Formulations comprising immunoglobulin-like transcript 7 (ILT7) binding proteins

Abstract

Immunoglobulin-like transcript 7 (ILT7) binding proteins and methods of making, using, and storing the same are provided. Also provided are improved formulations comprising an anti-ILT7 binding protein and devices comprising the disclosed formulations.

Description

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS

[0002] This application claims priority to U.S. Application No. 63 / 369,567, filed on July 27, 2022, which is hereby incorporated by reference in its entirety for all purposes.

[0003] References to Electronic Sequence Listings

[0004] The contents of the electronic sequence listing (HOPA_037_01WO_SeqList_ST26.xml; size: 13,040 bytes; creation date: July 14, 2023) are incorporated herein by reference in their entirety. Technical Field

[0005] The disclosure provided relates to improved immunoglobulin-like transcript 7 (ILT7) binding proteins and methods of making, using, and storing the same. Also provided are devices comprising the proteins and methods of using the devices to treat various diseases and conditions associated with ILT7 expressing cells. Background Art

[0006] Proteins can undergo a variety of degradation processes, including aggregation, deamidation, isomerization, oxidation, disulfide scrambling and truncation. These events can occur during fermentation, purification, formulation, manufacturing and storage. If degradation adversely affects the biological activity of the protein or induces immunogenicity, the clinical utility and shelf life of the protein will be affected. One of the most common degradation processes observed is the oxidation of unstable amino acid residues.

[0007] Light-induced tryptophan oxidation in the complementarity determining region (CDR) negatively affects the potency and shelf life of immunoglobulin-like transcript 7 (ILT7) binding proteins. Therefore, there is a need to address oxidation of affected residues in ILT7 binding proteins to maintain their integrity for use. In addition, there is a need to eliminate or reduce the need for engineering controls, including but not limited to lighting, and the need for nitrogen blankets during the manufacture of these proteins.

[0008] The present disclosure addresses these and more limitations of the current state-of-the-art and provides various improved compositions and methods. Summary of the invention

[0009] The compositions and methods of the present disclosure provide improvements over the current state-of-the-art and address limitations associated with existing manufacturing methods. In particular, existing methods are affected by light-induced tryptophan oxidation occurring in the complementarity determining regions (CDRs) of antibodies, which negatively impacts potency and shelf life.

[0010] Furthermore, provided herein are solutions that allow for the delivery of higher antibody concentrations that were previously limited due to increased aggregation rates and formulation viscosity. In fact, the methods of the present disclosure provide improved formulations containing higher concentrations of ILT7 binding proteins, allowing for more convenient administration regimens at higher doses.

[0011] Furthermore, the provided methods eliminate the need for engineering controls such as specific lighting conditions and including a nitrogen blanket during manufacturing, thereby reducing manufacturing costs, labor costs, and expenses associated with antibody manufacturing.

[0012] Provided herein are compositions comprising: (i) about 100 mg / mL to about 350 mg / mL of an anti-immunoglobulin-like transcript 7 (ILT7) binding protein; (ii) about 50 to about 350 mM sucrose; (iii) about 0.001% to about 1% polysorbate-80; (iv) L-methionine; and (v) a buffer selected from a histidine buffer, a citrate buffer, or a phosphate buffer.

[0013] Provided herein are compositions comprising: (i) about 100 mg / mL to about 165 mg / mL of an anti-immunoglobulin-like transcript 7 (ILT7) binding protein; (ii) about 150 to about 240 mM sucrose; (iii) about 0.003% to about 0.8% polysorbate-80; (iv) L-methionine; and (v) a buffer selected from a histidine buffer, a citrate buffer, or a phosphate buffer.

[0014] In an embodiment, the buffer in the composition is a histidine buffer. In an embodiment, the buffer is a phosphate buffer. In an embodiment, the buffer is a citrate buffer. In an embodiment, the pH of the composition is acidic, as determined by a pH meter. In an embodiment, the acidic pH is about 5 to about 7, as determined by a pH meter. In an embodiment, the acidic pH of the composition of the present disclosure is about 6, as determined by a pH meter. In an embodiment, the composition comprises about 5mM to about 25mM histidine / histidine-HCl. In an embodiment, the composition comprises 20mM histidine / histidine-HCl. In an embodiment, the composition comprises about 5mM to about 50mM L-methionine. In an embodiment, the composition comprises 15mM L-methionine. In an embodiment, the composition comprises 0.02% polysorbate-80. In an embodiment, the composition comprises up to about 150mg / mL of ILT7 binding protein. In an embodiment, the composition comprises about 150mg / mL of anti-ILT7 binding protein. In embodiments, the anti-ILT7 binding protein comprises: i. a VH comprising at least 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 1; ii. a VL comprising at least 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 2; or iii. both i. and ii. In embodiments, the anti-ILT7 binding protein comprises: i. a VH comprising SEQ ID NO: 1; ii. a VL comprising SEQ ID NO: 2; or iii. both i. and ii. In embodiments, the anti-ILT7 binding protein comprises complementarity determining regions (CDRs) HCDR1, HDR2, HCDR3, LCDR1, LCDR2 and LCDR3 comprising the sequences of SEQ ID NO: 3, 4, 5, 6, 7 and 8, respectively. In embodiments, the composition comprises a viscosity of about 5 cP to about 50 cP, as determined by a viscometer. In an embodiment, the anti-ILT7 binding protein is daxdilimab. Daxdilimab may also be referred to as HZN7734, VIB7734 or MEDI7734.

[0015] A composition is provided, comprising approximately: i. 150 mg / mL of an anti-immunoglobulin-like transcript 7 (ILT7) binding protein; ii. 20 mM histidine / histidine-HCl; iii. 180 mM sucrose; iv. 15 mM L-methionine; and v. 0.02% polysorbate-80.

[0016] A composition is provided, comprising approximately: i. 150 mg / mL of an anti-immunoglobulin-like transcript 7 (ILT7) binding protein; ii. 20 mM histidine / histidine-HCl; iii. 180 mM sucrose; iv. 15 mM L-methionine; and v. 0.02% polysorbate-80, wherein the ILT7 binding protein comprises: a VH comprising SEQ ID NO: 1 and a VL comprising SEQ ID NO: 2.

[0017] A composition is provided, comprising approximately: i. 150 mg / mL of an anti-immunoglobulin-like transcript 7 (ILT7) binding protein; ii. 20 mM histidine / histidine-HCl; iii. 180 mM sucrose; iv. 15 mM L-methionine; and v. 0.02% polysorbate-80, wherein the ILT7 binding protein comprises complementarity determining regions (CDRs) HCDR1, HDR2, HCDR3, LCDR1, LCDR2, and LCDR3, which comprise the sequences of SEQ ID NOs: 3, 4, 5, 6, 7, and 8, respectively.

[0018] In an embodiment, the viscosity of the composition is about 5 to about 50 cP. In an embodiment, the viscosity of the composition does not exceed 20 cP. In an embodiment, the aggregation rate of the composition is reduced as compared to an otherwise comparable composition lacking L-methionine, as determined by size exclusion chromatography at 40°C. In an embodiment, the aggregation rate is 0.5% to 1% per month, as determined by size exclusion chromatography at 40°C. In an embodiment, the oxidation level is reduced as compared to an otherwise comparable composition lacking L-methionine, as determined by peptide mapping analysis of W102 or W104 of SEQ ID NO: 1 of an anti-ILT7 binding protein at room temperature. In an embodiment, when the composition is exposed to light of 1600-1800 lux for 5 days, the percentage of oxidized material per day is 0.2% to 0.5%. In an embodiment, the composition is Fc oxidation resistant.

[0019] A container is provided, which contains a composition of the present disclosure in unit dosage form. In an embodiment, the container contains nitrogen. In an embodiment, the container does not contain nitrogen.

[0020] Methods for treating diseases are provided, comprising administering an effective amount of the compositions of the present disclosure to a subject in need thereof, thereby treating the disease. In embodiments, after administration, the administration is sufficient to alleviate the symptoms of the disease in a subject in need thereof. In embodiments, the symptoms are alleviated by at least about 1-fold.

[0021] Provided are methods for treating autoimmune diseases, comprising administering an effective amount of the compositions of the present disclosure to a subject in need thereof, thereby treating the autoimmune disease. In an embodiment, the autoimmune disease is selected from the group consisting of: discoid lupus erythematosus (DLE), local segmental glomerulosclerosis (FSGS), alopecia areata, myositis, diabetes, Hashimoto's disease, autoimmune adrenal insufficiency, pure red cell aplasia, multiple sclerosis, rheumatoid carditis, lupus nephritis, systemic lupus erythematosus, psoriasis, rheumatoid arthritis, chronic inflammation, Sjögren's syndrome, polymyositis, dermatomyositis, inclusion body myositis, juvenile myositis, IgG4-related disease (IgG4RD) and scleroderma. In an embodiment, the autoimmune disease is alopecia areata. In an embodiment, the autoimmune disease is systemic lupus erythematosus. In an embodiment, the autoimmune disease is FSGS.

[0022] Methods of treating alopecia areata are provided, comprising administering to a subject in need thereof an effective amount of a composition of the present disclosure, thereby treating the alopecia areata.

[0023] Methods of treating FSGS are provided, comprising administering to a subject in need thereof an effective amount of a composition of the disclosure, thereby treating the FSGS.

[0024] Methods of treating systemic lupus erythematosus are provided, comprising administering to a subject in need thereof an effective amount of a composition of the disclosure, thereby treating the systemic lupus erythematosus.

[0025] In embodiments, the composition of the disclosure is administered every 4 weeks. In embodiments, the composition of the disclosure is administered every 12 weeks. In embodiments, administration continues for at least about 2 administrations.

[0026] Methods of treating myositis are provided, comprising administering to a subject in need thereof an effective amount of a composition of the disclosure, thereby treating the myositis. In embodiments, administration of the composition of the disclosure is subcutaneous.

[0027] A composition is provided comprising approximately: i. 150 mg / mL of immunoglobulin-like transcript 7 (ILT7) binding protein; ii. 20 mM histidine / histidine-HCl; iii. 180 mM sucrose; iv. 15 mM L-methionine; and v. 0.02% polysorbate-80, wherein the anti-ILT7 binding protein comprises a sequence that is at least 85% identical to the sequence of Table 1.

[0028] A composition is provided, comprising approximately: i. 150 mg / mL of immunoglobulin-like transcript 7 (ILT7) binding protein; ii. 20 mM histidine / histidine-HCl; iii. 180 mM sucrose; iv. 15 mM L-methionine; and v. 0.02% polysorbate-80, wherein the anti-ILT7 binding protein comprises a VH comprising SEQ ID NO: 1, a VL comprising SEQ ID NO: 2, or both the VH and VL of SEQ ID NO: 1 and SEQ ID NO: 2, respectively.

[0029] Methods for treating autoimmune diseases are provided, comprising administering a composition comprising: i. about 150 mg / mL of immunoglobulin-like transcript 7 (ILT7) binding protein; ii. 20 mM histidine / histidine-HCl; iii. 180 mM sucrose; iv. 15 mM L-methionine; and v. 0.02% polysorbate-80, wherein the anti-ILT7 binding protein comprises complementary determining regions (CDRs) HCDR1, HDR2, HCDR3, LCDR1, LCDR2, and LCDR3, comprising the sequences of SEQ ID NOs: 3, 4, 5, 6, 7, and 8, respectively, wherein the dose of the anti-ILT7 binding protein comprises about 150 mg to about 450 mg; wherein the administration is subcutaneous, and wherein the dose is administered in a single injection. In embodiments, the dose of the anti-ILT7 binding protein comprises about 150 mg to about 275 mg. In embodiments, the dose of the anti-ILT7 binding protein comprises about 150 mg to about 200 mg.

[0030] A delivery device is provided comprising any of the compositions disclosed herein. In an embodiment, the delivery device is an autoinjector.

[0031] Kits are provided comprising a delivery device disclosed herein and instructions for use thereof. In an embodiment, the kit comprises a plurality of automatic injectors.

[0032] Treatment methods are provided, which include administering dasidilimumab to a subject in need thereof, wherein the administration includes an autoinjector. In embodiments, an autoinjector of the present disclosure is contacted with a thigh, abdomen, or arm of a subject in need thereof in a manner sufficient to effect administration of dasidilimumab in the subject in need thereof.

[0033] Provided is a method for treating an autoimmune disease, wherein the treatment is selected from the group consisting of an autoimmune disease or condition of discoid lupus erythematosus (DLE), local segmental glomerulosclerosis (FSGS), alopecia areata, lupus nephritis, myositis, diabetes, Hashimoto's disease, autoimmune adrenal insufficiency, pure red cell aplasia, multiple sclerosis, rheumatoid carditis, systemic lupus erythematosus, psoriasis, rheumatoid arthritis, chronic inflammation, Sjögren's syndrome, polymyositis, dermatomyositis, inclusion body myositis, juvenile myositis, IgG4-related disease (IgG4RD) and scleroderma. In an embodiment, the method disclosed herein provides the treatment of a non-autoimmune disease or condition. In an embodiment, a non-autoimmune disease or condition includes a disease mediated by ILT7 expressing cells.

[0034] A composition is provided, comprising (i) an immunoglobulin-like transcript 7 (ILT7) binding protein; and (ii) L-methionine; wherein when the composition is exposed to 1600-1800 lux of light for 5 days, the percentage of oxidized species of the ILT7 binding protein in the composition increases to at most about 1.0%. In embodiments, the percentage of oxidized species of the ILT7 binding protein in the composition increases to at most about 0.4%, 0.3%, 0.2% or 0.1%.

[0035] Provided is a composition comprising (i) an immunoglobulin-like transcript 7 (ILT7) binding protein; and (ii) L-methionine; wherein when the composition is exposed to 1600-1800 lux of light, the daily rate of formation of new oxidized species of the ILT7 binding protein in the composition is at most about 0.1%-1.0%. In an embodiment, the daily rate of formation of new oxidized species of the ILT7 binding protein in the composition is at most about 0.2%-0.4% or 0.1%-0.3%.

[0036] Compositions are provided comprising about 100 mg / mL to about 450 mg / mL of an ILT7 binding protein. In an embodiment, the ILT7 binding protein comprises complementarity determining regions (CDRs) HCDR1, HDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprising the sequences of SEQ ID NOs: 3, 4, 5, 6, 7, and 8, respectively.

[0037] These and other embodiments are described herein. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] The accompanying drawings, which are incorporated herein and form a part of this specification, illustrate some (but not the only or exclusive) example embodiments and / or features. It is intended that the embodiments and drawings disclosed herein should be considered illustrative rather than restrictive.

[0039] Figures 1A-1C Schematic diagram showing an exemplary afucosylated human IgG1λ anti-ILT7 mAb "anti-ILT7 mAb" ( Figure 1A ), and the percentage of oxidized species of formulations containing 10 mM excipient L-methionine (L-Met) or control (0 mM L-Met) as excipients and 100 mg / mL of anti-ILT7 mAb, 20 mM histidine / histidine-HCl, 240 mM sucrose, and 0.02% PS-80 (pH 6.0). Oxidized species at 5 °C ( Figure 1B ) and RT( Figure 1C ) were evaluated at RT = room temperature. The results show that L-Met reduces the rate of oxidative species.

[0040] Figure 2A-2C The percentage of aggregates is shown for formulations containing 10 mM excipient L-methionine (L-Met) or control (0 mM L-Met) as excipients and 100 mg / mL of anti-ILT7 mAb, 20 mM histidine / histidine-HCl, 240 mM sucrose, and 0.02% PS-80 (pH 6.0). Aggregates were observed at 40°C ( Figure 2A )、RT( Figure 2B ) and 5℃( Figure 2C The results showed that L-Met reduced the aggregation rate of anti-ILT7 mAb. RT = room temperature.

[0041] Figure 3A-3B Monthly oxidation percentage rates ( Figure 3A ) and gathering ( Figure 3B ). The percentage formation was measured at 5°C, RT and 40°C. 15 mM L-Met resulted in suitable stabilization and robustness. RT = room temperature.

[0042] Figures 4A-4B Formulations containing 100 mg / mL of anti-ILT7 mAb, 20 mM histidine / histidine-HCl, 240 mM sucrose, 0.02% PS-80 (pH 6.0) (P2) or 150 mg / mL of anti-ILT7 mAb, 20 mM histidine / histidine-HCl, 200 mM sucrose, and 0.02% PS-80 (pH 6.0) (P3) were exposed to light ( Figure 4A ) and dark ( Figure 4B) per day. The effect of the presence of air, nitrogen (N2) or 15 mM L-Met on the formation of oxidative species of formulations under light or dark conditions was evaluated. The vials were kept in a light box at ambient room temperature and the light intensity was measured to be 1600-1800 lux throughout the experiment. 15 mM L-Met minimized the formation of oxidative species when exposed to light for 5 days.

[0043] Figures 5A-5C Displayed at 40℃( Figure 5A )、RT( Figure 5B ) and 5℃( Figure 5C ) containing 10mg / mL, 25mg / mL, 50mg / mL, 75mg / mL or 100mg / mL of anti-ILT6 mAb over time. The change in % oxidative variant formation at 40°C was measured at approximately 0, 0.25, 0.5, 1, 2 and 3 months. The change in % oxidative variant formation at RT was measured at approximately 0, 1, 2, 3, 6, 8 and 12 months. The change in % oxidative variant formation at 5°C was measured at approximately 0, 3, 6, 9 and 12 months. The % oxidative variant formation was measured using size exclusion chromatography (SEC). RT = room temperature.

[0044] Figures 6A-6C Displayed at 40℃( Fig. 6A )、25℃( Figure 6B ) and 5℃( Figure 6C The change in % monomer at 40°C was measured at approximately 0, 0.5, 1, 2, and 3 months. The change in % monomer at 25°C was measured at approximately 0, 1, 2, 3, and 6 months. The change in % monomer at 5°C was measured at approximately 0, 3, 6, 9, 12, 16, and 20 months. The % monomer was measured using size exclusion chromatography (SEC).

