FORMULATION OF ANTIBODY AGAINST CSF-1R

Abstract

The present invention relates to a stable liquid pharmaceutical formulation comprising 40 mg / mL to 200 mg / mL of an antibody against CSF-1R; 0.01% (w / v) to 0.1% (w / v) of surfactant; 5 mM to 100 mM of a buffering agent; and 10 mM to 500 mM of at least one stabilizer; at a pH in the range of 4.5 to 7.0.

Description

FIELD OF INVENTION The present invention relates to a formulation of an antibody molecule against CSF-1R, a process for preparing said formulation, and uses of the formulation. BACKGROUND OF THE INVENTION The CSF-1 receptor (CSF-1R; colony-stimulating factor 1 receptor; synonyms: M-CSF receptor; macrophage colony-stimulating factor 1 receptor, Fms proto-oncogene, c-fms, SEQ ID NO: 13) has been known since 1986 (Coussens, L., et al., Nature 320 (1986) 277-280). CSF-1R is the receptor for CSF-1 (colony-stimulating factor 1, also called M-CSF, macrophage colony-stimulating factor) and mediates the biological effects of this cytokine (Sherr, CJ, et al., Cell 41 (1985) 665-676). Cloning of the colony-stimulating factor 1 receptor (CSF-1R) (also called c-fms) was first described in Roussel, MF, et al., Nature 325 (1987) 549-552. In that publication, CSF-1R was shown to have transforming potential as a function of changes in the C-terminus tail of the protein, including loss of phosphorylation of inhibitory tyrosine 969, which binds to Cbl and thereby regulates receptor downregulation (Lee, P.S., et al., Embo J. 18 (1999) 3616-3628). A second ligand for CSF-1R, called interleukin-34 (IL-34), was also identified (Lin, H., et al, Science 320 (2008) 807-811). Colony-stimulating factor 1 (CSF-1) and its receptor, CSF-1R, regulate the migration, differentiation, and survival of macrophages and their precursors. CSF-1R is a member of the protein tyrosine kinase receptor (PTK) family of growth factor receptors, which includes several known proto-oncogenes. Diffuse giant cell tumor of soft tissue (TGCT) (alternatively known as pigmented villonodular synovitis [PVNS]), a rare proliferative disease affecting large joints, is characterized by CSF-1 overexpression. In most patients with TGCT, chromosomal translocations involving the gene encoding CSF-1 result in overexpression of this cytokine by cells within the synovial lining.This results in massive recruitment of cells expressing CSF-1R, primarily benign mononuclear and multinuclear cells, which form the large tumor mass. Wound debridement or complete synovectomy remain the treatments of choice for TGCT, but sometimes the disorder requires mutilating surgery due to recurrent and locally destructive tumor growth. Emactuzumab, an antibody against CSF-1R, has been shown to be successful in treating this rare disease (Cassier, P., et al., Lancet Oncol. 16 (2015) 949-956). The main biological effects of CSF-1 receptor signaling are the differentiation, proliferation, migration, and survival of hematopoietic precursor cells with respect to the macrophage lineage (which includes osteoclasts). CSF-1 receptor activation is mediated by its ligands, CSF-1 (M-CSF) and IL-34. The binding of CSF-1 (M-CSF) to CSF-1 receptor induces homodimer formation and kinase activation via tyrosine phosphorylation (Li, W. et al., EMBO Journal. 10 (1991) 277-288; Stanley, ER, et al., Mol. Reprod. Dev. 46 (1997) 4-10). cefiznn / Lznz / Em The biologically active CSF-1 homodimer binds to CSF-1R within subdomains D1 to D3 of the extracellular domain of the CSF-1 receptor (CSF-1R-ECD). The CSF-1R-ECD comprises five immunoglobulin-like subdomains (designated D1 to D5). Subdomains D4 to D5 of the extracellular domain (CSF-1R-ECD) are not involved in CSF-1 binding. (Wang, Z., et al., Molecular and Cellular Biology 13 (1993) 5348-5359). Subdomain D4 is involved in dimerization (Yeung, YG., et al., Molecular & Cellular Proteomics 2 (2003) 1143-1155; Pixley, FJ., et al., Trends Cell Biol 14 (2004) 628-638). Antibodies that bind to the human CSF-1R fragment delD4 of SEQ ID NO: 11 (a human CSF-1R fragment in which the D4 subdomain of human CSF-1R-ECD has been deleted) are described in WO 2011 / 070024 A1. These antibodies block the receptor dimerization interface, where their epitope is located between D4 and D5, and are therefore unique. One such antibody is Emactuzumab or RG7155.Their CDR and VH / VL sequences are disclosed herein. Antibody molecules, as part of the protein pharmaceutical group, are highly susceptible to physical and chemical degradation. Chemical degradation includes any process that involves modifying the protein by forming or cleaving bonds, resulting in a new chemical entity. A variety of chemical reactions are known to affect proteins. These reactions can involve hydrolysis, which includes the cleavage of peptide bonds, as well as deamidation, isomerization, oxidation, and decomposition. Physical degradation refers to changes in higher-order structure and includes denaturation, adsorption to surfaces, aggregation, and precipitation. Protein stability is affected by the characteristics of the protein itself, such as the amino acid sequence and glycosylation pattern, and by external influences, such as temperature, solvent pH, excipients, interfaces, and shear rates.Therefore, it is important to define the optimal formulation conditions to protect the protein against degradation reactions during manufacturing, storage, and administration. (Manning, MC, et al. (1989), Stability of protein pharmaceuticals, Pharm Res 6(11), 903-918; Zheng, JY, Janis, LJ (2005), Influence of pH, buffer species, and storage temperature on physicochemical stability of a humanized monoclonal antibody LA298, Int. J. Pharmaceutics 308, 46-51). Obtaining stable liquid formulations of therapeutic antibodies is particularly challenging when the formulation must include antibodies at a high concentration. Therefore, it is an object of the present invention to provide a stable formulation for the anti-CSF-1R antibody with the least possible amount of excipients, allowing the desired dose and convenient administration of the antibody to a patient. The formulation of the present invention exhibits good stability after 24 months of storage at the desired storage temperature of 2 to 8°C, without the formation of visible particles, allowing for intravenous administration without the need for an in-line filter for greater ease of administration. The liquid formulation was subjected to agitation and multiple freeze-thaw cycles to simulate physical stress conditions that may occur during the manufacture or transport of the pharmaceutical product. The formulation of the present invention shows good stability after applying agitation and freeze / thaw stress. cefiznn / Lznz / Em BRIEF DESCRIPTION OF THE INVENTION The present invention relates to a stable, high-dose pharmaceutical formulation of an antibody that binds to CSF-1R, a process for preparing the formulation, and uses of the formulation. In one aspect, the invention relates to a pharmaceutical formulation comprising: mg / mL to 200 mg / mL of an antibody against CSF-1R; 0.01% to 0.1% (w / v) of a surfactant; mM to 100 mM of a buffering agent; mM to 500 mM of at least one stabilizer; at a pH in the range of 4.5 to 7.0. In one particular aspect, the antibody against CSF-1R comprises a heavy chain variable region comprising heavy chain CDR1 (CDR-H1) of SEQ ID NO: 1, CDR-H2 of SEQ ID NO: 2 and CDR-H3 of SEQ ID NO: 3; and a light chain variable region comprising light chain CDR1 (CDR-L1) of SEQ ID NO: 4, CDR-L2 of SEQ ID NO: 5 and CDR-L3 of SEQ ID NO: 6. More particularly, the antibody against CSF1R comprises a heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence of SEQ ID NO: 8. The formulation according to the invention can be provided in liquid form, lyophilized form, or in liquid form reconstituted from a lyophilized form. The antibodies against CSF-1 R useful in the pharmaceutical formulation according to the present invention are described in detail below. In a preferred embodiment, the concentration of the anti-CSF-1R antibody comprising the formulation according to the invention is in the range of 40 to 100 mg / mL, preferably 40 to 75 mg / mL, and more preferably 40 to 60 mg / mL. In particular, a concentration of 50 mg / mL is preferred. In another aspect, the pharmaceutical formulation comprises a surfactant in a concentration range of 0.01% to 0.1% (w / v). In the formulation of the invention, the surfactant concentration is described as a percentage, expressed as weight / volume (w / v). Preferably, the pharmaceutical formulation comprises a surfactant in a concentration range of 0.02% to approximately 0.05% (w / v), with a maximum preference of 0.04% (w / v). The pharmaceutical formulation according to claim 1 or 2, wherein the surfactant is a polysorbate. The preferred surfactants for use in the present invention are polyoxyethylene sorbitan fatty acid esters (i.e., polysorbates), preferably polysorbate 20 or polysorbate 80. In one particular aspect, the surfactant is polysorbate 20. In a further aspect, the pharmaceutical formulation according to the invention comprises a buffering agent. Preferably, the buffering agent is a histidine buffer. Histidine buffers are buffers that have histidine, generally L-histidine, as the buffering agent. The most preferred is an L-histidine / HCl buffer, comprising L-histidine or mixtures of L-histidine and L-histidine hydrochloride, and pH adjustment is achieved by hydrochloric acid. Unless otherwise stated, the term "histidine," when used herein to describe a buffering agent, refers to a histidine / HCl buffer, in particular, a histidine chloride buffer. In one aspect, the buffering agent has a concentration in the range of 10 to 30 mM, more particularly, 20 mM. Preferably, the pH of the formulation is in the range of 5.0 to 6.5, particularly around 6.0. Therefore, the pH of the formulation is preferably 6.0. Regardless of the buffering agent used, the pH can be adjusted with a known acid or base, for example, hydrochloric acid, acetic acid, phosphoric acid, sulfuric acid, citric acid, sodium hydroxide, and potassium hydroxide. In another aspect, the pharmaceutical formulation according to the invention comprises at least one stabilizer selected from the group consisting of salts, saccharides, and amino acids. In one particular aspect, the at least one stabilizer is a saccharide, specifically an oligosaccharide selected from the group consisting of sucrose, trehalose, lactose, maltose, and raffinose. More particularly, the saccharide is sucrose. In a preferred aspect, the stabilizer or the saccharide is present at a concentration in the range of 140 to 250 mM, particularly in the range of 210 to 230 mM. Preferably, the saccharide is present at a concentration of 220 mM. In another aspect, the pharmaceutical formulation according to the invention comprises a first stabilizer selected from the group of salts, saccharides, and amino acids, and methionine as a second stabilizer. In a preferred embodiment, the first stabilizer is present at a concentration of 120 to 300 mM, and the second stabilizer, methionine, is present at a concentration of 5 to 25 mM. More preferably, methionine is present at a concentration of 10 mM. The antibody against CSF-1R comprising the formulation of the present invention is preferably an antibody that binds to the human CSF-1R fragment delD4 (SEQ ID NO: 11) and to the human CSF-1R extracellular domain (SEQ ID NO: 12) in a ratio of 1:50 or less. In one particular aspect, the invention relates to a pharmaceutical formulation comprising 100 mg / mL of an antibody against CSF-1R; mM of L-histidine; 0.03 to 0.05% (w / v) polysorbate 20; 210 to 230 mM of sucrose; optionally, 5 to 25 mM methionine; at