet another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH that is or is between about 3.8 and about 4.2, and comprises droplets having an average diameter in the range of about 0.5 μm to about 3.5 μm. In one embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH between about 3.9 and about 4.1, and comprises droplets having an average diameter of less than 3.5 μm. In another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH between about 3.9 and about 4.1, and comprises droplets having an average diameter in the range of about 0.5 μm to about 3.5 μm. In yet another embodiment, the liquid formulation comprises only one surfactant. In one embodiment, this surfactant is PS80. In one embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH of about 5.0 or below about 4.5, and comprises droplets having an average diameter of less than 3 μm. In another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH of about 5.0 or below about 4.5, and comprises droplets having an average diameter ranging from about 0.5 μm to about 3 μm. In yet another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH ranging from about 3.5 to below about 4.5, and comprises droplets having an average diameter of less than 3 μm. In yet another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH ranging from about 3.5 to below about 4.5, and comprises droplets having an average diameter ranging from about 0.5 μm to about 3 μm. In one embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH between about 3.7 and about 4.3, and comprises droplets having an average diameter of less than 3 μm. In another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH between about 3.7 and about 4.3, and comprises droplets having an average diameter ranging from about 0.5 μm to about 3 μm. In yet another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH between about 3.8 and about 4.2, and comprises droplets having an average diameter of less than 3 μm. In yet another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH between about 3.8 and about 4.2, and comprises droplets having an average diameter ranging from about 0.5 μm to about 3 μm. In yet another embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH between about 3.9 and about 4.1, and comprises droplets having an average diameter of less than 3 μm. In one embodiment, the liquid formulation comprises a histidine buffer as a buffer, has a pH between about 3.9 and about 4.1, and comprises droplets having an average diameter ranging from about 0.5 μm to about 3 μm. In another embodiment, the liquid formulation comprises only one surfactant. In one embodiment, this surfactant is PS80. According to the present invention, the antibody or antibody derivative present in the aerosol or liquid formulation described herein is characterized by low aggregation, for example, compared to the same antibody or antibody derivative formulated in a citrate-containing formulation. In one embodiment, the antibody or antibody derivative present in the aerosol or liquid formulation described herein has one or more of the following characteristics: - The polydispersity index (PDI) of the antibody or antibody derivative present in the aerosol or liquid formulation described herein is 0.5 or less, or 0.4 or less, or 0.3 or less, or 0.2 or less, or 0.1 or less, as determined by DLS (e.g., substantially as described in Example 1); - The percentage of the degree of polymerization of the monomers of the antibody or antibody derivative present in the aerosol or liquid formulation described herein is 30% or less, or 25% or less, or 20% or less, or 15% or less, as determined by DLS (e.g., substantially as described in Example 1); - The mass percentage of the monomers of the antibody or antibody derivative present in the aerosol or liquid formulation described herein is 99.7% or more, or 99.8% or more, or more than 99.8%, as determined by DLS (e.g., substantially as described in Example 1); - The monomeric strength of the antibody or antibody derivative present in the aerosol or liquid formulation described herein is 80.0% or more, or 85.0% or more, or 90.0% or more, or more than 90.0%, as determined by DLS (e.g., substantially as described in Example 1); the number of particles > 2 μm is less than 10,000 / mL, or less than 7,500 / mL, or less than 5,000 / mL, or less than 4,000 / mL, or less than 3,000 / mL, or less than 2,000 / mL; the number of particles > 10 μm is less than 500 / mL, or less than 400 / mL, or less than 300 / mL, or less than 200 / mL; and the number of particles > 25 μm is less than 100 / mL, or less than 50 / mL, or less than 40 / mL, or less than 30 / mL, or less than 20 / mL. For example, as determined by FCM (e.g., essentially as described in Example 1). In another embodiment, the present invention relates to a method for preparing an aerosol comprising droplets containing a liquid formulation, the method comprising the steps of: (i) providing a liquid formulation as defined