[0045] Figures 7A-7C Displayed at 40℃( Fig. 7A )、25℃( Figure 7B ) and 5℃( Figure 7C ) with time, container type (prefilled syringe [PFS] or vial), and volume (1 mL PFS or 2 mL PFS). Changes in % oxidative variant formation at 40°C were measured at approximately 0, 0.5, 1, 2, and 3 months. Changes in % oxidative variant formation at 25°C were measured at approximately 0, 1, 2, 3, and 6 months. Changes in % oxidative variant formation at 5°C were measured at approximately 0, 3, 6, 9, 12, 16, and 20 months. % oxidative variant formation was measured using size exclusion chromatography (SEC). DETAILED DESCRIPTION

[0046] Compositions containing anti-ILT7 binding proteins are provided, which have increased efficacy and shelf life. Methods for preparing these compositions and using these compositions to treat diseases are also provided, including but not limited to autoimmune indications. These compositions are particularly useful for improving the stability of antibodies having a sequence of SEQ ID NO: 1. The amino acid residues on this antibody are damaged by light and oxygen. In particular, oxidized tryptophan residues, deamidated asparagine residues, and oxidized portions in the Fc region are described. With regard to reducing oxidation and aggregation, the disclosed compositions are particularly beneficial. Devices (e.g., automatic injectors) comprising the disclosed compositions and methods of use thereof are also provided.

[0047] In embodiments, compositions containing anti-ILT7 mAbs can be formulated to reduce or eliminate light-induced tryptophan oxidation of one or more residues in the complementarity determining regions of the anti-ILT7 mAb by including L-methionine in the formulation. In embodiments, L-methionine further reduces the aggregation level of the anti-ILT7 mAb formulation, thereby producing an improved formulation that confers an extended shelf life as compared to existing formulations.

[0048] definition

[0049] While the following terms are believed to be well understood by those of ordinary skill in the art, the following definitions are set forth to facilitate explanation of the presently disclosed subject matter.

[0050] Unless otherwise defined below, all technical and scientific terms used herein are intended to have the same meaning as commonly understood by those of ordinary skill in the art. References to the technology employed herein are intended to reference technology commonly understood in the art, including variations of those technologies that are clear to those skilled in the art and / or replacement of equivalent technologies.

[0051] Any range listed herein is intended to include the endpoints. For example, a range of 2-4 includes 2 and 4 and values ​​therebetween.

[0052] As used herein, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0053] The term "about" or "approximately" when it appears immediately before a numerical value means a range plus or minus 10% of the value. For example, unless otherwise indicated by the content of the present disclosure, or inconsistent with such an interpretation, "about 50" may mean 45 to 55, "about 25,000" may mean 22,500 to 27,500, etc. In the context of a numerical list such as "about 49, about 50, about 55 . . . ", "about 50" means a range extending to less than half of the interval between the preceding value and the following value, for example, greater than 49.5 to less than 52.5. In addition, in view of the definition of the term "about" provided herein, the phrase "less than about" a value or "greater than about" a value should be understood.

[0054] The term "identity" is used when referring to nucleic acid sequences or amino acid sequences to denote the similarity between two sequences. Unless otherwise indicated, the percent identities described herein were determined using the BLAST algorithm available on the World Wide Web at: blast.ncbi.nlm.nih.gov / Blast.cgi using default parameters.

[0055] As used herein, the term "subject" refers to any subject, such as a human or non-human mammal, that needs diagnosis, prognosis or therapy. The term "subject" may mean a human or non-human mammal that is affected, may be affected or suspected of being affected by a disease (such as an autoimmune disease or condition). The terms "subject" and "patient" are used interchangeably herein. Although the anti-ILT7 binding protein compositions provided herein are mainly directed to compositions suitable for administration to humans, it should be understood by the technician that such compositions are generally suitable for administration to various subjects. In an embodiment, the subject is a mammal. Mammals include primates, such as humans, monkeys, gorillas and apes; and non-primates, such as livestock, including laboratory animals (such as rabbits and rodents, such as guinea pigs, rats or mice) and domestic pets and farm animals (such as cats, dogs, pigs, cattle, sheep, goats, horses, rabbits), and non-livestock, such as wild animals, birds, reptiles, fish, etc.

[0056] As used herein, the term "room temperature" or "RT" refers to a temperature of about 20° C. to about 25° C. The RT may be 21° C., 22° C., 23° C., 24° C., or up to about 25° C. The RT may be about 20° C.-21° C., 21° C.-22° C., 22° C.-23° C., 23° C.-24° C., or 24° C.-25° C.

[0057] As used herein, "treatment (treating / treat)" describes the management and care of a subject to achieve the purpose of combating a disease, condition or disorder, and includes the administration of the ILT7 binding protein used in the methods described herein to alleviate the symptoms or complications of a disease, condition or disorder, or to eliminate the disease, condition or disorder. Therefore, the term "treatment (treat / treating)" refers to therapeutic measures and prophylactic / preventative measures, wherein the purpose is to prevent, slow down (mitigate) or improve the progress of a disease (e.g., an autoimmune disease). Beneficial or desired clinical results include, but are not limited to, relieving symptoms; reducing the extent of the disease; stabilizing (i.e., not worsening) the disease state; delaying or slowing the progression of the disease; improving or alleviating the disease state; and reversing the disease (whether partially or completely). The term "treatment" may also include the treatment of in vitro cells or animal models.

[0058] In general, the terms "ILT7 binding protein" and "ILT7 binding molecule" are used interchangeably to refer to a protein or molecule that binds to immunoglobulin-like transcript 7 (ILT7). The terms protein and peptide are used interchangeably herein. In embodiments, the anti-ILT7 binding protein used in the methods described herein binds to full-length ILT7. In embodiments, the anti-ILT7 binding protein used in the methods described herein binds to a fragment of ILT7. In embodiments, the fragment of ILT7 to which the ILT7 binding protein binds comprises the extracellular domain of ILT7. In embodiments, any of the ILT7 binding protein or ILT7 binding molecule may refer to an anti-ILT7 binding protein (e.g., an antibody).

[0059] Compositions comprising anti-ILT7 binding proteins

[0060] Immunoglobulin-like transcript 7 (ILT7) binding protein

[0061] In an embodiment, an anti-ILT7 binding protein is provided. In an embodiment, the anti-ILT7 binding protein binds to any mammalian ILT7. In an embodiment, the anti-ILT7 binding protein binds to human ILT7 or a fragment thereof, such as the extracellular portion of human ILT7. In an embodiment, the anti-ILT7 binding protein disclosed herein binds to cynomolgus monkey ILT7 or a fragment thereof, such as the extracellular portion of cynomolgus monkey ILT7.

[0062] Exemplary sequences of anti-ILT7 binding proteins are disclosed and described in PCT Publication No. WO 2017156298, U.S. Patent No. US 8084585, PCT Publication No. WO 2021113702, each of which is incorporated herein by reference in its entirety. Exemplary sequences of anti-ILT7 binding proteins are shown in Table 1. In an embodiment, the ILT7 to which the anti-ILT7 binding protein is bound is located on plasmacytoid dendritic cells (pDC). In an embodiment, clone ILT70137 in PCT Publication No. WO 2017 / 156298 is provided and is further described in Table 1 below.

[0063] In embodiments, any sequence in Table 1 may be modified. In embodiments, modifications to the sequences in Table 1 include any combination of one or more truncations, deletions, insertions, substitutions, and modifications thereof. Modifications may occur at any residue provided in Table 1 and in any number of residues in Table 1. In embodiments, modifications may include 1-3, 1-5, 1-10, 5-20, 1-3, 1-5, 1-10, 1-20, 3-8, 3-10, 3-15, 5-8, 5-10, or 5-20 residues. In embodiments, modifications may occur in up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 30, 40, 50 residues.

[0064] Table 1. Exemplary anti-ILT7 binding protein sequences

[0065]

[0066]

[0067] Provided herein are compositions comprising anti-ILT7 binding proteins. In embodiments, the compositions may comprise an effective amount of anti-ILT7 binding proteins. In embodiments, the anti-ILT7 binding proteins or polynucleotides encoding at least a portion of the proteins comprise at least about or at most about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% or up to about 100% identity to any of the sequences in Table 1 (SEQ ID NO: 1-12). In embodiments, the anti-ILT7 binding proteins or polynucleotides encoding at least a portion of the proteins comprise any of the sequences in Table 1.

[0068] In an embodiment, the isolated ILT7 binding protein is an anti-ILT7 binding protein that can bind to the same ILT7 epitope as an antibody comprising the heavy chain variable region (VH) of SEQ ID NO: 1 and the light chain variable region (VL) of SEQ ID NO: 2. In an embodiment, the isolated ILT7 binding protein is an anti-ILT7 binding protein that competitively inhibits ILT7 binding to an antibody comprising VH of SEQ ID NO: 1 and VL of SEQ ID NO: 2.

[0069] In an embodiment, the isolated ILT7 binding protein is an anti-ILT7 binding protein comprising complementarity determining regions (CDRs) HCDR1, HDR2, HCDR3, LCDR1, LCDR2 and LCDR3, which comprise the sequences of SEQ ID NOs: 3, 4, 5, 6, 7 and 8, respectively.

[0070] In embodiments, the anti-ILT7 binding protein comprises a VH that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 1, and / or a VL that is at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO:2.

[0071] In embodiments, the anti-ILT7 binding protein comprises a VH comprising SEQ ID NO: 1 and a VL comprising SEQ ID NO: 2. In embodiments, the isolated ILT7 binding protein is an anti-ILT7 binding protein comprising a VH comprising SEQ ID NO: 1. In embodiments, the isolated ILT7 binding protein is an anti-ILT7 binding protein comprising a VH comprising SEQ ID NO: 2.

[0072] In embodiments, the ILT7 binding protein comprises a light chain (LC) and a heavy chain (HC) having at least 85%, 90%, 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 9 and SEQ ID NO: 10, respectively. In embodiments, the ILT7 binding protein comprises a LC comprising SEQ ID NO: 9, having 1, 2, 3, 5, 6, 7, 8, 9, 10 or up to 20 residue modifications. In embodiments, the ILT7 binding protein comprises a HC comprising SEQ ID NO: 10, having 1, 2, 3, 5, 6, 7, 8, 9, 10 or up to 20 residue modifications. In embodiments, the ILT7 binding protein comprises a LC comprising SEQ ID NO: 9. In embodiments, the ILT7 binding protein comprises a HC comprising SEQ ID NO: 10.

[0073] In an embodiment, the composition of the present disclosure may include residue modifications, such as post-translational modifications (PTMs). Modifications described herein include PTMs. Exemplary PTMs may occur on amino acid side chains or at the C-terminus or N-terminus of a protein. In an embodiment, the modification includes at least a portion of a CDR region. In an embodiment, the modification includes at least a portion of a fragment crystallizable (Fc) region. In an embodiment, the modification is reversible. In an embodiment, the modification is irreversible. Exemplary modifications include phosphorylation, glycosylation, ubiquitination, nitrosylation, methylation, acetylation, lipidation, and proteolysis.

[0074] In embodiments, the ILT7 binding protein comprises an antibody or an antigen binding fragment thereof. In embodiments, the antibody or antigen binding fragment thereof is afucosylated.

[0075] In embodiments, the ILT7 binding protein binds to the Ig1 region of ILT7. In embodiments, the ILT7 binding protein binds to the Ig2 region of ILT7. In embodiments, the ILT7 binding protein binds to human and cynomolgus monkey ILT7.

[0076] In an embodiment, the ILT7 binding protein inhibits the release of interferon (IFN) α by peripheral blood mononuclear cells (PBMC). In an embodiment, the ILT7 binding protein has ADCC activity against plasmacytoid dendritic cells (pDC) in PMBC.

[0077] In an embodiment, the ILT7 binding protein comprises a murine, human, chimeric, humanized or surface remodeled antibody or an antigen-binding fragment thereof. In an embodiment, the anti-ILT7 binding protein comprises an antibody, Fab, Fab', F(ab')2, Fd, single-chain Fv or scFv, disulfide-linked Fv, V-NAR domain, IgNar, intracellular antibody, IgGΔCH2, mini antibody, F(ab')3, tetrabody, tribody, diabody, single domain antibody, DVD-Ig, Fcab, mAb2, (scFv)2 or scFv-Fc. In an embodiment, the ILT7 binding protein comprises a monoclonal antibody or an antigen-binding fragment thereof.

[0078] In an embodiment, the ILT7 binding protein comprises a HC immunoglobulin constant domain selected from the group consisting of: (a) an IgA constant domain; (b) an IgD constant domain; (c) an IgE constant domain; (d) an IgG1 constant domain; (e) an IgG2 constant domain; (f) an IgG3 constant domain; (g) an IgG4 constant domain; and (h) an IgM constant domain. In an embodiment, the anti-ILT7 binding protein comprises a LC immunoglobulin constant domain selected from the group consisting of: (a) an Igκ constant domain; and (b) an Igλ constant domain. In an embodiment, the anti-ILT7 binding protein comprises a human IgG1 constant domain and a human λ constant domain.

[0079] In an embodiment, provided herein is a host cell producing an anti-ILT7 binding molecule.

[0080] In embodiments, provided herein is an isolated polynucleotide comprising a nucleic acid encoding a VH, wherein the VH comprises an amino acid sequence having at least 85%, 90%, 95% identity or identity to the VH of SEQ ID NO: 1. In embodiments, the polynucleotide comprises a sequence having at least 85%, 90%, 95% identity to SEQ ID NO: 11. In embodiments, the polynucleotide comprises SEQ ID NO: 11.

[0081] In embodiments, provided herein is an isolated polynucleotide comprising a nucleic acid encoding a VL, wherein the VL comprises an amino acid sequence having at least 85%, 90%, 95% identity, or identity to the VL of SEQ ID NO: 2. In embodiments, the polynucleotide comprises a sequence having at least 85%, 90%, 95% identity to SEQ ID NO: 12. In embodiments, the polynucleotide comprises SEQ ID NO: 12.

[0082] In embodiments, the nucleic acid is operably linked to a control sequence. In embodiments, an antibody or antigen-binding fragment thereof comprising the VH or VL encoded by the nucleic acid can specifically bind to ILT7.

[0083] In embodiments, the polynucleotides encode the anti-ILT7 binding molecules provided herein.

[0084] In an embodiment, provided herein is a vector comprising the polynucleotide.

[0085] In the embodiments, provided herein is a polypeptide encoded by the polynucleotide.

[0086] In embodiments, provided herein is a host cell transformed with a polynucleotide provided herein (eg, a polynucleotide comprising a nucleic acid encoding VH and a polynucleotide comprising a nucleic acid encoding VL).

[0087] In embodiments, a host cell comprising a polynucleotide as provided herein (e.g., a polynucleotide comprising a nucleic acid encoding VH and a polynucleotide comprising a nucleic acid encoding VL), a vector as provided herein, or a polypeptide as provided herein is provided. In embodiments, the host cell is a mammalian host cell. In embodiments, the host cell is an NS0 murine myeloma cell, a PER. Human cells or Chinese Hamster Ovary (CHO) cells. In embodiments, the host cell lacks the enzyme α-1,6-fucosyltransferase.

[0088] In embodiments, the compositions of the present disclosure may comprise about, at least about, or at most about 100 mg / mL, 102 mg / mL, 104 mg / mL, 106 mg / mL, 108 mg / mL, 110 mg / mL, 112 mg / mL, 114 mg / mL, 116 mg / mL, 118 mg / mL, 120 mg / mL, 122 mg / mL, 124 mg / mL, 126 mg / mL, 128 mg / mL, 130 mg / mL, 132 mg / mL, 134 mg / mL, 136 mg / mL, 138 mg / mL, 140 mg / mL, 141 mg / mL, 142 mg / mL, 143 mg / mL, 144 mg / mL, 145 mg / mL, 146 mg / mL, 147 mg / mL, 148 mg / mL, 149 mg / mL, 150 mg / mL, 151 mg / mL, 152 mg / mL, 153 mg / mL, 154 mg / mL, 155 mg / mL, 156 mg / mL, 157 mg / mL, 158 mg / mL, 159 mg / mL, 160 mg / mL, 161 mg / mL, 162 mg / mL, 163 mg / mL, 164 mg / mL, 165 mg / mL, 166 mg / mL, 167 mg / mL, 168 mg / mL, 169 mg / mL, 170 mg / mL, 171 0 mg / mL, 142 mg / mL, 144 mg / mL, 146 mg / mL, 148 mg / mL, 150 mg / mL, 155 mg / mL, 165 mg / mL, 175 mg / mL, 185 mg / mL, 195 mg / mL, 205 mg / mL, 215 mg / mL, 225 mg / mL, 235 mg / mL, 245 mg / mL, 250 mg / mL, 300 mg / mL, 350 mg / mL, 375 mg / mL, 400 mg / mL or up to about 450 mg / mL of anti-ILT7 binding protein.

[0089] In an embodiment, the composition may include an anti-ILT7 binding protein of about 100 mg / mL to about 350 mg / mL. In an embodiment, the composition may include an anti-ILT7 binding protein of about 150 mg / mL to about 275 mg / mL. In an embodiment, the composition may include an anti-ILT7 binding protein of about 200 mg / mL to about 250 mg / mL. In an embodiment, the composition may include an anti-ILT7 binding protein of about 100 mg / mL to about 150 mg / mL. In an embodiment, the composition may include an anti-ILT7 binding protein of about 110 mg / mL to about 150 mg / mL. In an embodiment, the composition may include an anti-ILT7 binding protein of about 120 mg / mL to about 150 mg / mL. In an embodiment, the composition may include an anti-ILT7 binding protein of about 130 mg / mL to about 150 mg / mL.