a pH of 6.0 ± 0.5. In one particular aspect, the pharmaceutical formulation according to the invention comprises mg / mL of an antibody against CSF-1R; mM of L-histidine; 0.04% (w / v) polysorbate 20; 220 mM of sucrose; mM of methionine; at a pH of 6.0 ± 0.5. In an additional aspect, a pharmaceutical formulation is provided herein, comprising mg / mL of an antibody against CSF-1R; cefiznn / Lznz / Em mM L-histidine; 0.04% (w / v) polysorbate 20; 220 mM of sucrose; at a pH of 6.0 ± 0.5. In another aspect, a pharmaceutical formulation is provided herein, comprising mg / mL of an antibody against CSF-1R; mM of L-histidine; 0.04% (w / v) of Poloxamer 188; 220 mM of sucrose; at a pH of 6.0 ± 0.5. In an additional aspect, a pharmaceutical formulation is provided herein, comprising mg / mL of an antibody against CSF-1R; mM of L-histidine; 0.04% (w / v) polysorbate 20; 130 mM of sodium chloride; at a pH of 6.0 ± 0.5. In another aspect, a pharmaceutical formulation is provided herein, comprising mg / mL of an antibody against CSF-1R; mM of L-histidine; 0.04% (w / v) polysorbate 20; 130 mM of sodium chloride; mM of methionine; at a pH of 6.0 ± 0.5. In an additional aspect, a pharmaceutical formulation is provided herein, comprising mg / mL of an antibody against CSF-1R; mM of L-histidine; 0.04% (w / v) of Poloxamer 188; 130 mM of sodium chloride; at a pH of 6.0 ± 0.5. In another aspect, the pharmaceutical formulation according to the invention comprises mg / mL of an antibody against CSF-1R; mM of L-histidine; 0.04% (w / v) polysorbate 20; 220 mM of sucrose; even pH of 5.5±0.5. In another aspect, the pharmaceutical formulation according to the invention comprises cefiznn / Lznz / Em mg / mL of an antibody against CSF-1R; mM of L-histidine; 0.04% (w / v) polysorbate 20; 220 mM of sucrose; mM of methionine; even pH of 5.5±0.5. In an additional aspect, the pharmaceutical formulation according to the invention comprises mg / mL of an antibody against CSF-1R; mM of L-histidine; 0.04% (w / v) of Poloxamer 188; 220 mM of sucrose; at a pH of 5.5 ± 0.5. In an additional aspect, a pharmaceutical formulation is provided herein, comprising mg / mL of an antibody against CSF-1R; mM of L-histidine; 0.04% (w / v) polysorbate 20; 130 mM of sodium chloride; at a pH of 5.5 ± 0.5. In another aspect, a pharmaceutical formulation is provided herein, comprising mg / mL of an antibody against CSF-1R; mM of L-histidine; 0.04% (w / v) polysorbate 20; 130 mM of sodium chloride; mM of methionine; even pH of 5.5±0.5. In an additional aspect, a pharmaceutical formulation is provided herein, comprising mg / mL of an antibody against CSF-1R; mM of L-histidine; 0.04% (w / v) of Poloxamer 188; 130 mM of sodium chloride; even pH of 5.5±0.5. In another aspect, the pharmaceutical formulation according to the invention comprises mg / mL of an antibody against CSF-1R; mM of L-histidine; 0.04% (w / v) polysorbate 20; 240 mM of trehalose; cefiznn / Lznz / Em at a pH of 6.0 ± 0.5. In an additional aspect, the pharmaceutical formulation according to the invention comprises mg / mL of an antibody against CSF-1R; mM of L-histidine; 0.04% (w / v) polysorbate 20; 240 mM of trehalose; mM of methionine; at a pH of 6.0 ± 0.5. In another aspect, the pharmaceutical formulation according to the invention comprises mg / mL of an antibody against CSF-1R; mM of L-histidine; 0.04% (w / v) of Poloxamer 188; 240 mM of trehalose; at a pH of 6.0 ± 0.5. In one further aspect, the invention relates to the pharmaceutical formulation described herein for use in the treatment of cancer or metastasis. In another aspect, the pharmaceutical formulation described herein is for use in the treatment of bone loss. In a further aspect, the pharmaceutical formulation described herein is for use in the treatment of inflammatory diseases, such as inflammatory bowel disease. In a preferred aspect, the pharmaceutical formulation described herein is for use in the treatment of pigmented villonodular synovitis (PVNS) or giant cell tenosynovial tumors (GCTs). In another aspect, the pharmaceutical formulation described herein is for use in combination with another therapeutic agent, in particular, another immunotherapy. In one particular aspect, the pharmaceutical formulation is for use in combination with an agent that blocks the PD-L1 / PD-1 interaction. In another aspect, the invention relates to the use of the pharmaceutical formulation described herein for the preparation of a medicament useful for treating cancer or metastases. In another aspect, the use of the pharmaceutical formulation described herein is provided for the preparation of a medicament useful in the treatment of bone loss. In a further aspect, the use of the pharmaceutical formulation described herein is provided for the preparation of a medicament useful in the treatment of inflammatory diseases, such as inflammatory bowel disease.In a preferred aspect, the use of the pharmaceutical formulation described above is provided for the preparation of a drug useful in the treatment of pigmented villonodular synovitis (PVNS) or giant cell tenosynovial tumors (TGCT). DETAILED DESCRIPTION OF THE INVENTION The present invention relates to a stable pharmaceutical formulation comprising an antibody against CPRZnn / I 7Π7 / E / YILI CSF-1R. The expression “pharmaceutical formulation” or “pharmaceutical composition” refers to preparations that are in such a form as to allow the biological activity of the active ingredients to be fully effective, and that do not contain additional components that are toxic to the subjects to whom the formulation is administered. The term “liquid” as used herein in connection with the formulation according to the invention indicates a formulation that is liquid at a temperature of at least about 2°C to about 8°C at atmospheric pressure. The term “lyophilized” as used herein in connection with the formulation according to the invention indicates a formulation prepared by freeze-drying methods known in the prior art. The solvent (e.g., water) is removed by freezing and subsequent sublimation of the ice under vacuum and desorption of the residual water at elevated temperature. Typically, the lyophilized product has a residual moisture content of about 0.1 to 5% (w / w) and is presented as a physically stable powder or cake. The lyophilized product is characterized by rapid dissolution upon the addition of a reconstitution medium. The term “reconstituted form” as used herein in connection with the formulation according to the invention indicates a formulation that is lyophilized and reconstituted upon the addition of a reconstitution medium. Suitable reconstitution media include, but are not limited to, water for injection (WFI), bacteriostatic water for injection (BWFI), sodium chloride solutions (e.g., 0.9% (w / v) NaCl), glucose solutions (e.g., 5% glucose), solutions containing surfactants (e.g., 0.01% polysorbate 20), and pH-buffered solutions (e.g., phosphate-buffered solutions). The formulation according to the invention is physiologically well tolerated, can be easily prepared, can be accurately administered, and is stable with respect to decomposition products and aggregates during storage, during repeated freeze-thaw cycles, and mechanical stress. A “stable” formulation is one in which the protein, for example, the antibody, essentially retains its physical and chemical stability and, therefore, its biological activity during storage. A “stable liquid pharmaceutical antibody formulation” is a liquid antibody formulation that shows no significant change at refrigeration (2–8°C) for at least 12 months, specifically 2 years, and more specifically, 3 years. The stability criteria are as follows: no more than 10%, specifically 5%, of the antibody monomer degrades as measured by size exclusion chromatography (SEC-HPLC). Additionally, the solution is colorless or transparent to slightly opalescent as determined by visual analysis. The protein concentration of the formulation changes by no more than + / - 10%. No more than 10%, specifically 5%, of aggregation forms. Stability is measured using methods known in the prior art, such as UV spectroscopy, size exclusion chromatography (SEC-HPLC), ion exchange chromatography (IE-HPLC), turbidimetry, and visual inspection. The term “antibody” encompasses the various forms of antibody structures, including, but not limited to, whole antibodies and antibody fragments. The antibody according to the invention is, in particular, a human antibody, humanized antibody, chimeric antibody, antibody fragment, or other genetically engineered antibody, provided that the characteristic properties according to the invention are maintained. More specifically, the antibody is a humanized monoclonal antibody, especially a recombinant humanized antibody. In one particular aspect, the humanized antibody is of the human IgG1 isotype. The term “humanized antibody” refers to antibodies in which the structure or “complementarity-determining regions” (CDRs) have been modified to comprise the CDR of an immunoglobulin with a different specificity compared to the source immunoglobulin. In a preferred embodiment, a murine CDR is grafted onto the structural region of a human antibody to prepare the “humanized antibody.” See, for example, Riechmann, L., et al., Nature 332 (1988) 323–327; and Neuberger, M.S., et al., Nature 314 (1985) 268–270. In particular, CDRs corresponding to representative sequences that recognize the antigens indicated above for chimeric antibodies are preferred.Other forms of “humanized antibodies” comprising the present invention are those in which the constant region was further modified or changed from that of the original antibody to obtain the properties according to the invention, in particular, with respect to binding to C1q and / or binding to the Fe receptor (FcR). A “CSF-1R antibody” is an antibody that binds specifically to human CSF-1R. Particularly useful CSF-1R antibodies are those described, for example, in PCT publication WO 2011 / 070024 A1 (which is incorporated herein by reference in its entirety). These antibodies are unique in that they bind to the human CSF-1R fragment delD4 (comprising the extracellular subdomains D1–D3 and D5, SEQ ID NO: 11) and to the human CSF-1R extracellular domain (CSF-1R-ECD) (comprising the extracellular subdomains D1–D5, SEQ ID NO: 12) in a ratio of 1:50 or less. Therefore, since this epitope is located within D4 and D5, it can block the receptor dimerization interface. The term “specific binding” refers to the fact that the binding is selective for the antigen and can be distinguished from unwanted or nonspecific interactions. The ability of an antigen-binding portion to bind to a specific antigenic determinant can be measured by an enzyme-linked immunosorbent assay (ELISA) or other techniques commonly used by mid-level practitioners, such as surface plasmon resonance (SPR) (assessed, for example, on a BIAcore instrument) (Liljeblad et al., Glyco J 17, 323-329 (2000)), and traditional binding assays (Heeley, Endocr Res 28, 217-229 (2002)). In one embodiment, the degree of binding of an antigen-binding portion to an unrelated protein is less than approximately 10% of the binding of the antigen-binding portion to the antigen as measured, for example, by SPR.In some embodiments, an antigen-binding portion that binds to the antigen, or an antibody comprising such an antigen-binding portion, has a dissociation constant (Kd) of < 1 μM, < 100 nM, < 10 nM, < 1 nM, < 0.1 nM, < 0.01 nM or < 0.001 nM (e.g., 108M or less, e.g., from 108M to 1013M, e.g., from 109M to 10'13M). In one particular aspect, the antibody against CSF-1R comprises a heavy chain variable region comprising the heavy chain CDR1 (CDR-H1) of SEQ ID NO: 1, the CDR-H2 of SEQ ID NO: 2, and the CDR-H3 of SEQ ID NO: 3; and a variable region of the light chain comprising light chain CDR1 (CDR-L1) of SEQ ID NO: 4, CDR-L2 of SEQ ID NO: 5, and CDR-L3 of SEQ ID NO: 6. More particularly, the antibody against CSF1R comprises a variable region of the heavy chain comprising the amino acid sequence of SEQ ID NO: 7 and a variable region of the light chain comprising the amino acid sequence of SEQ ID NO: 8. In a particularly preferred aspect, the antibody against CSF-1R is a human IgG1 antibody and comprises heavy chains comprising the amino acid sequence of SEQ ID NO: 9 and light chains comprising the amino acid sequence of SEQ ID NO: 10. This antibody is designated emactuzumab or RG7155. The term “variable region” or “variable domain” refers to the domain of an antibody heavy or light chain that participates in antibody-antigen binding. The variable domains of the heavy and light chains (VH and VL, respectively) of a native antibody generally have similar structures, with each domain comprising four conserved structural regions (FRs) and three complementarity-determining regions (CDRs). A single VH or VL domain may be sufficient to confer antigen-binding specificity. As used herein in connection with variable region sequences, “Kabat numbering” refers to the numbering system established by Kabat et al., Sequences of Proteins of Immunological Interest, 5th ed., Public Health Service, National Institutes of Health, Bethesda, MD (1991). As used herein, the term “hypervariable region” or “HVR” refers to each of the regions of an antibody variable domain that are hypervariable in sequence and that determine antigen-binding specificity. HVRs comprise the amino acid residues of the “complementarity-determining regions” (“CDRs”). Typically, antibodies comprise six CDRs: three in the VH domain (CDR-H1, CDR-H2, CDR-H3) and three in the VL domain (CDR-L1, CDR-L2, CDR-L3). Examples of CDRs herein include: (a) hypervariable loops in amino acid residues 26-32 (L1), 50-52 (L2), 91-96 (L3), 26-32 (H1), 53-55 (H2) and 96-101 (H3) (Chothiay Lesk, J. Mol. Biol. 196:901-917 (1987)); (b) CDR at amino acid residues 24-34 (L1), 50-56 (L2), 89-97 (L3), 31-35b (H1), 50-65 (H2) and 95-102 (H3) (Kabat et al., Sequences of Proteins of Immunological Interest, 5th ed., Public Health Service, National Institutes of Health, Bethesda, MD (1991)); and (c) contacts with the antigen at amino acid residues 27c-36 (L1), 46-55 (L2), 89-96 (L3), 30-35b (H1), 47-58 (H2) and 93-101 (H3) (MacCallum et al., J. Mol. Biol. 262: 732-745 (1996)). Unless otherwise stated, CDRs are determined in accordance with Kabat et al., above. A person of mid-level skill will understand that CDR designations may also be determined in accordance with Chothia, above, McCallum, above, or any other scientifically accepted system of nomenclature. “Structure” or “FR” refers to variable domain residues other than complementarity-determining regions (CDRs). The FR of a variable domain generally consists of four FR domains: FR1, FR2, FR3, and FR4. Consequently, the CDR and FR sequences generally appear in the following sequence in VH (or VL): FR1-CDR-H1(L1)-FR2-CDR-H2(L2)-FR3-CDR-H3(L3)-FR4. The term “epitope” includes any polypeptide determinant that can specifically bind to an antibody. In some embodiments, an epitope determinant includes chemically active surface clusters of molecules, such as amino acids, sugar side chains, phosphoryl or sulfonyl groups, and, in some embodiments, may have specific three-dimensional structural features and / or specific charge characteristics. An epitope is a region of an antigen that binds to an antibody. The “constant regions” or “constant domains” do not participate directly in the binding of an antibody to an antigen, but they perform various effector functions. Based on the amino acid sequence of the constant region of their heavy chains, antibodies or immunoglobulins are divided into the classes: IgA, IgD, IgE, IgG, and IgM, and several of these can be further divided into subclasses (sotypes), for example, IgG1, IgG2, IgG3, and IgG4, IgG1, and IgG2. In particular, the antibodies used in the invention are of the IgG type, more specifically, of the human IgG1 or IgG4 subtype. The term “Fe region” is used herein to define a region at the C-terminus of an immunoglobulin heavy chain that contains at least a portion of the constant region. The term includes native-sequence Fe regions and variant Fe regions. In one respect, a human IgG heavy chain Fe region extends from Cys226, or from Pro230, to the carboxyl terminus of the heavy chain. However, antibodies produced by host cells may undergo cleavage after translation of one or more, in particular, one or two amino acids at the C-terminus of the heavy chain. Therefore, an antibody produced by a host cell by expressing a specific nucleic acid molecule encoding a full-length heavy chain may include the full-length heavy chain, or it may include a cleaved variant of the full-length heavy chain.This may be the case if the two terminal C-end amino acids of the heavy chain are glycine (G446) and lysine (K447, numbered according to the Kabat EU index). Therefore, the C-end lysine (Lys447), or the C-end glycine (Gly446) and lysine (Lys447), of the Fe region may or may not be present. Heavy chain amino acid sequences that include an Fe region are indicated herein without a C-end glycine-lysine dipeptide, unless otherwise stated. In one aspect, a heavy chain that includes an Fe region as specified herein, comprising an antibody according to the invention, comprises a C-end glycine-lysine dipeptide (G446 and K447, numbered according to the Kabat EU index).In one aspect, a heavy chain including an Fe region as specified herein, comprising an antibody according to the invention, comprises a C-terminus glycine residue (G446, numbered according to Kabat's EU index). Unless otherwise specified herein, the numbering of the amino acid residues in the Fe region or constant region is carried out according to the EU numbering system, also called the EU index, as described in Kabat et al., Sequences of Proteins of Immunological Interest, 5th ed., Public Health Service, National Institutes of Health, Bethesda, MD, 1991. The concentration of the antibody against CSF-1R included in the pharmaceutical formulation is in the range of 40 mg / mL to 200 mg / mL, in particular, in the range of 40 mg / mL to 100 mg / mL, more particularly, in the range of 40 mg / mL to 60 mg / mL and, with maximum particularity, 50 mg / mL. As used herein, the term “surfactant” indicates a pharmaceutically acceptable surface-active agent. Preferably, a nonionic surfactant is used. Examples of pharmaceutically acceptable surfactants include, but are not limited to, polyoxyethylene sorbitan fatty acid esters (Tween), polyoxyethylene alkyl ethers (Brij), alkylphenyl polyoxyethylene ethers (Triton X), polyoxyethylene polyoxypropylene copolymers (Poloxamer, Pluronic), and sodium dodecyl sulfate (SDS). The preferred polyoxyethylene sorbitan fatty acid esters are polysorbate 20 (polyoxyethylene sorbitan monolaureate, marketed as Tween 20™) and polysorbate 80 (polyoxyethylene sorbitan monooleate, marketed as Tween 80™). Cefiznn / The preferred Lznz / Em polyethylene-polypropylene materials are those marketed under the names Pluronic® F68 or Poloxamer 188™.The preferred polyoxyethylene alkyl ethers are those marketed under the brand name Brij™. The preferred alkylphenyl polyoxyethylene ethers are those marketed under the brand name Triton X, most preferably p-fer-octylphenoxy polyethoxyethanol (marketed under the brand name Triton X-100™). The preferred surfactants for use in the present invention are fatty acid esters of polyoxyethylene sorbitan, preferably polysorbate 20 or polysorbate 80, most preferably polysorbate 20. Another preferred surfactant is Poloxamer 188™. As used herein, the term “buffering agent” refers to pharmaceutically acceptable excipients that stabilize the pH of a pharmaceutical preparation. Suitable buffers are known in the prior art and can be found in the literature. Preferred pharmaceutically acceptable buffers include, among others, histidine buffers, citrate buffers, succinate buffers, acetate buffers, arginine buffers, phosphate buffers, or mixtures thereof. Therefore, buffering agents are histidine salts, citrate salts, succinate salts, acetate salts, malate salts, phosphate salts, and lactate salts. Buffering agents of particular interest include L-histidine or mixtures of L-histidine and L-histidine hydrochloride or L-histidine acetate, with pH adjustment using an acid or base known in the prior art.Generally, the buffers mentioned above are used in amounts ranging from about 5 mM to about 100 mM, specifically from about 10 mM to about 30 mM, and more specifically from about 20 mM. Regardless of the buffer used, the pH can be adjusted to a value in the range of 4.5 to 7.0, and specifically to a value in the range of 5.0 to 6.0, and most specifically to pH 6.0 ± 0.03 with a known acid or base, for example, hydrochloric acid, acetic acid, phosphoric acid, sulfuric acid, citric acid, sodium hydroxide, and potassium hydroxide. The term “stabilizer” indicates a pharmaceutically acceptable excipient that protects the pharmaceutically active ingredient and / or formulation from chemical and / or physical degradation during manufacturing, storage, and application. Stabilizers include, among others, saccharides, amino acids, polyols (e.g., mannitol, sorbitol, xylitol, dextran, glycerol, arabitol, propylene glycol, polyethylene glycol), cyclodextrins (e.g., hydroxypropyl-p-cyclodextrin, sulfobutylethyl-p-cyclodextrin, β-cyclodextrin), polyethylene glycols (e.g., PEG 3000, PEG 3350, PEG 4000, PEG 6000), albumins (human serum albumin (HSA), bovine serum albumin (BSA)), salts (e.g., sodium chloride (saline), magnesium chloride, calcium chloride), chelating agents (e.g., EDTA) as defined herein.In particular, the stabilizers used in the present invention are selected from the group consisting of saccharides, polyols, and amino acids. The stabilizers may be present in the formulation in an amount of approximately 10 mM to approximately 500 mM, specifically in an amount of approximately 140 to approximately 250 mM, and more specifically in an amount of approximately 210 mM to approximately 240 mM. More specifically, sucrose or trehalose are used as stabilizers in an amount of approximately 220 mM to approximately 240 mM. As used herein, the term “saccharide” includes monosaccharides and oligosaccharides. A monosaccharide is a monomeric carbohydrate that cannot be hydrolyzed by acids, including simple sugars and their derivatives, such as amino sugars. Saccharides are usually found in their D conformation. Examples of monosaccharides include glucose, fructose, galactose, mannose, sorbose, ribose, deoxyribose, and neuraminic acid. An oligosaccharide is a carbohydrate consisting of more than one monomeric saccharide unit connected by branched glycosidic linkages or in a linear chain. The monomeric saccharide units within an oligosaccharide may be identical or different. Depending on the number of monomeric saccharide units, the oligosaccharide is a di-, tri-, tetra-, penta-saccharide, and subsequent saccharides. In contrast to polysaccharides, monosaccharides and oligosaccharides are water-soluble.Examples of oligosaccharides include sucrose, trehalose, lactose, maltose, and raffinose. The preferred saccharides for use in the present invention are sucrose and trehalose (i.e., α,αD-trehalose), with sucrose being the most preferred. Trehalose is available as trehalose dihydrate. The saccharides may be present in the formulation in an amount