above, and (ii) atomizing the liquid formulation provided in step (i) by means of an atomizer, thereby preparing the aerosol. In one embodiment, the atomizer is a mesh atomizer. A nebulizer allows a liquid to be dispersed in a gas to atomize a liquid formulation into an aerosol, which is then inhaled into the respiratory tract of a subject. Examples of nebulizers include soft mist nebulizers, mesh nebulizers (e.g., vibrating mesh nebulizers), jet nebulizers, and ultrasonic nebulizers. Suitable nebulizer devices include Aerogen. ® Solo (Aerogen), Pari eFlow ® Pari GmbH, Philips I-neb™ (Philips), Pari LC Sprint (Pari GmbH), AERxRTM Lung Delivery System (Aradigm Corp.), and Pari LC Plus Reusable Nebulizer (Pari GmbH). In one embodiment, the nebulizer is a mesh nebulizer, particularly a vibrating mesh nebulizer. The nebulizer typically contains a liquid formulation ranging from about 1 mL to about 200 mL, more typically from 1 mL to 20 mL. In one embodiment, the method further includes the following steps between steps (i) and (ii): (ia) lyophilizing the liquid formulation provided in step (i) to provide lyophilized powder, and (ib) adding an appropriate amount of aqueous medium to reconstitute the lyophilized powder provided in step (ia). In another embodiment, the invention relates to an aerosol comprising droplets containing a liquid formulation, wherein the aerosol can be obtained by the methods defined above. In one embodiment, the droplets have an average diameter ranging from about 0.5 μm to about 5 μm or from about 0.5 μm to about 3 μm. In another embodiment, the invention relates to a method of delivering an antibody or antibody derivative to the lungs of a subject using a liquid formulation or aerosol as defined above, wherein the aerosol is administered to the subject by inhalation, or the liquid formulation is administered to the subject by inhalation via a nebulizer. In one embodiment, the antibody or antibody derivative is an IgG1 antibody or antibody derivative. In one embodiment, the atomizer is a mesh atomizer. According to the invention, the term "subject" means a subject used for treatment, particularly a sick subject (also referred to as a "patient"), including humans, non-human primates or other animals, especially mammals such as cattle, horses, pigs, sheep, goats, dogs, cats, rabbits or rodents (such as mice, rats, guinea pigs and hamsters). In one embodiment, the subject / patient is a human. In another embodiment, the present invention relates to a method of using a liquid formulation as defined above for treating or preventing a disease in a subject, wherein the aerosol is administered to the subject by inhalation, or the liquid formulation is administered to the subject by inhalation via a nebulizer. In one embodiment, the disease is a lung disease. In one embodiment, the atomizer is a mesh atomizer. As used in this article, the term "treatment" refers to any treatment that improves a patient's health and / or prolongs (increases) lifespan. According to the present invention, the term "disease" refers to any pathological state, particularly cancer, infectious diseases, inflammatory diseases, metabolic diseases, autoimmune diseases, degenerative diseases, apoptosis-related diseases, and transplant rejection. The term "cancer" according to the invention also includes cancer metastasis. "Metastasis" refers to the spread of cancer cells from their original site to another part of the body. The formation of metastasis is a highly complex process and depends on malignant cells detaching from the primary tumor, invading the extracellular matrix, penetrating the endothelial basement membrane into body cavities and blood vessels, and then infiltrating the target organ via blood transport. Finally, the growth of the new tumor (i.e., secondary or metastatic tumor) at the target site depends on angiogenesis. Tumor metastasis often occurs even after the removal of the primary tumor because tumor cells or components may remain and develop metastatic potential. In one embodiment, the term "metastasis" according to the invention refers to "distant metastasis," which involves metastasis far from the primary tumor and regional lymph node system. The term "infectious disease" refers to any illness that can be transmitted from person to person or from organism to organism and is caused by a microbial agent (e.g., the common cold). Examples of infectious diseases include viral infectious diseases such as AIDS (HIV), hepatitis A, B, or C, herpes, shingles (chickenpox), rubella (rubella virus), yellow fever, dengue fever, flaviviruses, influenza viruses, respiratory syncytial virus (RSV), hemorrhagic infectious diseases (Marusburg virus or Ebola virus), and severe acute respiratory syndrome (SARS), and bacterial infectious diseases such as Legionnaires' disease (Legionella spp.). Legionella), sexually transmitted diseases (e.g., chlamydia or gonorrhea), and stomach ulcers (Helicobacter pylori). Helicobacter ), cholera (Vibrio spp.) Vibrio), tuberculosis, diphtheria, caused by Escherichia coli ( E. coli), Staphylococcus spp. Staphylococci), Salmonella ( Salmonella) or Streptococcus spp. Infections caused by Streptococci (tetanus); infections caused by protozoan pathogens, such as malaria, sleeping sickness, leishmaniasis; toxoplasmosis, i.e., infections caused by Plasmodium, Trypanosoma, Leishmania, and Toxoplasma; or infections caused by, for example, Cryptococcus neoformans (… Cryptococcus neoformans), Histoplasma capsulatum ( Histoplasma capsulatum, coccidioides ( Coccidioides immitis, dermatitis blastomyces ( Blastomyces dermatitidis or Candida albicans ( Fungal infections caused by Candida albicans. The term "inflammatory disease" refers to any disease characterized by a high level of inflammation or degeneration of tissues, particularly connective tissues, or related conditions. Chronic inflammatory diseases are medical conditions characterized by persistent inflammation. Examples of (chronic) inflammatory diseases include celiac disease, vasculitis, lupus, chronic obstructive pulmonary disease (COPD), asthma, irritable bowel disease, atherosclerosis, arthritis, ankylosing spondylitis, Crohn's disease, colitis, chronic active hepatitis, dermatitis, and psoriasis. The term "metabolic disease" refers to any disease or disorder that disrupts normal metabolism. Examples include cystacidosis, diabetes, dyslipidemia, hyperthyroidism, hypothyroidism, hyperlipidemia, hypolipidemia, galactosemia, Gaucher's disease, obesity, and phenylketonuria. The term "autoimmune disease" refers to any disease / disorder in which the body produces an immunogenic (i.e., immune system) response to certain components of its own tissues. In other words, the immune system loses its ability to recognize certain tissues or systems in the body as its own and target and attack them as if they were foreign. Autoimmune diseases can be divided into autoimmune diseases that primarily affect one organ (e.g., hemolytic anemia and antiimmune thyroiditis) and autoimmune diseases whose processes spread to many tissues (e.g., systemic lupus erythematosus). For example, multiple sclerosis is thought to be caused by T cells attacking the myelin sheath of nerve fibers surrounding the brain and spinal cord. This leads to loss of coordination, weakness, and blurred vision. Autoimmune diseases are known in the art and include, for example, Hashimoto's thyroiditis, Graves' disease, lupus, multiple sclerosis, rheumatoid arthritis, hemolytic anemia, antiimmune thyroiditis, systemic lupus erythematosus, celiac disease, Crohn's disease, colitis, diabetes, scleroderma, psoriasis, etc. The term "degenerative disease" refers to any disease in which the function or structure of the affected tissue or organ deteriorates over time. Examples include Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis (ALS), Huntington's disease, macular degeneration, multiple sclerosis, muscular dystrophy, Niemann Pick disease, osteoporosis, and rheumatoid arthritis. The term "apoptosis-related disease" refers to any disease involving alterations in cell apoptosis. Examples include cancer; neurological disorders such as Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis (ALS), and stroke; heart diseases such as ischemia-reperfusion and chronic heart failure; infectious diseases; and autoimmune diseases. The term "transplant rejection" refers to the recipient's immune system rejecting transplanted tissues or organs, which may ultimately destroy the transplanted tissues or organs. The term "lung disease" (also referred to herein as "pulmonary disease") generally refers to a disease or disorder affecting the lungs of a subject. In one embodiment, lung disease is selected from asthma, chronic obstructive pulmonary disease (COPD), lung cancer (e.g., non-small cell lung cancer), cystic fibrosis (CF), interstitial lung disease (ILD) (such as idiopathic pulmonary fibrosis, hypersensitivity pneumonia, sarcoidosis, and asbestosis), bacterial infection (e.g., mycobacterial infection), viral infection (e.g., influenza virus infection or respiratory syncytial virus (RSV) infection), acute respiratory distress syndrome (ARDS), pulmonary alveolar proteinosis (PAP), acute bronchitis, bronchiolitis obliterans, and pulmonary hypertension. In another embodiment, the present invention relates to a method of delivering an antibody or antibody derivative to the lungs of a subject, the method comprising administering an effective amount of an aerosol as defined above to the subject by inhalation, or administering an effective amount of a liquid formulation as defined above to the subject by inhalation via a nebulizer. In one embodiment, the antibody or antibody derivative is an IgG1 antibody or antibody derivative. In one embodiment, the atomizer is a mesh atomizer. As used herein, the term "effective amount" specifically refers to a "therapeutic effective amount," which is an amount, alone