[0090] sugar

[0091] In an embodiment, the composition of the present disclosure comprises an anti-ILT7 binding protein and a carrier. In an embodiment, the carrier is a stabilizer. In an embodiment, the stabilizer is a sugar. In an embodiment, the composition provided herein comprises a sugar. In an embodiment, the sugar used with the composition of the present disclosure includes but is not limited to monosaccharides, disaccharides and trisaccharides or a combination thereof. In an embodiment, the composition comprises a sugar, wherein the sugar may be, for example, sucrose, trehalose, raffinose, maltose, sorbitol or mannitol or a combination thereof. In an embodiment, the sugar may be a sugar alcohol or an amino sugar. In an embodiment, the sugar is sucrose.

[0092] In an embodiment, the composition comprising anti-ILT7 binding protein comprises sugar. Any amount of sugar can be used. In an embodiment, about, at least about or at most about: 150nM to about 240mM sugar is used. In an embodiment, the composition comprises about 160nM to about 240mM sugar. In an embodiment, the composition comprises about 170nM to about 240mM sugar. In an embodiment, the composition comprises about 180nM to about 240mM sugar. In an embodiment, the composition comprises about 190nM to about 240mM sugar. In an embodiment, the composition comprises about 200nM to about 240mM sugar. In an embodiment, the composition comprises about 210nM to about 240mM sugar. In an embodiment, the composition comprises about 220nM to about 240mM sugar. In an embodiment, the composition comprises about 230nM to about 240mM sugar. In an embodiment, the composition comprises about 150nM to about 200mM sugar. In an embodiment, the composition comprises about 170nM to about 190mM sugar.

[0093] In an embodiment, the composition comprising anti-ILT7 binding protein comprises sugar. Any amount of sugar can be used. In an embodiment, about, at least about or at most about: 150mM to about 240mM sugar is used. In an embodiment, the composition comprises about 160mM to about 240mM sugar. In an embodiment, the composition comprises about 170mM to about 240mM sugar. In an embodiment, the composition comprises about 180mM to about 240mM sugar. In an embodiment, the composition comprises about 190mM to about 240mM sugar. In an embodiment, the composition comprises about 200mM to about 240mM sugar. In an embodiment, the composition comprises about 210mM ​​to about 240mM sugar. In an embodiment, the composition comprises about 220mM to about 240mM sugar. In an embodiment, the composition comprises about 230mM to about 240mM sugar. In an embodiment, the composition comprises about 150mM to about 200mM sugar. In an embodiment, the composition comprises about 170mM to about 190mM sugar.

[0094] In an embodiment, the composition comprising an anti-ILT7 binding protein comprises sucrose. In an embodiment, the composition may comprise any amount of sucrose. In an embodiment, the composition may comprise about, at least about, or at most about the following amount of sucrose: 150nM to about 240mM. In an embodiment, the composition comprises about 160nM to about 240mM sucrose. In an embodiment, the composition comprises about 170nM to about 240mM sucrose. In an embodiment, the composition comprises about 180nM to about 240mM sucrose. In an embodiment, the composition comprises about 190nM to about 240mM sucrose. In an embodiment, the composition comprises about 200nM to about 240mM sucrose. In an embodiment, the composition comprises about 210nM to about 240mM sucrose. In an embodiment, the composition comprises about 220nM to about 240mM sucrose. In an embodiment, the composition comprises about 230nM to about 240mM sucrose. In an embodiment, the composition comprises about 150nM to about 200mM sucrose. In embodiments, the composition comprises about 170 nM to about 190 mM sucrose.

[0095] In an embodiment, the composition comprising anti-ILT7 binding protein comprises about, at least about or at most about: 150mM, 155mM, 160mM, 165mM, 170mM, 175mM, 180mM, 185mM, 190mM, 195mM, 200mM, 205mM, 210mM, 215mM, 220mM, 225mM, 230mM, 235mM, 240mM, 245mM, 250mM sugar (e.g., sucrose). In an embodiment, the composition comprises about 180mM sucrose.

[0096] Polysorbate-80

[0097] In embodiments, the compositions of the present disclosure comprise an anti-ILT7 binding protein and a carrier. In embodiments, the carrier is a stabilizer. In embodiments, the stabilizer is polysorbate-80 (PS-80). In embodiments, the compositions comprise an anti-ILT7 binding protein and PS-80. In embodiments, the compositions comprise about, at least about, or at most about: 0.002%, 0.008%, 0.01%, 0.02%, 0.022%, 0.042%, 0.062%, 0.082%, 0.102%, 0.122%, 0.142%, 0.162%, 0.182%, 0.202%, 0.222%, 0.242%, 0.262%, 0.282%, 0.302%, 0.322%, 0.34 In an embodiment, the composition comprises about 0.002% to about 0.8% polysorbate-80. In an embodiment, the composition comprises about 0.01% to about 0.8% PS-80. In an embodiment, the composition comprises about 0.01% to about 0.3% PS-80. In an embodiment, the composition comprises about 0.01% to about 0.3% PS-80. In embodiments, the compositions comprise about 0.01% to about 0.05% PS-80. In embodiments, the compositions provided herein comprise about 0.02% PS-80.

[0098] In embodiments, about 0.02% PS-80 is effective to reduce particle formation under freeze / thaw (F / T) (e.g., 30°C / exposure to a temperature greater than about 30°C), stirring stress, or both F / T and stirring stress of the compositions provided herein. In embodiments, about 0.02% PS-80 is effective to reduce particle formation under F / T, stirring stress, or both F / T and stirring stress of the compositions provided herein, as compared to an otherwise comparable composition lacking PS-80 or lacking about 0.02% PS-80. In embodiments, about 0.02% PS-80 is effective to reduce particle formation under F / T, stirring stress, or both F / T and stirring stress of the compositions provided herein, as compared to an otherwise comparable composition lacking PS-80 or lacking about 0.02% PS-80, by at least about 1-fold, 5-fold, 10-fold, 30-fold, 50-fold, 100-fold, 150-fold, or 300-fold. In embodiments, about 0.02% PS-80 is effective to reduce particle formation at F / T, agitation stress, or both F / T and agitation stress of the compositions provided herein by at least about 3%, 10%, 20%, 40%, 60%, 80%, 100%, 150%, 200%, or about 300% as compared to an otherwise comparable composition lacking PS-80 or lacking about 0.02% PS-80.

[0099] Methionine

[0100] In an embodiment, the composition of the present disclosure comprises an anti-ILT7 binding protein and a carrier. In an embodiment, the carrier is a stabilizer. In an embodiment, the stabilizer is an amino acid (e.g., methionine). In an embodiment, the composition comprises an anti-ILT7 binding protein and methionine. In an embodiment, methionine is L-methionine. L-methionine is the L-enantiomer of methionine. In an embodiment, the composition provided herein comprises L-methionine (i.e., (S)-2-amino-4-(methylmercapto)butyric acid, L-2-amino-4-(methylthio)butyric acid). In an embodiment, methionine is D-methionine. In an embodiment, the composition comprises L-methionine and D-methionine. In an embodiment, the composition comprises an anti-ILT7 binding protein and L-methionine.

[0101] Any concentration of methionine can be used in the composition. In an embodiment, the composition comprising anti-ILT7 binding protein comprises about, at least about, or at most about 5nM to about 30mM L-methionine. In an embodiment, the composition comprising anti-ILT7 binding protein comprises about, at least about, or at most about 1nM to about 25mM L-methionine. In an embodiment, the composition comprising anti-ILT7 binding protein comprises about, at least about, or at most about 15nM to about 30mM L-methionine. In an embodiment, the composition comprising anti-ILT7 binding protein comprises about, at least about, or at most about 20nM to about 25mM L-methionine. In an embodiment, the composition comprising anti-ILT7 binding protein comprises about, at least about, or at most about 15nM to about 30mM L-methionine. In an embodiment, the composition comprising anti-ILT7 binding protein comprises about, at least about, or at most about 15nM to about 30mM L-methionine. In an embodiment, the composition comprising anti-ILT7 binding protein comprises about, at least about, or at most about 10nM to about 20mM methionine (e.g., L-methionine).

[0102] In embodiments, the composition comprising an anti-ILT7 binding protein comprises about 5mM to 10mM, 5mM to 20mM, 8mM to 15mM, 8mM to 20mM, 10mM to 20mM, 12mM to 25mM, 15mM to 30mM, or 20mM to 30mM L-methionine. In an embodiment, the composition comprising an anti-ILT7 binding protein comprises about, at least about, or at most about: 5mM, 6mM, 7mM, 8mM, 9mM, 10mM, 11mM, 12mM, 13mM, 14mM, 15mM, 16mM, 17mM, 18mM, 19mM, 20mM, 21mM, 22mM, 23mM, 24mM, 25mM, 26mM, 27mM, 28mM, 29mM, 30mM, 35mM, 40mM, 45mM, 50mM, 55mM, 60mM, 65mM, 70mM or 75mM L-methionine. In an embodiment, the composition comprising an anti-ILT7 binding protein comprises about, at least about, or at most about 15mM methionine (e.g., L-methionine). In embodiments, the composition comprising an anti-ILT7 binding protein comprises about, at least about, or at most about 15 mM L-methionine.

[0103] Buffer

[0104] In embodiments, the compositions included herein include a buffer. In embodiments, the compositions provided herein include an anti-ILT7 binding protein and a buffer. In embodiments, the composition comprising an anti-ILT7 binding protein and a buffer can be administered to a subject. In embodiments, the composition comprising an anti-ILT7 binding protein and a buffer can be administered to a subject in a dosage form.

[0105] In an embodiment, the composition comprises a buffer, wherein the buffer may be a histidine buffer, a phosphate buffer, a citrate buffer, an alkali metal phosphate, an acetate buffer, a tris buffer, an alkali metal carbonate, or an alkaline earth metal carbonate. In an embodiment, the buffer is a histidine buffer. In an embodiment, the histidine buffer may comprise L-histidine hydrochloride. In an embodiment, the buffer is a phosphate buffer. In an embodiment, the buffer is a citrate buffer. In an embodiment, the buffer is a citrate buffer. In an embodiment, the buffer does not comprise citrate or comprises reduced citrate. In an embodiment, a citrate buffer is not used because the subject may experience injection-related pain and / or discomfort associated with citrate. In an embodiment, the buffer does not comprise citrate.

[0106] In embodiments, the buffer provided herein may be at any concentration. In embodiments, the buffer is at a concentration of about 10mM to 40mM. In embodiments, the buffer is at a concentration of about 15mM to 40mM. In embodiments, the buffer is at a concentration of about 20mM to 40mM. In embodiments, the buffer is at a concentration of about 25mM to 35mM. In embodiments, the buffer is at a concentration of about 20mM to 30mM. In embodiments, the buffer is at a concentration of about 20mM to 25mM. In embodiments, the buffer is a histidine buffer, such as histidine / histidine-HCl, and is at a concentration of about 15mM to 40mM. In embodiments, the buffer is a histidine buffer, such as histidine / histidine-HCl, and is at a concentration of about 15mM to 25mM. In embodiments, the buffer is a histidine buffer, such as histidine / histidine-HCl, and is at a concentration of about 18mM to 22mM.

[0107] In embodiments, the buffer is at a concentration of about, at least about, or at most about 10 mM, 11 mM, 12 mM, 13 mM, 14 mM, 15 mM, 16 mM, 17 mM, 18 mM, 19 mM, 20 mM, 21 mM, 22 mM, 23 mM, 24 mM, 25 mM, 26 mM, 27 mM, 28 mM, 29 mM, 30 mM, 31 mM, 32 mM, 33 mM, 34 mM, 35 mM, 36 mM, 37 mM, 38 mM, 39 mM, or 40 mM. In an embodiment, the buffer is a histidine buffer, such as histidine / histidine-HCl, and is at a concentration of about 20mM, 21mM, 22mM, 23mM, 24mM, 25mM, 26mM, 27mM, 28mM, 29mM, or 30mM. In an embodiment, the buffer is a histidine buffer, at a concentration of about, up to about, or at least about 20mM. In an embodiment, the buffer is histidine / histidine-HCl, at a concentration of about, up to about, or at least about 20mM. In an embodiment, the buffer is histidine / histidine-HCl, at a concentration of 20mM.

[0108] Hydrogen Index

[0109] The compositions provided herein include a hydrogen index (pH). In embodiments, the pH is acidic. In embodiments, the pH is neutral. In embodiments, the pH is alkaline. In embodiments, the composition has a pH of about 6 to about 7. In embodiments, the composition has a pH of about 7. In embodiments, the composition has a pH of about 6.5 to about 7.

[0110] In embodiments, the composition has a pH of about 5 to about 7. In embodiments, the composition has a pH of about 6 to about 7. In embodiments, the composition has a pH of about 6.5 to about 7. In embodiments, the composition has a pH of about 6.8 to about 7. In embodiments, the composition has a pH of about 6.9 to about 7.1. In embodiments, the composition has a pH of about 6 to about 8. In embodiments, the composition has a pH of about 5.6 to about 6. In embodiments, the composition has a pH of about 6 to about 6.1. In embodiments, the composition has a pH of about 7 to about 9.

[0111] In embodiments, the compositions provided herein have a pH of about 5, 6, 7, or 8. In embodiments, the compositions provided herein have a pH of about 6.

[0112] The pH can be determined using a pH meter or similar techniques known in the art.

[0113] Pharmaceutical compositions comprising anti-ILT7 binding proteins

[0114] The disclosure also relates to pharmaceutical compositions comprising an anti-ILT7 binding protein as described herein. In an embodiment, the disclosure provides the use of a pharmaceutical composition comprising an anti-ILT7 binding protein (eg, mAb) for use in the methods described herein in the manufacture of a medicament for treating a subject.

[0115] In an embodiment, the pharmaceutical composition of the present disclosure comprises the ILT7 binding protein disclosed herein and one or more pharmaceutically acceptable carriers, diluents or excipients. In this regard, "pharmaceutically acceptable carriers, diluents or excipients" include but are not limited to any adjuvant, carrier, excipient, glidant, sweetener, diluent, preservative, dye / colorant, flavor enhancer, surfactant, wetting agent, dispersant, suspending agent, stabilizer, isotonic agent, solvent or emulsifier, which may have been approved by the United States Food and Drug Administration (United States Food and Drug Administration) for use in humans or livestock, or may not be approved. In an embodiment, carriers are known to those skilled in the art and include stabilizers, diluents and buffers. In an embodiment, stabilizers may include but are not limited to polyanions, salts, chelating agents (e.g., EDTA), metal ions (e.g., Cu 2+ 、Zn 2+ ), carbohydrates (e.g., sorbitol, lactose, mannitol, starch, sucrose, dextran, and glucose), polysorbate (PS; e.g., PS-20, PS-40, PS-60, PS-80), proteins (e.g., albumin or casein), and amino acids (e.g., arginine, aspartic acid, glutamic acid, lysine, proline, glycine, histidine, methionine). In an embodiment, the diluent may include, but is not limited to, saline, Hanks Balanced Salt, and Ringers solution.

[0116] In an embodiment, the composition is formulated as a pharmaceutical composition. In an embodiment, the formulation comprises: 100-200 mg / mL of anti-ILT7 mAb, 10-30 mM histidine / histidine-HCl, 150-200 mM sucrose, 10-20 mM L-methionine, 0.01%-0.05% PS-80, and a pH of 5.5-6.5. In an embodiment, the formulation comprises: 150 mg / mL of anti-ILT7 mAb, 20 mM histidine / histidine-HCl, 180 mM sucrose, 15 mM L-methionine, 0.02% PS-80, and a pH of 6. In an embodiment, the amount of the components of the formulation may be in the range of about 25%. Exemplary amounts are described herein.

[0117] In an embodiment, the anti-ILT7 mAb disclosed herein and the composition comprising it can be used in vitro, ex vivo or incorporated into a pharmaceutical composition. In an embodiment, the anti-ILT7 mAb disclosed herein and the composition comprising it can be used in vitro, ex vivo or incorporated into a pharmaceutical composition and administered to a subject (e.g., to treat, improve or prevent a disease or a combination thereof). In an embodiment, the administration of the pharmaceutical composition is independent of the formulation (e.g., dosage). In an embodiment, the administration of the pharmaceutical composition can depend on the formulation (e.g., dosage). In an embodiment, the administration of the pharmaceutical composition disclosed herein can depend on the formulation (e.g., dosage) and the therapeutically effective amount of the subject (e.g., to treat, improve or prevent a disease or a combination thereof). In an embodiment, the pharmaceutical composition disclosed herein is formulated into a preparation in a solid, semisolid, liquid or gaseous form, including but not limited to solutions, injections, liquid compositions, microspheres and aerosols. In an embodiment, the pharmaceutical composition comprising the anti-ILT7 binding protein used in the method described herein can be in the form of a solid or liquid. In an embodiment, the carrier is a liquid (e.g., an injectable liquid). In an embodiment, the carrier (e.g., an injectable liquid) is used for administration (e.g., intravenous or subcutaneous).

[0118] Route of administration

[0119] In an embodiment, any composition comprising an anti-ILT7 binding protein of the present disclosure can be administered in any form. In an embodiment, the anti-ILT7 binding protein is administered intravenously, subcutaneously, orally, intramuscularly, intrathecally, sublingually, rectally, vaginally, on the skin, systemically, topically, transdermally or by inhalation. In an embodiment, the anti-ILT7 binding protein is administered intravenously. In an embodiment, the anti-ILT7 binding protein is administered subcutaneously. In an embodiment, the anti-ILT7 binding protein is administered subcutaneously via an automatic injector.

[0120] In an embodiment, the disclosed composition is formulated and loaded into a self-administered delivery device. Exemplary devices are described herein and include exemplary devices such as automatic injectors. The automatic injector may allow intramuscular or subcutaneous administration routes. The automatic injector may target any site of the subject for use. In an embodiment, the syringe targeting site is selected from the group consisting of: thigh, buttocks, abdomen, arm, waist and combinations thereof. In an embodiment, the syringe is contacted with the thigh of the subject to achieve delivery of the composition of the present disclosure. In an embodiment, the syringe is contacted with the abdomen of the subject to achieve delivery of the composition of the present disclosure. In an embodiment, the syringe is contacted with the buttocks of the subject to achieve delivery of the composition of the present disclosure.