of about 10 to about 500 mM, preferably in an amount of about 200 to about 300 mM, more preferably in an amount of about 220 to about 250 mM, particularly in an amount of about 220 mM or about 240 mM, with the highest preference being in an amount of about 220 mM. As used herein, the term “amino acid” means a pharmaceutically acceptable organic molecule having an amino group located at the α-position relative to a carboxyl group. Examples of amino acids include, but are not limited to, arginine, glycine, ornithine, lysine, histidine, glutamic acid, aspartic acid, isoleucine, leucine, alanine, phenylalanine, tyrosine, tryptophan, methionine, serine, and proline. Preferably, the amino acid is used in each case in the L-form. Basic amino acids, such as arginine, histidine, or lysine, are preferably used in the form of their inorganic salts (advantageously, in the form of their hydrochloric acid salts, i.e., as amino acid hydrochlorides). A preferred amino acid for use in the present invention is methionine. Methionine is preferably used at a concentration of around 5 to around 25 mM, with maximum preference around 10 mM. A subgroup within stabilizers consists of lyoprotectants. The term “lyoprotectant” refers to pharmaceutically acceptable excipients that protect the labile active ingredient (e.g., a protein) from destabilization conditions during the freeze-drying process, followed by storage and reconstitution. Lyoprotectants include, among others, saccharides, polyols (e.g., sugar alcohols), and amino acids. Lyoprotectants can be selected from the group consisting of saccharides, such as sucrose, trehalose, lactose, glucose, mannose, maltose, galactose, fructose, sorbose, raffinose, neuraminic acid, amino sugars, such as glucosamine, galactosamine, and N-methylglucosamine (“Meglumine”), polyols, such as mannitol and sorbitol, and amino acids, such as arginine and glycine, or mixtures thereof.Lyoprotectants are generally used in an amount of about 10 to 500 mM, preferably in an amount of about 10 to about 300 mM and, most preferably, in an amount of about 100 to about 300 mM. Another subgroup within stabilizers consists of antioxidants. The term “antioxidant” indicates pharmaceutically acceptable excipients that prevent oxidation of the pharmaceutically active ingredient. Antioxidants include, among others, ascorbic acid, glutathione, cysteine, methionine, citric acid, and EDTA. Antioxidants can be used in amounts from approximately 0.01 to approximately 100 mM, preferably from approximately 5 to approximately 50 mM, and, most preferably, from approximately 5 to approximately 25 mM. The formulations according to the invention may also comprise one or more tonicity agents. The term “tonicity agents” refers to pharmaceutically acceptable excipients used to modulate the tonicity of the formulation. The formulation may be hypotonic, isotonic, or hypertonic. In general, isotonicity refers to the osmotic pressure of a solution, usually relative to that of human blood serum (approximately 250–350 mOsmol / kg). The formulation according to the invention may be hypotonic, isotonic, or hypertonic; however, it is preferably isotonic. An isotonic formulation is a liquid or a liquid reconstituted from a solid form, for example, a lyophilized form, and indicates a solution that has the same tonicity as another solution to which it is compared, such as physiological saline and blood serum.Suitable tonic agents include, among others, sodium chloride, potassium chloride, glycerin, and any component of the amino acid or sugar group, particularly glucose. Tonic agents are typically used in concentrations ranging from approximately 5 mM to 500 mM. Within the group of stabilizers and tonic agents, there is a subset of compounds that can function in both ways; that is, they can be both stabilizers and tonic agents. Examples of these include sugars, amino acids, polyols, cyclodextrins, polyethylene glycols, and salts. Trehalose is an example of a sugar that can act as both a stabilizer and a tonic agent. As used herein, the term “polyols” refers to pharmaceutically acceptable alcohols with more than one hydroxyl group. Suitable polyols include, but are not limited to, mannitol, sorbitol, glycerin, dextran, glycerol, arabitol, propylene glycol, polyethylene glycol, and combinations thereof. Polyols may be used in amounts from about 10 mM to about 500 mM, particularly from about 10 to about 250 mM, and more specifically from about 200 to about 250 mM. The formulations may also contain adjuvants, such as preservatives, wetting agents, emulsifiers, and dispersants. The prevention of microbial growth can be ensured through sterilization procedures and the inclusion of various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, and similar agents. Preservatives are typically used in amounts ranging from approximately 0.001 to approximately 2% (w / v). These preservatives include, but are not limited to, ethanol, benzyl alcohol, phenol, m-cresol, p-chloro-m-cresol, methyl or propyl parabens, and benzalkonium chloride. The pharmaceutical formulation may also contain adjuvants, such as preservatives, wetting agents, emulsifiers, and dispersants. The prevention of microbial growth can be ensured through sterilization procedures and the inclusion of various antibacterial and antifungal agents, for example, parabens, chlorobutanol, phenol, sorbic acid, and similar substances. Preservatives are typically used in amounts ranging from approximately 0.001 to approximately 2% (w / v). These preservatives include, but are not limited to, ethanol, benzyl alcohol, phenol, m-cresol, p-chloro-m-cresol, methyl or propyl parabens, and benzalkonium chloride. A formulation of the present invention can be administered by a variety of methods known in the prior art. As a person of average skill will appreciate, the route and / or mode of administration will vary depending on the desired results. In order to administer a formulation of the cefiznn / Lznz / Em invention by certain routes of administration, it may be necessary to dilute the formulation in a diluent. Pharmaceutically acceptable diluents include aqueous buffer solutions, saline, glucose, and Ringer's solution. Preferably, the formulation according to the invention is administered by intravenous (IV), subcutaneous (SC), or any other parenteral means of administration, such as those known in the pharmaceutical field. In a preferred embodiment, the pharmaceutical formulation is administered by IV infusion. When administered by intravenous injection, it can be given as a bolus injection or as a continuous infusion. For example, the pharmaceutical formulation of the invention can be diluted with sterile saline solution and administered using an infusion pump as commonly used in clinical settings. The phrases parenteral administration and parenterally administered as used herein refer to modes of administration other than enteric and topical administration, generally by injection, and include, but are not limited to, intravenous, intramuscular, intra-arterial, intrathecal, intracapsular, intraorbital, intracardiac, intradermal, intraperitoneal, transtracheal, subcutaneous, subcuticular, intra-articular, subcapsular, subarachnoid, intraspinal, epidural, or intrasternal injection and infusion. The pharmaceutical formulation according to the invention is appropriately administered to the patient once or during a series of treatments and can be administered to the patient at any time from diagnosis onwards; it can be administered as a single treatment or in conjunction with other drugs or treatments useful for treating the conditions as described above herein. The antibody against CSF-1R may be the sole active ingredient in the liquid pharmaceutical composition. Alternatively, the antibody against CSF-1R may be administered in combination, for example, simultaneously, sequentially, or separately, with one or more other therapeutically active ingredients. The term “active ingredient,” as used herein, refers to an ingredient with a pharmacological effect, such as a therapeutic effect, at a relevant dose. Accordingly, the antibody against CSF-1R in the liquid pharmaceutical composition may be accompanied by other active ingredients, including other antibody ingredients, for example, an antibody against CD40, an antibody against VEGF, or an agent that blocks the PD-L1 / PD-1 interaction. In particular, the agent that blocks the PD-L1 / PD-1 interaction is an anti-PD-L1 antibody or an anti-PD-1 antibody.More specifically, the PD-L1 / PD-1 interaction blocking agent is selected from the group consisting of atezolizumab, durvalumab, pembrolizumab, and nivolumab. Specifically, the PD-L1 / PD-1 interaction blocking agent is atezolizumab. Specifically, the anti-CD40 antibody is selicrelumab. In another preferred aspect, the anti-VEGF antibody is bevacizumab (Avastin). Pharmaceutical compositions adequately comprise a therapeutically effective amount of antibody. The term "therapeutically effective amount," as used herein, refers to the quantity of a therapeutic agent required to treat, ameliorate, or prevent a target disease or condition, or to exhibit a detectable therapeutic, pharmacological, or preventive effect. For any antibody, the therapeutically effective amount can be initially estimated in cell culture assays or animal models, typically rodents, rabbits, dogs, pigs, or primates. The animal model can also be used to determine the appropriate cefiznn / Lznz / Em concentration range and route of administration. This information can then be used to determine suitable dosages and routes of administration for humans. The precise therapeutically effective amount for a human subject will depend on the severity of the disease, the subject's general health, age, weight, and gender, diet, timing and frequency of administration, drug combinations, sensitivity, and tolerance / response to treatment. This amount can be determined through routine experimentation and is at the discretion of the treating physician. Specifically, the antibody against CSF-1R is administered at a (fixed) dose of 600-1200 mg, specifically at a dose of 750-1100 mg, more specifically at a dose of 750-1000 mg, and even more specifically at a dose of 900-1000 mg. A preferred dose is 1000 mg. In a preferred embodiment of the invention, the pharmaceutical formulation is for use in treatment cycles. In particular, the treatment cycles last between 2 and 4 weeks, preferably between 18 and 24 days. More preferably, the treatment cycles last approximately 3 weeks. The pharmaceutical formulation can be conveniently presented in unit-dose forms containing a predetermined amount of the antibody against CSF-1R. In one particular aspect, the pharmaceutical formulation is provided in vials for storage at 2 to 8°C. In a preferred aspect, the pharmaceutical formulation is provided in 20 mL vials. In another preferred aspect, the pharmaceutical formulation is provided in 50 mL vials. Stable formulations for in vivo administration must be sterile. This is easily achieved by filtration through sterile filtration membranes. The formulation must be fluid enough to allow administration via syringe or infusion system. In addition to water, the carrier may be an isotonic buffered saline solution, ethanol, polyol (e.g., glycerol, propylene glycol, liquid polyethylene glycol, and the like), and suitable mixtures thereof. Due to its high stability, the pharmaceutical formulation according to the invention can be administered intravenously without the need for an in-line filter, making it much more convenient to handle compared to conventional formulations that require administration with an in-line filter. In-line filters, such as