or in combination with other doses, that achieves a desired therapeutic response or effect without causing unacceptable side effects. In the treatment of a particular disease or condition, the desired response specifically involves the suppression of disease progression. This includes slowing the progression of the disease and specifically interrupting or reversing its progression. A desired response in the treatment of a disease or condition may also be the delay of the onset of the disease or condition or the prevention of its onset. The effective amount of the aerosol or liquid formulation described herein, and therefore the effective amount of the antibody or antibody derivative contained therein, will depend on the condition being treated, the severity of the disease, the individual parameters of the subject (including age, physiological condition, body size, and weight), the duration of treatment, the type of concomitant therapy (if present), the specific route of administration, and similar factors. Therefore, the dose of the aerosol or liquid formulation described herein administered may depend on some of these parameters. A higher dose may be used if the initial dose is insufficient to elicit a response in the subject. In another respect, the present invention relates to a method for treating or preventing a disease in a subject, the method comprising administering an effective amount of an aerosol as defined above to the subject by inhalation, or administering an effective amount of a liquid preparation as defined above to the subject by inhalation via a nebulizer. In one embodiment, the disease is a lung disease. In one embodiment, the atomizer is a mesh atomizer. In another respect, the present invention relates to an atomizer comprising a liquid formulation as defined above. In one embodiment, the atomizer is a mesh atomizer. In another embodiment, the invention relates to a kit comprising (i) a container containing a liquid formulation as defined above or a powder obtained by lyophilizing a liquid formulation, and (ii) an atomizer. In one embodiment, the atomizer is a mesh atomizer. As used herein, the term "kit" refers to an article comprising one or more containers, an atomizer (e.g., a mesh atomizer), and, where applicable, a data carrier. The one or more containers are filled with a liquid formulation as defined above and / or powder obtained by lyophilizing the liquid formulation. The kit may include additional containers containing, for example, a diluent (e.g., an aqueous medium), a buffer, and other reagents as defined herein. The data carrier may be a non-electronic data carrier, such as a graphic data carrier, like an information leaflet, information page, barcode, or access code; or an electronic data carrier, such as an optical disc (CD), a digital multifunction disc (DVD), a microchip, or another semiconductor-based electronic data carrier. The access code may allow access to a database, such as an internet database, a centralized database, or a decentralized database. The data carrier may include instructions for using the kit as described and used herein. In another respect, the present invention relates to the use of the liquid formulation as defined above for preparing an aerosol via atomization using an atomizer. In one embodiment, the atomizer is a mesh atomizer. In another respect, the present invention relates to the use of a buffer selected from acetates, histidines, and combinations thereof for increasing the stability of a liquid formulation containing an antibody or antibody derivative after nebulization via a nebulizer, wherein the buffer is contained in the liquid formulation prior to nebulization. In one embodiment, the antibody or antibody derivative is an IgG1 antibody or antibody derivative. In one embodiment, the atomizer is a mesh atomizer. In one embodiment, the term "increased stability" refers to preventing or reducing the degree of aggregation of antibodies or antibody derivatives. In one embodiment, the liquid formulation has a pH equal to or lower than about 5.5. In one embodiment, the antibody is a monoclonal antibody. In one embodiment, the liquid formulation does not contain citrate. In one embodiment, the liquid formulation has a pH in the range of about 3.5 to about 5.5. In one embodiment, the buffer is an acetate, and the liquid formulation has a pH below about 5.0 or below about 4.5. In one embodiment, the buffer is an acetate, and the liquid formulation has a pH in the range of about 3.5 to below about 4.5, or between about 3.7 and about 4.3, or between about 3.8 and about 4.2, or between about 3.9 and about 4.1. In one embodiment, the liquid formulation has a pH of about 4.0. In one embodiment, the liquid formulation further comprises a surfactant. In one embodiment, the surfactant is selected from polysorbate, poloxamer, polyoxyethylene alkyl ether, alkylphenol polyoxyethylene, and sodium dodecyl sulfate. In one embodiment, the concentration of