[0121] Alternatively, the disclosed compositions can be administered orally as liquids, capsules, or tablets (e.g., chewable tablets). Because the oral route is the most convenient and generally the safest and cheapest, it is the most commonly used route. However, due to the way in which drugs typically move through the digestive tract, this route has limitations. For drugs administered orally, absorption can begin in the mouth and stomach. However, most drugs are typically absorbed from the small intestine. The drug is delivered through the intestinal wall and enters the liver, and then transported to its target site via the bloodstream. The intestinal wall and liver chemically change (metabolize) many drugs, thereby reducing the amount of drugs that reach the bloodstream. Therefore, these drugs are usually given in smaller doses when injected intravenously to produce the same effect.

[0122] For the subcutaneous route, a needle is inserted into the fatty tissue just below the skin. After the drug is injected, the drug then moves into the small blood vessels (capillaries) and is carried away by the bloodstream. Alternatively, the drug reaches the bloodstream through the lymphatic vessels. When a larger volume of drug product is needed, the intramuscular route is better than the subcutaneous route. Because the muscle is located below the skin and fatty tissue, a longer needle is used. The drug is usually injected into the muscles of the upper arm, thigh or buttocks. How fast the drug is absorbed into the bloodstream depends in part on the blood supply of the muscle: the sparser the blood supply, the longer the drug absorption takes. For the intravenous route, the needle is directly inserted into the vein. The solution containing the drug can be given in a single dose or by continuous infusion. For infusion, the solution moves by gravity (from a foldable plastic bag) or more commonly, by an infusion pump through a flexible tubule to a tube (catheter) inserted into a vein, usually inserted into a forearm.

[0123] Timing of administration

[0124] The pharmaceutical composition of the present disclosure can be applied at any time. In an embodiment, the composition is applied before, during or after the symptom of the disease or composition is detected. In an embodiment, the composition is applied by means of a delivery device (e.g., an automatic injector). In an embodiment, the composition of the present disclosure is applied every 4 weeks, 5 weeks, 6 weeks, 8 weeks, 10 weeks, 20 weeks, 25 weeks, 30 weeks or 50 weeks. In an embodiment, the composition of the present disclosure is applied every month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 1 year, 2 years, 3 years, 4 years or 5 years.

[0125] In an embodiment, the pharmaceutical composition provided herein is administered via infusion or push injection. Infusion can be performed over a period of time. For example, infusion can be for administering medicine over a period of about 5 minutes to about 10 hours. Infusion can be performed over a period of about 5 min, 10 min, 20 min, 30 min, 40 min, 50 min, 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours or up to about 10 hours. In an embodiment, intravenous administration is used to deliver precise doses in vivo quickly and in a well-controlled manner. It is also used for irritant solutions, which, if given by subcutaneous or intramuscular injection, will cause pain and damage tissue. When given intravenously, the drug is delivered directly to the bloodstream and tends to take effect more quickly than when given by any other route. Therefore, health care practitioners closely monitor the people receiving intravenous injections to find that the drug is working or causing signs of adverse side effects. Moreover, the effect of the drug given by this approach tends to last for a shorter time. In some embodiments, the present invention relates to the administration of anti-ILT7 binding proteins. For example, the administration of anti-ILT7 binding proteins may be carried out by continuous infusion to prevent the occurrence of infusion reactions, such as headache, nausea, somnolence, dyspnea, fever, myalgia, rash or other symptoms. The potential risks associated with the administration of anti-ILT7 binding proteins are infection, redness, swelling, pain and induration at the application site. Before each IV infusion, the subject may receive IV methylprednisolone, oral diphenhydramine and oral acetaminophen or equivalent to prevent the risk or severity of potential reactions.

[0126] In an embodiment, medicine is administered intrathecally. For the intrathecal approach, a needle is inserted between two vertebrae of the lower spine and into the space around the spinal cord. The drug is then injected into the spinal canal. A small amount of local anesthetic is usually used to numb the injection site. This approach is used when the drug is needed to produce a rapid or local effect on the brain, spinal cord, or the tissue layer (meninges) covering them—for example, to treat infections of these structures. Drugs administered by oral inhalation can be atomized into droplets smaller than those administered by the nasal route, so that the drug can be delivered through the trachea (windpipe / trachea) and into the lungs. How deep the drug enters the lungs depends on the size of the droplets. Smaller droplets enter deeper, thereby increasing the amount of absorbed drug. Inside the lungs, it is absorbed into the bloodstream. Drugs applied to the skin are usually used for their local effects and are therefore most commonly used to treat superficial skin disorders, such as psoriasis, eczema, skin infections (viral, bacterial and fungal), itching and dry skin. The drug is mixed with an inactive substance. Depending on the consistency of the inactive substance, the formulation may be an ointment, cream, lotion, solution, powder or gel.

[0127] In an embodiment, a treatment regimen comprising a pharmaceutical composition may be administered based on the subject's body weight. In subjects determined to be obese (BMI>35), actual weight may need to be used. In an embodiment, body surface area may be used to calculate dosage.

[0128] Formulations

[0129] In an embodiment, the pharmaceutical composition of the present disclosure is in the form of a liquid, such as a solution, emulsion or suspension. In an embodiment, in a pharmaceutical composition intended to be administered by injection, one or more of a surfactant, a preservative, a wetting agent, a dispersant, a suspending agent, a buffer, a stabilizer and an isotonic agent may be included. In an embodiment, the pharmaceutical composition of the present disclosure is administered intravenously to a subject in need. In an embodiment, the pharmaceutical composition of the present disclosure is administered to a subject in need by subcutaneous injection. In an embodiment, the pharmaceutical composition of the present disclosure is administered to a subject in need by subcutaneous injection via an automatic syringe.

[0130] In an embodiment, a liquid pharmaceutical composition (whether a solution, suspension, or other similar form) containing an ILT7 binding protein for use in the methods described herein may include one or more of the following components: a sterile diluent, such as water for injection, saline solution (e.g., physiological saline), Ringer's solution, isotonic sodium chloride, a fixed oil that can serve as a solvent or suspension medium (such as a synthetic monoglyceride or diglyceride), polyethylene glycol, glycerol, propylene glycol, or other solvent; an antibacterial agent, such as benzyl alcohol or methyl paraben; an antioxidant, such as ascorbic acid or sodium bisulfite; a chelating agent, such as ethylenediaminetetraacetic acid; a buffer, such as acetate, citrate, or phosphate; and an agent for adjusting tonicity, such as sodium chloride or dextrose. In an embodiment, the formulation may be enclosed in one or more ampoules, disposable syringes, or vials (e.g., glass or plastic). In an embodiment, the formulation is enclosed in one or more vials (e.g., glass or plastic). In an embodiment, the formulation is enclosed in one or more disposable syringes (e.g., prefilled syringes (PFS)). In an embodiment, the formulation is enclosed in an automatic syringe. In an embodiment, the formulation is enclosed in a pen needle. In an embodiment, the formulation is enclosed in one or more vials (e.g., glass or plastic) prior to administration and then transferred to an auto-injector for administration to a subject. In an embodiment, the formulation is enclosed in one or more disposable syringes (e.g., PFS) prior to administration and then transferred to an auto-injector for administration to a subject. In an embodiment, the injectable pharmaceutical composition is sterile and complies with GMP specifications.

[0131] In an embodiment, the anti-ILT7 binding protein disclosed herein and the composition comprising the binding protein can be used as a pharmaceutical composition and can be combined with a pharmaceutically acceptable carrier. In an embodiment, the composition may include anti-ILT7 binding protein, a carrier, various diluents, fillers, salts, buffers, stabilizers, solubilizers and other materials well known in the art. In an embodiment, the characteristics of the carrier may depend on the route of administration. In an embodiment, the pharmaceutical composition comprises a histidine buffer (e.g., histidine / histidine-HCl). In an embodiment, the pharmaceutical composition disclosed herein comprises a pharmaceutically acceptable non-toxic, sterile carrier. In an embodiment, the pharmaceutical composition disclosed herein comprises an anti-ILT7 binding protein disclosed herein and one or more pharmaceutically acceptable carriers, diluents or excipients. In this regard, "pharmaceutically acceptable carriers, diluents or excipients" include, but are not limited to, any adjuvant, carrier, excipient, glidant, sweetener, diluent, preservative, dye / colorant, flavor enhancer, surfactant, wetting agent, dispersant, suspending agent, stabilizer, isotonic agent, solvent or emulsifier, which may have been approved by the United States Food and Drug Administration for use in humans or livestock, or may not be approved. For example, suitable carriers are known to those skilled in the art and include stabilizers, diluents and buffers. Exemplary stabilizers include carbohydrates (sorbitol, lactose, mannitol, starch, sucrose, dextran and glucose, etc.) and proteins (e.g., albumin or casein). Exemplary diluents include saline, Hank's balanced salts and Ringer's solution, etc. Exemplary buffers include alkali metal phosphates, alkali metal carbonates or alkaline earth metal carbonates, etc.

[0132] In an embodiment, the pharmaceutical composition of the present disclosure may include one or more auxiliary substances, such as one or more lipids, phospholipids, carbohydrates and lipopolysaccharides. In an embodiment, the pharmaceutical composition of the present disclosure may include one or more additional active substances. In an embodiment, the pharmaceutical composition of the present disclosure includes one or more additional therapeutic active substances. In an embodiment, a therapeutically effective dose of the pharmaceutical composition of the present disclosure is administered in combination with one or more additional therapeutic active substances to a subject in need. As used herein, "combination" refers to the following combination, which includes the anti-ILT7 binding protein provided herein and one or more additional therapeutic active substances, each of which can be administered continuously (sequentially), in parallel or simultaneously. In an embodiment, the pharmaceutical composition of the present disclosure can be administered at several time intervals to maintain a therapeutic level. In an embodiment, the pharmaceutical composition of the present disclosure can be used in combination with other bactericidal or antibacterial methods.

[0133] In embodiments, pharmaceutical compositions suitable for administration may be sterile. Prevention of microbial action may be achieved by various antibacterial and antifungal agents. Formulations suitable for use in the methods of treatment disclosed herein are described in Remington's Pharmaceutical Sciences (Mack Publishing Co.), 16th edition (1980).

[0134] The therapeutically effective dose of the compositions disclosed herein for treating ILT7-expressing cell-mediated diseases (such as certain types of autoimmune diseases) varies depending on a variety of different factors, including mode of administration, target site, subject physiological state, whether the subject is human or non-human animal, other drugs administered, and whether the treatment is preventive or therapeutic. In an embodiment, the subject is human. In an embodiment, the subject is a non-human animal (e.g., a transgenic mammal). In an embodiment, the therapeutic dose can be titrated to optimize safety and efficacy.

[0135] In an embodiment, the pharmaceutical composition used in the disclosed method can be manufactured in a conventional manner. In an embodiment, a pharmaceutical composition in lyophilized form is provided. In an embodiment, the pharmaceutical composition in lyophilized form is dissolved in a suitable aqueous carrier (e.g., sterile water for injection or sterile buffered saline) before being administered to a subject in need. In an embodiment, the pharmaceutical composition is prepared for infusion. In an embodiment, the pharmaceutical composition is prepared for infusion and albumin (e.g., human serum albumin [HSA]) or the subject's own heparinized blood is mixed into saline during preparation. The presence of an excess of this physiologically inert protein prevents the loss of antibodies by adsorption to the container wall and the tube used for the infusion solution. In an embodiment, the pharmaceutical composition is prepared for infusion and uses albumin. In an embodiment, the pharmaceutical composition is prepared for infusion and uses albumin in a saline solution at a concentration of about 0.5 to about 4.5% by weight. Other formulations may include liquid or lyophilized formulations.

[0136] In an embodiment, the lyophilisate of the present disclosure comprises an anti-ILT7 binding protein. In an embodiment, the lyophilisate comprising an anti-ILT7 binding protein may be reconstituted to generate an aqueous composition having an anti-ILT7 binding protein concentration of at least about 150 mg / mL. In an embodiment, in addition to the anti-ILT7 binding protein, the lyophilisate may also comprise other components, such as one or more of the following: (i) sugar (e.g., sucrose); (ii) buffer (e.g., histidine / histidine-HCl); (iii) PS-80; and (iv) methionine (e.g., L-methionine). An exemplary reconstituted product of a lyophilized binding protein (e.g., an antibody) comprises sterile water, a buffer, and / or a preservative. In an embodiment, the lyophilisate comprises a buffer and the reconstituted product comprises a buffer (which may be the same or different from the buffer of the lyophilisate). In an embodiment, the lyophilisate comprises a buffer and the reconstituted product does not comprise a buffer (e.g., sterile water for injection [WFI], saline). In an embodiment, the reconstituted product comprises a pharmacological agent, such as a chemotherapeutic compound, which may facilitate co-delivery with a binding protein (e.g., an antibody). In embodiments, the reconstitution comprises buffers, salts, stabilizers, glycerol, alcohol, preservatives, surfactants, etc. A comprehensive discussion of such pharmaceutical ingredients is available from Gennaro (2000) Remington: The Science and Practice of Pharmacy. 20th edition, ISBN: 0683306472.

[0137] In an embodiment, the pharmaceutical composition of the present disclosure can be prepared by techniques known to those skilled in the art. General considerations in the preparation and / or manufacture of pharmaceutical compositions can be found in, for example, Remington: The Science and Practice of Pharmacy [Remington: Pharmaceutical Technology and Practice] 21st edition, Lippincott Williams & Wilkins [Lippincott Williams and Wilkins Publishing Company], 2005 (incorporated herein by reference as a whole). In an embodiment, the anti-ILT7 binding protein or its fragment used in the method described herein can be mixed with a carrier to form a solution, a suspension or an emulsion. In an embodiment, one or more additives discussed herein may be added to the carrier or may be subsequently added. In an embodiment, the pharmaceutical composition of the present disclosure may be an aqueous solution (e.g., an emulsion or suspension), or may be a dry preparation. In an embodiment, the pharmaceutical composition of the present disclosure may be dehydrated or lyophilized, for example, by freeze drying or spray drying to achieve storage or formulation purposes. In an embodiment, the dehydrated or lyophilized pharmaceutical composition can be reconstituted into a liquid composition by adding a liquid carrier. In an embodiment, the dehydrated or lyophilized pharmaceutical composition can be administered as a dry formulation using methods known to those skilled in the art. In an embodiment, the anti-ILT7 binding protein used in the methods described herein is stored as a lyophilized powder and then reconstituted into a liquid composition before being administered to a subject in need. In an embodiment, the pharmaceutical composition comprising the anti-ILT7 binding protein is stored as a lyophilized powder and then reconstituted into a liquid composition before being administered to a subject in need.

[0138] Delivery device

[0139] The various compositions disclosed herein can be loaded into a delivery device or preloaded and stored for future use. Liquid drugs are delivered to subjects in need using a drug delivery device (such as a syringe). After activation, the drug delivery device can discharge drugs (e.g., anti-ILT7 antibodies) stored in the internal reservoir of the primary container into the subject by a needle, cannula or other delivery member.

[0140] Exemplary delivery devices include but are not limited to pen injectors, manual injectors, automatic injectors, and on-body devices. In an embodiment, the delivery device delivers, for example, drugs, compositions, formulations, etc., by automatic administration. In an embodiment, the delivery device is a pen injector. In an embodiment, the delivery device is an automatic injector. In an embodiment, the delivery device is an on-body device. In an embodiment, the delivery device is a manual injector. In an embodiment, the delivery device is the same as the storage device. In an embodiment, the delivery device, for example, delivers an anti-ILT7 binding protein or a pharmaceutical composition comprising an anti-ILT7 binding protein to a delivery site via the skin of a subject in need. In an embodiment, the delivery device is wearable.

[0141] In an embodiment, a delivery device, such as an auto-injector and a manual injector, comprises a needle shield and a needle, the needle shield extending from the housing in a forward direction. In an embodiment, the needle shield protects the needle from exposure prior to delivery. In an embodiment, the needle shield may be arranged to move further into the housing along the longitudinal axis of the housing when the drug delivery device is pushed toward the delivery site. In an embodiment, for an auto-injector, this movement of the needle shield may cause the drug delivery device to be activated to expel the drug through the needle.

[0142] An autoinjector preloaded with 150 mg / mL of anti-ILT7 antibody / 20 mM histidine, 15 mM methionine, 180 mM sucrose, 0.02% PS80 (pH 6.0) is provided. In an embodiment, the autoinjector is a single-use or disposable syringe.

[0143] In an embodiment, a device is provided: it includes a subassembly of a drug delivery device, the subassembly includes a housing configured to contain a drug container structure, the drug (e.g., anti-ILT7 antibody) is discharged from the structure during use of the drug delivery device, the housing having a proximal end and a distal end; and a drive assembly, the drive assembly includes a plunger rod at the proximal end of the drive assembly, the plunger rod is configured to apply an activation force on the drug container structure when activated, thereby discharging the drug from the drug delivery device, wherein the proximal end of the housing includes an opening, and the distal end includes a sealable portion, wherein the drive assembly can be inserted into the housing at the proximal end to form the subassembly. In an embodiment, the drug is discharged after contact with a target injection site (e.g., abdomen, thigh and / or arm). In an embodiment, the drug is discharged after being activated by a button.

[0144] Exemplary delivery devices (e.g., automatic injectors) and methods of use thereof are described in International Patent Publication Nos. WO / 2023 / 016889, WO / 2023 / 016893, WO / 2023 / 016933, WO / 2023 / 016888, WO / 2022 / 212227, WO / 2022 / 203830, WO / 2022 / 192100, WO / 2022 / 192308, WO / 2022 / 098593, WO / 2022 / 098592, WO / 2021 / 011716, WO / 2021 / 011717, WO / 2020 / 023220, and WO / 2018 / 034784, each of which is incorporated herein by reference in its entirety. For example, in embodiments, the compositions of the present disclosure may be delivered using the delivery devices described in any of the above-mentioned patent applications.