Sterifix®, must be installed in the intravenous drug infusion line.To prevent the administration of any particles, air, or microorganisms that may be present in the solution or IV line, particles 5 to 20 microns in size and larger can obstruct blood flow through pulmonary capillaries, which can lead to complications such as pulmonary embolism. External particles can also cause phlebitis at the injection site, and filters can help reduce the incidence of phlebitis. The stable pharmaceutical formulation according to the invention can be prepared by methods known in the prior art, for example, ultrafiltration-diafiltration, dialysis, addition and mixing, lyophilization, reconstitution, and combinations thereof. Examples of preparations of formulations according to the invention can be found below. Thus, the invention comprises a process for preparing the formulations according to the invention. Said process comprises exchanging the antibody buffer with a diafiltration buffer containing the anticipated buffer composition, and, when required, concentrating the cefiznn / Lznz / Em antibody by diafiltration, followed by the addition of excipients (e.g., sucrose, sodium chloride, methionine) as stock solutions to the antibody solution, followed by the addition of the surfactant as a stock solution to the antibody / excipient solution, and finally, adjusting the antibody concentration to the desired final concentration using a buffer solution, wherein the final excipient and surfactant concentrations are also achieved. Alternatively, the excipients can also be added as solids to the starter solution comprising the antibody. If the antibody is in solid form, for example, a lyophilized powder, the formulation according to the invention can be prepared by first dissolving the antibody in water or buffer solution, which may optionally comprise one or more of the excipients, and then adding the other excipients as stock solutions or solids. The antibody can also advantageously be dissolved directly in a solution comprising all the other excipients.One or more of the excipients present in the formulation according to the invention may be added during or at the end of the antibody preparation process, for example, by directly dissolving the antibody in a solution comprising one, more than one, or preferably all of the excipients of the formulation in the final purification step carried out after antibody preparation. If the solution comprising the antibody and the excipients does not yet have the desired pH, the pH is adjusted by adding an acid or base, preferably using the acid or base already present in the buffer system. Sterile filtration is then performed. The stable liquid pharmaceutical formulations according to the invention may also be in a lyophilized form or in a liquid reconstituted form of the lyophilized form. The “lyophilized form” is prepared by freeze-drying methods known in the prior art. Typically, the lyophilized form has a residual moisture content of about 0.1 to 5% (w / w) and is presented as a physically stable powder or cake. The “reconstituted form” may be obtained from the lyophilized form by rapid dissolution after the addition of the reconstitution medium. Suitable reconstitution media include, among others, water for injection (WFI), bacteriostatic water for injection (BWFI), sodium chloride solutions (e.g., 0.9% (w / v) NaCl), glucose solutions (e.g., 5% (w / v) glucose), and solutions containing surfactants (e.g., 0.9% (w / v) NaCl).01% (w / v) of polysorbate 20 and pH buffered solutions (e.g., phosphate buffered solutions). The invention also comprises formulations according to the invention for use in the treatment of diseases, or the use of formulations according to the invention for the preparation of a medicament useful for treating diseases, in particular for the treatment of cancer, and in the treatment of pigmented villonodular synovitis (PVNS) or giant cell tenosynovial tumors (TGCT). As used herein, the term “cancer” may include, for example, lung cancer, non-small cell lung cancer (NSCL), bronchioloalveolar cell lung cancer, bone cancer, pancreatic cancer, skin cancer, head or neck cancer, cutaneous or intraocular melanoma, uterine cancer, ovarian cancer, rectal cancer, cancer of the anal region, stomach cancer, gastric cancer, colon cancer, breast cancer, uterine cancer, carcinoma of the fallopian tube, carcinoma of the endometrium, carcinoma of the cervix, carcinoma of the vagina, carcinoma of the vulva, Hodgkin's disease, cancer of the esophagus, cancer of the small intestine, cancer of the endocrine system, cancer of the thyroid gland, cancer of the parathyroid gland, cancer of the adrenal glands, soft tissue sarcoma, cancer of the urethra, cancer of the penis, prostate cancer, cancer of bladder, kidney or ureter cancer, renal cell carcinoma,renal pelvis carcinoma, mesothelioma, hepatocellular carcinoma, biliary carcinoma, central nervous system (CNS) neoplasms, spinal cord tumors, brainstem glioma, glioblastoma multiforme, astrocytomas, schwannomas, ependymomas, medulloblastomas, meningiomas, squamous cell carcinomas, pituitary gland adenoma, lymphoma, lymphocytic leukemia, including treatment-resistant versions of any of the above cancer types, or combinations of one or more of the above cancer types. In a preferred aspect, the cancer is breast cancer, colorectal cancer, melanoma, head and neck cancer, lung cancer, or prostate cancer. In another preferred aspect, said cancer type is breast cancer, lung cancer, colon cancer, ovarian cancer, melanoma cancer, bladder cancer, renal cancer, kidney cancer, liver cancer, head and neck cancer, colorectal cancer, pancreatic cancer, gastric carcinoma cancer.esophageal cancer, mesothelioma, prostate cancer, leukemia, lymphoma, myeloma. In a preferred embodiment, these cancer types are further characterized by the expression or overexpression of CSF-1 or CSF-IR. In another embodiment, the pharmaceutical formulation of the present invention is for use in the simultaneous treatment of primary tumors and new metastases. In a further embodiment, the pharmaceutical formulation of the invention is for use in the treatment of periodontitis, Langerhans cell histiocytosis, osteoporosis, Paget's disease of bone (PDB), decreased bone mass due to antineoplastic therapy, periprosthetic osteolysis, glucocorticoid-induced osteoporosis, rheumatoid arthritis, psoriatic arthritis, osteoarthritis, inflammatory arthritis, and inflammation. In another preferred embodiment, the pharmaceutical formulation is for use in melanoma, urinary bladder cancer (UBC), or lung cancer (e.g., non-small cell lung cancer (NSCLC)). In yet another preferred embodiment,The pharmaceutical formulation is for use in renal cell carcinoma (RCC) or head and neck squamous cell carcinoma (HNSCC). In a particularly preferred aspect, the pharmaceutical formulation of the present invention is for use in the treatment of pigmented villonodular synovitis (PVNS) or giant cell tenosynovial tumors (TGCT). cefiznn / Lznz / Em Table with sequences: SEQ ID NO: Name Sequence 1 CDR-H1 SYDIS 2 CDR-H2 VIWTDGGTNY AQKLQG 3 CDR-H3 DQRLYFDV 4 CDR-L1 RASEDVNTYV S 5 CDR-L2 AASNRYT 6 CDR-L3 QQSFSYPT 7 VH QVQLVQSGAE VKKPGASVKV SCKASGYTFT SYDISWVRQA PGQGLEWMGV IWTDGGTNYA QKLQGRVTMT TDTSTSTAYM ELRSLRSDDT AVYYCARDQR LYFDVWGQGT TVTVSS 8 VL DIQMTQSPSS LSASVGDRVT ITCRASEDVN TYVSWYQQKP GKAPKLLIYAASNRYTGVPS RFSGSGSGTD FTLTISSLQP EDFATYYCQQ SFSYPTFGQG TKLEIK 9 Heavy chain QVQLVQSGAE VKKPGASVKV SCKASGYTFT SYDISWVRQA PGQGLEWMGV IWTDGGTNYA SEQ ID NO: Nombre Secuencia QKLQGRVTMT TDTSTSTAYM ELRSLRSDDT AVYYCARDQR LYFDVWGQGT TVTVSSASTK GPSVFPLAPS SKSTSGGTAA LGCLVKDYFP EPVTVSWNSG ALTSGVHTFP AVLQSSGLYS LSSWTVPSS SLGTQTYICN VNHKPSNTKV DKKVEPKSCD KTHTCPPCPA PELLGGPSVF LFPPKPKDTL MISRTPEVTC VWDVSHEDP EVKFNWYVDG VEVHNAKTKP REEQYNSTYR WSVLTVLHQ DWLNGKEYKC KVSNKALPAP IEKTISKAKG QPREPQVYTL PPSRDELTKN QVSLTCLVKG FYPSDIAVEW ESNGQPENNY KTTPPVLDSD GSFFLYSKLT VDKSRWQQGN VFSCSVMHEA LHNHYTQKSL SLSP 10 Cadena liviana DIQMTQSPSS LSASVGDRVTITCRASEDVN TYVSWYQQKP GKAPKLLIYAASNRYTGVPS RFSGSGSGTD FTLTISSLQP EDFATYYCQQ SFSYPTFGQG TKLEIKRTVA APSVFIFPPS DEQLKSGTAS WCLLNNFYP REAKVQWKVD NALQSGNSQE SVTEQDSKDS TYSLSSTLTL SKADYEKHKV YACEVTHQGL SSPVTKSFNR GEC 11 Fragmento de CSF-1R humano delD4 IPVIEPSVPE LWKPGATVT LRCVGNGSVE WDGPPSPHWT LYSDGSSSIL STNNATFQNT GTYRCTEPGD PLGGSAAIHL YVKDPARPWN VLAQEVWFE DQDALLPCLL TDPVLEAGVS LVRVRGRPLM RHTNYSFSPW HGFTIHRAKF IQSQDYQCSA LMGGRKVMSI SIRLKVQKVI PGPPALTLVP AELVRRIRGEA AQIVCSASSV DVNFDVFLQH NNTKLAIPQQ SDFHNNRYQKVLTLNLDQVD FQHAGNYSCV ASNVQGKHST SMFFRYPPEV SVIWTFINGS GTLLCAASGY PQPNVTWLQC SGHTDRCDEA QVLQVWDDPY PEVLSQEPFH KTVQSLLTVE TLEHNQTYEC RAHNSVGSGS WAFIPISAGA HTHPPDE 12 Dominio extracelular de CSF-1R humano IPVIEPSVPE LWKPGATVT LRCVGNGSVE WDGPPSPHWT LYSDGSSSIL STNNATFQNT GTYRCTEPGD PLGGSAAIHL YVKDPARPWN VLAQEVWFE DQDALLPCLL TDPVLEAGVS LVRVRGRPLM RHTNYSFSPW HGFTIHRAKF IQSQDYQCSA LMGGRKVMSI SIRLKVQKVI PGPPALTLVP AELVRIRGEA AQIVCSASSV DVNFDVFLQH NNTKLAIPQQ SDFHNNRYQK VLTLNLDQVD FQHAGNYSCV ASNVQGKHST SMFFRWESA YLNLSSEQNL IQEVTVGEGL NLKVMVEAYP GLQGFNWTYL GPFSDHQPEP KLANATTKDT YRHTFTLSLP RLKPSEAGRY SFLARNPGGW RALTFELTLR YPPEVSVIWT FINGSGTLLC AASGYPQPNV TWLQCSGHTD RCDEAQVLQV WDDPYPEVLS QEPFHKVTVQ SLLTVETLEH NQTYECRAHN SVGSGSWAFI PISAGAHTHP PDE 13 CSF-1R humano UniProt P07333 MGPGVLLLLL VATAWHGQGI PVIEPSVPEL WKPGATVTL RCVGNGSVEW DGPPSPHWTL crfiznn / ίζηζ / Β / γι SEQ ID NO: Nombre Secuencia YSDGSSSILS TNNATFQNTG TYRCTEPGDP LGGSAAIHLY VKDPARPWNV LAQEVWFED QDALLPCLLT DPVLEAGVSL VRVRGRPLMR HTNYSFSPWH GFTIHRAKFI QSQDYQCSAL MGGRKVMSIS IRLKVQKVIP GPPALTLVPA ELVRIRGEAA QIVCSASSVD VNFDVFLQHN NTKLAIPQQS DFHNNRYQKV LTLNLDQVDF QHAGNYSCVA SNVQGKHSTS MFFRWESAY LNLSSEQNLI QEVTVGEGLN LKVMVEAYPG LQGFNWTYLG PFSDHQPEPK LANATTKDTY RHTFTLSLPR LKPSEAGRYS FLARNPGGWR ALTFELTLRY PPEVSVIWTF INGSGTLLCA ASGYPQPNVT WLQCSGHTDR CDEAQVLQVW DDPYPEVLSQ EPFHKVTVQS LLTVETLEHN QTYECRAHNS VGSGSWAFIP ISAGAHTHPP DEFLFTPVW ACMSIMALLL LLLLLLLYKY KQKPKYQVRW KlIESYEGNS YTFIDPTQLP YNEKWEFPRN NLQFGKTLGA GAFGKWEAT AFGLGKEDAV LKVAVKMLKS TAHADEKEAL MSELKIMSHL GQHENIVNLL GACTHGGPVL VITEYCCYGD LLNFLRRKAE AMLGPSLSPG QDPEGGVDYK NIHLEKKYVR RDSGFSSQGV DTYVEMRPVS TSSNDSFSEQ DLDKEDGRPL ELRDLLHFSS QVAQGMAFLA SKNCIHRDVA ARNVLLTNGH VAKIGDFGLA RDIMNDSNYI VKGNARLPVK WMAPESIFDC VYTVQSDVWS YGILLWEIFS LGLNPYPGIL VNSKFYKLVK DGYQMAQPAF APKNIYSIMQ ACWALEPTHR PTFQQICSFL QEQAQEDRRE RDYTNLPSSS RSGGSGSSSSELEEESSSEH LTCCEQGDIA QPLLQPNNYQ FC cefiznn / Lznz / E / YL EXAMPLES The liquid drug product formulations for intravenous (iv) administration according to the invention were carried out as follows. Example 1: Preparation of liquid formulations for initial formulation screening The liquid formulations huMAb CSF-1R F1 to F16 as detailed in Table 1 were prepared at a protein concentration of 50 mg / mL. The anti-CSF-1R antibody (emactuzumab) was prepared using techniques generally known for the production of recombinant proteins and as described in WO 2011 / 070024. To prepare the pharmaceutical formulations according to the examples, the antibody was provided at a concentration of approximately 20 mg / mL in 20 mM histidine buffer (an L-histidine / HCl buffer) at a pH of approximately 5.5. The anti-CSF-1R antibody used in the examples is a humanized antibody comprising heavy chains comprising the amino acid sequence of SEQ ID NO: 9 and light chains comprising the amino acid sequence of SEQ ID NO: 10. The excipients in the formulation according to the present invention are widely used in practice and are known to the average person in the trade. Therefore, it is not necessary to analyze them in detail herein. For the preparation of the liquid formulations, the anti-CSF-1R antibody was exchanged with a diafiltration buffer containing the anticipated buffer