Pharmaceutical composition of antibody to tslp

Abstract

The present invention relates to the field of medicine, in particular to a pharmaceutical composition comprising an antibody to TSLP, as well as to a method for treating and to use for treating of the pharmaceutical composition comprising an antibody to TSLP.

Description

[0001] Pharmaceutical composition of antibody to TSLP Field of the invention

[0002] The present invention relates to the field of biotechnology and medicine, in particular to pharmaceutical compositions of an antibody that specifically binds to thymic stromal lymphopoietin (TSLP). The invention also relates to a method for treating diseases or disorders mediated by thymic stromal lymphopoietin (TSLP) using the pharmaceutical compositions provided in the present invention, as well as to a method for using the disclosed pharmaceutical compositions for treating diseases or disorders mediated by thymic stromal lymphopoietin (TSLP).

[0003] Background of the invention

[0004] Thymic stromal lymphopoietin (TSLP) is a cytokine produced by epithelial cells that plays a crucial role in initiating type 2 inflammation through both innate and adaptive immune responses (Mitchell PD, O'Byrne PM. Epithelial-derived cytokines in asthma. CHEST. 2017; 151 (6): 1338— 1344; Corren J, Ziegler SF. TSLP: from allergy to cancer. Nat Immunol. 2019;20(12): 1603-1609). TSLP is primarily found in epithelial cells of barrier surfaces such as the skin, airways, and gastrointestinal tract, where it helps the organism sensitize the external environment (Gauvreau, G. M., Sehmi, R., Ambrose, C. S., & Griffiths, J. M. (2020). Thymic stromal lymphopoietin: its role and potential as a therapeutic target in asthma. Expert Opinion on Therapeutic Targets, 24(8), 777-792). TSLP is also produced by fibroblasts and dendritic cells in response to a variety of external factors.

[0005] The functions of TSLP are diverse (Brusselle G, Bracke K. Targeting immune pathways for therapy in asthma and chronic obstructive pulmonary disease. Ann Am Thorac Soc. 2014;l l(Suppl 5):S322-328), and include:

[0006] • facilitation of development of Th2 cells by means of increasing OX40L expression in dendritic cells,

[0007] • promotion of differentiation of CD4+ T cells into Th2 cells,

[0008] • induction of basophils to produce IL-4, activation of ILC2s (group 2 innate lymphoid cell),

[0009] • induction of corticosteroid resistance.

[0010] Antibodies to TSLP may be used to treat diseases such as severe bronchial asthma (NCT05274815), eosinophilic esophagitis (NCT05583227), rhinosinusitis with nasal polyps (NCT04851964), non-severe atopic asthma (NCT01405963), allergic rhinitis (NCT06189742), eosinophilic granulomatosis with polyangiitis (NCT06230354), chronic obstructive pulmonary disease (NCT04039113), atopic dermatitis (NCT00757042), allergy (NCT02237196), autoimmune skin diseases such as vitiligo, psoriasis, bullous pemphigoid, rosacea, alopecia areata (Si-Hang Wang, Ya-Gang Zuo, Thymic Stromal Lymphopoietin in Cutaneous Immune-Mediated Diseases. Front. Immunol., 24 June 2021; NCT03367273). It follows from the above that there is currently a need for the creation of novel improved stable pharmaceutical compositions for the antibody to TSLP.

[0011] Summary of the invention

[0012] The authors of the present group of inventions have developed stable pharmaceutical compositions comprising an antibody to TSLP. The developed pharmaceutical compositions may be used for treatment and prophylaxis of a variety of diseases.

[0013] Definitions and general methods

[0014] Unless defined otherwise herein, all technical and scientific terms used in connection with the present invention will have the same meaning as is commonly understood by those skilled in the art.

[0015] Furthermore, unless otherwise required by context, singular terms shall include plural terms, and the plural terms shall include the singular terms.

[0016] As used in the present description and claims that follow, unless otherwise dictated by the context, the words "include" and "comprise", or variations thereof such as "includes", "including", "comprises", or "comprising", will be understood to imply the inclusion of a stated integer or group of integers but not the exclusion of any other integer or group of integers.

[0017] The term "pharmaceutical composition" refers to a composition and / or formulation comprising an antibody to thymic stromal lymphopoietin (TSLP) in a therapeutically effective amount and excipients or auxiliary substances (carriers, diluents, fillers, solvents, and the like), the choice and proportions of which depend on the type and route of administration and dosage.

[0018] The term "aqueous composition" as used herein refers to a water-based composition, the water in the composition may be: water, water for injections, physiologic saline (0.9%-1.0% aqueous solution of sodium chloride).

[0019] The term "viscosity modifier" refers to an excipient that can provide the desired viscosity of a solution of a pharmaceutical composition. To reduce the viscosity, into a composition introduced may be a viscosity modifier (for example, arginine or arginine hydrochloride, or arginine glutamate, or lysine, or lysine hydrochloride, or arginine phosphate, or arginine sulfate, and the like).

[0020] A pharmaceutical composition is "stable" if the active agent retains physical stability and / or chemical stability and / or biological activity thereof during the specified shelf life at storage temperature, for example, at (5 ± 3) °C, or at room temperature. Further, the active agent may retain both physical and chemical stability, as well as biological activity. Storage period is adjusted based on the results of stability test in accelerated or natural aging conditions.

[0021] The term “long-term storage” or “long term stability” should be understood to mean that a pharmaceutical composition may be stored for three months or more, for six months or more, for one year or more, and the composition may have a minimum stable shelf life of at least two years as well. Generally speaking, the terms "long term storage" and "long term stability" further include stable storage durations that are at least comparable to or better than the stable shelf life typically required for currently available commercial formulations, without losses in stability that would render the formulation unsuitable for its intended pharmaceutical application.

[0022] The term "buffering agent" refers to an acid or base component (typically a weak acid or weak base) of the buffer or buffer solution. A buffering agent helps to maintain the pH value of a solution at or near to a pre-determined value, and the buffering agents are generally chosen to achieve a pre-determined value. A buffering agent may be a single compound which gives rise to a desired buffering effect, especially when said buffering agent is mixed with (and suitably capable of proton exchange with) an appropriate amount (depending on the pre-determined value desired) of corresponding "acid / base conjugate" thereof.

[0023] The term "buffer" or "buffer solution" refers to an aqueous solution comprising a mixture of an acid (typically a weak acid, such as e.g. acetic acid, citric acid) and a conjugated base thereof (such as e.g. an acetate or citrate salt, e.g. sodium acetate, sodium citrate, as well as hydrates of said salts, e.g. sodium acetate trihydrate) or alternatively a mixture of a base (typically a weak base, e.g. histidine) and a conjugated acid thereof (e.g. histidine hydrochloride or histidine hydrochloride monohydrate or L-histidine hydrochloride (h / c) monohydrate (m / h) or L-histidine h / c m / h or histidine h / c m / h). The pH value of a "buffer solution" changes only slightly upon addition thereto of a small quantity of strong base or strong acid, as well as upon dilution or concentration due to the "buffering effect" imparted by a "buffering agent".

[0024] "Stabilizer" refers to an excipient or a mixture of two or more excipients that provide the physical and / or chemical stability of the active agent.

[0025] The terms "osmotic agent" or "tonicity-regulating agent", as well as "osmolyte", as used herein, refer to an excipient that can provide the required osmotic pressure of a liquid antibody solution. In some embodiments, the tonicity-regulating agent may increase the osmotic pressure of a liquid antibody liquid antibody formulation to isotonic pressure such that said liquid antibody formulation is physiologically compatible with the cells of the tissue of a subject's organism. In another embodiment, the tonicity-regulating agent may contribute to increased stability of antibodies. "Isotonic" formulation is a formulation that has an osmotic pressure equivalent to that of human blood.

[0026] As used herein, the term "solubilizer", or "surfactant", "non-ionic surfactant" refers to a pharmaceutically acceptable non-ionic surface-active agent. Both one solubilizer and combinations of solubilizers may be used. Exemplary solubilizers are, without limitation, polysorbate 20 or polysorbate 80, pol oxamer 184 or pol oxamer 188, or PLURONIC®.

[0027] "Treat", "treatment" and "therapy" refer to a method for alleviating or abrogating a biological disorder and / or at least one of attendant symptoms thereof. The term “to alleviate” a disease, disorder or condition means reducing the severity and / or occurrence frequency of the symptoms of the disease, disorder, or condition. Further, references herein to "treatment" include references to curative, palliative and prophylactic treatment.

[0028] The term "disorder" or "disease" means any condition, the manifestations of which may benefit or subject's prognosis with that condition may benefit from treatment according to the present invention. The definition of the term includes chronic and acute disorders or diseases including those pathological conditions that predispose a mammal to the disorder in question. Nonlimiting examples of diseases to be treated include bronchial asthma, severe bronchial asthma, atopic asthma, mild atopic asthma, eosinophilic esophagitis, eosinophilic granulomatosis with polyangiitis, chronic obstructive pulmonary disease, rhinitis, allergic rhinitis, rhinosinusitis with nasal polyps, dermatitis, atopic dermatitis, allergy, autoimmune skin diseases, vitiligo, psoriasis, bullous pemphigoid, rosacea, alopecia areata.

[0029] "Kabat numbering scheme" or "numbering according to Kabat" as used in the present application refers to the system for numbering of amino acid residues that are more variable (i.e. hypervariable) than other amino acid residues in variable regions of heavy and light chains of antibody (Kabat et al. Ann. N.Y. Acad. Sci., 190:382-93 (1971); Kabat et al. Sequences of Proteins of Immunological Interest, Fifth Edition, U.S. Department of Health and Human Services, NIH Publication No. 91-3242 (1991)).

[0030] The terms "anti-TSLP antibody," "antibody to TSLP," "antibody that specifically binds to TSLP," "monoclonal antibody to TSLP," "antibody BCD-272," or "antibody comprising LCDR1, LCDR2, and LCDR3 having the amino acid sequences shown in SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3, respectively, and HCDR1, HCDR2, and HCDR3 having the amino acid sequences shown in SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6, respectively," or "antibody comprising the variable region of the light chain with SEQ ID NO: 7 and of the heavy chain with SEQ ID NO: 8," or "antibody comprising the amino acid sequence of the light chain with SEQ ID NO: 9 and of the heavy chain with SEQ ID NO: 10," or "recombinant antibody to TSLP," or "monoclonal antibody to TSLP" are used interchangeably in the context of the present application and refer to an antibody that specifically binds to TSLP and uses the Kabat numbering scheme.

[0031] The term "recombinant antibody" refers to an antibody that is expressed in a cell or cell line comprising nucleotide sequence(s) encoding an antibody, wherein said nucleotide sequence(s) is (are) not associated with the cell in nature. Detailed description of the invention.

[0032] The present invention relates to pharmaceutical compositions comprising an antibody or antigen-binding fragment thereof that specifically binds to thymic stromal lymphopoietin (TSLP).