[0145] The device, assembly, component, subsystem, method or drug delivery device may further include or be used with a drug, including but not limited to those compositions described herein and any variations thereof. In embodiments, the composition may be in liquid form, lyophilized form, or in a form reconstituted from a lyophilized form.

[0146] Kit containing anti-ILT7 binding protein

[0147] Disclosed herein are kits (i.e., articles of manufacture) that can be used to provide anti-ILT7 binding protein compositions (e.g., anti-ILT7 antibodies). Such kits may include anti-ILT7 binding proteins (e.g., in liquid or lyophilized form) or pharmaceutical compositions containing the anti-ILT7 binding proteins. In addition, such kits may include anti-ILT7 binding proteins or pharmaceutical compositions containing anti-ILT7 binding proteins sealed in storage containers (e.g., syringes, prefilled pen needles, vials), delivery devices (e.g., automatic injectors, on-body devices, pen injectors), and instructions for use. These kits may contain additional therapeutic agents for treating the above-mentioned autoimmune diseases, for example, delivered in combination with the enclosed anti-ILT7 binding proteins.

[0148] In an embodiment, the kit comprises a plurality of delivery devices. For example, the kit may comprise 1, 2, 3, 4, 5, 6, 7, 8, 9 or up to 10 delivery devices (e.g., auto-injectors). In an embodiment, the kit comprises a disposable auto-injector. In an embodiment, the kit further comprises instructions for use thereof. In an embodiment, the kit further comprises a device for disposing of the used auto-injector (e.g., a sharps container).

[0149] In an embodiment, a kit is provided, comprising: a) a pre-filled auto-injector comprising a pharmaceutical composition comprising an anti-ILT7 binding protein; and b) instructions for use thereof. In an embodiment, the pre-filled auto-injector comprises dastilimab.

[0150] In an embodiment, a kit is provided, comprising: a) a pharmaceutical composition comprising an anti-ILT7 binding protein composition for administration to a subject in need thereof; b) instructions describing how to administer the pharmaceutical composition to a subject in need thereof; and c) a delivery device for delivering the pharmaceutical composition to a subject in need thereof.

[0151] In an embodiment, a kit is provided, comprising: a) a pharmaceutical composition comprising an anti-ILT7 binding protein composition for administration to a subject in need, wherein the subject suffers from an autoimmune disease; b) instructions describing how to administer the pharmaceutical composition to a subject in need; and c) a delivery device for delivering the pharmaceutical composition to a subject in need. Exemplary autoimmune diseases include, but are not limited to, local segmental glomerulosclerosis (FSGS), alopecia areata, myositis, diabetes, Hashimoto's disease, autoimmune adrenal insufficiency, pure red cell aplasia, multiple sclerosis, IgG4RD, rheumatoid carditis, systemic lupus erythematosus, psoriasis, rheumatoid arthritis, chronic inflammation, Sjögren's syndrome, polymyositis, dermatomyositis, inclusion body myositis, juvenile myositis, and scleroderma.

[0152] Containers comprising an anti-ILT7 binding protein (eg, dasitimumab) are provided. In an embodiment, provided herein are containers comprising a composition in unit dosage form.

[0153] In embodiments, the container is a vial. In embodiments, the vial is glass. In embodiments, the vial is plastic. In embodiments, the vial may contain a lyophilized dosage form of a composition provided herein.

[0154] In embodiments, a vial can contain a liquid dosage form of a composition provided herein. In embodiments, the container is a vial and contains about 0.1 mL, 0.2 mL, 0.3 mL, 0.4 mL, 0.5 mL, 0.6 mL, 0.7 mL, 0.8 mL, 0.9 mL, 1.0 mL, 1.25 mL, 1.5 mL, 1.75 mL, 2.0 mL, 2.25 mL, 2.5 mL, 2.75 mL, 3.0 mL, 3.25 mL, 3.5 mL, 3.75 mL, 4.0 mL, 4.25 mL, 10.0 mL, 10.25 mL, 10.5 mL, 10.75 mL, 10.0 mL, 10.25 mL, 10.5 mL, 10.75 mL, 10.0 mL, 10.25 mL, 10.5 mL, 10.75 mL, 10.0 mL, 10.25 mL, 10.5 mL, 10.75 mL, 10.0 mL, 10.25 mL, 10.5 mL, 10.75 mL, 10.0 mL, 10.25 mL, 10.5 mL, 10.75 mL, 10.0 mL, 10.25 mL, 10.5 mL, 10.75 mL, In an embodiment, the container is a vial and contains about 0.1mL to about 0.5mL, about 0.1mL to about 1.0mL, about 0.5mL to about 1.5mL, about 0.7mL to about 2.0mL, about 1.0mL to about 2.5mL, about 1.25mL to about 2.0mL, about 1.25mL to about 2.75mL, about 2.0mL to about 4.0mL, about 1.5mL to about 3.0mL, about 3.0mL to about 5.0mL, about 4.0mL to about 6.0mL, about 5.0mL to about 7.0mL, about 6.0mL to about 8.0mL, about 7.0mL to about 9.0mL, about 8.0mL to about 10.0mL or about 9.0mL to about 10.0mL liquid dosage form. In an embodiment, the container is a vial, containing about 1.0mL liquid dosage. In an embodiment, the container is a vial, containing about 1.5mL liquid dosage. In an embodiment, the container is a vial, containing about 2.0mL liquid dosage.

[0155] In embodiments, the container is a syringe (e.g., PFS). In embodiments, the syringe is a PFS. In embodiments, the vial may contain a liquid dosage form of the composition provided herein. In embodiments, the container is a PFS and contains about 0.1 mL, 0.2 mL, 0.3 mL, 0.4 mL, 0.5 mL, 0.6 mL, 0.7 mL, 0.8 mL, 0.9 mL, 1.0 mL, 1.25 mL, 1.5 mL, 1.75 mL, 2.0 mL, 2.25 mL, 2.5 mL, 2.75 mL, 3.0 mL, 3.25 mL, 3.5 mL, 3.75 mL, 4.0 mL, 4.25 10.0 mL, 10.25 mL, 10.5 mL, 10.75 mL, 10.0 mL, 10.25 mL, 10.5 mL, 10.75 mL, 10.0 mL, 10.25 mL, 10.5 mL, 10.75 mL, 10.0 mL, 10.25 mL, 10.5 mL, 10.75 mL, 10.0 mL, 10.25 mL, 10.5 mL, 10.75 mL, 10.0 mL, 10.25 mL, 10.5 mL, 10.75 mL, 10.0 mL, 10.25 mL, 10.5 mL, 10.75 mL, In an embodiment, the container is a PFS and contains about 0.1 mL to about 0.5 mL, about 0.1 mL to about 1.0 mL, about 0.5 mL to about 1.5 mL, about 0.7 mL to about 2.0 mL, about 1.0 mL to about 2.5 mL, about 1.25 mL to about 2.0 mL, about 1.25 mL to about 2.75 mL, about 2.0 mL to about 4.0 mL, about 1.5 mL to about 3.0 mL, about 3.0 mL to about 5.0 mL, about 4.0 mL to about 6.0 mL, about 5.0 mL to about 7.0 mL, about 6.0 mL to about 8.0 mL, about 7.0 mL to about 9.0 mL, about 8.0 mL to about 10.0 mL, or about 9.0 mL to about 10.0 mL of liquid dosage form. In an embodiment, the container is a PFS and contains about 1.0 mL of liquid dosage. In an embodiment, the container is a PFS and contains about 1.5 mL of liquid dosage. In an embodiment, the container is a PFS and contains about 2.0 mL of liquid dosage.

[0156] In embodiments, the formulation is stable as a liquid formulation, e.g., when in liquid form. In embodiments, the formulation in liquid form promotes ease of administration, as compared to an otherwise comparable formulation not in liquid form. In embodiments, the formulation in liquid form comprises fewer manufacturing steps, as compared to an otherwise comparable formulation not in liquid form.

[0157] In an embodiment, a kit comprising a delivery device is provided. In an embodiment, the delivery device is, for example, an injection device, an inhalation device, or a medical nebulizer. In an embodiment, the delivery device is an autoinjector.

[0158] In an embodiment, a kit comprises a delivery device, wherein the delivery device is a delivery device that is assembled prior to addition to the kit. In an embodiment, a kit comprises a delivery device, wherein the delivery device is a delivery device that is partially assembled prior to addition to the kit. In an embodiment, a kit comprises a delivery device, wherein the delivery device is a delivery device that is fully assembled prior to addition to the kit. In an embodiment, a kit comprises a delivery device, wherein the delivery device is a delivery device that is assembled prior to administration. In an embodiment, a kit comprises a delivery device, wherein the delivery device is a delivery device that is fully assembled prior to administration.

[0159] In an embodiment, the kit includes a delivery device, wherein the delivery device is assembled as a part of the kit instructions. In an embodiment, the anti-ILT7 binding protein or the pharmaceutical composition comprising the anti-ILT7 binding protein enclosed in the storage container is combined with the delivery device before administration. In an embodiment, the kit includes instructions, wherein these instructions describe how to combine the delivery device and the anti-ILT7 binding protein or the pharmaceutical composition comprising the anti-ILT7 binding protein enclosed in the storage container. In an embodiment, the kit includes instructions, wherein these instructions describe how to combine the delivery device and the anti-ILT7 binding protein or the pharmaceutical composition comprising the anti-ILT7 binding protein enclosed in the storage container, thereby producing a fully assembled delivery device for delivery to the delivery site (e.g., by the skin of a subject in need).

[0160] In an embodiment, a kit is provided, comprising a) a pharmaceutical composition comprising an anti-ILT7 binding protein composition for administration to a subject in need thereof, wherein the subject suffers from an autoimmune disease; b) instructions describing how to administer the pharmaceutical composition to a subject in need thereof; and c) a delivery device for delivering the pharmaceutical composition to a subject in need thereof.

[0161] In an embodiment, a kit is provided, comprising a) a pharmaceutical composition comprising an anti-ILT7 binding protein composition for administration to a subject in need thereof, wherein the subject has an autoimmune disease; b) instructions describing how to administer the pharmaceutical composition to a subject in need thereof; and c) an automatic injector for delivering the pharmaceutical composition to a subject in need thereof.

[0162] In embodiments, the formulations disclosed herein are for subcutaneous administration. In embodiments, the volume of the formulations of the disclosure for subcutaneous administration is about 0.5 mL to about 2.5 mL. In embodiments, the volume of a formulation of the disclosure administered subcutaneously is about 0.5 mL, 0.55 mL, 0.6 mL, 0.65 mL, 0.7 mL, 0.75 mL, 0.8 mL, 0.85 mL, 0.9 mL, 0.95 mL, 1 mL, 1.05 mL, 1.1 mL, 1.15 mL, 1.2 mL, 1.25 mL, 1.3 mL, 1.35 mL, 1.4 mL, 1.45 mL, 1.5 mL, 1.55 mL, 1.6 mL, 1.65 mL, 1.7 mL, 1.75 mL, 1.8 mL, 1.85 mL, 1.9 mL, 1.95 mL, 2 mL, 2.05 mL, 2.1 mL, 2.15 mL, 2.2 mL, 2.25 mL, 2.3 mL, 2.35 mL, 2.4 mL, 2.45 mL, or up to about 2.5 mL. In embodiments, the volume of a formulation of the disclosure administered subcutaneously is about 0.5 to about 1.0 mL, about 0.5 mL to about 1.5 mL, about 1.0 mL to about 2.0 mL, about 0.75 mL to about 2.25 mL, about 1.0 mL to about 2.5 mL, about 1.5 mL to about 2.5 mL, or about 1.0 mL to about 2.25 mL.

[0163] In an embodiment, the volume of the formulation of the present disclosure administered subcutaneously is about 1.0mL. In an embodiment, the volume of the formulation of the present disclosure administered subcutaneously is about 1.5mL. In an embodiment, the volume of the formulation of the present disclosure administered subcutaneously is about 2.0mL. In an embodiment, the volume of the formulation of the present disclosure administered subcutaneously is about 1.0mL, wherein the formulation is stored in a syringe (e.g., a prefilled syringe; PFS) before administration. In an embodiment, the volume of the formulation of the present disclosure administered subcutaneously is about 1.5mL, wherein the formulation is stored in a syringe (e.g., a prefilled syringe; PFS) before administration. In an embodiment, the volume of the formulation of the present disclosure administered subcutaneously is about 2.0mL, wherein the formulation is stored in a syringe (e.g., a prefilled syringe; PFS) before administration. In an embodiment, the volume of the formulation of the present disclosure administered subcutaneously is about 1.0mL, wherein the formulation is stored in two or more syringes (e.g., prefilled syringes; PFS) before administration. In an embodiment, the volume of the formulation of the present disclosure administered subcutaneously is about 1.5 mL, wherein the formulation is stored in two or more syringes (e.g., prefilled syringes; PFS) prior to administration. In an embodiment, the volume of the formulation of the present disclosure administered subcutaneously is about 2.0 mL, wherein the formulation is stored in two or more syringes (e.g., prefilled syringes; PFS) prior to administration.

[0164] In an embodiment, the volume of the formulation of the disclosure administered subcutaneously is about 1.0 mL, wherein the formulation is stored in two or more syringes (e.g., prefilled syringes; PFS) before administration and the formulation is administered by a delivery device. In an embodiment, the volume of the formulation of the disclosure administered subcutaneously is about 1.5 mL, wherein the formulation is stored in two or more syringes (e.g., prefilled syringes; PFS) before administration and the formulation is administered by a delivery device. In an embodiment, the volume of the formulation of the disclosure administered subcutaneously is about 2.0 mL, wherein the formulation is stored in two or more syringes (e.g., prefilled syringes; PFS) before administration and the formulation is administered by a delivery device.

[0165] In an embodiment, the volume of the formulation of the present disclosure administered subcutaneously is about 1.0 mL, wherein the formulation is stored in two or more syringes (e.g., prefilled syringes; PFS) prior to administration and the formulation is administered by an automatic injector. In an embodiment, the volume of the formulation of the present disclosure administered subcutaneously is about 1.5 mL, wherein the formulation is stored in two or more syringes (e.g., prefilled syringes; PFS) prior to administration and the formulation is administered by an automatic injector. In an embodiment, the volume of the formulation of the present disclosure administered subcutaneously is about 2.0 mL, wherein the formulation is stored in two or more syringes (e.g., prefilled syringes; PFS) prior to administration and the formulation is administered by an automatic injector.

[0166] In an embodiment, the preparaton disclosed herein includes a binding protein (e.g., anti-ILT7 binding protein) of a high protein concentration, but retains a viscosity level suitable for subcutaneous administration. In an embodiment, a high protein concentration promotes a higher dose that can be delivered by a single injection. In an embodiment, the viscosity level in the preparaton disclosed herein ranges from about 1cP to about 50cP. In an embodiment, the preparaton disclosed herein includes about 0cP, 2cP, 4cP, 6cP, 8cP, 10cP, 12cP, 14cP, 16cP, 18cP, 20cP, 22cP, 24cP, 26cP, 28cP, 30cP, 32cP, 34cP, 36cP, 38cP, 40cP, 42cP, 44cP, 46cP, 48cP or up to about 50cP viscosity. In embodiments, the viscosity levels in the formulations of the present disclosure range from about 1 cP to about 20 cP, 5 cP to about 30 cP, 10 cP to about 35 cP, 25 cP to about 35 cP, or about 30 cP to about 50 cP.

[0167] In embodiments, a single injection of any disclosed formulation is administered to a subject in need thereof. In embodiments, multiple injections of any disclosed formulation are administered to a subject in need thereof. In embodiments, multiple injections of any disclosed formulation may be performed as part of the methods of the present disclosure. In embodiments, a single injection of any disclosed composition may be performed as part of the methods of the present disclosure. In embodiments, subcutaneous administration allows for fewer or single injections of the disclosed compositions.

[0168] In an embodiment, the anti-ILT7 binding protein of the present disclosure is administered in a schedule that provides the best results. In an embodiment, about once a week, about twice a week, about every two weeks, about once a month, about every four weeks, about every two months, about every 3 months, about every 12 weeks, about every 15 weeks, about every 16 weeks, about every four months, about every five months, about every six months or every six months, the anti-ILT7 binding protein is administered to a subject in need. Any number of administrations may be provided to a subject in need.

[0169] In embodiments, an anti-ILT7 binding protein disclosed herein is administered at a dose of at least about or at most about 50 mg, 60 mg, 70 mg, 75 mg, 80 mg, 90 mg, 100 mg, 110 mg, 120 mg, 125 mg, 130 mg, 140 mg, 150 mg, 160 mg, 170 mg, 175 mg, 180 mg, 190 mg, 200 mg, 210 mg, 220 mg, 225 mg, 230 mg, 240 mg, 250 mg, 260 mg, 270 mg, 275 mg, 280 mg, 290 mg, 300 mg, 325 mg, 350 mg, 375 mg, 400 mg, 425 mg, 450 mg, 475 mg, 500 mg, 525 mg, 550 mg, 575 mg or about 600 mg. In an embodiment, about weekly, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 20 weeks or about monthly, about every two months, about every three months, about every four months, about every six months Anti-ILT7 binding protein is administered. In an embodiment, anti-ILT7 binding protein is administered at a dosage of about 120 mg to about 200 mg every 4 weeks, about 50 mg to about 300 mg every 4 weeks, about 300 mg to about 600 mg every 4 weeks, about 450 mg to about 600 mg every 4 weeks, about 150 mg to about 300 mg every 12 weeks (ie, every three months), about 200 mg to about 500 mg every 12 weeks (ie, every three months), or about 300 mg to about 600 mg every 12 weeks (ie, every three months). In an embodiment, anti-ILT7 binding protein is administered at a dosage of about 150 mg every 4 weeks. In embodiments, the anti-ILT7 binding protein is administered at a dose of about 300 mg every 4 weeks. In embodiments, the anti-ILT7 binding protein is administered at a dose of about 450 mg every 4 weeks.