composition and concentrated by ultrafiltration to an antibody concentration of approximately 80 mg / mL. After ultrafiltration, excipients (e.g., sucrose, methionine) were added as stock solutions to the antibody solution. The surfactant was then added as a 125x stock solution. Finally, the protein concentration was adjusted with buffer to a final anti-CSF-1R antibody concentration of approximately 50 mg / mL. All formulations were sterilized by filtration through 0.22 µm low-protein-binding filters and aseptically loaded into sterile 6 mL glass vials sealed with ETFE (ethylene tetrafluoroethylene copolymer) coated rubber stoppers and alucrimp caps. The loading volume was approximately 2.4 mL. These formulations were stored under different ICH climatic conditions (5°C, 25°C, and 40°C) for varying time intervals and subjected to stress by shaking (1 week at a shaking frequency of 200 min⁻¹ at 5°C and 25°C) and freeze-thaw stress methods (five cycles at -80°C / +5°C). cefiznn / ίζηζ / Β / γι Table 1 - Summary of the different formulations pH Buffer Protein Concentration PS20 (% w / v) P188 (% w / v) Methionine (mM) Sucrose (mM) Trehalose (mM) NaCl (mM) Filling Volume (mL) F1 20 mM histidine-HCl 6.0 50 mg / mL 0.04 220 2.7 F2 0.04 10 220 F3 0.04 220 F4 0.04 130 F5 0.04 10 130 F6 0.04 130 F7 20 mM histidine-acetate 5.5 0.04 220 F8 0.04 10 220 F9 0.04 220 F10 0.04 130 F11 0.04 10 130 F12 0.04 130 F13 20 mM histidine-HCl 6.0 25 mg / mL 0.02 240 F14 50 mg / mL 0.04 240 F15 0.04 10 240 F16 0.04 240 The samples were analyzed before and after applying the tensile tests using the following analytical methods UV Spectrophotometry Size exclusion chromatography (SEC) • Ion exchange chromatography (IEC) • Clarity and opalescence of the solution • Analytical protein A chromatography • Visual inspection UV spectroscopy, used for protein content determination, was performed on a Perkin Elmer A35 UV spectrophotometer in a wavelength range of 240 nm to 400 nm. Pure protein samples were diluted to approximately 0.5 mg / mL with the corresponding formulation buffer. The protein concentration was calculated according to Equation 1. cefiznn / Lznz / E / YL .4(280) - .4(320) x dil factor. / mS / Equation 1: Protein content The UV light absorption at 280 nm was corrected for light scattering at 320 nm and multiplied by the dilution factor, which was determined from the weighted masses and densities of the pure sample and the dilution buffer. The numerator was divided by the product of the cuvette path length d and the extinction coefficient ε. Size exclusion chromatography (SEC) was used to detect soluble high molecular weight species (aggregates) and low molecular weight (LMW) hydrolysis products in the formulations. The method was performed on a Waters Alliance 2695 HPLC instrument with a Waters W2487 dual absorbance detector and equipped with a Waters BioSuite 250 column. Intact monomer, aggregates, and hydrolysis products were separated by isocratic elution using 0.2 M K₂HPO₄ and 0.25 M KCl, pH 7.0, as the mobile phase, and were detected at a wavelength of 280 nm. Ion-exchange chromatography (IEC) was performed to detect chemical degradation products that altered the pure antibody charge in the formulations. The method used a Waters Alliance 2695 HPLC instrument with a Waters W2487 dual absorbance detector and was equipped (detection wavelength 280 nm) with a MabPac SCX-10 column, 4 mm x 150 mm. Mobile phases A, B, and C, respectively, were used as 5 mM MES, 15 mM NaCl, pH 6.5; 5 mM BICINE, 30 mM NaCl, pH 8.5; and 5 mM BICINE, 1 M NaCl, pH 8.5, at a flow rate of 0.5 mL / min. Gradient program: Time % of A % of B % of C 0.0 100 0 0 5.0 100 0 0 50.0 0 100 0 54.0 0 100 0 55.0 100 0 0 65.0 100 0 0 80.0 0 0 100 85.0 0 0 100 86.0 100 0 0 96.0 100 0 0 Clarity and opalescence were measured as formazin turbidity units (FTU) using nephelometry. The pure sample was transferred to an 11 mm diameter clear glass tube and placed in a HACH 2100AN turbidimeter. Analytical protein A chromatography was performed to monitor the oxidation status of the four conserved methionine side chains in the Fe portion of the anti-CSF-1 R antibody. The method was carried out on a Waters Alliance 2695 HPLC instrument with a Waters W2487 dual absorbance detector (detection wavelength 280 nm), equipped with a Poros A720 4.6 mm x 50 mm column from Applied Biosystems, USA. Gibco PBS, Invitrogen, and 0.1 M acetic acid, 0.15 M sodium chloride, pH 2.8 were used as mobile phases A and B, respectively, at a flow rate of 2.0 mL / min. Gradient program: cefiznn / ίζηζ / Β / γι Time (min) % of mobile phase A % of mobile phase B 1 0.01 100 0 2 10 100 0 3 40 40 60 4 41 0 100 5 51 0 100 6 52 100 0 7 62 100 0 The samples were inspected for the presence of visible particles using a Simpiex Ampoule OPTIMA! testing apparatus. The stability test results for formulations F1 through F16 are provided in the tables below. Formulation F2 was determined to be the most favorable for achieving maximum antibody stability and particle-free antibody formulations. Example 1: Compositions and stability data of liquid formulations of anti-CSF-1 R antibody F1 is a liquid formulation containing the anti-CSF-1 R antibody at a concentration of 50 mg / mL, 20 mM histidine HCl, 220 mM sucrose, and 0.04% polysorbate 20, at pH 6.0 Storage Condition Storage Time Protein Concentration (mg / mL) Size Exclusion HPLC Ion Exchange HPLC Turbidity (FTU) Visible Particles HMW (%) Monomer (%) LMW (%) Main Peak (%) Acid Species (%) Basic Species (%) - Initial 45.2 0.7 99.2 0.1 72.13 24.5 3.38 10 Particle-free Agitation 5°C 1 week 44.7 0.8 98.7 0.5 Particle-free Agitation 25°C 1 week 45 0.8 98.6 0.6 Particle-free Freeze / thaw 4 cycles 44.5 0.8 98.7 0.5 Particle-free 5°C 6 months 45.7 1.0 98.9 0.1 72.11 23.63 4.26 9.3 Particle-free 25°C 6 months 45.2 1.5 96.4 2.2 61.52 34.18 4.30 9.5 Particle-free Storage condition Storage time Analytical protein chromatography Fe methionine oxidation (%) - Initial 4.2 5°C 6 months 4.5 25°C 6 months 6.2 F2 is a liquid formulation containing the anti-CSF-1 R antibody at a concentration of 50 mg / mL, 20 mM histidine HCl, 220 mM sucrose, 0.04% polysorbate 20, and 10 mM methionine, at pH 6.0 Storage Condition Storage Time Protein Concentration (mg / mL) Size Exclusion HPLC Ion Exchange HPLC Turbidity (FTU) Visible Particles HMW (%) Monomer (%) LMW (%) Main Peak (%) Acidic Species (%) Basic Species (%) - Initial 45.4 0.7 99.3 0.1 71.1 25.2 3.7 9.7 Particle-free Agitation 5°C 1 week 45.0 0.8 98.8 0.5 10.2 Particle-free Agitation 25°C 1 week 45.3 0.8 98.7 0.6 11.1 Particle-free Freeze / thaw 4 cycles 45.4 0.8 98.7 0.5 9.7 Particle-free 5°C 6 months 45.9 0.9 99.0 0.1 71.9 23.7 4.4 9.3 Particle-free 25°C 6 months 45.5 1.1 96.7 2.2 62.72 32.72 4.6 9.6 Particle-free 5°C 9 months 49.3 0.8 98.5 0.7 71.8 23.2 5.1 10.4 Particle-free 25°C 9 months 49.1 1.1 96.8 2.1 58.4 36.4 5.2 8.9 Particle-free 5°C 12 months 49.7 0.8 99.1 0.1 71.6 23.4 5.1 9.7 Particle-free 25°C 12 months 49.1 1.1 96.1 2.8 54.5 40.8 4.8 9.7 Particle-free 5°C 24 months 52.2 0.8 98.2 0.9 71.4 23.9 4.7 9.7 Particle-free -20°C* 24 months 52.1 0.7 99.3 0.0 73.1 22.2 4.8 9.7 -40°C* 24 months 51.9 0.7 99.3 0.0 73.6 22.1 4.3. 9.8. * in a stainless steel container Storage condition Storage time Analytical protein chromatography Fe methionine oxidation (%) - Initial 4.0 5°C 6 months 3.9 25°C 6 months 3.9 Storage Condition Storage Time Methionine Content (mM) PS20 Content (mg / mL) Potency - Initial 0.41 5°C 24 months 10 0.33 99% -20°C* 24 months 11.1 0.38 100% -40°C* 24 months 10.5 0.37 98% crfiznn / ίζηζ / E / γι * in a stainless steel container F3 is a liquid formulation containing the anti-CSF-1R antibody at a concentration of 50 mg / mL, 20 mM histidine HCI, 220 mM sucrose, and 0.04% Poloxamer 188, at pH 6.0 Storage Condition Storage Time Protein Concentration (mg / mL) Size Exclusion HPLC Ion Exchange HPLC Turbidity (FTU) Visible Particles HMW (%) Monomer (%) LMW (%) Main Peak (%) Acidic Species (%) Basic Species (%) - Initial 45.4 0.7 99.3 0.1 71.4 25.1 3.5 9.7 Particle-free Agitation 5°C 1 week 45.9 0.8 98.7 0.5 10.1 Particle-free Agitation 25°C 1 week 45.2 0.8 98.6 0.6 10.8 Particle-free Freeze / thaw 4 cycles 45.3 0.8 98.7 0.5 10.0 Particle-free 5°C 6 months 45.9 1.0 98.9 0.1 72.16 23.7 4.1 9.3 Particle-free 25°C 6 months 45.3 1.5 96.3 2.2 61.68 34.0 4.3 9.7 Particle-free Storage condition Storage time Analytical protein chromatography Fe methionine oxidation (%) - Initial 3.8 5°C 6 months 5.0 25°C 6 months 6.3 F4 is a liquid formulation containing the anti-CSF-1 R antibody at a concentration of 50 mg / mL, 20 mM histidine HCl, 130 mM NaCl, and 0.04% polysorbate 20, at pH 6.0 Storage Condition Storage Time Protein Concentration (mg / mL) Size Exclusion HPLC Ion Exchange HPLC Turbidity (FTU) Visible Particles HMW (%) Monomer (%) LMW (%) Main Peak (%) Acidic Species (%) Basic Species (%) - Initial 47.8 0.7 99.2 0.1 71.2 25.2 3.6 22.7 Particle-free Agitation 5°C 1 week 47.6 0.8 98.7 0.5 23.1 Particle-free Particles Agitation 25°C 1 week 47.3 0.9 98.6 0.6 23.7 Particle-free Freeze / thaw 5 cycles 47.4 0.8 98.7 0.5 9.8 Particle-free 5°C 6 months 47.6 1.1 98.8 0.1 72.3 23.4 4.2 23.2 With many particles 25°C 6 months 47.0 1.6 96.3 02.2 63.1 32.4 4.5 24.9 With many particles cefiznn / Lznz / E / YL Storage condition Storage time Analytical protein chromatography Fe methionine oxidation (%) - Initial 3.9 5°C 6 months 5.1 25°C 6 months 6.0 F5 is a liquid formulation containing the anti-CSF-1 R antibody at 50 mg / mL, 20 mM histidine HCl, 130 mM NaCl, 0.04% polysorbate, and 10 mM methionine at pH 6.0 Storage Condition Storage Time Protein Concentration (mg / mL) Size Exclusion HPLC Ion Exchange HPLC Turbidity (FTU) Visible Particles HMW (%) Monomer (%) LMW (%) Main Peak (%) Acidic Species (%) Basic Species (%) - Initial 47.6 0.7 99.3 0.1 71.6 24.8 3.8 23.1 Particle-free Agitation 5°C 1 week 47.8 0.8 98.7 0.5 23.2 Particle-free Agitation 25°C 1 week 47.1 0.8 98.7 0.5 23.4 Particle-free Freeze / thaw 5 cycles 47.6 0.8 98.7 0.5 23.3 Particle-free 5°C 6 months 47.4 1.0 99.0 0.1 71.6 23.0 5.3 22.8 With many particles 25°C 6 months 47.8 1.2 96.6 2.1 63.7 31.7 4.6 22.8 With many particles Storage condition Storage time Analytical protein chromatography Fe methionine oxidation (%) - Initial 3.8 5°C 6 months 3.6 25°C 6 months 4.3 F6 is a liquid formulation containing the anti-CSF-1 R antibody at a concentration of 50 mg / mL, 20 mM histidine HCl, 130 mM NaCl, and 0.04% Poloxamer 188, at pH 6.0 Storage Condition Storage Time Protein Concentration (mg / mL) Size Exclusion HPLC Ion Exchange HPLC Turbidity (FTU) Visible Particles HMW (%) Monomer (%) LMW (%) Main Peak (%) Acidic Species (%) Basic Species (%) - Initial 47.4 0.8 99.2 0.1 71.6 24.8 3.6 23.8 Particle-free Agitation 5°C 1 week 47.5 0.8 98.7 0.5 36.6 Particle-free Agitation 25°C 1 week 47.4 0.9 98.6 0.6 23.9 Particle-free Freeze / thaw 5 cycles 47.1 0.8 98.7 0.5 22.8 Particle-free 5°C 6 months 47.6 1.1 98.8 0.1 71.9 23.6 4.5 23.6 With many particles 25°C 6 months 47.3 1.6 96.3 2.1 63.2 32.4 4.5 23.5 With many particles Storage condition Storage time Analytical protein chromatography Fe methionine oxidation (%) - Initial 3.8 5°C 6 months 4.9 25°C 6 months 5.9 F7 is a liquid formulation containing the anti-CSF-1 R antibody at a concentration of 50 mg / mL, 20 mM histidine acetate, 220 mM sucrose, 0.04% polysorbate 20, at pH 5.5 Storage Condition Storage Time 0 Protein Concentration (mg / mL) Size Exclusion HPLC Ion Exchange HPLC Turbidity (FTU) Visible Particles HMW (%) Monomer (%) LMW (%) Main Peak I (%) Acidic Species (%) Basic Species (%) - Initial 46.3 0.7 99.3 0.1 71.8 24.5 3.7 10.0 Particle-free Agitation 5°C 1 week 46.2 0.8 98.7 0.5 Particle-free Agitation 