[0033] In one aspect, the present invention relates to a pharmaceutical composition of an antibody to TSLP.

[0034] In one aspect, the present invention relates to a highly concentrated pharmaceutical composition of an antibody to TSLP.

[0035] In some embodiments of the invention, the pharmaceutical composition comprises: a. an antibody to TSLP; b. a buffer; c. a stabilizer; d. an osmotic agent; e. water.

[0036] In some embodiments of the invention, the pharmaceutical composition comprises: a. an antibody to TSLP; b. an acetate buffer; c. a stabilizer; d. an osmotic agent; e. water.

[0037] In some embodiments of the invention, the pharmaceutical composition comprises: a. an antibody to TSLP that comprises LCDRI, LCDR2 and LCDR3 with the amino acid sequences shown in SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, respectively, and HCDR1, HCDR2 and HCDR3 with the amino acid sequences shown in SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, respectively; b. an acetate buffer; c. a stabilizer; d. an osmotic agent; e. water.

[0038] In some embodiments of the invention, the pharmaceutical composition comprises: a. an antibody to TSLP that comprises amino acid sequences of the variable region of the light chain with SEQ ID NO: 7, and of the heavy chain with SEQ ID NO: 8; b. an acetate buffer; c. a stabilizer; d. an osmotic agent; e. water. In some embodiments of the invention, the pharmaceutical composition comprises: a. an antibody to TSLP that comprises an amino acid sequence of the light chain with SEQ ID NO: 9, and of the heavy chain with SEQ ID NO: 10; b. an acetate buffer; c. a stabilizer; d. an osmotic agent; e. water.

[0039] In some embodiments of the invention, the pharmaceutical composition comprises an antibody to TSLP that comprises amino acid sequences of the variable region of the light chain with SEQ ID NO: 7, and of the heavy chain with SEQ ID NO: 8.

[0040] In some embodiments of the invention, the pharmaceutical composition comprises an antibody to TSLP that comprises an amino acid sequence of the light chain with SEQ ID NO: 9, and of the heavy chain with SEQ ID NO: 10.

[0041] In some embodiments of the invention, the antibody to TSLP is a monoclonal antibody.

[0042] In some embodiments of the invention, the antibody to TSLP is a full-length IgG antibody.

[0043] In some embodiments of the invention, the antibody to TSLP is of human IgGl, IgG2, IgG3 or IgG4 isotype.

[0044] In some embodiments of the invention, the antibody to TSLP is of human IgGl isotype.

[0045] In some embodiments of the invention, the antibody to TSLP is at a concentration of 100 mg / ml to 200 mg / ml.

[0046] In some embodiments of the invention, the antibody to TSLP is at a concentration of 120 mg / ml to 180 mg / ml, or 130 mg / ml to 170 mg / ml, or 140 mg / ml to 160 mg / ml, or 100 mg / ml to 120 mg / ml, or 120 mg / ml to 140 mg / ml, or 145 mg / ml to 155 mg / ml, or 155 mg / ml to 160 mg / ml, or 160 mg / ml to 180 mg / ml, or 180 mg / ml to 200 mg / ml.

[0047] In some embodiments of the invention, the antibody to TSLP is at a concentration of 100 mg / ml, or 105 mg / ml, or 110 mg / ml, or 115 mg / ml, or 120 mg / ml, or 125 mg / ml, or 130 mg / ml, or 135 mg / ml, or 140 mg / ml, or 145 mg / ml, or 146 mg / ml, or 147 mg / ml, or 148 mg / ml, or 149 mg / ml, or 150 mg / ml, or 151 mg / ml, or 152 mg / ml, or 153 mg / ml, or 154 mg / ml, or 155 mg / ml, or 160 mg / ml, or 165 mg / ml, or 170 mg / ml, or 175 mg / ml, or 180 mg / ml, or 185 mg / ml, or 190 mg / ml, or 195 mg / ml, or 200 mg / ml.

[0048] In some embodiments of the invention, the acetate buffer is at a concentration of 1 mM to

[0049] 35 mM.

[0050] In some embodiments of the invention, the acetate buffer is at a concentration of 1 mM to

[0051] 35 mM, or 1 mM to 30 mM, or 1 mM to 25 mM, or 1 mM to 20 mM, or 1 mM to 15 mM, or 1 mM to 10 mM, or 2 mM to 8 mM, or 3 mM to 7 mM, or 4 mM to 6 mM, or 4.5 mM to 5.5 mM, or 4.7 mM to 5.2 mM, or 10 mM to 15 mM, or 15 mM to 25 mM, or 25 mM to 30 mM, or 30 mM to 35 mM.

[0052] In some embodiments of the invention, the acetate buffer is at a concentration of 1 mM, or 2 mM, or 3 mM, or 4 mM, or 4.5 mM, or 5 mM, or 5.5 mM, or 6 mM, or 7 mM, or 8 mM, or 9 mM, or 10 mM, or 11 mM, or 12 mM, or 13 mM, or 14 mM, or 15 mM, or 16 mM, or 17 mM, or 18 mM, or 19 mM, or 20 mM, or 21 mM, or 22 mM, or 23 mM, or 24 mM, or 25 mM, or 26 mM, or 27 mM, or 28 mM, or 29 mM, or 30 mM, or 31 mM, or 32 mM, or 33 mM, or 34 mM, or 35 mM.

[0053] In some embodiments of the invention, the acetate buffer consists of sodium acetate and glacial acetic acid.

[0054] In some embodiments of the invention, sodium acetate is sodium acetate trihydrate.

[0055] In some embodiments of the invention, sodium acetate trihydrate is at a concentration of 0.2 mg / ml to 4.1 mg / ml.

[0056] In some embodiments of the invention, sodium acetate trihydrate is at a concentration of 0.2 mg / ml to 1.9 mg / ml.

[0057] In some embodiments of the invention, sodium acetate trihydrate is at a concentration of 0.2 mg / ml to 0.8 mg / ml, or 0.3 mg / ml to 0.7 mg / ml, or 0.3 mg / ml to 0.6 mg / ml, or 0.2 mg / ml to 0.4 mg / ml, or 0.4 mg / ml to 0.5 mg / ml, or 0.41 mg / ml to 0.46 mg / ml, or 0.5 mg / ml to 0.7 mg / ml, or 0.7 mg / ml to 0.9 mg / ml, or 0.9 mg / ml to 1.1 mg / ml, or 1.1 mg / ml to 1.3 mg / ml, or 1.3 mg / ml to 1.5 mg / ml, or 1.5 mg / ml to 1.7 mg / ml, or 1.7 mg / ml to 1.9 mg / ml, or 4.0 mg / ml to 4.1 mg / ml.

[0058] In some embodiments of the invention, sodium acetate trihydrate is at a concentration of 0.2 mg / ml, or 0.240 mg / ml, or 0.241 mg / ml, or 0.242 mg / ml, or 0.243 mg / ml, or 0.244 mg / ml, or 0.245 mg / ml, or 0.246 mg / ml, or 0.247 mg / ml, 0.248 mg / ml, or 0.249 mg / ml, or 0.250 mg / ml, or 0.3 mg / ml, or 0.4 mg / ml, or 0.430 mg / ml, or 0.431 mg / ml, or 0.432 mg / ml, or 0.433 mg / ml, or 0.434 mg / ml, or 0.435 mg / ml, or 0.436 mg / ml, or 0.437 mg / ml, or 0.438 mg / ml, or 0.439 mg / ml, or 0.44 mg / ml, or 0.45 mg / ml, or 0.5 mg / ml, or 0.570 mg / ml, or 0.571 mg / ml, or 0.572 mg / ml, or 0.573 mg / ml, or 0.574 mg / ml, or 0.575 mg / ml, or 0.576 mg / ml, or 0.577 mg / ml, or 0.578 mg / ml, or 0.579 mg / ml, or 0.580 mg / ml, or 0.6 mg / ml, or 0.7 mg / ml, or 0.8 mg / ml, or 0.9 mg / ml, or 1.0 mg / ml, or 1.1 mg / ml, or 1.2 mg / ml, or 1.3 mg / ml, or 1.4 mg / ml, or 1.5 mg / ml, or 1.6 mg / ml, or 1.7 mg / ml, or 1.710 mg / ml, or 1.711 mg / ml, or 1.712 mg / ml, or 1.713 mg / ml, or 1.714 mg / ml, or 1.715 mg / ml, or 1.716 mg / ml, or 1.717 mg / ml, or 1.718 mg / ml, 1.719 mg / ml, or 1.720 mg / ml, or 1.730 mg / ml, or 1.740 mg / ml, or 1.741 mg / ml, or 1.742 mg / ml, or 1.743 mg / ml, or 1.744 mg / ml, or 1.745 mg / ml, or 1.746 mg / ml, or 1.747 mg / ml, or 1.748 mg / ml, or 1.749 mg / ml, or 1.750 mg / ml, or 1.8 mg / ml, or 1.9 mg / ml, or 4.0 mg / ml, or 4.044 mg / ml, or 4.1 mg / ml. In some embodiments of the invention, sodium acetate is at a concentration of 0.05 mg / ml to 2.5 mg / ml.

[0059] In some embodiments of the invention, sodium acetate is at a concentration of 0.05 mg / ml to 1.5 mg / ml.

[0060] In some embodiments of the invention, sodium acetate is at a concentration of 0.05 mg / ml to 1 mg / ml, or 0.1 mg / ml to 0.5 mg / ml, or 0.2 mg / ml to 0.3 mg / ml, or 0.24 mg / ml to 0.27 mg / ml, or 0.05 mg / ml to 0.1 mg / ml, or 0.1 mg / ml to 0.2 mg / ml, or 0.3 mg / ml to 0.4 mg / ml, or 0.4 mg / ml to 0.6 mg / ml, or 0.6 mg / ml to 0.8 mg / ml, or 0.8 mg / ml to 1.0 mg / ml, or 1.0 mg / ml to 1.2 mg / ml, or 1.2 mg / ml to 1.4 mg / ml, or 1.4 mg / ml to 1.5 mg / ml, or 1.5 mg / ml to 2.5 mg / ml.