the surfactant in the liquid formulation is equal to or less than about 0.1% (w / v) or equal to or less than about 0.05% (w / v). In one embodiment, the liquid formulation does not contain any surfactants. In one embodiment, the liquid formulation does not contain NaCl. In one embodiment, the liquid formulation does not contain any non-buffered salts. The invention will now be further described with reference to the following examples, which are intended to illustrate rather than limit the scope of the invention. Example Example 1: Materials and Methods The immunoglobulins used in the examples are shown in Table 1 below. Table 1: Immunoglobulins. Dynamic light scattering ( DLS ) DLS measurements were performed using a DynaPro NanoStar (Wyatt Technology) instrument with a 663 nm laser wavelength. Each sample was introduced into a disposable cuvette (Uvette, Eppendorf) and measured by 10 seven-second acquisitions. The data were analyzed using Dynamics 7.1.9 software (Wyatt Technology) to determine the fine distribution in the submicron range. The results are shown as Z-mean, degree of polymerization distribution index (PDI), monomer radius, degree of polymerization distribution percentage of monomer pic, monomer strength percentage, and mass percentage. The degree of polymerization distribution is considered low when the PDI is less than 0.1 and high when the sample is multimodal. When the degree of polymerization distribution of monomers is less than 15%, the homogeneity level is considered high. When the homogeneity level is low (degree of polymerization distribution greater than 30%), the particle group can be considered to contain significantly different sizes or be polydisperse. Aggregates with a mass percentage greater than 99.8% of the monomer are considered low, and aggregates with a mass percentage less than 99.6% are considered high. Aggregates with a strength percentage greater than 90.0% of the monomer are considered low, and aggregates with a strength percentage less than 80.0% are considered high. Flow cell microscopy ( FCM ) Flow cell microscopy measurements were performed using a Flowcell FC200-IPAC (Occhio) instrument. Each analysis involved introducing 200 μL of sample into a disposable cone. Data were analyzed using Callisto software (Occhio) to determine the fine distribution in the subvisible range. The results showed the concentrations (particles / mL) of particles > 2 μm, > 10 μm, and > 25 μm. Aggregation is considered low when there are fewer than 2000 particles / mL of >2 μm, fewer than 200 particles / mL of >10 μm, and fewer than 20 particles / mL of >25 μm. Aggregation is considered high when there are more than 10000 particles / mL of >2 μm, more than 500 particles / mL of >10 μm, and more than 100 particles / mL of >25 μm. Size exclusion chromatography (SUC) SEC ) SEC measurements were performed using an Agilent 1200 ultra-high performance liquid chromatography (UHPLC) system. Results are shown as the percentage of high molecular weight (HMW). For mAb1: Measurements were performed at 24°C at a mobile phase flow rate of 0.3 mL / min, wherein the mobile phase consisted of 0.1 M phosphate buffer and NaClO. 4. A solution of 0.3 M (pH 6.2) and acetonitrile was used. Samples were stored in vials, and 10 μL were injected into a series of columns consisting of a protective column (Prosec 300S 50 x 7.5 mm (Agilent)) and two columns (Prosec 300S 300 x 7.5 mm (Agilent)). Detection was performed at 280 nm. Results were processed using Empower software. For mAb3: SEC measurements were performed using an Agilent 1200 ultra-high performance liquid chromatography (UPLC) column. Measurements were taken at 30°C with a mobile phase flow rate of 0.3 mL / min, consisting of 50 mM sodium phosphate and 300 mM sodium perchlorate (pH 7). Samples were stored in vials, and 1 μL was injected into an Aquity UPLC BEH200 SEC 200 Å, 1.7 μm, 4.6 mm x 300 mm column (Waters). Detection was performed at 280 nm. Results were processed using Empower software. Visual inspection The samples placed in glass vials were visually inspected and illuminated against a black background using an MLC-150 cold light source (Motic). Example 2: Effects of buffers and pH on IgG1 stability This example demonstrates that, compared to citrate buffers, acetate and histidine buffers at acidic pH promote the stability of IgG1 antibody resistance to nebulization aggregation after nebulization. Two types of PS80-free IgG1 immunoglobulins (mAb1 and mAb3) formulated in different buffers were nebulized at different pH values, and their stability was characterized after nebulization. Six different buffer / pH systems were used: acetate pH 4.0, acetate pH 5.5, histidine pH 5.5, histidine pH 7.0, citrate pH 5.5, and citrate pH 6.5, with mAb1 and mAb3 formulated at a concentration of 10 mg / mL. The buffer concentration for each system was 10 mM. Two mL of IgG1 formulated in different buffers was nebulized using a Solo (Aerogen) vibrating mesh