[0170] In an embodiment, the anti-ILT7 binding protein disclosed herein can be administered subcutaneously at a dose of about 150 mg to about 450 mg in a volume between 1 mL and 2 mL in a single injection. In an embodiment, the anti-ILT7 binding protein is administered at a dose of about 300 mg in a 1 mL single injection. In an embodiment, the anti-ILT7 binding protein is administered at a dose of about 300 mg in a 1.5 mL single injection. In an embodiment, the anti-ILT7 binding protein is administered at a dose of about 300 mg in a 2 mL single injection.

[0171] In embodiments, the compositions disclosed herein can be administered subcutaneously at a dose of about 150 mg to about 450 mg in a volume between 1 mL and 2 mL in a single injection. In embodiments, the compositions are administered at a dose of about 300 mg in a 1 mL single injection. In embodiments, the compositions are administered at a dose of about 300 mg in a 1.5 mL single injection. In embodiments, the compositions are administered at a dose of about 300 mg in a 2 mL single injection.

[0172] In embodiments, the formulations disclosed herein can be administered subcutaneously at a dose of about 150 mg to about 450 mg in a volume between 1 mL and 2 mL in a single injection. In embodiments, the formulation is administered at a dose of about 300 mg in a 1 mL single injection. In embodiments, the formulation is administered at a dose of about 300 mg in a 1.5 mL single injection. In embodiments, the formulation is administered at a dose of about 300 mg in a 2 mL single injection.

[0173] method

[0174] Use of formulations

[0175] In embodiments, the formulations provided herein comprising an anti-ILT7 binding protein effectively address one or more of: light-induced tryptophan oxidation, reduced potency, reduced shelf life, the need for a nitrogen blanket, and combinations thereof. In embodiments, the formulation does not use a nitrogen blanket or lacks a nitrogen blanket in the manufacturing process.

[0176] In embodiments, the formulations and methods disclosed herein reduce or eliminate the need for engineering controls during manufacturing, including but not limited to lighting adjustments, and the need for a nitrogen blanket. In embodiments, the methods do not include lighting adjustments. In embodiments, the methods do not include a nitrogen blanket. In embodiments, the formulations are produced without the use of a nitrogen blanket.

[0177] In embodiments, L-methionine at a concentration of 15 mM is effective to reduce aggregation, reduce oxidation (e.g., light-induced tryptophan and / or methionine oxidation) of the compositions provided herein, or reduce aggregation and reduce oxidation. In embodiments, reduced oxidation may refer to reduced L-methionine oxidation. In embodiments, reduced oxidation may refer to any of the following: reduced CDR modifications, reduced Fc deamidation (e.g., N330, N389, and / or N394 of SEQ ID NO: 10; or N55 and / or N99 of SEQ ID NO: 1 or SEQ ID NO: 10), reduced Fc oxidation (e.g., M257 and / or M433 of SEQ ID NO: 10), and any combination thereof. In embodiments, reduced oxidation may refer to W102 and / or W104 of SEQ ID NO: 1 or SEQ ID NO: 10. In embodiments, L-methionine is effective to reduce light-induced tryptophan oxidation and / or its rate in the CDRs of the anti-ILT7 binding protein. In embodiments, L-methionine is effective to reduce light-induced tryptophan oxidation in the CDRs of the anti-ILT7 binding protein (eg, the CDRs of SEQ ID NO: 1).

[0178] The reduction of light-induced tryptophan oxidation can range from stabilizing to eliminating oxidation of the affected or presumed affected residues in the compositions of the present disclosure. The oxidation level of the composition can be determined at any time. In embodiments, oxidation is determined at the beginning of manufacture of the disclosed composition, during an intermediate step, or at the end. In embodiments, oxidation can be determined at the end of manufacture. In embodiments, oxidation can be determined relative to the levels before and after addition of L-methionine.

[0179] In an embodiment, the use of the provided method effectively stabilizes the oxidation level of the composition disclosed herein. Various provided methods can be used to maintain the oxidation level of the provided composition (e.g., a composition comprising a sequence of Table 1 or a composition having at least about 85% identity with those sequences of Table 1) during the manufacturing process and / or in the transportation and subject administration. The maintenance of oxidation can be used to maintain the effectiveness of the provided composition. For example, the composition disclosed herein can have a stable oxidation level of one or more residues after light exposure. For example, the composition provided herein has no more than about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28% or 30% of oxidized substances when exposed to light of 1600-1800 lux for 3 days. For example, the compositions provided herein have no more than about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28% or 30% oxidative species when exposed to 1600-1800 lux of light for 4 days. For example, the compositions provided herein have no more than about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28% or 30% oxidative species when exposed to 1600-1800 lux of light for 5 days. For example, the compositions provided herein have no more than about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28% or 30% of oxidative species selected from the group consisting of: M257 of SEQ ID NO: 10 and M433 of SEQ ID NO: 10 when exposed to 1600-1800 lux of light for 5 days.For example, the compositions provided herein have no more than about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28% or 30% of oxidative species selected from the group consisting of M257 of SEQ ID NO: 10, M433 of SEQ ID NO: 10, W102 of SEQ ID NO: 10, and W104 of SEQ ID NO: 10 when exposed to 1600-1800 lux of light for 5 days. For example, the compositions provided herein have no more than about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28% or 30% of oxidative species selected from the group consisting of M257 of SEQ ID NO: 10, M433 of SEQ ID NO: 10, W102 of SEQ ID NO: 10, W104 of SEQ ID NO: 10, and combinations thereof when exposed to 1600-1800 lux of light for 3 to 5 days.

[0180] In an embodiment, the use of the provided methods effectively stabilizes the post-translational modification levels of the CDR residues in the compositions disclosed herein. Various provided methods can be used to maintain the PTM levels of the provided compositions (e.g., compositions comprising the sequences of Table 1 or compositions having at least about 85% identity to those sequences of Table 1) during manufacturing and / or in transportation and subject administration. The maintenance of PTMs can be used to maintain the efficacy of the provided compositions. For example, the compositions disclosed herein can have stable PTM levels of one or more residues after light exposure. For example, the compositions provided herein have no more than about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28%, or 30% of modified species when exposed to 1600-1800 lux of light for 3 days. For example, the compositions provided herein have no more than about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28% or 30% of modified species when exposed to 1600-1800 lux of light for 4 days. For example, the compositions provided herein have no more than about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28%, or 30% of modified species when exposed to 1600-1800 lux of light for 5 days. For example, the compositions provided herein have no more than about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28% or 30% of a modified substance selected from the group consisting of: M257 of SEQ ID NO: 10 and M433 of SEQ ID NO: 10 when exposed to 1600-1800 lux of light for 5 days.For example, the compositions provided herein have no more than about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28% or 30% of a modified substance selected from the group consisting of M257 of SEQ ID NO: 10, M433 of SEQ ID NO: 10, W102 of SEQ ID NO: 10, and W104 of SEQ ID NO: 10 when exposed to 1600-1800 lux of light for 5 days. For example, the compositions provided herein have no more than about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28% or 30% of a modified substance selected from the group consisting of: M257 of SEQ ID NO: 10, M433 of SEQ ID NO: 10, W102 of SEQ ID NO: 10, W104 of SEQ ID NO: 10, and combinations thereof, when exposed to 1600-1800 lux of light for 3 to 5 days. In an embodiment, the composition binds ILT7 and comprises complementarity determining regions (CDRs) HCDR1, HDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprising the sequences of SEQ ID NOs: 3, 4, 5, 6, 7, and 8, respectively.

[0181] In embodiments, the methods described herein are effective to produce Fc oxidation resistant compositions. For example, oxidation of vulnerable residues can be prevented using any of the compositions and methods disclosed herein as compared to oxidation of otherwise comparable compositions when the methods or compositions of the disclosure are not used. In embodiments, the vulnerable residues are M257 and / or M433 of SEQ ID NO: 10.

[0182] In embodiments, compositions provided herein comprising L-methionine (e.g., about 15 mM L-methionine) have a reduced percentage of oxidative species. In embodiments, compositions provided herein have a lower percentage of oxidative species when exposed to 1600-1800 lux of light for about 3 days to about 5 days, as compared to otherwise comparable compositions lacking a formulation provided herein and / or lacking L-methionine (e.g., about 15 mM L-methionine). In embodiments, the percentage of oxidized species is reduced by about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28%, 30%, 32%, 34%, 36%, 38%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or up to about 100% as compared to an otherwise comparable composition lacking a formulation provided herein and / or lacking L-methionine. In an embodiment, when the composition provided herein is exposed to the light of 1600-1800 lux for about 5 days, the percentage of oxidizing substances is in the range of 0.2% to about 0.5%. In an embodiment, when the light of 1600-1800 lux is exposed for 1, 2, 3, 4, 5, 6, 7, 8, 9 or up to 10 days, the percentage of oxidizing substances in the disclosed composition is less than 0.5%. In an embodiment, when the light of 1600-1800 lux is exposed for 1, 2, 3, 4, 5, 6, 7, 8, 9 or up to 10 days, the percentage of oxidizing substances in the disclosed composition is less than 0.4%. In an embodiment, when the light of 1600-1800 lux is exposed for 1, 2, 3, 4, 5, 6, 7, 8, 9 or up to 10 days, the percentage of oxidizing substances in the disclosed composition is less than 0.3%. In embodiments, the percentage of oxidative species in the disclosed compositions is less than 0.2% when exposed to light at 1600-1800 lux for 1, 2, 3, 4, 5, 6, 7, 8, 9 or up to 10 days. In embodiments, the percentage of oxidative species in the disclosed compositions is less than 0.1% when exposed to light at 1600-1800 lux for 1, 2, 3, 4, 5, 6, 7, 8, 9 or up to 10 days.

[0183] In an embodiment, the composition may be Fc oxidation resistant or with reduced vulnerable residues. The reduction of Fc oxidation may refer to a slowing or reduction in the oxidation rate when exposed to degradation factors such as light. For example, when the composition of the present disclosure is exposed to 1600-1800 lux of light for 3 to 5 days, the percentage of oxidized substances of the ILT7 binding protein in the composition is increased at a rate of only 0.2%-0.5% per day. In an embodiment, when a composition comprising a sequence of Table 1 or a sequence having at least about 85% identity to the sequence is exposed to 1600-1800 lux of light for 3 to 5 days, the percentage of oxidized substances in the composition is increased at a rate of up to about 0.2% per day. In an embodiment, when a composition comprising a sequence of Table 1 or a sequence having at least about 85% identity to the sequence is exposed to 1600-1800 lux of light for 3 to 5 days, the percentage of oxidized substances in the composition is increased at a rate of up to about 0.3% per day. In embodiments, when a composition comprising a sequence of Table 1 or a sequence having at least about 85% identity thereto is exposed to 1600-1800 lux of light for 3 to 5 days, the percentage of oxidized species in the composition increases at a rate of up to about 0.4% per day. In embodiments, when a composition comprising a sequence of Table 1 or a sequence having at least about 85% identity thereto is exposed to 1600-1800 lux of light for 3 to 5 days, the percentage of oxidized species in the composition increases at a rate of up to about 0.5% per day. In embodiments, the composition binds to ILT7 and comprises complementary determining regions (CDRs) HCDR1, HDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprising the sequences of SEQ ID NOs: 3, 4, 5, 6, 7, and 8, respectively.

[0184] In embodiments, L-methionine at a concentration of about 15 mM is effective to reduce aggregation of a composition provided herein or its rate thereof, as compared to an otherwise comparable composition lacking a formulation provided herein and / or lacking L-methionine (e.g., less than 15 mM L-methionine). In embodiments, L-methionine at a concentration of about 15 mM is effective to reduce aggregation of a composition provided herein by at least about 1-fold, 5-fold, 10-fold, 15-fold, 25-fold, 50-fold, 75-fold, 100-fold, 150-fold, or 250-fold, as compared to an otherwise comparable composition lacking L-methionine (e.g., less than 15 mM L-methionine). In embodiments, L-methionine at a concentration of about 15 mM is effective to reduce aggregation of a composition provided herein under stress conditions (e.g., 40° C.), as compared to an otherwise comparable composition lacking L-methionine (e.g., less than 15 mM L-methionine). In embodiments, L-methionine at a concentration of about 15 mM is effective to reduce aggregation of a composition provided herein under stress conditions (e.g., 40° C.) by at least about 1-fold, 5-fold, 10-fold, or 15-fold, as compared to an otherwise comparable composition lacking L-methionine (e.g., less than 15 mM L-methionine).

[0185] In embodiments, L-methionine at a concentration of about 15 mM is effective to reduce aggregation, reduce oxidation, or reduce aggregation and reduce oxidation of a composition provided herein, as compared to an otherwise comparable composition having a different concentration of L-methionine, by at least about: 0.1%, 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28%, 30%, 32%, 34%, 36%, 38%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or up to about 100%, as compared to an otherwise comparable composition lacking a formulation provided herein and / or lacking L-methionine (e.g., about 15 mM L-methionine). In embodiments, oxidation can be determined using any analysis in the art (e.g., peptide mapping, reverse phase HPLC (RP-HPLC), LC-MS methods, such as electrospray ionization (ESI) MS, etc.). In embodiments, the oxidation rate is determined. In embodiments, the presence or absence of oxidation is determined. In embodiments, oxidation is determined at various temperatures. In embodiments, oxidation is determined under stress conditions (e.g., 40° C.). In embodiments, oxidation is determined at room temperature. In an embodiment, oxidation is determined at 0°C, 1°C, 2°C, 3°C, 4°C, 5°C, 6°C, 7°C, 8°C, 9°C, 10°C, 11°C, 12°C, 13°C, 14°C, 15°C, 16°C, 17°C, 18°C, 19°C, 20°C, 21°C, 22°C, 23°C, 24°C, 25°C, 26°C, 27°C, 28°C, 29°C, 30°C, 31°C, 32°C, 33°C, 34°C, 35°C, 36°C, 37°C, 38°C, 39°C or 40°C.

[0186] Aggregates and particle formation can be determined using any analysis in the art. In an embodiment, in vitro analysis is used, including but not limited to size exclusion chromatography (SEC), microfluidic imaging (MFI) and combinations thereof to determine aggregates and particle formation. In an embodiment, SEC is used to determine aggregates and particle formation. In an embodiment, MFI is used to determine aggregates and particle formation.

[0187] In embodiments, 15 mM concentration of L-methionine is effective to reduce color change of compositions provided herein, as compared to otherwise comparable compositions lacking L-methionine, lacking about 10-20 mM L-methionine, or lacking about 15 mM L-methionine. In embodiments, color change may be caused by stress conditions, such as increased temperature, agitation, increased pressure, or any combination thereof.

[0188] In an embodiment, the composition is colorless. In an embodiment, the composition is transparent. In an embodiment, the composition does not contain visible particles. In an embodiment, the composition may be milky white. In an embodiment, the color change may be determined using any means, including but not limited to visual inspection, microscopy, colorimetry, turbidimetry, and combinations thereof.

[0189] In embodiments, the composition comprising the anti-ILT7 binding protein is more stable in a histidine buffer as compared to an otherwise comparable composition in a different buffer. In embodiments, the composition comprising the anti-ILT7 binding protein is more stable in a histidine buffer as compared to an otherwise comparable composition in a phosphate buffer or a citrate buffer. In embodiments, the histidine buffer acid is effective to reduce aggregation, reduce oxidation, or reduce aggregation and reduce oxidation. In embodiments, reduced oxidation may refer to reduced L-methionine oxidation. In embodiments, reduced oxidation may refer to reduced oxidation of residues of L-methionine, including but not limited to W102 and / or W104 of SEQ ID NO: 1.

[0190] In embodiments, compositions comprising anti-ILT7 binding proteins are at least about 1-fold, 5-fold, 10-fold, 15-fold, 25-fold, 50-fold, 75-fold, 100-fold, 150-fold, or 250-fold more stable in histidine buffers as compared to otherwise comparable compositions in different buffers. In embodiments, compositions comprising anti-ILT7 binding proteins are at least about 1-fold, 5-fold, 10-fold, 15-fold, 25-fold, 50-fold, 75-fold, 100-fold, 150-fold, or 250-fold more stable in histidine buffers as compared to otherwise comparable compositions in different buffers. In embodiments, compositions comprising anti-ILT7 binding proteins are at least about 1-fold, 5-fold, or 10-fold more stable in histidine buffers as compared to otherwise comparable compositions in different buffers. In embodiments, the histidine buffer is effective to reduce aggregation of a composition comprising an anti-ILT7 binding protein by at least about 1-fold, 5-fold, 10-fold, 15-fold, 25-fold, 50-fold, 75-fold, 100-fold, 150-fold, or 250-fold as compared to an otherwise comparable composition in a different buffer. In embodiments, the histidine buffer is effective to reduce aggregation of a composition comprising an anti-ILT7 binding protein by at least about 1-fold, 5-fold, or 10-fold as compared to an otherwise comparable composition in a different buffer.

[0191] The stability of the anti-ILT7 binding protein can be assessed using any method in the art. In embodiments, assessing stability can include determining any of the following: specificity, binding affinity, purity, aggregation, degradation, and thermal stability. In embodiments, stability is determined by ELISA, Western blot and affinity analysis, SPR / BIACORETM , which can be used to indicate the retention of biological function (e.g., antigen binding, specificity, affinity, monomer percentage) during the conditions encountered during production / isolation and following storage. In addition, circular dichroism (CD), nuclear magnetic resonance (NMR) and mass spectrometry can be used to probe antibody stability. In an embodiment, stability is determined by an analysis selected from the group consisting of size exclusion chromatography (e.g., SEC-HPLC, SEC-FPLC), ELISA, Western blotting, BIACORE TM , SDS-PAGE, dynamic light scattering (DLS), differential scanning calorimetry (DSC), analytical ultracentrifugation (AUC), differential scanning fluorimetry, and combinations thereof.