[0061] In some embodiments of the invention, sodium acetate is at a concentration of 0.05 mg / ml, or 0.1 mg / ml, or 0.14 mg / ml, or 0.145 mg / ml, or 0.146 mg / ml, or 0.147 mg / ml, or 0.148 mg / ml, or 0.149 mg / ml, or 0.15 mg / ml, or 0.2 mg / ml, or 0.25 mg / ml, or 0.26 mg / ml, or 0.261 mg / ml, or 0.262 mg / ml, or 0.263 mg / ml, or 0.264 mg / ml, or 0.265 mg / ml, or 0.266 mg / ml, or 0.267 mg / ml, or 0.268 mg / ml, or 0.269 mg / ml, or 0.27 mg / ml, or 0.3 mg / ml, or 0.345 mg / ml, or 0.346 mg / ml, or 0.347 mg / ml, or 0.348 mg / ml, or 0.349 mg / ml, or 0.35 mg / ml, or 0.4 mg / ml, or 0.5 mg / ml, or

[0062] 0.6 mg / ml, or 0.7 mg / ml, or 0.8 mg / ml, or 0.9 mg / ml, or 1.0 mg / ml, or 1.03 mg / ml, or 1.031 mg / ml, or 1.032 mg / ml, or 1.033 mg / ml, 1.034 mg / ml, or 1.035 mg / ml, or 1.04 mg / ml, or 1.045 mg / ml, or 1.046 mg / ml, or 1.047 mg / ml, or 1.048 mg / ml, or 1.049 mg / ml, or 1.05 mg / ml, or 1.1 mg / ml, or 1.2 mg / ml, or 1.3 mg / ml, or 1.4 mg / ml, or 1.5 mg / ml, or 2.0 mg / ml, or 2.4 mg / ml, or 2.438 mg / ml, or 2.5 mg / ml.

[0063] In some embodiments of the invention, glacial acetic acid is at a concentration of 0.05 gl to 0.3 gl.

[0064] In some embodiments of the invention, glacial acetic acid is at a concentration of 0.05 gl to 0.2 gl, or 0.05 gl to 0.15 gl, or 0.07 gl to 0.130 gl, or 0.05 gl to 0.1 gl, or 0.1 gl to 0.15 gl, or 0.15 gl to 0.2 gl, or 0.2 gl to 0.25 gl, or 0.25 gl to 0.3 gl.

[0065] In some embodiments of the invention, glacial acetic acid is at a concentration of 0.05 gl, or 0.06 gl, or 0.07 gl, or 0.08 gl, or 0.09 gl, or 0.1 gl, or 0.101 gl, or 0.102 gl, or 0.103 gl, or 0.104 gl, or 0.105 gl, or 0.11 gl, or 0.12 gl, or 0.13 gl, or 0.14 gl, or 0.15 gl, or 0.16 gl, or 0.17, or 0.18 gl, or 0.19 gl, or 0.2 gl, or 0.21 gl, or 0.22 gl, or 0.23 gl, or 0.24 gl, or 0.25 gl, or 0.26 gl, or 0.27 gl, or 0.28 gl, or 0.29 gl, or 0.3 gl.

[0066] In some embodiments of the invention, glacial acetic acid is at a concentration of 0.01 mg / ml to 1.45 mg / ml.

[0067] In some embodiments of the invention, glacial acetic acid is at a concentration of 0.02 mg / ml to 1 mg / ml, or 0.03 mg / ml to 0.8 mg / ml, or 0.04 to 0.5 mg / ml, or 0.05 mg / ml to 0.3 mg / ml, or 0.08 mg / ml to 0.12 mg / ml, or 0.01 mg / ml to 0.05 mg / ml, or 0.05 mg / ml to 0.25 mg / ml, or 0.25 mg / ml to 0.45 mg / ml, or 0.45 mg / ml to 0.65 mg / ml, or 0.65 mg / ml to 0.85 mg / ml, or 0.85 mg / ml to 1.05 mg / ml, or 1.05 mg / ml to 1.25 mg / ml, or 1.25 mg / ml to 1.45 mg / ml.

[0068] In some embodiments of the invention, glacial acetic acid is at a concentration of 0.01 mg / ml, or 0.04 mg / ml, or 0.041 mg / ml, or 0.042 mg / ml, or 0.043 mg / ml, or 0.044 mg / ml, or 0.045 mg / ml, or 0.046 mg / ml, or 0.047 mg / ml, or 0.048 mg / ml, or 0.049 mg / ml, or 0.05 mg / ml, or 0.1 mg / ml, or 0.101 mg / ml, or 0.102 mg / ml, or 0.103 mg / ml, or 0.104 mg / ml, or 0.105 mg / ml, or 0.106 mg / ml, or 0.107 mg / ml, or 0.108 mg / ml, or 0.109 mg / ml, or 0.11 mg / ml, or 0.15 mg / ml, or 0.190 mg / ml, or 0.191 mg / ml, or 0.192 mg / ml, or 0.193 mg / ml, or 0.194 mg / ml, or 0.195 mg / ml, or 0.2 mg / ml, or 0.25 mg / ml, or 0.3 mg / ml, or 0.315 mg / ml, or 0.316 mg / ml, or 0.317 mg / ml, or 0.318 mg / ml, or 0.319 mg / ml, or 0.320 mg / ml, or 0.35 mg / ml, or 0.4 mg / ml, or 0.431 mg / ml, or 0.432 mg / ml, or 0.433 mg / ml, or 0.434 mg / ml, or 0.435 mg / ml, or 0.45 mg / ml, or 0.5 mg / ml, or 0.55 mg / ml, or 0.6 mg / ml, or 0.65 mg / ml, or 0.7 mg / ml, or 0.75 mg / ml, or 0.8 mg / ml, or 0.85 mg / ml, or 0.9 mg / ml, or 0.95 mg / ml, or 1.0 mg / ml, or 1.05 mg / ml, or 1.1 mg / ml, or 1.15 mg / ml, or 1.2 mg / ml, or 1.25 mg / ml, or 1.3 mg / ml, or 1.340 mg / ml, or 1.341 mg / ml, or 1.342 mg / ml, or 1.343 mg / ml, or 1.344 mg / ml, or 1.345 mg / ml, or 1.346 mg / ml, or 1.347 mg / ml, or 1.348 mg / ml, or 1.349 mg / ml, or 1.345 mg / ml, or 1.35 mg / ml, or 1.4 mg / ml, or 1.45 mg / ml,

[0069] In some embodiments of the invention, glacial acetic acid is added to adjust the pH to 3.5 to 6.0.

[0070] In some embodiments of the invention, glacial acetic acid is added to adjust the pH to 4.0 to 6.0, or 4.5 to 5.5.

[0071] In some embodiments of the invention, glacial acetic acid is added to adjust the pH to 3.5, or 4.0, or 4.5, or 5.0, or 5.5, or 6.0, or 6.0.

[0072] In some embodiments of the invention, the stabilizer is arginine and / or hydrochloric acid and / or an arginine salt.

[0073] In some embodiments of the invention, the stabilizer is arginine.

[0074] In some embodiments of the invention, the stabilizer is hydrochloric acid.

[0075] In some embodiments of the invention, the stabilizer is an arginine salt.

[0076] In some embodiments of the invention, the stabilizer is arginine and hydrochloric acid.

[0077] In some embodiments of the invention, the stabilizer is arginine hydrochloride, or arginine phosphate, or arginine sulfate, or arginine phosphate, arginine nitrate.

[0078] In some embodiments of the invention, the stabilizer is arginine and / or hydrochloric acid and / or arginine hydrochloride.

[0079] In some embodiments of the invention, the stabilizer is arginine hydrochloride.

[0080] In some embodiments of the invention, arginine hydrochloride is at a concentration of 5 mg / ml to 40 mg / ml. In some embodiments of the invention, arginine hydrochloride is at a concentration of 5 mg / ml to 35 mg / ml.

[0081] In some embodiments of the invention, arginine hydrochloride is at a concentration of 5 mg / ml to 30 mg / ml, or 10 mg / ml to 30 mg / ml, or 20 mg / ml to 30 mg / ml, or 5 mg / ml to 15 mg / ml, or 15 mg / ml to 20 mg / ml, or 30 mg / ml to 35 mg / ml, or 35 mg / ml to 40 mg / ml.

[0082] In some embodiments of the invention, arginine hydrochloride is at a concentration of 5 mg / ml, or 6 mg / ml, or 7 mg / ml, or 8 mg / ml, or 9 mg / ml, or 10 mg / ml, or 11 mg / ml, or 12 mg / ml, or 13 mg / ml, or 14 mg / ml, or 15 mg / ml, or 16 mg / ml, or 17 mg / ml, or 18 mg / ml, or 19 mg / ml, or 20 mg / ml, or 21 mg / ml, or 21.6 mg / ml, or 22 mg / ml, or 23 mg / ml, or 23.4 mg / ml, or 23.45 mg / ml, or 23.46 mg / ml, or 23.47 mg / ml, or 23.48 mg / ml, or 23.49 mg / ml, or 23.5 mg / ml, or 24 mg / ml, or 25 mg / ml, or 25.5 mg / ml, or 25.6 mg / ml, or 25.7 mg / ml, or 25.8 mg / ml, or 25.9 mg / ml, or 26 mg / ml, or 26.1 mg / ml, or 26.2 mg / ml, or 26.3 mg / ml, or 26.4 mg / ml, or 26.5 mg / ml, or 27 mg / ml, or 28 mg / ml, or 28.5 mg / ml, or 28.6 mg / ml, or 28.7 mg / ml, or 28.71 mg / ml, or 28.72 mg / ml, or 28.73 mg / ml, or 29 mg / ml, or 30 mg / ml, or 31 mg / ml, or 32 mg / ml, or 33 mg / ml, or 34 mg / ml, or 35 mg / ml, or 36 mg / ml, or 37 mg / ml, or 38 mg / ml, or 39 mg / ml, or 40 mg / ml.

[0083] In some embodiments of the invention, arginine is at a concentration of 5 mg / ml to 35 mg / ml.

[0084] In some embodiments of the invention, arginine is at a concentration of 10 mg / ml to 30 mg / ml, or 15 mg / ml to 25 mg / ml, or 18 mg / ml to 23 mg / ml, or 5 mg / ml to 15 mg / ml, or 25 mg / ml to 35 mg / ml.

[0085] In some embodiments of the invention, arginine is at a concentration of 5 mg / ml, or 6 mg / ml, or 7 mg / ml, or 8 mg / ml, or 9 mg / ml, or 10 mg / ml, or 11 mg / ml, or 12 mg / ml, or 13 mg / ml, or 14 mg / ml, or 15 mg / ml, or 16 mg / ml, or 17 mg / ml, or 18 mg / ml, or 19 mg / ml, or 19.4 mg / ml, or 19.41 mg / ml, or 19.42 mg / ml, or 19.43 mg / ml, or 19.44 mg / ml, or 19.45 mg / ml, or 19.5 mg / ml, or 20 mg / ml, or 21 mg / ml, or 21.1 mg / ml, or 21.2 mg / ml, or 21.3 mg / ml, or 21.4 mg / ml, or 21.5 mg / ml, or 21.6 mg / ml, or 21.7 mg / ml, or 21.8 mg / ml, or 21.9 mg / ml, or 22 mg / ml, or 23 mg / ml, or 23.5 mg / ml, or 23.6 mg / ml, or 23.7 mg / ml, or 23.71 mg / ml, or 23.72 mg / ml, or 23.73 mg / ml, or 23.74 mg / ml, or 23.75 mg / ml, or 23.78 mg / ml, or 24 mg / ml, or 25 mg / ml, or 26 mg / ml, or 27 mg / ml, or 28 mg / ml, or 29 mg / ml, or 29.7 mg / ml, or 29.71 mg / ml, or 29.72 mg / ml, or 29.73 mg / ml, or 29.74 mg / ml, or 29.75 mg / ml, or 29.76 mg / ml, or 29.77 mg / ml, or 29.78 mg / ml, or 30 mg / ml, or 31 mg / ml, or 32 mg / ml, or 33 mg / ml, or 34 mg / ml, or 35 mg / ml.