nebulizer. Aggregation was measured using dynamic light scattering (DLS), flow cell microscopy (FCM), SEC, and visual inspection. The results are summarized in Figures 1A–C (mAb1) and 1D–F (mAb3). Visual inspection revealed the presence of visible particles in the citrate formulation of mAb1. DLS results showed low aggregation into submicron particles in acetate and histidine buffers (particularly at acidic pH), and the citrate formulation was unsuitable for analysis without filtration (likely due to the high particle content in the sample). FCM results confirmed high aggregation in the citrate buffer. Example 3: Effect of polysorbate 80 (PS80) on IgG1 stability This example shows that a high amount of PS80 (1000 ppm) helps to limit aggregation of IgG1 after nebulization in citrate buffer, but not completely, because the submicron particles of mAb1 exceed the quantification level by DLS. Two immunoglobulins (mAb1 and mAb3) were formulated in different buffers at different pH values ​​and in the presence of polysorbate 80 (PS80). Acetate, histidine, and citrate buffers were used, with PS80 as the surfactant. Six different buffer / pH systems were used: acetate pH 4.0, acetate pH 5.5, histidine pH 5.5, histidine pH 7.0, citrate pH 5.5, and citrate pH 6.5, at a concentration of 10 mg / mL for both IgGs. A 10 mM buffer concentration was used. PS80 was added to obtain a concentration of 1000 ppm in the formulation. Two mL of IgG1 formulated in different buffers was nebulized using a Solo (Aerogen) vibrating mesh nebulizer. Aggregation was measured using dynamic light scattering (DLS), flow cell microscopy (FCM), SEC, and visual inspection. The results are summarized in Figures 2A to C (mAb1) and Figures 2D to F (mAb3). Visual inspection revealed the absence of visible particles in all formulations containing PS80. DLS results indicated that the citrate formulations were unsuitable for unfiltered analysis, likely due to the high particle content / large particles in the samples. FCM results demonstrated a lower level of aggregation compared to the same formulation without PS80 tested in Example 2. Example 4 Atomization was performed using two different mesh vibrating atomizers. In this example, the stabilizing properties of acetate and histidine buffers are illustrated using two different vibrating mesh nebulizers (i.e., the Solo nebulizer (see previous example) and the eFlow nebulizer from PARI). The stabilizing effect of acetate and histidine buffers (compared to citrate buffer) on IgG1 antibodies was also observed using the eFlow system. Acetate, histidine, and citrate buffers were used. Six different buffer / pH systems were used: acetate pH 4.0, acetate pH 5.5, histidine pH 5.5, histidine pH 7.0, citrate pH 5.5, and citrate pH 6.5, at a concentration of 10 mg / mL for both IgG1 groups. Nebulization stress was applied to 2 mL of IgG1 prepared in the different buffers using a custom-made eFlow (PARI) vibrating mesh nebulizer. Aggregation was measured using dynamic light scattering (DLS), flow cell microscopy (FCM), SEC, and visual inspection. Results are summarized in Figures 3A through C (mAb1). Example 5 Stability of different IgG isoforms (IgG1 and IgG4) in acetate buffer at pH 5.5 This example illustrates the stabilizing effect of acetate buffers at acidic pH on certain IgG1 antibodies. The stabilizing properties of these buffers are less pronounced in the case of IgG4 antibodies. Nebulization stress was applied to four IgG1 (mAb1, mAb2, mAb3, and mAb4) and one IgG4 (mAbX) at a concentration of 10 mg / mL in the same formulation (acetate buffer, pH 5.5). 2 mL of nebulizer solution was applied using a Solo (Aerogen) vibrating mesh nebulizer. Aggregation was measured using dynamic light scattering (DLS), flow cell microscopy (FCM), SEC, and visual inspection. Results are summarized in Figures 4A through 4C. Visual inspection revealed visible particles in the IgG4 X sample. DLS results indicated that the IgG4 X sample was unsuitable for unfiltered analysis, most likely due to the particles present in the sample. FCM counting confirmed high aggregation in the IgG4 X sample and low aggregation in the four IgG1 samples. Example 6 Stabilizing effect of histidine This example illustrates the stabilizing properties of histidine buffers in formulations containing additional excipients (polyols and nonionic surfactants), thereby allowing for the manufacture of pharmaceutical products and their long-term storage prior to nebulization. IgG1 antibody (mAb1) was formulated at 20 g / L in 20 mM histidine buffer (pH 6.0) containing a nonionic surfactant and a polyol as an additional excipient (a combination that provides long-term storage stability for the drug product solution). Nebulization stress was applied to 2 mL of the mAb1 formulation using a Solo (Aerogen) vibrating mesh nebulizer. Droplet size was determined by laser diffraction. The VMD obtained after nebulization was 4.4 μm, and most droplets had a diameter