[0192] In an embodiment, stability is determined. In an embodiment, stability is determined at various temperatures. In an embodiment, stability is determined under stress conditions (e.g., 40°C). In an embodiment, stability is determined at room temperature. In an embodiment, stability is determined at 0°C, 1°C, 2°C, 3°C, 4°C, 5°C, 6°C, 7°C, 8°C, 9°C, 10°C, 11°C, 12°C, 13°C, 14°C, 15°C, 16°C, 17°C, 18°C, 19°C, 20°C, 21°C, 22°C, 23°C, 24°C, 25°C, 26°C, 27°C, 28°C, 29°C, 30°C, 31°C, 32°C, 33°C, 34°C, 35°C, 36°C, 37°C, 38°C, 39°C or 40°C.

[0193] In embodiments, the anti-ILT7 binding protein or a composition comprising the same comprises an increased shelf-life. In embodiments, the anti-ILT7 binding protein or a composition comprising the same comprises an increased shelf-life as compared to an otherwise comparable composition lacking a histidine buffer. In an embodiment, the shelf life increases by at least about 1 month, 2 months, 4 months, 6 months, 8 months, 10 months, 12 months, 14 months, 16 months, 18 months, 20 months, 22 months, 24 months, 26 months, 28 months, 30 months, 32 months, 34 months, 36 months, 38 months, 40 months, 42 months, 44 months, 46 months, 48 ​​months, 50 months, 52 months, 54 months, 56 months, 58 months, 60 months, 62 months, 64 months, 66 months, 68 months, 70 months, 72 months, 74 months, 76 months, 78 months, 80 months, 82 months, 84 months, 86 months, 88 months, 90 months, 92 months, 94 months, 96 months, 98 months or 100 months. In an embodiment, the composition provided herein has a shelf life of about 60 months. In an embodiment, the composition provided herein has a shelf life of about 36 months. In embodiments, the shelf life may be a period at a temperature of about 2°C to about 8°C.

[0194] In an embodiment, the histidine buffer is effective to reduce pain after injecting the composition to a subject in need. In an embodiment, as compared with other aspects of using different buffers (e.g., citrate buffer), the histidine buffer is effective to reduce pain after injecting the composition to a subject in need. In an embodiment, the histidine buffer is effective to reduce pain after injecting the composition to a subject in need. In an embodiment, the histidine buffer is effective to reduce pain associated with subcutaneous injection of the composition provided herein (e.g., a composition comprising anti-ILT7 binding proteins). In an embodiment, the subject can assess pain by means of a scale selected from the group consisting of: a digital rating scale, a visual analog scale, an adult non-verbal pain scale, a behavioral pain scale, an intensive care observation tool, a national defense and veterans pain rating scale, a late dementia pain assessment scale, a doctor's visit or any combination thereof. In an embodiment, the histidine buffer is effective to reduce pain associated with the use of the composition provided herein, and reduces at least about 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 points on the scale. In an embodiment, the histidine buffer is effective to reduce pain associated with the use of the composition provided herein, and reduces at least about 1-2 points, 1-3 points or 1-4 points.

[0195] Any means may be used to determine viscosity. In an embodiment, a viscosity modifier (eg, arginine, NaCl) is used to determine viscosity. In an embodiment, a viscometer may be used to determine viscosity.

[0196] Alternative and complementary methods of reducing and eliminating the degradable modification (e.g., oxidation) of the amino acid residues of the composition are also contemplated. For example, the purification methods described in PCT / US2016 / 022003 are also contemplated, and the document is incorporated by reference as a whole. In an embodiment, the provided method can be combined with the purification method of PCT / US2016 / 022003.

[0197] treat

[0198] Also provided herein are methods of using compositions comprising anti-ILT7 binding proteins. In an embodiment, provided herein are methods of treating a subject with an autoimmune disease, comprising administering an effective amount of an anti-ILT7 binding protein to the subject. Also provided are methods of treating a subject in need thereof, the subject comprising a disease or condition associated with ILT7 expressing cells. Also provided are methods of treatment, comprising administering the disclosed compositions subcutaneously via an automatic injector.

[0199] In an embodiment, treatment includes administering an anti-ILT7 binding protein as part of the method described herein to a subject in need or a subject suspected of needing treatment. In an embodiment, administering an anti-ILT7 binding protein as part of the method described herein from a subject to separate tissue, one or more cells, wherein the subject suffers from a disease, disease symptoms, or a tendency to a disease (e.g., an autoimmune disease). In an embodiment, as compared to a subject without need, a subject in need or a subject suspected of needing treatment may have a high pDC number or activity. In an embodiment, as compared to a subject without need, a subject in need or a subject suspected of needing treatment may have a high pDC number or activity even if there is no formal diagnosis (e.g., a subject may or may not have systemic lupus erythematosus (SLE) or cutaneous lupus erythematosus (CLE)), but presents symptoms, such as high pDC number or activity. In an embodiment, it is suspected that a subject in need of treatment has a high baseline blood type I IFNGS level. In an embodiment, treatment includes administering a pharmaceutical composition comprising an anti-ILT7 binding protein for use in the method described herein to a subject in need or a subject suspected of needing treatment. In embodiments, treatment comprises administering a pharmaceutical composition comprising an anti-ILT7 binding protein as part of the methods described herein to a tissue, cell or cells isolated from a subject suffering from a disease, disease symptoms, or predisposition to a disease (e.g., an autoimmune disease).

[0200] Examples of autoimmune disorders that can be treated when a subject exhibits elevated type I IFNGS include, but are not limited to, discoid lupus erythematosus (DLE), systemic lupus erythematosus (SLE), lupus nephritis, cutaneous lupus erythematosus (CLE), Sjögren's syndrome, inflammatory myositis (e.g., dermatomyositis, inclusion body myositis, juvenile myositis, and polymyositis), systemic sclerosis, diabetes, local segmental glomerulosclerosis (FSGS), alopecia areata, Hashimoto's disease, autoimmune adrenal insufficiency, pure red cell aplasia, multiple sclerosis, rheumatoid carditis, IgG4RD, psoriasis, psoriatic arthritis, rheumatoid arthritis, chronic inflammation, chronic rheumatic disease, vitiligo, alopecia areata, suppurative hidradenitis, celiac disease, acute graft versus host disease (GVHD), chronic GVHD, vascular inflammation, myocardial infarction, and type 1 interferon disease. In embodiments, the autoimmune disease is DLE. In embodiments, the autoimmune disease is SLE. In embodiments, the autoimmune disease is CLE. In embodiments, the autoimmune disease is lupus, but not DLE. In embodiments, the autoimmune disease is Sjögren's syndrome. In embodiments, the autoimmune disease is dermatomyositis. In embodiments, the autoimmune disease is polymyositis. In embodiments, the autoimmune disease is systemic sclerosis. In embodiments, the autoimmune disease is hidradenitis suppurativa. In embodiments, the autoimmune disease is vitiligo. In embodiments, the autoimmune disease comprises FSGS. In embodiments, the autoimmune disease comprises alopecia areata.

[0201] Without being bound by theory, the anti-ILT7 binding proteins as part of the methods described herein can induce antibody-dependent cell-mediated cytotoxicity (ADCC) activity against plasmacytoid dendritic cells (pDC), thereby reducing or depleting pDC. In an embodiment, the ADCC mediated by the anti-ILT7 binding protein causes a reduction in circulating pDC. In an embodiment, the ADCC mediated by the anti-ILT7 binding protein causes a reduction in local or tissue pDC. In an embodiment, the tissues in which pDC are reduced include but are not limited to skin cells, skin biopsy samples, kidney cells, lung cells, liver cells, heart cells, brain cells, nerve tissue, thyroid cells, eye cells, skeletal muscle cells, cartilage, bone tissue, and cells from airway passages. In an embodiment, the tissue is a skin biopsy sample. In an embodiment, the application of the anti-ILT7 binding protein will cause a reduction in pDC. In an embodiment, the application of the anti-ILT7 binding protein will cause a reduction in skin pDC. Typically, pDC is not present in skin tissue, and immature pDC is typically only visible in blood, thymic lymphoid tissue, tonsils, and lung tissue. Therefore, the presence of pDC in a skin biopsy sample indicates an abnormal condition in which pDC is recruited to the skin. In an embodiment, the method of the present disclosure includes administering an anti-ILT7 binding protein to a subject in need of treatment of a condition marked by the presence of pDC in the subject's skin. In an embodiment, the method of the present disclosure includes reducing the level of pDC in the subject's skin by administering an anti-ILT7 binding protein to a subject in need of treatment.

[0202] In an embodiment, as compared with the pDC level (that is, the baseline level of the subject) of the subject before applying anti-ILT7 binding proteins, the pDC level of the subject is reduced to about 1% to about 100%. In an embodiment, compared with pDC levels (baseline level of the subject), the pDC level of the subject is reduced to at least about 1%, 2%, 3%, 4%, 5%, 6%, 7%, 8%, 9%, 10%, 12%, 14%, 16%, 18%, 20%, 22%, 24%, 26%, 28%, 30%, 32%, 34%, 36%, 38%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or up to about 100%. In an embodiment, compared with pDC levels (baseline level of the subject), the pDC level of the subject is reduced to at least about 50%. In an embodiment, the administration of a therapeutically effective amount of an anti-ILT7 binding protein results in a reduction of at least about 10% of the total number of pDCs in a subject. In an embodiment, the administration of a therapeutically effective amount of an anti-ILT7 binding protein results in a reduction of at least about 10% of the activated pDCs in a subject. In an embodiment, pDC levels are measured in a test biological sample taken from a subject. In an embodiment, a therapeutically effective amount of an anti-ILT7 binding protein as part of the methods described herein is administered to a subject in need thereof, resulting in a reduction in the pDC level in a test biological sample taken from a subject. In an embodiment, the pDC level in a test biological sample taken from a subject is reduced to at least about 10% compared to the pDC level in the test biological sample before the administration of an anti-ILT7 binding protein used as part of the methods described herein. Whole blood, plasma, urine, saliva, tissue, cell, and serum samples can be collected as test biological samples to assess pDC levels. In an embodiment, the test biological sample is whole blood. In an embodiment, the test biological sample is a tissue, including but not limited to skin cells and skin biopsy samples. In an embodiment, pDC is a circulating pDC. In an embodiment, pDC is a pDC in the skin. In embodiments, the pDC reduction is reversible.

[0203] In embodiments, a subject may have elevated or high levels of pDCs in skin tissue prior to treatment. In embodiments, a subject having high pDC levels in skin tissue prior to treatment is more responsive to treatment. In embodiments, a subject having high pDC levels in skin tissue has at least about 50 pDC / mm 2 Skin tissue, at least about 60pDC / mm 2 Skin tissue, at least about 70pDC / mm 2 Skin tissue, at least about 80pDC / mm 2 Skin tissue, at least about 90pDC / mm 2 Skin tissue, at least about 100 pDC / mm 2Skin tissue, at least about 110 pDC / mm 2 Skin tissue, at least about 120pDC / mm 2 Skin tissue, at least about 125pDC / mm 2 Skin tissue, at least about 150pDC / mm 2 Skin tissue, at least about 175pDC / mm 2 Skin tissue, at least about 200pDC / mm 2 In embodiments, low pDC levels in skin tissue are considered to be less than about 10 pDC / mm 2 Skin tissue. In embodiments, high pDC levels in skin tissue are considered to be at least about 100 pDC / mm 2 Skin tissue.

[0204] In an embodiment, a therapeutically effective amount of an anti-ILT7 binding protein used as part of the methods described herein is administered to a subject in need thereof such that at about 3 hours, about 6 hours, about 12 hours, about 24 hours, or about 48 hours after administration of the anti-ILT7 binding protein, the subject's pDC is reduced by at least about 10%. In an embodiment, a therapeutically effective amount of an anti-ILT7 binding protein as part of the methods described herein is administered to a subject in need thereof such that at about 5 minutes, about 10 minutes, about 15 minutes, about 30 minutes, about 1 hour, about 2 hours, about 3 hours, about 6 hours, about 12 hours, about 24 hours, or about 48 hours after administration of the anti-ILT7 binding protein, the pDC level in a test biological sample taken from the subject is reduced by at least about 10%.

[0205] In an embodiment, after administering a therapeutically effective amount of an anti-ILT7 binding protein as part of the methods described herein to a subject in need, the pDC level is reduced for at least about 1 day, at least about 2 days, at least about 3 days, at least about 4 days, at least about 5 days, at least about 6 days, at least about 7 days, at least about 14 days, at least about 21 days, at least about 28 days, at least about 30 days, at least about 45 days, at least about 60 days, at least about 90 days, or at least about 180 days or more. In an embodiment, after administering a therapeutically effective amount of an anti-ILT7 binding protein as part of the methods described herein to a subject in need, the pDC level is reduced for at least about 30 days. In an embodiment, after administering a therapeutically effective amount of an anti-ILT7 binding protein as part of the methods described herein to a subject in need, the pDC level is reduced for at least about 60 days.

[0206] In an embodiment, the method disclosed herein can be used to monitor the effectiveness of treatment by monitoring type I interferon gene signatures (IFNGS) and / or pDC levels. As described above, autoimmune conditions are generally marked by elevated type I IFNGS and / or elevated pDC. In an embodiment, monitoring the effectiveness of treatment administered to a subject in need (e.g., with a diagnosis and / or symptom of an autoimmune disease or condition) may include monitoring type I IFNGS and / or pDC levels.

[0207] In an embodiment, the present disclosure provides a method for monitoring the effectiveness of a treatment for an autoimmune disorder or condition, the method comprising: (a) measuring type I IFNGS in a biological sample taken from a subject to obtain a baseline value of type I IFNGS; and (b) measuring type I IFNGS in a biological sample taken from the subject after administration of a treatment, wherein the treatment comprises administration of an anti-ILT7 binding protein, and wherein a decrease in type I IFNGS in (b) compared to the baseline value in (a) indicates that the treatment is effective in the subject.

[0208] In an embodiment, treatment results in a reduction in type I IFNGS compared to a baseline value. In an embodiment, the reduction in type I IFNGS compared to a baseline value is between about 1% and about 99%. In an embodiment, the reduction in type I IFNGS levels compared to a baseline value is at least about 5%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95% or at least about 99%. In an embodiment, the reduction in type I IFNGS levels compared to a baseline value is at least about 30%. In an embodiment, the reduction in type I IFNGS levels compared to a baseline value is at least about 50%.

[0209] In an embodiment, the type I IFNGS in the test biological sample is at least about 1.1 to about 1000 times higher than the type I IFNGS in the normal biological sample or in the subject in need. In an embodiment, the type I IFNGS in the test biological sample is at least about 1.1, 1.2, 1.3, 1.4, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90 or 100 times higher than the type I IFNGS in the normal biological sample or in the subject in need. In an embodiment, the type I IFNGS level in the test biological sample is at least about 4 times higher than the type I IFNGS level in the normal biological sample or in the subject in need.

[0210] In an embodiment, after administering a therapeutically effective amount of an anti-ILT7 binding protein as part of the methods described herein to a subject in need, the level of type I IFNGS is reduced for at least about 1 day, at least about 2 days, at least about 3 days, at least about 4 days, at least about 5 days, at least about 6 days, at least about 7 days, at least about 14 days, at least about 21 days, at least about 28 days, at least about 30 days, at least about 45 days, at least about 60 days, at least about 90 days, or at least about 180 days or more. In an embodiment, after administering a therapeutically effective amount of an anti-ILT7 binding protein as part of the methods described herein to a subject in need, type I IFNGS is reduced for up to about 30 days. In an embodiment, after administering a therapeutically effective amount of an anti-ILT7 binding protein as part of the methods described herein to a subject in need, type I IFNGS is reduced for up to about 60 days.

[0211] In an embodiment, the method of the present disclosure includes administering an anti-ILT7 binding protein as part of the method described herein to inhibit the release of type I IFN by pDC, regardless of the location of the pDC. In an embodiment, the method of the present disclosure includes administering an anti-ILT7 binding protein to inhibit the release of type I IFN by pDC in the blood or circulation. In an embodiment, the method of the present disclosure includes administering an anti-ILT7 binding protein to inhibit the release of type I IFN by local pDC. In an embodiment, the method of the present disclosure includes administering an anti-ILT7 binding protein to inhibit the release of type I IFN by pDC in the subject's skin. In an embodiment, the inhibited type I IFN is IFNα. In an embodiment, the inhibition of the release of type I IFN by pDC mediated by the anti-ILT7 binding protein causes a reduction in type I IFNGS.

[0212] The present disclosure provides a method for treating an autoimmune disorder of a subject with an anti-ILT7 binding protein. In an embodiment, the method includes treating an autoimmune disorder of a subject in need, wherein the subject is determined to have a high blood type I interferon gene signature (IFNGS) level. In an embodiment, the present disclosure provides a method for reducing the IFNGS of a subject in need. In an embodiment, the method includes administering a pharmaceutically effective amount of an anti-ILT7 binding protein to a subject. In an embodiment, when the type I IFNGS in a subject increases relative to the type I IFNGS in a normal subject, the anti-ILT7 binding protein is administered to the subject. In an embodiment, for example, an anti-ILT7 binding protein is administered to a subject having an elevated baseline type I IFNGS relative to the type I IFNGS in a normal subject. In an embodiment, the method includes selecting a subject for treatment with an anti-ILT7 binding protein, the method including: (i) determining the baseline blood type I IFNGS level of the subject, and (ii) selecting one or more subjects with a high baseline blood type I IFNGS level to treat with an ILT7 binding protein. In an embodiment, the anti-ILT7 binding protein is an ILT7 protein-specific antibody.