[0086] In some embodiments of the invention, hydrochloric acid is added to adjust the pH to 3 to 7.

[0087] In some embodiments of the invention, hydrochloric acid is added to adjust the pH to 4 to

[0088] 6, or 4.5 to 5.5, or 4.8 to 5.2. In some embodiments of the invention, hydrochloric acid is added to adjust the pH to 3, or 4, or 4.5, or 5, or 5.5, or 6, or 7.

[0089] In some embodiments of the invention, the pharmaceutical composition further comprises a nonionic surfactant.

[0090] In some embodiments of the invention, the nonionic surfactant is pol oxamer 188, or polysorbate 20, or polysorbate 80.

[0091] In some embodiments of the invention, poloxamer 188 is at a concentration of 0.05 mg / ml to 1.05 mg / ml.

[0092] In some embodiments of the invention, polysorbate 80 is at a concentration of 0.05 mg / ml to 1.5 mg / ml.

[0093] In some embodiments of the invention, polysorbate 20 is at a concentration of 0.05 mg / ml to 1.5 mg / ml.

[0094] In some embodiments of the invention, poloxamer 188 is at a concentration of 0,08 mg / ml to 1 mg / ml, or 0,1 mg / ml to 0,9 mg / ml, or 0,2 mg / ml to 0,8 mg / ml, or 0,3 mg / ml to 0,7 mg / ml, or 0,4 mg / ml to 0,6 mg / ml, or 0,05 mg / ml to 0, 15 mg / ml, or 0, 15 mg / ml to 0,25 mg / ml, or 0,25 mg / ml to 0,35 mg / ml, or 0,35 mg / ml to 0,45 mg / ml, or 0,45 mg / ml to 0,55 mg / ml, or 0,55 mg / ml to 0,65 mg / ml, or 0,65 mg / ml to 0,75 mg / ml, or 0,75 mg / ml to 0,85 mg / ml, or 0,85 mg / ml to 0,95 mg / ml, or 0,95 mg / ml to 1.05 mg / ml.

[0095] In some embodiments of the invention, poloxamer 188 is at a concentration of 0,05 mg / ml, or 0,1 mg / ml, or 0,15 mg / ml, or 0,2 mg / ml, or 0,25 mg / ml, or 0,3 mg / ml, or 0,35 mg / ml, or 0,4 mg / ml, or 0,45 mg / ml, or 0,46 mg / ml, or 0,47 mg / ml, or 0,48 mg / ml, or 0,49 mg / ml, or 0,5 mg / ml, or 0,51 mg / ml, or 0,52 mg / ml, or 0,53 mg / ml, or 0,54 mg / ml, or 0,55 mg / ml, or 0,6 mg / ml, or 0,65 mg / ml, or 0,7 mg / ml, or 0,75 mg / ml, or 0,8 mg / ml, or 0,85 mg / ml, or 0,9 mg / ml, or 0,95 mg / ml, or 1.0 mg / ml, or 1.05 mg / ml.

[0096] In some embodiments of the invention, polysorbate 20 is at a concentration of 0,05 mg / ml to 1.0 mg / ml, or 0,2 mg / ml to 0,8 mg / ml, or 0,4 mg / ml to 0,6 mg / ml, or 0,05 mg / ml to 0,5 mg / ml, or 0,5 mg / ml to 1.0 mg / ml, or 1.0 mg / ml to 1.5 mg / ml.

[0097] In some embodiments of the invention, polysorbate 20 is at a concentration of 0,05 mg / ml, or 0,1 mg / ml, or 0,2 mg / ml, or 0,3 mg / ml, or 0,4 mg / ml, or 0,5 mg / ml, or 0,6 mg / ml, or 0,7 mg / ml, or 0,8 mg / ml, or 0,9 mg / ml, or 1.0 mg / ml, or 1.1 mg / ml, or 1.2 mg / ml, or 1.3 mg / ml, or 1.4 mg / ml, or 1.5 mg / ml.

[0098] In some embodiments of the invention, polysorbate 80 is at a concentration of 0,05 mg / ml to 1.0 mg / ml, or 0,2 mg / ml to 0,8 mg / ml, or 0,4 mg / ml to 0,6 mg / ml, or 0,05 mg / ml to 0,5 mg / ml, or 0,5 mg / ml to 1.0 mg / ml, or 1.0 mg / ml to 1.5 mg / ml. In some embodiments of the invention, polysorbate 80 is at a concentration of 0,05 mg / ml, or 0,1 mg / ml, or 0,2 mg / ml, or 0,3 mg / ml, or 0,4 mg / ml, or 0,5 mg / ml, or 0,6 mg / ml, or 0,7 mg / ml, or 0,8 mg / ml, or 0,9 mg / ml, or 1.0 mg / ml, or 1.1 mg / ml, or 1.2 mg / ml, or 1.3 mg / ml, or 1.4 mg / ml, or 1.5 mg / ml.

[0099] In some embodiments of the invention, the osmotic agent is trehalose dihydrate, or trehalose, or sorbitol.

[0100] In some embodiments of the invention, trehalose dihydrate is at a concentration of 5 mg / ml to 40 mg / ml.

[0101] In some embodiments of the invention, trehalose dihydrate is at a concentration of 5 mg / ml to 35 mg / ml, or 5 mg / ml to 30 mg / ml, or 10 mg / ml to 30 mg / ml, or 10 mg / ml to 20 mg / ml, or 12 mg / ml to 18 mg / ml, or 14 mg / ml to 16 mg / ml, or 20 mg / ml to 30 mg / ml.

[0102] In some embodiments of the invention, trehalose dihydrate is at a concentration of 5 mg / ml, or 6 mg / ml, or 7 mg / ml, or 8 mg / ml, or 9 mg / ml, or 10 mg / ml, or 11 mg / ml, or 12 mg / ml, or 13 mg / ml, or 13.5 mg / ml, or 14 mg / ml, or 14,5 mg / ml, or 14,6 mg / ml, or 14,7 mg / ml, or 14,8 mg / ml, or 14,9 mg / ml, or 15 mg / ml, or 15.1 mg / ml, or 15.2 mg / ml, or 15.3 mg / ml, or 15.4 mg / ml, or 15.5 mg / ml, or 16 mg / ml, or 16.5 mg / ml, or 17 mg / ml, or 18 mg / ml, or 19 mg / ml, or 20 mg / ml, or 21 mg / ml, or 22 mg / ml, or 23 mg / ml, or 24 mg / ml, or 25 mg / ml, or 26 mg / ml, or 27 mg / ml, or 28 mg / ml, or 29 mg / ml, or 30 mg / ml, or 31 mg / ml, or 32 mg / ml, or 33 mg / ml, or 34 mg / ml, or 35 mg / ml, or 36 mg / ml, or 37 mg / ml, or 38 mg / ml, or 39 mg / ml, or 40 mg / ml.

[0103] In some embodiments of the invention, trehalose is at a concentration of 5 mg / ml to 30 mg / ml.

[0104] In some embodiments of the invention, trehalose is at a concentration of 5 mg / ml to 25 mg / ml, or 10 mg / ml to 20 mg / ml, or 10 mg / ml to 15 mg / ml, or 20 mg / ml to 30 mg / ml.

[0105] In some embodiments of the invention, trehalose is at a concentration of 5 mg / ml, or 6 mg / ml, or 7 mg / ml, or 8 mg / ml, or 9 mg / ml, or 10 mg / ml, or 11 mg / ml, or 12 mg / ml, or 12.2 mg / ml, or 12.24 mg / ml, or 13 mg / ml, or 13.1 mg / ml, or 13.2 mg / ml, or 13.3 mg / ml, or 13.4 mg / ml, or 13.5 mg / ml, or 13.6 mg / ml, or 13.7 mg / ml, or 13.8 mg / ml, or 13.9 mg / ml, or 14 mg / ml, or 14,5 mg / ml, or 14,9 mg / ml, or 14,96 mg / ml, or 15 mg / ml, or 16 mg / ml, or 17 mg / ml, or 18 mg / ml, or 19 mg / ml, or 20 mg / ml, or 21 mg / ml, or 22 mg / ml, or 23 mg / ml, or 24 mg / ml, or 25 mg / ml, or 26 mg / ml, or 27 mg / ml, or 28 mg / ml, or 29 mg / ml, or 30 mg / ml.

[0106] In some embodiments of the invention, sorbitol is at a concentration of 4 mg / ml to 10 mg / ml.

[0107] In some embodiments of the invention, sorbitol is at a concentration of 4 mg / ml to 9 mg / ml, or 5 mg / ml to 9 mg / ml, or 6 mg / ml to 8 mg / ml, or 4 mg / ml to 6 mg / ml, or 8 mg / ml to 10 mg / ml. In some embodiments of the invention, sorbitol is at a concentration of 4 mg / ml, or 5 mg / ml, or 6 mg / ml, or 7 mg / ml, or 8 mg / ml, or 9 mg / ml, or 10 mg / ml.