less than 5 μm. Approximately 30% of the droplets had a diameter ranging from 0.5 μm to 3 μm. Aggregation was characterized by dynamic light scattering (DLS), flow cell microscopy (FCM), SEC, and visual inspection. Additional analytical methods were performed. The formulation can be stored at 2ºC–8ºC for 24 months. Results are summarized in Figures 5A and 5B. Example 7: Effect of PS80 concentration on IgG1 in citrate buffer The effect of PS80 concentration on the stability of IgG1 nebulized in citrate was evaluated. In this study, nebulization stress was applied to two different IgG1 molecules (mAb 1 and mAb 3) prepared in citrate at pH 5.5 with different concentrations of PS80. PS80 concentrations of 0, 200, and 1000 ppm were used. Both IgG1 molecules were prepared at a concentration of 10 mg / mL in citrate buffer, and PS80 was added at the target concentration. Nebulization stress was applied to 2 mL of IgG1 prepared in citrate at different PS80 concentrations using a vibrating mesh nebulizer. Aggregation was measured using dynamic light scattering (DLS) and flow microscopy (FCM; Figure 6). picture 6 The results showed that IgG1 in citrate buffer exhibited high aggregation levels at 0 ppm PS80. A high concentration (1000 ppm) of PS80 was required to stabilize IgG1 in citrate. DLS results indicated that the citrate formulation was unsuitable for unfiltered analysis, likely due to particles in the sample. FCM results revealed high particle concentrations at 0 ppm PS80. Particle number / mL decreased as the PS80 concentration increased. 200 ppm PS80 was insufficient to stabilize mAb 1. DLS results indicated that the citrate formulation was unsuitable for unfiltered analysis, likely due to particles in the sample at 0 ppm PS80 in most cases (n=5 / 6). Aggregation was observed at 200 ppm PS80. Aggregation was low at 1000 ppm PS80. FCM results revealed high particle concentrations at 0 ppm PS80. Adding PS80 at 200 and 1000 ppm reduced the particle concentration. Example 8: Effect of PS80 concentration on IgG1 in histidine buffer The effect of PS80 concentration on the stability of IgG1 nebulized in histidine was evaluated. In this study, nebulization stress was applied to one IgG1 (mAb 1) prepared in histidine at pH 5.5 with different concentrations of PS80. PS80 concentrations of 0, 50, 200, and 1000 ppm were used. IgG1 was prepared at a concentration of 10 mg / mL in histidine buffer, and PS80 was added at the target concentration. Nebulization stress was applied to 2 mL of IgG1 prepared in histidine with different PS80 concentrations using a vibrating mesh nebulizer. The degree of aggregation was measured using dynamic light scattering (DLS) and flow microscopy (FCM; Figure 7). picture 7 The results showed that IgG1 in histidine buffer exhibited moderate aggregation levels at 0 ppm PS80. Low concentrations of PS80 (50 ppm) appeared sufficient to stabilize IgG1 in histidine. DLS results showed moderate aggregation at 0 ppm PS80. At 50, 200, and 100 ppm PS80, aggregation levels were low and similar across different concentrations. FCM results revealed moderate particle concentrations at 0 ppm PS80. Adding PS80 at 50, 200, and 1000 ppm allowed for comparable reductions in particle concentration. none Figure 1 shows the results of analysis of the stability of two antibodies (mAb1 and mAb3) in formulations containing different buffering systems for lung delivery after nebulization by dynamic light scattering (DLS; A and D), SEC (B and E), flow cell microscopy (FCM; C and F) and visual inspection (B and E). picture 2. Results of analysis of the stability of two antibodies (mAb1 and mAb3) in a PS80-containing formulation for lung delivery after nebulization are shown by DLS (A and D), SEC (B and E), FCM (C and F) and visual inspection (B and E). picture 3 shows the results of analysis of the stability of antibody (mAb1) in the formulation for lung delivery after nebulization with two different mesh nebulizers by DLS (A), SEC (B), FCM (C) and visual inspection (B). picture 4 shows the results of analysis of the stability of different isotypes of antibodies (IgG1 and IgG4) in the formulation for lung delivery after nebulization by DLS (A), SEC (B), FCM (C) and visual inspection (B). picture 5 shows the results of analysis of the stability of the antibody (mAb1) in the formulation delivered to the lungs after nebulization by DLS and FCM (A), SEC and visual inspection (B), and by additional analytical methods (B). picture Figure 6 shows the results of DLS and FCM analysis of the stability of two antibodies (mAb1 and mAb3) in formulations containing different concentrations of PS80 in citrate buffer for lung delivery after nebulization. Figure 6A shows the results for mAb1, and Figure 6B shows the results for mAb3. picture 7 shows the results of DLS and FCM analysis of the stability of antibody (mAb1) in formulations containing different concentrations of PS80 in histidine buffer for lung delivery after nebulization.