25°C 1 week 46 0.8 98.6 0.5 Particle-free Freeze / Thaw 0 5 cycles 46 0.8 98.7 0.5 Particle-free 5°C 6 months 45.8 1.0 98.9 0.1 72.1 23.19 4.7 10.6 Essentially free of Particles 25°C 6 months 46.2 1.6 96.1 2.3 58.4 36.6 5.1 11.2 Essentially particle-free cefiznn / Lznz / E / YL Storage condition Storage time Analytical protein chromatography Fe methionine oxidation (%) - Initial 3.9 5°C 6 months 4.7 25°C 6 months 6.7 F8 is a liquid formulation containing the anti-CSF-1 R antibody at a concentration of 50 mg / mL, 20 mM histidine acetate, 220 mM sucrose, 0.04% polysorbate, and 20.10 mM methionine at pH 5.5. Storage Condition Storage Time Protein Cone (mg / mL) Size Exclusion HPLC Ion Exchange HPLC Turbidity (FTU) Visible Particles HMW (%) Monomer (%) LMW (%) Main Peak (%) Acid Species (%) Basic Species (%) - Initial 46.2 0.7 99.3 0.1 71.6 24.5 3.9 12.7 Particle-free Agitation 5°C 1 week 46.3 0.8 98.8 0.5 9.2 Particle-free Agitation 25°C 1 week 46.1 0.8 98.7 0.5 9.4 Particle-free Freeze / thaw 5 cycles 46.4 0.8 98.8 0.5 8.7 Particle-free 5°C 6 months 46.1 0.9 99.0 0.1 72.5 23.1 4.4 8.7 Particle-free 25°C 6 months 46.0 1.2 96.5 2.3 59.6 35.5 4.8 8.1 Particle-free Storage condition Storage time Analytical protein chromatography Fe methionine oxidation (%) - Initial 3.9 5°C 6 months 4.1 25°C 6 months 4.3 F9 is a liquid formulation containing the anti-CSF-1 R antibody at a concentration of 50 mg / mL, 20 mM histidine acetate, 220 mM sucrose, and 0.04% Poloxamer 188, at pH 5.5. Storage Condition Storage Time Protein Cone (mg / mL) Size Exclusion HPLC Ion Exchange HPLC Turbidity (FTU) Visible Particles HMW (%) Monomer (%) LMW (%) Main Peak (%) Acidic Species (%) Basic Species (%) - Initial 46.2 0.7 98.3 0.1 71.0 24.6 4.4 9.0 Particle Free Agitation 5°C 1 week 46.3 0.8 98.7 0.5 9.1 Particle-free Agitation 25°C 1 week 46.1 0.8 98.7 0.5 9.1 Particle-free Freeze / thaw 5 cycles 45.7 0.8 98.8 0.4 9.0 Particle-free 5°C 6 months 46.2 1.0 98.9 1.0 72.13 23.22 4.7 8.7 Particle-free 25°C 6 months 46.0 1.6 96.1 1.6 58.3 36.6 5.1 9.2 Particle-free cefiznn / Lznz / E / YL Storage condition Storage time Analytical protein chromatography Fe methionine oxidation (%) - Initial 3.8 5°C 6 months 4.4 25°C 6 months 6.8 F10 is a liquid formulation containing the anti-CSF-1R antibody at a concentration of 50 mg / mL, 20 mM histidine acetate, 130 mM NaCl, 0.04% polysorbate 20, at pH 5.5 Storage Condition Storage Time Protein Concentration (mg / mL) Size Exclusion HPLC Ion Exchange HPLC Turbidity (FTU) Visible Particles HMW (%) Monomer (%) LMW (%) Main Peak (%) Acidic Species (%) Basic Species (%) - Initial 48.5 0.7 99.2 0.1 71.2 24.7 4.2 24.4 Particle-free Agitation 5°C 1 week 48.5 0.8 98.7 0.5 24.6 Particle-free Agitation 25°C 1 week 48.3 0.8 98.6 0.5 24.9 Particle-free Freeze / thaw 5 cycles 48.3 0.8 98.8 0.5 23.7 Particle-free 5°C 6 months 48.2 1.2 98.7 0.1 72.4 23.1 4.5 24.4 With many particles 25°C 6 months 48.0 1.9 95.7 2.4 60.3 34.1 5.6 24.2 With many particles Storage condition Storage time Analytical protein chromatography Fe methionine oxidation (%) - Initial 3.7 5°C 6 months 4.7 25°C 6 months 5.8 F11 is a liquid formulation containing the anti-CSF-1R antibody at a concentration of 50 mg / mL, 20 mM histidine acetate, 130 mM NaCl, 0.04% polysorbate, and 10 mM methionine at pH 5.5. Storage Condition Storage Time Protein Cone (mg / mL) Size Exclusion HPLC Ion Exchange HPLC Turbidity (FTU) Visible Particles HMW (%) Monomer (%) LMW (%) Main Peak (%) Acidic Species (%) Basic Species (%) - Initial 48.4 0.7 99.3 0.1 71.4 24.5 4.2 23.7 Particle-free Agitation 5°C 1 week 48.7 0.7 98.8 0.5 23.7 Particle-free Agitation 25°C 1 week 48.2 0.8 98.7 0.6 23.5 Particle-free Freeze / thaw 5 cycles 48.3 0.8 98.87 0.5 23.4 Particle-free 5°C 6 months 48.6 1.0 98.93 0.1 72.6 22.6 4.8 23.7 With many particles 25°C 6 months 48.2 1.4 96.1 2.4 60.9 33.6 5.5 24.0 With many particles cefiznn / Lznz / E / YL Storage condition Storage time Analytical protein chromatography Fe methionine oxidation (%) - Initial 4.0 5°C 9 months 4.0 25°C 9 months 4.3 F12 is a liquid formulation containing the anti-CSF-1 R antibody at a concentration of 50 mg / mL, 20 mM histidine acetate, 130 mM NaCl, and 0.04% Poloxamer 188, at pH 5.5. Storage Condition Storage Time Protein Cone (mg / mL) Size Exclusion HPLC Ion Exchange HPLC Turbidity (FTU) Visible Particles HMW (%) Monomer (%) LMW (%) Main Peak (%) Acid Species (%) Basic Species (%) - Initial 48.3 0.7 99.2 0.1 71.6 24.4 4.0 24.1 Particle-free Agitation 5°C 1 week 48.5 0.8 98.6 0.54 24.9 Particle-free Agitation 25°C 1 week 48.2 0.8 98.6 0.6 25.0 Particle-free Freeze / thaw 5 cycles 47.9 0.8 98.7 0.5 23.7 Particle-free 5°C 6 months 47.0 1.2 98.7 0.1 72.8 23.0 4.217.9 24.8 With many particles 25°C 6 months 48.2 1.95 95.7 2.4 60.6 34.0 5.4 25.2 With many particles Storage condition Storage time Analytical protein chromatography Fe methionine oxidation (%) - Initial 4.1 5°C 6 months 4.7 25°C 6 months 6.352 cefiznn / Lznz / E / YL F13 is a liquid formulation with the anti-CSF-1R antibody composition of 25 mg / mL, 20 mM histidine HCI, 240 mM trehalose, 0.02% polysorbate 20, at pH 6.0 Storage Condition Storage Time Protein Concentration (mg / mL) Size Exclusion HPLC Ion Exchange HPLC Turbidity (FTU) Visible Particles HMW (%) Monomer (%) LMW (%) Main Peak (%) Acid Species (%) Basic Species (%) - Initial 23.1 0.6 99.3 0.1 71.1 25.2 3.7 7.1 Particle-free Agitation 5°C 1 week 22.9 0.7 98.7 0.5 7.6 Particle-free Agitation 25°C 1 week 22.8 0.7 98.7 0.6 7.5 Particle-free Freeze / thaw 5 cycles 22.9 0.7 98.8 0.5 7.1 Particle-free 5°C 6 months 22.9 0.9 99.0 0.1 72.3 23.7 4.0 7.1 Particle-free 25°C 6 months 22.8 1.1 96.7 2.2 61.8 33.9 4.3 7.1 Particle-free Storage condition Storage time Analytical protein chromatography Fe methionine oxidation (%) - Initial 3.6 5°C 6 months 4.6 25°C 6 months 5.8 F14 is a liquid formulation containing the anti-CSF-1 R antibody at a concentration of 50 mg / mL, 20 mM histidine HCl, 240 mM trehalose, and 0.04% polysorbate 20, at pH 6.0 Storage Condition Storage Time Protein Concentration (mg / mL) Size Exclusion HPLC Ion Exchange HPLC Turbidity (FTU) Visible Particles HMW (%) Monomer (%) LMW (%) Main Peak (%) Acidic Species (%) Basic Species (%) - Initial 45.5 0.7 99.3 0.1 72.0 24.7 3.4 9.7 Particle-free Agitation 5°C 1 week 45.1 0.8 98.7 0.5 9.9 Particle-free Agitation 25°C 1 week 45.0 0.8 98.6 0.6 10.2 Particle-free Particles Freezing / thawing 5 cycles 45.1 0.8 98.7 0.5 10.0 Particle-free 5°C 6 months 45.1 1.0 98.9 0.1 72.3 23.6 4.1 9.6 Particle-free 25°C 6 months 44.9 1.5 96.4 2.2 62.0 33.7 4.3 9.5 Particle-free crfiznn / ίζηζ / E / γι Storage condition Storage time Analytical protein chromatography Fe methionine oxidation (%) - Initial 2.1 5°C 6 months 4.2 25°C 6 months 5.1 F15 is a liquid formulation with the anti-CSF-1R antibody composition of 50 mg / mL, 20 mM histidine HCI, 240 mM trehalose, 0.04% polysorbate 20.10 mM methionine at pH 6.0 Storage Condition Storage Time 0 Protein Concentration (mg / mL) Size Exclusion HPLC Ion Exchange HPLC Turbidity (FTU) Visible Particles HMW (%) Monomer (%) LMW (%) Main Peak I (%) Acidic Species (%) Basic Species (%) - Initial 45.4 0.7 99.3 0.1 71.6 24.8 3.7 9.3 Particle-free Agitation 5°C 1 week 44.9 0.8 98.7 0.5 10.0 Particle-free Agitation 25°C 1 week 44.9 0.8 98.6 0.6 10.5 1.1 Essentially particle-free Freeze / thaw 0 5 cycles 45.2 0.8 98.87 0.5 9.8 Particle-free 5°C 6 months 45.0 0.9 99.0 0.1 72.7 23.3 4.0 9.5 Essentially particle-free 25°C 6 months 45.1 1.2 96.7 2.1 62.7 32.6 4.7 9.3 Particle-free Storage condition Storage time Analytical protein chromatography Fe methionine oxidation (%) - Initial 3.7 5°C 6 months 3.6 25°C 6 months 4.5 F16 is a liquid formulation containing the anti-CSF-1 R antibody at a concentration of 50 mg / mL, 20 mM histidine HCI, 240 mM trehalose, and 0.04% Poloxamer 188, at pH 6.0 Storage Condition Storage Time 0 Protein Concentration (mg / mL) Size Exclusion HPLC Ion Exchange HPLC Turbidity (FTU) Visible Particles HMW (%) Monomer (%) LMW (%) Main Peak I (%) Acidic Species (%) Basic Species (%) - Initial 45.3 0.7 99.2 0.1 71.2 24.7 4.1 9.6 Particle-free Agitation 5°C 1 week 45.0 0.8 98.7 0.5 10.1 Particle-free Agitation 25°C 1 week 45.1 0.8 98.7 0.5 10.1 Particle-free Freeze / Thaw 0 5 cycles 44.6 0.8 98.7 0.5 10.0 Particle-free 5°C 6 months 45.1 1.0 98.9 0.1 72.4 23.7 3.9 9.4 Particle-free 25°C 6 months 45.4 1.5 96.4 2.2 61.8 33.7 18.6 9.7 Essentially particle-free cefiznn / Lznz / E / YL Storage condition Storage time Analytical protein chromatography Fe methionine oxidation (%) - Initial 3.8 5°C 6 months 4.7 25°C 6 months 6.4 Example 2: Compositions and stability data of liquid anti-CSF1R antibody drug products comprising formulation F2 in vials Two pharmaceutical products were prepared based on formulation F2 and demonstrated good stability. Pharmaceutical product 1 contained 9.0 mL of formulation F2 in a 20 mL glass vial, and pharmaceutical product 2 contained 46.4 mL of formulation F2 in a 50 mL glass vial. Drug product stability data 1 (F2) Storage condition 0 Storage time 0 Protein concentration (mg / mL) Size exclusion HPLC Ion exchange HPLC Turbidity (NTU) Visible particles HMW (%) Monomer (%) LMW (%) Main peak (%) Acid species (%) Basic species (%) - Initial 51.6 0.9 99.1 0.0 70.1 24.4 5.5 8.6 Particle-free 40°C+75% RH 1 week 52.1 1.1 98.8 0.1 66.6 27.6 5.9 8.9 Particle-free 40°C+75% RH 2 weeks 52.0 1.2 98.6 0.2 63.1 31.1 5.9 8.9 Storage condition 0 Storage time 0 Protein concentration (mg / mL) Size exclusion HPLC Ion exchange HPLC Turbidity (NTU) Visible particles HMW (%) Monomer (%) LMW (%) Main peak (%) Acidic species (%) Basic species (%) Particles 5°C 1 month 51.8 0.9 99.1 0.0 70.7 23.9 5.4 8.9 Particle-free 25°C+60% RH 1 month 52.3 1.0 98.9 0.1 69.3 25.2 5.5 8.8 Particle-free 40°C+75% RH 1 month 52.3 1.3 98.3 0.4 56.2 38.1 5.6 9.2 Particle-free 40°C+75% RH 6 weeks 52.0 1.5 97.9 0.6 49.0 45.9 5.1 9.2 Particle-free 40°C+75% RH 8 weeks 51.8 1.7 97.5 0.8 43.2 51.8 5.0 8.9 Particle-free 5°C 3 months 51.8 1.0 99.0 0.0 69.8 24.5 5.7 7.6 Particle-free 25°C 3 months 51.8 1.2 98.6 0.2 64.4 30.1 5.5 8.3 Particle-free 5°C 6 months 51.6 1.0 98.9 0.0 70.0 24.9 5.1 8.1 Particle-free 25°C 6 months 51.5 1.3 98.3 0.4 58.4 36.8 4.8 8.3 Particle-free 5°C 9 months 51.3 1.1 98.8 0.1 68.3 26.1 5.6 8.2 Particle-free 5°C 12 months 51.2 1.1 98.8 0.1 69.1 25.4 5.5 8.3 Particle-free 25°C 12 months 51.5 1.5 97.7 0.8 47.4 48.0 4.6 8.3 Particle-free. crfiznn / ίζηζ / Β / γι Drug product stability data 2 (F2) Storage Condition 0 Storage Time 0 Protein Concentration (mg / mL) Size Exclusion HPLC Ion Exchange HPLC Turbidity (NTU) Visible Particles HMW (%) Monomer (%) LMW (%) Main Peak (%) Acid Species (%) Basic Species (%) - Initial 50.9 0.9 99.1 0.0 70.2 24.3 5.5 9.3 Particle-free 40°C+75% RH 1 week 51.0 1.1 98.8 0.1 67.2 27.0 5.8 8.9 Particle-free 40°C+75% RH 2 weeks 51.0 1.2 98.6 0.2 63.5 30.7 5.8 8.9 Particle-free 5°C 1 month 52.2 0.9 99.0 0.0 70.7 23.9 5.4 8.6 Particle-free 25°C+60% RH 1 month 52.3 1.1 98.8 0.1 69.4 25.1 5.5 8.8 Particle-free 40°C+75% RH 1 month 52.4 1.3 98.3 0.4 56.5 37.8 5.7 9.1 Particle-free 40°C+75% RH 6 weeks 52.3 1.6 97.8 0.6 49.4 45.6 5.0 9.3 Particle-free 40°C+75% RH 8 weeks 51.7 1.7 97.5 0.8 43.4 51.5 5.0 9.1 Particle-free 5°C 3 months 51.8 1.0 98.9 0.0 70.0 24.4 5.6 8.3 Particle-free 25°C 3 months 51.6 1.2 98.6 0.2 64.5 30.0 5.5 8.4 Particle-free 5°C 6 months 51.6 1.0 98.9 0.0 70.1 24.8 5.1 8.4 Particle-free 25°C 6 months 51.6 1.3 98.3 0.4 58.9 36.5 4.6 8.5 Particle-free 5°C 9 months 51.6 1.1 98.8 0.1 68.3 26.1 5.6 8.3 Particle-free 5°C 12 months 51.7 1.2 98.8 0.1 69.3 25.4 5.3 8.0 Particle-free 25°C 12 months 51.7 1.5 97.7 0.8 47.4 47.8 4.5 8.7 Particle-free. cefiznn / Lznz / E / YL