[0108] In some embodiments of the invention, the pharmaceutical composition comprises: an antibody to TSLP 100-200 mg / ml an acetate buffer 1-20 mM a nonionic surfactant 0.05-1.05 mg / ml and / or and / or arginine, 5-35 mg / ml, and / or and / or arginine hydrochloride, 5-35 mg / ml, and / or and / or hydrochloric acid ad pH=5.0 trehalose dihydrate 5-40 mg / ml or or trehalose 5-30 mg / ml

[0109] In some embodiments of the invention, the pharmaceutical composition comprises: an antibody to TSLP 100-200 mg / ml sodium acetate trihydrate 0.2-1.9 mg / ml glacial acetic acid 0.05-0.3 pl a nonionic surfactant 0.05-1.05 mg / ml and / or and / or arginine, 5-35 mg / ml, and / or and / or arginine hydrochloride, 5-35 mg / ml, and / or and / or hydrochloric acid ad pH=5.0 trehalose dihydrate 5-40 mg / ml or or trehalose 5-30 mg / ml

[0110] In some embodiments of the invention, the pharmaceutical composition comprises: an antibody to TSLP 100-200 mg / ml sodium acetate trihydrate 0.2-1.9 mg / ml glacial acetic acid ad pH 4-6 a nonionic surfactant 0.05-1.05 mg / ml and / or and / or arginine, 5-35 mg / ml, and / or and / or arginine hydrochloride, 5-35 mg / ml, and / or and / or hydrochloric acid ad pH=5.0 trehalose dihydrate 5-40 mg / ml or or trehalose 5-30 mg / ml

[0111] In some embodiments of the invention, the pharmaceutical composition comprises: an antibody to TSLP 100-200 mg / ml sodium acetate trihydrate 0.2-1.9 mg / ml glacial acetic acid 0.05-0.3 pl pol oxamer 188 0.05-1.05 mg / ml arginine 5-35 mg / ml trehalose dihydrate 5-40 mg / ml or or trehalose 5-30 mg / ml hydrochloric acid ad pH=5.0

[0112] In some embodiments of the invention, the pharmaceutical composition comprises: an antibody to TSLP 100-200 mg / ml sodium acetate trihydrate 0.2-1.9 mg / ml glacial acetic acid ad pH 4-6 pol oxamer 188 0.05-1.05 mg / ml arginine hydrochloride 5-35 mg / ml trehalose dihydrate 5-40 mg / ml or or trehalose 5-30 mg / ml

[0113] In some embodiments of the invention, the pharmaceutical composition comprises: an antibody to TSLP 120-180 mg / ml sodium acetate trihydrate 0.2-1.0 mg / ml glacial acetic acid 0.05-0.2 pl pol oxamer 188 0.1-1.05 mg / ml arginine 10-30 mg / ml trehalose dihydrate 5-30 mg / ml or or trehalose 5-25 mg / ml hydrochloric acid ad pH=5.0

[0114] In some embodiments of the invention, the pharmaceutical composition comprises: an antibody to TSLP 120-180 mg / ml sodium acetate trihydrate 0.2-1.0 mg / ml glacial acetic acid ad pH 5.0 pol oxamer 188 0.1-1.05 mg / ml arginine hydrochloride 10-35 mg / ml trehalose dihydrate 5-30 mg / ml or or trehalose 5-25 mg / ml

[0115] In some embodiments of the invention, the pharmaceutical composition comprises: an antibody to TSLP 130-170 mg / ml sodium acetate trihydrate 0.2-0.8 mg / ml glacial acetic acid 0.05-0.2 pl pol oxamer 188 0.2-0.8 mg / ml arginine 15-25 mg / ml trehalose dihydrate 10-25 mg / ml or or trehalose 10-20 mg / ml hydrochloric acid ad pH=5.0

[0116] In some embodiments of the invention, the pharmaceutical composition comprises: an antib ody to T SLP 130-170 mg / ml sodium acetate trihydrate 0.2-0.8 mg / ml glacial acetic acid ad pH 5.0 pol oxamer 188 0.2-0.8 mg / ml arginine hydrochloride 15-30 mg / ml trehalose dihydrate 10-25 mg / ml or or trehalose 10-20 mg / ml

[0117] In some embodiments of the invention, the pharmaceutical composition comprises: an antibody to TSLP 150.0 mg / ml sodium acetate trihydrate 0.436 mg / ml glacial acetic acid 0.103 pl pol oxamer 188 0,5 mg / ml arginine 21.6 mg / ml trehalose dihydrate 15 mg / ml hydrochloric acid ad pH 5.0

[0118] In some embodiments of the invention, the pharmaceutical composition comprises: an antibody to TSLP 150.0 mg / ml sodium acetate trihydrate 0.436 mg / ml glacial acetic acid ad pH 5.0 pol oxamer 188 0,5 mg / ml arginine hydrochloride 26.1 mg / ml trehalose dihydrate 15 mg / ml

[0119] In some embodiments of the invention, the pharmaceutical composition comprises: an antibody to TSLP 150.0 mg / ml sodium acetate trihydrate 0.436 mg / ml glacial acetic acid ad pH 5.0 pol oxamer 188 0,5 mg / ml arginine hydrochloride 26.1 mg / ml trehalose 13.6 mg / ml

[0120] In some embodiments of the invention, the pharmaceutical composition comprises: an antibody to TSLP 150.0 mg / ml sodium acetate trihydrate 0.436 mg / ml glacial acetic acid 0.103 pl pol oxamer 188 0,5 mg / ml arginine 21.6 mg / ml trehalose 13.6 mg / ml hydrochloric acid ad pH 5.0

[0121] In some embodiments of the invention, the pharmaceutical composition comprises: an antibody to TSLP 100,0 mg / ml sodium acetate trihydrate 0.436 mg / ml glacial acetic acid ad pH 5.0 pol oxamer 188 0,4 mg / ml arginine hydrochloride 23.49 mg / ml trehalose dihydrate 13.5 mg / ml

[0122] In some embodiments of the invention, the pharmaceutical composition comprises: an antibody to TSLP 100,0 mg / ml sodium acetate trihydrate 0.436 mg / ml glacial acetic acid ad pH 5.0 poloxamer 188 0,4 mg / ml arginine hydrochloride 23.49 mg / ml trehalose dihydrate 16.5 mg / ml

[0123] In some embodiments of the invention, the pharmaceutical composition comprises: an antibody to TSLP 100,0 mg / ml sodium acetate trihydrate 0.436 mg / ml glacial acetic acid ad pH 5.0 pol oxamer 188 0,4 mg / ml arginine hydrochloride 23.49 mg / ml trehalose dihydrate 13.5 mg / ml

[0124] In some embodiments of the invention, the pharmaceutical composition comprises: an antibody to TSLP 150.0 mg / ml sodium acetate trihydrate 0.436 mg / ml glacial acetic acid 0.103 pl poloxamer 188 0,5 mg / ml arginine 21.6 mg / ml trehalose dihydrate 15 mg / ml hydrochloric acid ad pH 5.0 per 1 ml

[0125] In some embodiments of the invention, the pharmaceutical composition comprises: an antibody to TSLP 150.0 mg / ml sodium acetate trihydrate 0.436 mg / ml glacial acetic acid ad pH 5.0 pol oxamer 188 0,5 mg / ml arginine hydrochloride 26.1 mg / ml trehalose dihydrate 15 mg / ml per 1 ml

[0126] In some embodiments of the invention, the pharmaceutical composition consists of 150 mg / ml of antibody to TSLP, arginine 21.6 mg, trehalose dihydrate 15.0 mg, poloxamer 188 0.5 mg, sodium acetate trihydrate 0.436 mg, glacial acetic acid 0.103 pl, hydrochloric acid ad pH 5.0, water for injection ad 1 ml.

[0127] In some embodiments of the invention, the pharmaceutical composition consists of 150 mg / ml of antibody to TSLP, arginine hydrochloride 26.1 mg, trehalose dihydrate 15.0 mg, poloxamer 188 0.5 mg, sodium acetate trihydrate 0.436 mg, glacial acetic acid ad pH 5.0, water for injection ad 1 ml.

[0128] In one embodiment, the pharmaceutical composition of the present invention may be in a form suitable for subcutaneous, intravenous or intramuscular administration.

[0129] In some embodiments, the present invention relates to a pharmaceutical composition intended for manufacturing or producing a medicament. In some embodiments, the present invention relates to a pharmaceutical composition intended for manufacturing or producing a medicament for treatment of a disease or disorder mediated by TSLP activity.

[0130] In some embodiments, the present invention relates to a pharmaceutical composition intended for manufacturing or producing a medicament for treatment of a disease or disorder mediated by TSLP activity, being an autoimmune or allergic disease.

[0131] In some embodiments of the invention, the autoimmune or allergic disease is bronchial asthma, severe bronchial asthma, atopic asthma, mild atopic asthma, eosinophilic esophagitis, eosinophilic granulomatosis with polyangiitis, chronic obstructive pulmonary disease, rhinitis, allergic rhinitis, rhinosinusitis with nasal polyps, dermatitis, atopic dermatitis, allergy, autoimmune skin diseases, vitiligo, psoriasis, bullous pemphigoid, rosacea, alopecia areata.

[0132] In some embodiments, the pharmaceutical composition of the present invention is intended for treating a disease or disorder mediated by TSLP activity.

[0133] In some embodiments, the pharmaceutical composition of the present invention is intended for treating a disease or disorder mediated by TSLP activity, being an autoimmune or allergic disease.

[0134] In some embodiments of the invention, the autoimmune or allergic disease is bronchial asthma, severe bronchial asthma, atopic asthma, mild atopic asthma, eosinophilic esophagitis, eosinophilic granulomatosis with polyangiitis, chronic obstructive pulmonary disease, rhinitis, allergic rhinitis, rhinosinusitis with nasal polyps, dermatitis, atopic dermatitis, allergy, autoimmune skin diseases, vitiligo, psoriasis, bullous pemphigoid, rosacea, alopecia areata.

[0135] In some embodiments, the present invention relates to a method of treating, with the pharmaceutical composition, a disease or disorder mediated by TSLP activity.

[0136] In some embodiments, the present invention relates to a method of treating, with the pharmaceutical composition, a disease or disorder mediated by TSLP activity, being an autoimmune or allergic disease.

[0137] In some embodiments of the invention, the autoimmune or allergic disease is bronchial asthma, severe bronchial asthma, atopic asthma, mild atopic asthma, eosinophilic esophagitis, eosinophilic granulomatosis with polyangiitis, chronic obstructive pulmonary disease, rhinitis, allergic rhinitis, rhinosinusitis with nasal polyps, dermatitis, atopic dermatitis, allergy, autoimmune skin diseases, vitiligo, psoriasis, bullous pemphigoid, rosacea, alopecia areata.

[0138] In another embodiment, the pharmaceutical composition of the present invention is used in treating a disease or disorder mediated by TSLP activity.

[0139] In some embodiments of the invention, the disease or disorder mediated by TSLP activity is an autoimmune or allergic disease. In some embodiments of the invention, the autoimmune or allergic disease is bronchial asthma, severe bronchial asthma, atopic asthma, mild atopic asthma, eosinophilic esophagitis, eosinophilic granulomatosis with polyangiitis, chronic obstructive pulmonary disease, rhinitis, allergic rhinitis, rhinosinusitis with nasal polyps, dermatitis, atopic dermatitis, allergy, autoimmune skin diseases, vitiligo, psoriasis, bullous pemphigoid, rosacea, alopecia areata.

[0140] In one embodiment, the pharmaceutical composition of the present invention is intended for use for treating a disease or disorder mediated by TSLP activity.

[0141] In one of embodiments, the present invention relates to the use for treating, with the pharmaceutical composition, a disease or disorder mediated by TSLP activity.

[0142] In another embodiment, the pharmaceutical composition of the present invention is used for treating a disease or disorder mediated by TSLP activity.

[0143] In some embodiments of the invention, the disease or disorder mediated by TSLP activity is an autoimmune or allergic disease.

[0144] In some embodiments of the invention, the autoimmune or allergic disease is bronchial asthma, severe bronchial asthma, atopic asthma, mild atopic asthma, eosinophilic esophagitis, eosinophilic granulomatosis with polyangiitis, chronic obstructive pulmonary disease, rhinitis, allergic rhinitis, rhinosinusitis with nasal polyps, dermatitis, atopic dermatitis, allergy, autoimmune skin diseases, vitiligo, psoriasis, bullous pemphigoid, rosacea, alopecia areata.