Claims

1. An aerosol comprising droplets, the droplets comprising a liquid formulation, wherein the liquid formulation comprises (i) an antibody or antibody derivative, (ii) a buffer selected from acetate, histidine, and combinations thereof, and (iii) an aqueous medium; and wherein (1) the liquid formulation has a pH below about 5.0 or below about 4.5; and (2) the droplets have an average diameter in the range of 0.5 μm to 5 μm, 0.5 μm to 4.5 μm, 0.5 μm to 4 μm, 0.5 μm to 3.5 μm, or 0.5 μm to 3 μm.

2. The aerosol as claimed in claim 1, wherein the liquid formulation does not contain citrate.

3. The aerosol as claimed in claim 1 or 2, wherein the liquid formulation further comprises a surfactant.

4. The aerosol as claimed in claim 3, wherein the concentration of the surfactant in the liquid formulation is equal to or less than about 0.1% (w / v) or equal to or less than about 0.05% (w / v).

5. The aerosol as claimed in claim 3, wherein the surfactant is selected from polysorbate, poloxamer, polyoxyethylene alkyl ether, alkylphenol polyoxyethylene, and sodium dodecyl sulfate.

6. The aerosol as claimed in claim 1 or 2, wherein the liquid formulation does not contain any surfactants.

7. The aerosol as claimed in claim 1 or 2, wherein the antibody or antibody derivative is an IgG1 antibody or antibody derivative.

8. A method for preparing an aerosol comprising droplets, the droplets comprising a liquid formulation, the method comprising the steps of: (i) providing a liquid formulation as claimed in any one of claims 1 to 7, and (ii) atomizing the liquid formulation provided in step (i) using an atomizer to prepare the aerosol.

9. The method as described in claim 8, wherein optionally, the method further comprises between steps (i) and (ii) the following steps: (ia) lyophilizing the liquid formulation provided in step (i) to provide a lyophilized powder, and (ib) reconstituted the lyophilized powder provided in step (ia) by adding an appropriate amount of an aqueous medium.

10. An aerosol comprising droplets containing a liquid formulation, wherein the aerosol is obtained by the method as described in claim 8 or 9.

11. The aerosol as claimed in any one of claims 1 to 2 and 10, in a method of delivering an antibody or antibody derivative to the lungs of a subject, wherein the aerosol is administered to the subject by inhalation.

12. The aerosol as claimed in claim 1 or 2, in a method of delivering an antibody or antibody derivative to the lungs of a subject, wherein the liquid formulation is administered to the subject by inhalation via a nebulizer.

13. The aerosol as claimed in any one of claims 1 to 2 and 10, in a method of treating or preventing a disease in a subject, wherein the aerosol is administered to the subject by inhalation.

14. In a method of using an aerosol as claimed in claim 1 or 2 to treat or prevent a disease in a subject, wherein the liquid formulation is administered to the subject by inhalation via a nebulizer.

15. An atomizer comprising a liquid formulation as defined in any one of claims 1 to 7.

16. A set comprising: (i) a container comprising a liquid formulation as defined in any one of claims 1 to 7 or a powder obtained by freeze-drying the liquid formulation, and (ii) an atomizer.

17. Use of a liquid formulation as defined in any one of claims 1 to 7 for preparing an aerosol by means of an atomizer.

18. Use of a buffer selected from acetates, histidines, and combinations thereof for increasing the stability of a liquid formulation containing an antibody or antibody derivative by means of a nebulizer, wherein the buffer is contained in the liquid formulation prior to nebulization.

19. The use as claimed in claim 18, wherein the liquid formulation has a pH of less than about 5.0 or less than about 4.5.

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