Claims

1. A pharmaceutical formulation comprising: 40 mg / mL to 200 mg / mL of an antibody against CSF-1R; 0.01% to 0.1% (w / v) of a surfactant; 5 mM to 100 mM of a buffering agent; 10 mM to 500 mM of at least one stabilizer; at a pH in the range of 4.5 to 7.

0.

2. The pharmaceutical formulation according to claim 1, wherein the anti-CSF-1 R antibody comprises a heavy chain variable region comprising heavy chain CDR1 (CDR-H1) of SEQ ID NO: 1, CDR-H2 of SEQ ID NO: 2 and CDR-H3 of SEQ ID NO: 3; and a light chain variable region comprising light chain CDR1 (CDR-L1) of SEQ ID NO: 4, CDR-L2 of SEQ ID NO: 5 and CDR-L3 of SEQ ID NO:

6.

3. The pharmaceutical formulation according to claim 1 or 2, wherein the antibody against CSF-1 R comprises a variable region of the heavy chain comprising the amino acid sequence of SEQ ID NO: 7 and a variable region of the light chain comprising the amino acid sequence of SEQ ID NO:

8.

4. The pharmaceutical formulation according to any of claims 1 to 3, wherein the concentration of the antibody against CSF-1 R is in the range of 40 mg / mL to 100 mg / mL, in particular, 50 mg / mL.

5. The pharmaceutical formulation according to any of claims 1 to 4, wherein the surfactant is a polysorbate.

6. The pharmaceutical formulation according to any of claims 1 to 5, wherein the polysorbate is present in a concentration in the range of 0.01% to 0.1% (w / v), in particular, 0.04% (w / v).

7. The pharmaceutical formulation according to any of claims 1 to 6, wherein the buffering agent is a histidine buffer, in particular, a histidine chloride buffer.

8. The pharmaceutical formulation according to any of claims 1 to 7, wherein the buffering agent has a concentration in the range of 10 to 30 mM, in particular, 20 mM.

9. The pharmaceutical formulation according to any of claims 1 to 8, wherein the pH of the formulation is in the range of 5.0 to 6.5, in particular 6.

0.

10. The pharmaceutical formulation according to any of claims 1 to 9, wherein at least one stabilizer is selected from the group consisting of salts, saccharides, and amino acids.

11. The pharmaceutical formulation according to any of claims 1 to 10, wherein the at least one stabilizer is a saccharide, in particular, sucrose.

12. The pharmaceutical formulation according to any of claims 1 to 11, wherein the at least one stabilizer is present at a concentration in the range of 140 to 250 mM, in particular in the range of 210 to 230 mM.

13. The pharmaceutical formulation according to claim 10, comprising a first cefiznn / Lznz / E / YL stabilizer selected from the group of salts, saccharides and amino acids, and methionine as a second stabilizer.

14. The pharmaceutical formulation according to claim 13, wherein the first stabilizer is present at a concentration of 120 to 300 mM, and the second stabilizer methionine is present at a concentration of 5 to 25 mM.

15. The pharmaceutical formulation according to any of claims 1 to 14, wherein the antibody against CSF-1R is bound to the human CSF-1R fragment delD4 (SEQ ID NO: 11) and to the human CSF-1R extracellular domain (SEQ ID NO: 12) in a ratio of 1:50 or less.

16. The pharmaceutical formulation according to any of claims 1 to 12, comprising 40 to 100 mg / mL of antibody against CSF-1R; 20 mM of L-histidine; 0.03 to 0.05% (w / v) of polysorbate 20; 210 to 230 mM of sucrose; optionally, 5 to 25 mM of methionine; at a pH of 6.0 ± 0.

5.

17. The pharmaceutical formulation according to any of claims 1 to 16, comprising 50 mg / mL of antibody against CSF-1R; 20 mM of L-histidine; 0.04% (w / v) of polysorbate 20; 220 mM of sucrose; 10 mM of methionine; at a pH of 6.0 ± 0.

5.

18. The pharmaceutical formulation according to any of claims 1 to 17, which is in a liquid form, in a lyophilized form, or in a liquid form reconstituted from a lyophilized form.

19. The pharmaceutical formulation according to any of claims 1 to 18 for use in the treatment of cancer.

20. The pharmaceutical formulation according to any of claims 1 to 19 for use in combination with another therapeutic agent, in particular, an agent that blocks the PD-L1 / PD-1 interaction.

21. The pharmaceutical formulation according to any of claims 1 to 18 for use in the treatment of pigmented villonodular synovitis (PVNS) or giant cell tenosynovial tumors (TGCT).

22. Use of a formulation according to any of claims 1 to 18 for the preparation of a medicament useful for the treatment of cancer or for the treatment of pigmented villonodular synovitis (PVNS) or giant cell tenosynovial tumors (TGCT).