[0145] Examples

[0146] Abbreviations

[0147] IC - input control

[0148] A - difference between input control values with respect to a stress n / a - not applicable, the result could not be processed

[0149] HMW impurities - high molecular weight impurities

[0150] TS - thermal stress

[0151] SH - shaking

[0152] FT - freezing-thawing

[0153] SE HPLC - size-exclusion high-performance liquid chromatography

[0154] Materials and general methods

[0155] One or more of the following parameters were investigated for the compositions given in the examples below:

[0156] A. Purity and related impurities

[0157] Al. Method: size-exclusion HPLC (high performance liquid chromatography). Reagents: Disodium hydrogen phosphate anhydrous (USP, Eur. Ph.), Sodium chloride (USP, Eur. Ph), Orthophosphoric acid (USP, Eur. Ph), Sodium azide (USP, Eur. Ph), Purified water (n / a).

[0158] We used an Agilent 1260 Infinity chromatograph with the following columns: TSK-gel G3000SWXL, 7.8X300 mm, particle size: 5 pm, pore size: 300 A, Xtimate SEC-300 HPLC Column, 7.8x300 mm, particle size: 5 pm, pore size: 300 A. Pre-column: TSK-Gel Guard SWXL, 6.0 mm ID * 4.0 cm, 7 pm.

[0159] A2. Method: capillary gel electrophoresis in the presence of sodium dodecyl sulfate under non-reducing conditions (n / r CGE)

[0160] Reagents: Disodium hydrogen phosphate anhydrous (USP, Eur. Ph.), Sodium chloride (USP, Eur. Ph), Orthophosphoric acid (USP, Eur. Ph), Sodium azide (USP, Eur. Ph), Purified water (n / a).

[0161] The test was performed on a capillary electrophoresis system equipped with a PA 800 Plus UV / PDA detector. Materials used: quartz capillary, uncoated, inner diameter: 50 pm, aperture: 100 x 200 pm.

[0162] B. Hydrodynamic radius

[0163] Method: dynamic light scattering (DLS).

[0164] The test was carried out using a DynaPro Plate Reader II (Wyatt) under the following parameters: initial measurement temperature - 25 °C; scattered light intensity at 0 = 158°; number of measurements per repeat - 3; time of a measurement - 5 s.

[0165] 35 pl of each sample is added to the well of a 384-well black polymer plate with an optically clear bottom, thereafter the plate is sealed with a heat-resistant self-adhesive film. The sealed plate is centrifuged for 3 minutes at 3000 rpm. The plate bottom is then purged using a stream of compressed air to remove dust.

[0166] After the test, the resulting data is processed using the Dynamics V7, Version 7.5.0.17 (Wyatt) software.

[0167] Example 1. Selection of excipients for pharmaceutical composition

[0168] This example investigates the formulations provided in Table 1 to evaluate the effect of excipients on the stability of antibody BCD-272.

[0169] Table 1. Test formulations

[0170] Test 1. Thermal stress (TS)

[0171] Test samples in two 150 pl aliquots for each formulation are loaded in separate glass vials as follows: one vial is stored in a refrigerator at (5 ± 3) °C (input control may be transferred for analysis once for all studies at the start of storage); the second vial is loaded into a thermostat and incubated at 50 °C for 96 hours. After subjecting to thermal stress, the vials are removed from the thermostat, kept at room temperature for about 15 minutes and transferred for analysis along with an intact sample. Test results are shown in Tables 2 and 3.

[0172] Table 2. A2 parameter control results.

[0173] Table 3. B parameter control results

[0174] Conclusion: after being subjected to thermal stress, the compositions showed the hydrodynamic radius at acceptable values as controlled by dynamic light scattering, and showed acceptable changes in the monomer content and sum of impurities as controlled by capillary electrophoresis under non-reducing conditions.

[0175] Test 2. Shaking (SH)

[0176] Test samples are divided into two aliquots of 150 pl each and loaded in glass vials, one vial for each formulation: one vial is stored in a refrigerator at (5 ± 3) °C (input control may be transferred for analysis once for all studies at the start of storage), the remaining vials are placed in a shaker and shaken at 800 rpm, (5 ± 3) °C for 96 hours. After the stress, the vials are removed from the shaker and transferred for analysis. Test results are shown in Table 4.

[0177] Table 4. Al parameter control results.

[0178]

[0179] Conclusion: The parameter "Purity and related impurities", as analyzed by SE HPLC, changed slightly in all test formulations.

[0180] Test 3. Freezing and thawing (FT)

[0181] Test samples are divided into two aliquots and loaded in polymer tubes, one vial for each formulation: one vial is stored in a refrigerator at (5 ± 3) °C (input control may be transferred for analysis once for all studies at the start of storage), the remaining vials are placed in a freezer and stored at minus (16 - 20) °C. The analysis includes five freeze-thaw cycles. After the stress, the vials are removed from the freezer, kept at room temperature until the content is completely thawed; the solutions are then vortexed and transferred for analysis. Test results are shown in Table 5.

[0182] Table 5. Al parameter control results.

[0183] Conclusion: The parameter "Purity and related impurities", as analyzed by SE HPLC, changed slightly in all test formulations.

[0184] Based on the study results, the following storage formulation was selected: trehalose dihydrate 15.0 mg / ml, arginine hydrochloride 26.1 mg / ml, poloxamer 188 0.5 mg / ml, sodium acetate trihydrate 0.436 mg / ml, glacial acetic acid ad pH 5.0.

[0185] The selected formulation demonstrated improved stabilizing properties among all test samples: after being subjected to thermal stress, the selected candidate showed the hydrodynamic radius at the smallest value as controlled by dynamic light scattering, and showed the smallest change in monomer content and sum of impurities as controlled by capillary electrophoresis. However, other test formulations also showed good results in terms of stabilizing properties. During shaking and freeze-thaw cycles, the "Purity and related impurities" parameter, as analyzed by SE HPLC, changed insignificantly in all test formulations.

[0186] Example 2. Assessment of effect of quantitative content of excipients

[0187] Compositions in Table 6 were subjected to an assessment of the effect of the quantitative content of excipients on the quality parameters of the composition for antibody BCD-272.

[0188] Table 6. Test formulations

[0189] Findings of trial:

[0190] Test 1. Thermal stress (TS)

[0191] Test samples in two 150 pl aliquots for each formulation are loaded in separate glass vials as follows: one vial is stored in a refrigerator at (5 ± 3) °C (input control may be transferred for analysis once for all studies at the start of storage); the second vial is loaded into a thermostat and incubated at 40 °C for 96 hours. After subjecting to thermal stress, the vials are removed from the thermostat, kept at room temperature for about 15 minutes and transferred for analysis along with an intact sample. Test results are shown in Tables 7, 8 and 9.

[0192] Table 7. Al parameter control results.

[0193] Table 8. A2 parameter control results.

[0194] Table 9. B parameter control results

[0195] Conclusion: The parameter "Purity and related impurities", as analyzed by SE HPLC and n / r CGE, changed slightly in all test formulations. Values of the hydrodynamic radius, as controlled by dynamic light scattering, also changed slightly.

[0196] Test 2. Shaking (SH)

[0197] Test samples are divided into two aliquots of 150 pl each and loaded in glass vials, one vial for each formulation: one vial is stored in a refrigerator at (5 ± 3) °C (input control may be transferred for analysis once for all studies at the start of storage), the remaining vials are placed in a shaker and shaken at 800 rpm, (5 ± 3) °C for 96 hours. After the stress, the vials are removed from the shaker and transferred for analysis. Test results are shown in Table 10.

[0198] Table 10. Al parameter control results.

[0199] Conclusion: The parameter "Purity and related impurities", as analyzed by SE HPLC, changed slightly in all test formulations.

[0200] Test 3. Freezing and thawing (FT)

[0201] Test samples are divided into two aliquots and loaded in polymer tubes, one vial for each formulation: one vial is stored in a refrigerator at (5 ± 3) °C (input control may be transferred for analysis once for all studies at the start of storage), the remaining vials are placed in a freezer and stored at minus (16 - 20) °C. The analysis includes five freeze-thaw cycles. After the stress, the vials are removed from the freezer, kept at room temperature until the content is completely thawed; the solutions are then vortexed and transferred for analysis. Test results are shown in Table 11

[0202] Table 11. Al parameter control results.

[0203] Conclusion: based on the results in Table 11, the analytical data for the obtained formulations was processed and no trends were revealed indicating a significant negative effect of various values of the factors on protein stability.

[0204] Example 3. Interchangeability of arginine hydrochloride and arginine base.

[0205] The composition comprising the monoclonal antibody to TSLP 150 mg, arginine 21.6 mg; trehalose dihydrate 15.0 mg; poloxamer 188 0.5 mg; sodium acetate trihydrate 0.436 mg; glacial acetic acid 0.103 pl; hydrochloric acid ad pH=5.0 and water for injection ad 1 ml, was subjected to a stability study while storing test samples for 3 months, with a 1 -month intermediate control point at 2-8 C followed by comparison with the input control. Test results are shown in Table 12.

[0206] Table 12. Results of controlling the Al parameter at 2-8 °C.

[0207] Data in Table 12 demonstrates no significant changes in the monomer content, sum of high-molecular impurities, and sum of impurities following 3 -month storage of test samples as compared to the input control. This shows the stabilizing effect of the selected excipients and concentrations thereof.

Claims

Claims1. A pharmaceutical composition comprising: a. an antibody to TSLP that comprises LCDR1, LCDR2 and LCDR3 with the amino acid sequences shown in SEQ ID NO: 1, SEQ ID NO: 2 and SEQ ID NO: 3, respectively, and HCDR1, HCDR2 and HCDR3 with the amino acid sequences shown in SEQ ID NO: 4, SEQ ID NO: 5 and SEQ ID NO: 6, respectively; b. an acetate buffer; c. a stabilizer; d. an osmotic agent; e. water.

2. The pharmaceutical composition according to claim 1, wherein the antibody to TSLP comprises amino acid sequences of the variable region of the light chain with SEQ ID NO: 7, and of the heavy chain with SEQ ID NO: 8.

3. The pharmaceutical composition according to claim 1, wherein the antibody to TSLP comprises an amino acid sequence of the light chain with SEQ ID NO: 9, and of the heavy chain with SEQ ID NO: 10.

4. The pharmaceutical composition according to claim 1, wherein the antibody to TSLP is at a concentration of 100 mg / ml to 200 mg / ml.

5. The pharmaceutical composition according to claim 4, wherein the antibody to TSLP is at a concentration of 100 mg / ml, or 105 mg / ml, or 110 mg / ml, or 115 mg / ml, or 120 mg / ml, or 125 mg / ml, or 130 mg / ml, or 135 mg / ml, or 140 mg / ml, or 145 mg / ml, or 150 mg / ml, or 155 mg / ml, or 160 mg / ml, or 165 mg / ml, or 170 mg / ml, or 175 mg / ml, or 180 mg / ml, or 185 mg / ml, or 190 mg / ml, or 195 mg / ml, or 200 mg / ml.

6. The pharmaceutical composition according to claim 1, wherein the acetate buffer is at a concentration of 1 mM to 35 mM, or 1 mM to 30 mM, or 1 mM to 25 mM, or 1 mM to 20 mM, or 1 mM to 15 mM, or 1 mM to 10 mM, or 2 mM to 8 mM, or 3 mM to 7 mM, or 4 mM to 6 mM, or 4.5 mM to 5.5 mM, or 4.7 mM to 5.2 mM.

7. The pharmaceutical composition according to claim 1, wherein the acetate buffer consists of sodium acetate and glacial acetic acid.

8. The pharmaceutical composition according to claim 7, wherein sodium acetate is sodium acetate trihydrate.

9. The pharmaceutical composition according to claims 7-8, wherein(i) sodium acetate trihydrate is at a concentration of 0.2 mg / ml to 1.9 mg / ml; or(ii) sodium acetate is at a concentration of 0.05 mg / ml to 1.5 mg / ml.

10. The pharmaceutical composition according to claim 9, wherein(i) sodium acetate trihydrate is at a concentration of 0.2 mg / ml, or 0.240 mg / ml, or 0.245 mg / ml, or 0.250 mg / ml, or 0.3 mg / ml, or 0.4 mg / ml, or 0.436 mg / ml, or 0.45 mg / ml, or 0.5 mg / ml, or 0.578 mg / ml, or 0.6 mg / ml, or 0.7 mg / ml, or 0.8 mg / ml, or 0.9 mg / ml, or 1.0 mg / ml, or 1.1 mg / ml, or 1.2 mg / ml, or 1.3 mg / ml, or 1.4 mg / ml, or 1.5 mg / ml, or 1.6 mg / ml, or 1.7 mg / ml, or 1.714 mg / ml, or 1.742 mg / ml, or 1.8 mg / ml, or 1.9 mg / ml; or(ii) sodium acetate is at a concentration of 0.05 mg / ml, or 0.1 mg / ml, or 0.14 mg / ml, or 0.148 mg / ml, or 0.15 mg / ml, or 0.2 mg / ml, or 0.25 mg / ml, or 0.26 mg / ml, or 0.263 mg / ml, or 0.3 mg / ml, or 0.348 mg / ml, or 0.4 mg / ml, or 0.5 mg / ml, or 0.6 mg / ml, or 0.7 mg / ml, or 0.8 mg / ml, or 0.9 mg / ml, or 1.0 mg / ml, or 1.033 mg / ml, or 1.05 mg / ml, or 1.1 mg / ml, or 1.2 mg / ml, or 1.3 mg / ml, or 1.4 mg / ml, or 1.5 mg / ml.

11. The pharmaceutical composition according to claim 7, wherein glacial acetic acid is at a concentration of(i) 0.05 pl to 0.3 pl; or(ii) 0.01 mg / ml to 1.45 mg / ml; or(iii) ad pH 3.5 to 6.

12. The pharmaceutical composition according to claim 11, wherein glacial acetic acid is at a concentration of(i) 0.05 pl, or 0.06 pl, or 0.07 pl, or 0.08 pl, or 0.09 pl, or 0.1 pl, or 0.101 pl, or 0.102 pl, or 0.103 pl, or 0.104 pl, or 0.105 pl, or 0.11 pl, or 0.12 pl, or 0.13 pl, or 0.14 pl, or 0.15 pl, or 0.16 pl, or 0.17, or 0.18 pl, or 0.19 pl, or 0.2 pl, or 0.21 pl, or 0.22 pl, or 0.23 pl, or 0.24 pl, or 0.25 pl, or 0.26 pl, or 0.27 pl, or 0.28 pl, or 0.29 pl, or 0.3 pl; or(ii) 0.01 mg / ml, or 0.045 mg / ml, or 0.05 mg / ml, or 0.1 mg / ml, or 0.101 mg / ml, or 0.102 mg / ml, or 0.103 mg / ml, or 0.104 mg / ml, or 0.105 mg / ml, or 0.106 mg / ml, or 0.107 mg / ml, or 0.108 mg / ml, or 0.109 mg / ml, or 0.11 mg / ml, or 0.15 mg / ml, or 0.192 mg / ml, or 0.2 mg / ml, or 0.25 mg / ml, or 0.3 mg / ml, or 0.317 mg / ml, or 0.35 mg / ml, or 0.4 mg / ml, or 0.432 mg / ml, or 0.45 mg / ml, or 0.5 mg / ml, or 0.55 mg / ml, or 0.6 mg / ml, or 0.65 mg / ml, or 0.7 mg / ml, or 0.75 mg / ml, or 0.8 mg / ml, or 0.85 mg / ml, or 0.9 mg / ml, or 0.95 mg / ml, or 1.0 mg / ml, or 1.05 mg / ml, or 1.1 mg / ml, or 1.15 mg / ml, or 1.2 mg / ml, or 1.25 mg / ml, or 1.3 mg / ml, or 1.345 mg / ml, or 1.35 mg / ml, or 1.4 mg / ml, or 1.45 mg / ml; or(iii) ad pH 4.5, or ad pH 5, or ad pH 5.5.

13. The pharmaceutical composition according to claim 1, wherein the stabilizer is arginine and / or hydrochloric acid and / or an arginine salt.

14. The pharmaceutical composition according to claim 13, wherein the stabilizer is arginine and / or hydrochloric acid and / or arginine hydrochloride.

15. The pharmaceutical composition according to claim 14, wherein the stabilizer is selected from:(i) arginine and hydrochloric acid, or(ii) arginine hydrochloride.

16. The pharmaceutical composition according to claims 13-15, wherein(i) arginine is at a concentration of 5 mg / ml to 35 mg / ml; or(ii) arginine hydrochloride is at a concentration of 5 mg / ml to 35 mg / ml; or(iii) hydrochloric acid ad pH 3 to 7.

17. The pharmaceutical composition according to claim 16, wherein(i) arginine is at a concentration of 10 mg / ml to 30 mg / ml, or 15 mg / ml to 25 mg / ml, or 18 mg / ml to 23 mg / ml, or 5 mg / ml to 15 mg / ml, or 25 mg / ml to 35 mg / ml; or(ii) arginine hydrochloride is at a concentration of 5 mg / ml to 30 mg / ml, or 10 mg / ml to 30 mg / ml, or 20 mg / ml to 30 mg / ml, or 5 mg / ml to 15 mg / ml, or 15 mg / ml to 20 mg / ml, or 30 mg / ml to 35 mg / ml; or(iii) hydrochloric acid ad pH 4 to 6, or 4.5 to 5.5, or 4.8 to 5.2.

18. The pharmaceutical composition according to claim 17, wherein(i) arginine is at a concentration of 5 mg / ml, or 6 mg / ml, or 7 mg / ml, or 8 mg / ml, or 9 mg / ml, or 10 mg / ml, or 11 mg / ml, or 12 mg / ml, or 13 mg / ml, or 14 mg / ml, or 15 mg / ml, or 16 mg / ml, or 17 mg / ml, or 18 mg / ml, or 19 mg / ml, or 19.42 mg / ml, or 20 mg / ml, or 21 mg / ml, or 21.1 mg / ml, or 21.2 mg / ml, or 21.3 mg / ml, or 21.4 mg / ml, or 21.5 mg / ml, or 21.6 mg / ml, or 21.7 mg / ml, or 21.8 mg / ml, or 21.9 mg / ml, or 22 mg / ml, or 23 mg / ml, or 23.74 mg / ml, or 24 mg / ml, or 25 mg / ml, or 26 mg / ml, or 27 mg / ml, or 28 mg / ml, or 29 mg / ml, or 29.76 mg / ml, or 30 mg / ml, or 31 mg / ml, or 32 mg / ml, or 33 mg / ml, or 34 mg / ml, or 35 mg / ml; or(ii) arginine hydrochloride is at a concentration of 5 mg / ml, or 6 mg / ml, or 7 mg / ml, or 8 mg / ml, or 9 mg / ml, or 10 mg / ml, or 11 mg / ml, or 12 mg / ml, or 13 mg / ml, or 14 mg / ml, or 15 mg / ml, or 16 mg / ml, or 17 mg / ml, or 18 mg / ml, or 19 mg / ml, or 20 mg / ml, or 21 mg / ml, or 21.6 mg / ml, or 22 mg / ml, or 23 mg / ml, or 23.49 mg / ml, or 24 mg / ml, or 25 mg / ml, or 25.5 mg / ml, or 25.6 mg / ml, or 25.7 mg / ml, or 25.8 mg / ml, or 25.9 mg / ml, or 26 mg / ml, or 26.1 mg / ml, or 26.2 mg / ml, or 26.3 mg / ml, or 26.4 mg / ml, or 26.5 mg / ml, or 27 mg / ml, or 28 mg / ml, or 28.71 mg / ml, or 29 mg / ml, or 30 mg / ml, or 31 mg / ml, or 32 mg / ml, or 33 mg / ml, or 34 mg / ml, or 35 mg / ml; or hydrochloric acid ad pH to 3, or 4, or 4.5, or 5, or 5.5, or 6, or 7.

19. The pharmaceutical composition according to claims 13-18, wherein it further comprises a nonionic surfactant.

20. The pharmaceutical composition according to claim 19, wherein the non-ionic surfactant is selected from pol oxamer 188, or polysorbate 20, or polysorbate 80.

21. The pharmaceutical composition according to claim 20, wherein pol oxamer 188 is at a concentration of 0.05 mg / ml to 1.05 mg / ml; polysorbate 80 is at a concentration of 0.05 mg / ml to 1.5 mg / ml; polysorbate 20 is at a concentration of 0.05 mg / ml to 1.5 mg / ml.

22. The pharmaceutical composition according to claim 21, wherein pol oxamer 188 is at a concentration of 0,08 mg / ml to 1 mg / ml, or 0,1 mg / ml to 0,9 mg / ml, or 0,2 mg / ml to 0,8 mg / ml, or 0,3 mg / ml to 0,7 mg / ml, or 0,4 mg / ml to 0,6 mg / ml, or 0,05 mg / ml to 0,15 mg / ml, or 0,15 mg / ml to 0,25 mg / ml, or 0,25 mg / ml to 0,35 mg / ml, or 0,35 mg / ml to 0,45 mg / ml, or 0,45 mg / ml to 0,55 mg / ml, or 0,55 mg / ml to 0,65 mg / ml, or 0,65 mg / ml to 0,75 mg / ml, or 0,75 mg / ml to 0,85 mg / ml, or 0,85 mg / ml to 0,95 mg / ml, or 0,95 mg / ml to 1.05 mg / ml.

23. The pharmaceutical composition according to claim 22, wherein pol oxamer 188 is at a concentration of 0.05 mg / ml, or 0.1 mg / ml, or 0.15 mg / ml, or 0.2 mg / ml, or 0.25 mg / ml, or 0.3 mg / ml, or 0.35 mg / ml, or 0.4 mg / ml, or 0.45 mg / ml, or 0.5 mg / ml, or 0.55 mg / ml, or 0.6 mg / ml, or 0.65 mg / ml, or 0.7 mg / ml, or 0.75 mg / ml, or 0.8 mg / ml, or 0.85 mg / ml, or 0.9 mg / ml, or 0.95 mg / ml, or 1.0 mg / ml, or 1.05 mg / ml.

24. The pharmaceutical composition according to claim 1, wherein the osmotic agent is trehalose dihydrate, or trehalose, or sorbitol.

25. The pharmaceutical composition according to claim 24, wherein:(i) trehalose dihydrate is at a concentration of 5 mg / ml to 40 mg / ml; or(ii) trehalose at a concentration of 5 mg / ml to 30 mg / ml; or(iii) sorbitol at a concentration of 4 mg / ml to 10 mg / ml.

26. The pharmaceutical composition according to claim 25, wherein:(i) trehalose dihydrate is at a concentration of 5 mg / ml to 35 mg / ml, or 5 mg / ml to 30 mg / ml, or 10 mg / ml to 30 mg / ml, or 10 mg / ml to 20 mg / ml, or 20 mg / ml to 30 mg / ml; or(ii) trehalose is at a concentration of 5 mg / ml to 25 mg / ml, or 10 mg / ml to 20 mg / ml, or 10 mg / ml to 15 mg / ml, or 20 mg / ml to 30 mg / ml; or(iii) sorbitol is at a concentration of 4 mg / ml to 9 mg / ml, or 5 mg / ml to 9 mg / ml, or 6 mg / ml to 8 mg / ml, or 4 mg / ml to 6 mg / ml, or 8 mg / ml to 10 mg / ml.

27. The pharmaceutical composition according to claim 26, wherein:(i) trehalose dihydrate is at a concentration of 5 mg / ml, or 6 mg / ml, or 7 mg / ml, or 8 mg / ml, or 9 mg / ml, or 10 mg / ml, or 11 mg / ml, or 12 mg / ml, or 13 mg / ml, or 13.5 mg / ml, or 14 mg / ml, or 15 mg / ml, or 16 mg / ml, or 16.5 mg / ml, or 17 mg / ml, or 18 mg / ml, or 19 mg / ml, or 20 mg / ml, or 21 mg / ml, or 22 mg / ml, or 23 mg / ml, or 24 mg / ml, or 25 mg / ml, or 26 mg / ml, or 27 mg / ml, or 28 mg / ml, or 29 mg / ml, or 30 mg / ml, or 31 mg / ml, or 32 mg / ml, or 33 mg / ml, or 34 mg / ml, or 35 mg / ml, or 36 mg / ml, or 37 mg / ml, or 38 mg / ml, or 39 mg / ml, or 40 mg / ml; or(ii) trehalose is at a concentration of 5 mg / ml, or 6 mg / ml, or 7 mg / ml, or 8 mg / ml, or9 mg / ml, or 10 mg / ml, or 11 mg / ml, or 12 mg / ml, or 12.2 mg / ml, or 12.24 mg / ml, or 13 mg / ml, or 13.1 mg / ml, or 13.2 mg / ml, or 13.3 mg / ml, or 13.4 mg / ml, or 13.5 mg / ml, or 13.6 mg / ml, or 13.7 mg / ml, or 13.8 mg / ml, or 13.9 mg / ml, or 14 mg / ml, or 14.9 mg / ml, or 14.96 mg / ml, or 15 mg / ml, or 16 mg / ml, or 17 mg / ml, or 18 mg / ml, or 19 mg / ml, or 20 mg / ml, or 21 mg / ml, or 22 mg / ml, or 23 mg / ml, or 24 mg / ml, or 25 mg / ml, or 26 mg / ml, or 27 mg / ml, or 28 mg / ml, or 29 mg / ml, or 30 mg / ml; or(iii) sorbitol is at a concentration of 4 mg / ml, or 5 mg / ml, or 6 mg / ml, or 7 mg / ml, or 8 mg / ml, or 9 mg / ml, or 10 mg / ml.

28. The pharmaceutical composition according to claim 1, which is an antibody to TSLP 100-200 mg / ml an acetate buffer 1-20 mM a nonionic surfactant 0.05-1.05 mg / ml and / or and / or arginine, 5-35 mg / ml, and / or and / or arginine hydrochloride, 5-35 mg / ml, and / or and / or hydrochloric acid ad pH 5.0 trehalose dihydrate 5-40 mg / ml or or trehalose 5-30 mg / ml or an antibody to TSLP 100-200 mg / ml sodium acetate trihydrate 0.2-1.9 mg / ml glacial acetic acid 0.05-0.3 pl a nonionic surfactant 0.05-1.05 mg / ml and / or and / or arginine, 5-35 mg / ml, and / or and / or arginine hydrochloride, 5-35 mg / ml, and / or and / or hydrochloric acid ad pH 5.0 trehalose dihydrate 5-40 mg / ml or or trehalose 5-30 mg / ml or an antibody to TSLP 100-200 mg / ml sodium acetate trihydrate 0.2-1.9 mg / ml glacial acetic acid ad pH 4-6 a nonionic surfactant 0.05-1.05 mg / ml and / or and / or arginine, 5-35 mg / ml, and / or and / orarginine hydrochloride, 5-35 mg / ml, and / or and / or hydrochloric acid ad pH 5.0 trehalose dihydrate 5-40 mg / ml or or trehalose 5-30 mg / ml29. The pharmaceutical composition according to claim 28, which is an antibody to TSLP 100-200 mg / ml sodium acetate trihydrate 0.2-1.9 mg / ml glacial acetic acid 0.05-0.3 pl pol oxamer 188 0.05-1.05 mg / ml arginine 5-35 mg / ml trehalose dihydrate 5-40 mg / ml or or trehalose 5-30 mg / ml hydrochloric acid ad pH 5.0 or an antibody to TSLP 100-200 mg / ml sodium acetate trihydrate 0.2-1.9 mg / ml glacial acetic acid ad pH 4-6 pol oxamer 188 0.05-1.05 mg / ml arginine hydrochloride 5-35 mg / ml trehalose dihydrate 5-40 mg / ml or or trehalose 5-30 mg / ml30. The pharmaceutical composition according to claim 29, which is an antibody to TSLP 120-180 mg / ml sodium acetate trihydrate 0.2-1.0 mg / ml glacial acetic acid 0.05-0.2 pl pol oxamer 188 0.1-1.05 mg / ml arginine 10-30 mg / ml trehalose dihydrate 5-30 mg / ml or or trehalose 5-25 mg / ml hydrochloric acid ad pH 5.0 or an antibody to TSLP 120-180 mg / ml sodium acetate trihydrate 0.2-1.0 mg / ml glacial acetic acid ad pH 5.0 pol oxamer 188 0.1-1.05 mg / ml arginine hydrochloride 10-35 mg / ml trehalose dihydrate 5-30 mg / ml or or trehalose 5-25 mg / ml31. The pharmaceutical composition according to claim 30, which is an antibody to TSLP 130-170 mg / ml sodium acetate trihydrate 0.2-0.8 mg / ml glacial acetic acid 0.05-0.2 pl pol oxamer 188 0.2-0.8 mg / mlarginine 15-25 mg / ml trehalose dihydrate 10-25 mg / ml or or trehalose 10-20 mg / ml hydrochloric acid ad pH 5.0 or an antibody to TSLP 130-170 mg / ml sodium acetate trihydrate 0.2-0.8 mg / ml glacial acetic acid ad pH 5.0 pol oxamer 188 0.2-0.8 mg / ml arginine hydrochloride 15-30 mg / ml trehalose dihydrate 10-25 mg / ml or or trehalose 10-20 mg / ml32. The pharmaceutical composition according to claim 1, which is an antibody to TSLP 150.0 mg / ml sodium acetate trihydrate 0.436 mg / ml glacial acetic acid 0.103 pl pol oxamer 188 0,5 mg / ml arginine 21.6 mg / ml trehalose dihydrate 15.0 mg / ml hydrochloric acid ad pH 5.0 or an antibody to TSLP 150.0 mg / ml sodium acetate trihydrate 0.436 mg / ml glacial acetic acid ad pH 5.0 pol oxamer 188 0,5 mg / ml arginine hydrochloride 26.1 mg / ml trehalose dihydrate 15.0 mg / ml or an antibody to TSLP 100,0 mg / ml sodium acetate trihydrate 0.436 mg / ml glacial acetic acid ad pH 5.0 pol oxamer 188 0,4 mg / ml arginine hydrochloride 23.49 mg / ml trehalose dihydrate 13.5 mg / ml or an antibody to TSLP 100,0 mg / ml sodium acetate trihydrate 0.436 mg / ml glacial acetic acid ad pH 5.0 pol oxamer 188 0,4 mg / ml arginine hydrochloride 23.49 mg / ml trehalose dihydrate 16.5 mg / ml or an antibody to TSLP 100,0 mg / ml sodium acetate trihydrate 0.436 mg / ml glacial acetic acid ad pH 5.0 pol oxamer 188 0,4 mg / ml arginine hydrochloride 23.49 mg / mltrehalose dihydrate 13.5 mg / ml33. The pharmaceutical composition according to claim 1, comprising: an antibody to TSLP 150.0 mg / ml sodium acetate trihydrate 0.436 mg / ml glacial acetic acid 0.103 pl pol oxamer 188 0,5 mg / ml arginine 21.6 mg / ml trehalose dihydrate 15.0 mg / ml hydrochloric acid ad pH 5.0 per 1 ml or an antibody to TSLP 150.0 mg / ml sodium acetate trihydrate 0.436 mg / ml glacial acetic acid ad pH 5.0 pol oxamer 188 0,5 mg / ml arginine hydrochloride 26.1 mg / ml trehalose dihydrate 15.0 mg / ml per 1 ml34. The pharmaceutical composition according to claim 1, comprising, per 1 ml of solution:150 mg / ml of antibody to TSLP, arginine 21.6 mg, trehalose dihydrate 15.0 mg, poloxamer 188 0.5 mg, sodium acetate trihydrate 0.436 mg, glacial acetic acid 0.103 pl, hydrochloric acid ad pH 5.0, water for injection ad 1 ml; or150 mg / ml of antibody to TSLP, arginine hydrochloride 26.1 mg, trehalose dihydrate 15.0 mg, poloxamer 188 0.5 mg, sodium acetate trihydrate 0.436 mg, glacial acetic acid ad pH 5.0, water for injection ad 1 ml.

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