[0213] In certain diseases (e.g., autoimmune diseases), activated pDCs secrete large amounts of type I and type III interferons (IFNs). Type I IFN is a large group of IFN proteins that help regulate the immune system. Mammalian IFNs are named IFNα, PTNIb, IFNco, IFNK, IFNT, IFN6, IPMz, and IFNu. In an embodiment, the type I IFN that generates type I IFNGS is IFNα. Type I IFN protein levels cannot be directly measured in a reliable manner; however, the measured values ​​of IFN-induced genes are used as reliable substitutes for type 1 IFN protein levels. In an embodiment, the expression levels of type I IFN-induced genes can be measured in biological samples (e.g., blood, skin, skeletal muscle, etc.) and analyzed as a composite result, referred to as "type I interferon gene signature" or "type I IFNGS" or "IFNGS".

[0214] In an embodiment, the type I IFNGS is determined by analyzing the expression level of at least 2, at least 5, at least 10, at least 15, at least 20, at least 25, at least 30, at least 40, at least 50, at least 60, at least 70, at least 80, at least 90, at least 100, at least 200, at least 300, at least 400 or at least 500 type I IFN induced genes in a biological sample. In an embodiment, the determination of type I IFNGS includes the collective expression level of two or more type I IFN induced genes. In an embodiment, the two or more type I interferon (IFN) induced genes include but are not limited to two or more genes selected from SPATS2L, EPSTI1, HERC5, IF 127, IFI44, IFI44L, IFI6, IFIT1, IFIT3, ISG15, LAMP3, LY6E, MX1, OAS1, OAS2, OAS3, PLSCR1, RSAD2, RTP4, SIGLEC1 and USP18. In an embodiment, type I IFNGS is determined by analyzing the collective expression levels of SPATS2L, EPSTI1, HERC5, IFI27, IFI44, IFI44L, IFI6, IFIT1, IFIT3, ISG15, LAMP3, LY6E, MX1, OAS1, OAS2, OAS3, PLSCR1, RSAD2, RTP4, SIGLEC1, and USP18. These gene symbols are well known in the art and refer to the human and non-human orthologs of the listed genes.

[0215] In an embodiment, type I IFNGS is determined by analyzing the collective expression of genes, wherein the set expression includes 21-gene features. In an embodiment, type I IFNGS in a subject increases at least 1.5 times relative to the normal score before treatment. In an embodiment, type I IFNGS in a subject increases at least 2 times relative to the normal score before treatment. In an embodiment, the subject with elevated type I IFNGS before treatment is more responsive to treatment. In an embodiment, type I IFNGS is at least about 4 times, at least about 5 times, at least about 6 times, at least about 7 times, at least about 8 times, at least about 9 times, at least about 10 times, at least about 11 times, at least about 12 times or more relative to the normal score before treatment with an anti-ILT7 binding protein as a part of the method described herein. In an embodiment, type I IFNGS is determined by skin biopsy. In an embodiment, type I IFNGS is determined using IFN-inducible myxovirus protein A (MxA) immunohistochemistry (IHC) test.

[0216] As used herein, when used in conjunction with IFGNS, the term "high" or "increase" means that type I IFNGS is at least about 1.1 to about 1000 times the normal type I IFNGS level. "Normal type I IFNGS" is intended to be type I IFNGS obtained from a normal subject. When used in conjunction with type I IFNGS, the terms "high" or "increase" are used interchangeably. In an embodiment, when the type I IFNGS used as part of the method described herein is at least about 1.1, 1.2, 1.3, 1.4, 1.5, 2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 20, 30, 40, 50, 60, 70, 80, 90 or 100 times the type I IFNGS in a normal subject, type I IFNGS is "high" or "increased". In an embodiment, when type I IFNGS increases at least about 4 times relative to normal type I IFNGS, the treatment methods described herein are applied.

[0217] The present disclosure provides a method for treating a subject with elevated type I IFNGS, the methods comprising administering an anti-ILT7 binding protein as described herein. The subject may exhibit elevated type I IFNGS when suffering from an autoimmune disorder. In an embodiment, the present disclosure provides a method for treating an autoimmune disorder when the subject exhibits elevated type I IFNGS. In an embodiment, the autoimmune disorder is otherwise asymptomatic. In an embodiment, the method comprises selecting a subject for treatment with an anti-ILT7 binding protein, the method comprising: (i) determining the baseline blood type I IFNGS level of the subject, and (ii) selecting one or more subjects with a high baseline blood type I IFNGS level to be treated with an ILT7 binding protein.

[0218] In an embodiment, the method disclosed herein can be used to monitor the therapeutic effectiveness of a condition or illness by monitoring the level of type I IFNGS and / or activated pDC. As described above, autoimmune conditions are generally marked by elevated type I IFNGS and / or elevated pDC, so monitoring therapeutic effectiveness may include monitoring type I IFNGS and / or pDC levels. In an embodiment, the disclosure provides a method for monitoring the therapeutic effectiveness of an autoimmune disorder or condition, the method comprising: (a) measuring type I interferon gene signatures (IFNGS) in a biological sample taken from a subject to obtain a baseline value of type I IFNGS; and (b) measuring type I IFNGS in a biological sample taken from a subject after administering treatment, wherein the treatment includes administering an anti-ILT7 binding protein, and wherein the reduction of type I IFNGS in step (b) compared to the baseline value in (a) indicates that the treatment is effective in the subject. In an embodiment, treatment results in a reduction of type I IFNGS compared to a baseline value. In an embodiment, the reduction of type I IFNGS compared to a baseline value is between about 1% and about 99%. In embodiments, the reduction in type I IFNGS compared to baseline values ​​is at least about 5%, at least about 10%, at least about 20%, at least about 30%, at least about 40%, at least about 50%, at least about 60%, at least about 70%, at least about 80%, at least about 90%, at least about 95%, or at least about 99%. In embodiments, the reduction in type I IFNGS compared to baseline values ​​is at least about 30%. In embodiments, the reduction in type I IFNGS compared to baseline values ​​is at least about 50%.

[0219] In an embodiment, the method of the present disclosure may include reducing the skin lupus erythematosus disease activity and severity index (CLASI) in the tissue of a subject in need. The method of the present disclosure may include administering a pharmaceutically effective amount of an anti-ILT7 binding protein to a subject. As used herein, the term "CLASI" refers to the skin lupus erythematosus disease activity and severity index. CLASI is a validated instrument for measuring CLE skin manifestations. CLASI consists of two scores: the first summarizes the inflammatory activity of the disease; the second is a measure of the damage caused by the disease. Activity scores include erythema (0-3), scales / hypertrophy (0-2), mucosal lesions (0-1), recent hair loss (0-1) and scarless hair loss (0-3). Damage scores include abnormal pigmentation (0-1), scars / atrophy / lipid inflammation (0-2) and scalp scars (0-6). Subjects were asked whether their abnormal pigmentation lasted for 12 months or longer, in which case the abnormal pigmentation score was doubled. Each of the above parameters is measured in 13 different anatomical locations, and the reason for specifically including these locations is that they are most commonly involved in CLE. The most severe lesions in each area are measured. As used herein, the term "CLASI reduction" refers to a weakening of the CLASI-activity (CLASI-A) score level in a subject or a biological sample (e.g., skin tissue, skin cells, skin biopsy samples, etc.) taken from a subject, or a weakening of the CLASI-damage (CLASI-D) score level in a subject or a biological sample taken from a subject, or both. In an embodiment, the method disclosed herein promotes a reduction in the CLASI-A score of a subject. In an embodiment, the reduction in the CLASI-A score of a subject involves a reduction of at least 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 points in the CLASI-A score relative to the baseline value. In an embodiment, the reduction in the CLASI-A score of a subject involves a reduction of at least 4 points in the CLASI-A score relative to the baseline value. In an embodiment, the reduction in the CLASI-A score of a subject involves a reduction of at least 7 points in the CLASI-A score relative to the baseline value. In an embodiment, the CLASI-A score reduction of the subject involves a CLASI-A score reduction of at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95% or 99% relative to the baseline value. In an embodiment, the CLASI-A score reduction of the subject involves a CLASI-A score reduction of at least 50% relative to the baseline value. In an embodiment, the baseline value is the CLASI-A score value of the subject before treatment with an anti-ILT7 binding protein as part of the method described herein. In an embodiment, the method disclosed herein results in a reduction in the CLASI-D score of the subject. In an embodiment, the method disclosed herein results in a reduction in the CLASI-A score of the subject and a reduction in the CLASI-D score.

[0220] A variety of regimens can be used to administer the disclosed compositions. In embodiments, the compositions are administered hourly, daily, weekly, monthly, or yearly.

[0221] In embodiments, the pharmaceutical compositions provided herein can be administered hourly. In embodiments, the pharmaceutical compositions are administered every 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours, 9 hours, 10 hours, 11 hours, 12 hours, 13 hours, 14 hours, 15 hours, 16 hours, 17 hours, 18 hours, 19 hours, 20 hours, 21 hours, 22 hours, 23 hours or 24 hours. In embodiments, the pharmaceutical compositions are administered every day, 2 days, 3 days, 4 days, 5 days, 6 days or 7 days. In embodiments, the pharmaceutical composition is administered every week, 2 weeks, 3 weeks, 4 weeks, 5 weeks, 6 weeks, 7 weeks, 8 weeks, 9 weeks, 10 weeks, 11 weeks, 12 weeks, 13 weeks, 14 weeks, 15 weeks, 16 weeks, 17 weeks, 18 weeks, 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, 28 weeks, 29 weeks, 30 weeks, 31 weeks, 32 weeks, 33 weeks, 34 weeks, 35 weeks, 36 weeks, 37 weeks, 38 weeks, 39 weeks, 40 weeks, 41 weeks, 42 weeks, 43 weeks, 44 weeks, 45 weeks, 46 weeks, 47 weeks, 48 ​​weeks, 49 weeks, 50 weeks, 51 weeks, or 52 weeks. In embodiments, the pharmaceutical composition is administered every month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, or 12 months.

[0222] In an embodiment, a method for treating systemic lupus erythematosus is provided, comprising administering an effective amount of a composition provided herein, wherein the administration is performed every 4 weeks. In an embodiment, a method for treating systemic lupus erythematosus is provided, comprising administering an effective amount of a composition provided herein, wherein the administration is performed every 12 weeks.

[0223] According to the method disclosed herein, anti-ILT7 binding proteins as defined elsewhere herein are used to promote positive therapeutic responses regarding autoimmune responses. "Positive therapeutic response" regarding autoimmune therapy means disease improvement associated with the activity of anti-ILT7 binding proteins. Exemplary positive therapeutic responses include, but are not limited to, reduced levels of interferon-α, reduced levels or activity of plasmacytoid dendritic cells, or alleviation of one or more symptoms associated with the disease can be observed. In an embodiment, disease improvement can be characterized as complete remission. "Complete remission" means the absence of clinically detectable disease, wherein any previous test results are standardized. In an embodiment, after administration according to the method disclosed herein, such remission can last for at least one month. In an embodiment, disease improvement can be classified as partial remission. In addition to these positive therapeutic responses, subjects experiencing anti-ILT7 binding protein therapy may also experience beneficial effects of improved symptoms associated with the disease.

[0224] In an embodiment, the method disclosed herein may include anti-ILT7 binding proteins as part of a method for treating autoimmune diseases and immune system defects or disorders associated with ILT7 expressing cells. Autoimmune diseases are characterized by cell, tissue and / or organ damage caused by an immune response of the subject to its own cells, tissues and / or organs. In an embodiment, the autoimmune disease is systemic lupus erythematosus.

[0225] Clinical response may be assessed using screening techniques such as magnetic resonance imaging (MRI) scans, x-ray imaging, computed tomography (CT), flow cytometry or fluorescence activated cell sorter (FACS) analysis, histology, gross pathology, and blood chemistry, including but not limited to changes detectable by ELISA, RIA, chromatography, and the like.

[0226] In an embodiment, a method for diagnostic monitoring of tissue protein levels using an anti-ILT7 binding protein as part of a clinical testing procedure is provided herein, for example, to determine the efficacy of a given treatment regimen. For example, detection can be facilitated by coupling the anti-ILT7 binding protein to a detectable substance. Examples of detectable substances include various enzymes, prosthetic groups, fluorescent materials, luminescent materials, bioluminescent materials, and radioactive materials. Exemplary enzymes include horseradish peroxidase, alkaline phosphatase, β-galactosidase, or acetylcholinesterase; exemplary prosthetic group complexes include streptavidin / biotin and avidin / biotin; exemplary fluorescent materials include umbelliferone, fluorescein, fluorescein isothiocyanate, rhodamine, dichlorotriazinylamine fluorescein, dansyl chloride, or phycoerythrin; examples of luminescent materials include luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin; and exemplary radioactive materials include 125 I. 131 I. 35 S or3 H.

[0227] In an embodiment, disclosed herein are in vitro testing methods for selecting a subject for disease treatment, including determining whether the subject suffers from an autoimmune disease provided herein. In an embodiment, the in vitro method can be performed on a biological sample (e.g., blood, cartilage, bone, serum, etc.) extracted from a subject and can be used to determine a treatment mode or course for a particular subject, e.g., whether an anti-ILT7 binding protein (alone or in combination with another compound) is administered to the subject.

[0228] In embodiments, methods of administering an anti-ILT7 binding protein to a subject are disclosed herein. In embodiments, methods of administering an anti-ILT7 binding protein to a subject in need are disclosed herein. In embodiments, methods of administering an anti-ILT7 binding protein to a subject in need are disclosed herein, wherein the subject has an autoimmune disease or condition diagnosis. In embodiments, methods of administering an anti-ILT7 binding protein to a subject in need are disclosed herein, wherein the subject has a symptom of an autoimmune disease or condition.

[0229] In an embodiment, disclosed herein are methods of administering a composition comprising an anti-ILT7 binding protein to a subject. In an embodiment, disclosed herein are methods of administering a composition comprising an anti-ILT7 binding protein to a subject in need. In an embodiment, disclosed herein are methods of administering a composition comprising an anti-ILT7 binding protein to a subject in need, wherein the subject has an autoimmune disease or condition diagnosis. In an embodiment, disclosed herein are methods of administering a composition comprising an anti-ILT7 binding protein to a subject in need, wherein the subject has a symptom of an autoimmune disease or condition.

[0230] In an embodiment, disclosed herein is a method of administering a formulation comprising an anti-ILT7 binding protein to a subject. In an embodiment, disclosed herein is a method of administering a formulation comprising an anti-ILT7 binding protein to a subject in need. In an embodiment, disclosed herein is a method of administering a formulation comprising an anti-ILT7 binding protein to a subject in need, wherein the subject has an autoimmune disease or condition diagnosis. In an embodiment, disclosed herein is a method of administering a formulation comprising an anti-ILT7 binding protein to a subject in need, wherein the subject has a symptom of an autoimmune disease or condition.

[0231] In an embodiment, disclosed herein are methods of administering a composition comprising an anti-ILT7 binding protein to a subject. In an embodiment, disclosed herein are methods of administering a composition comprising an anti-ILT7 binding protein to a subject in need. In an embodiment, disclosed herein are methods of administering a composition comprising an anti-ILT7 binding protein to a subject in need, wherein the subject has an autoimmune disease or condition diagnosis. In an embodiment, disclosed herein are methods of administering a composition comprising an anti-ILT7 binding protein to a subject in need, wherein the subject has a symptom of an autoimmune disease or condition.

[0232] In embodiments, methods of administering a composition comprising an anti-ILT7 binding protein to a subject are disclosed herein; wherein the composition is stored in a pre-filled syringe prior to administration. In embodiments, methods of administering a composition comprising an anti-ILT7 binding protein to a subject in need thereof are disclosed herein; wherein the composition is stored in a pre-filled syringe prior to administration. In embodiments, methods of administering a composition comprising an anti-ILT7 binding protein to a subject in need thereof are disclosed herein, wherein the subject has a diagnosis of an autoimmune disease or disorder; wherein the composition is stored in a pre-filled syringe prior to administration. In embodiments, methods of administering a composition comprising an anti-ILT7 binding protein to a subject in need thereof are disclosed herein, wherein the subject has a symptom of an autoimmune disease or disorder; wherein the composition is stored in a pre-filled syringe prior to administration.

[0233] In an embodiment, disclosed herein is a method of administering to a subject a composition comprising 150 mg / mL of an anti-ILT7 binding protein, 20 mM histidine / histidine-HCl, 180 mM sucrose, 15 mM L-methionine, and 0.02% polysorbate-80. In an embodiment, disclosed herein is a method of administering to a subject in need thereof a composition comprising 150 mg / mL of an anti-ILT7 binding protein, 20 mM histidine / histidine-HCl, 180 mM sucrose, 15 mM L-methionine, and 0.02% polysorbate-80. In an embodiment, disclosed herein is a method of administering to a subject in need thereof a composition comprising 150 mg / mL of an anti-ILT7 binding protein, 20 mM histidine / histidine-HCl, 180 mM sucrose, 15 mM L-methionine, and 0.02% polysorbate-80, wherein the subject has an autoimmune disease or disorder diagnosis. In an embodiment, disclosed herein is a method of administering a composition comprising 150 mg / mL of an anti-ILT7 binding protein, 20 mM histidine / histidine-HCl, 180 mM sucrose, 15 mM L-methionine, and 0.02% polysorbate-80 to a subject in need thereof, wherein the subject has symptoms of an autoimmune disease or disorder.

[0234] In an embodiment, disclosed herein is a method of administering to a subject a composition comprising 150 mg / mL of an anti-ILT7 binding protein, 20 mM histidine / histidine-HCl, 180 mM sucrose, 15 mM L-methionine, and 0.02% polysorbate-80, wherein the composition is stored in a pre-filled syringe prior to administration. In an embodiment, disclosed herein is a method of administering to a subject in need thereof a composition comprising 150 mg / mL of an anti-ILT7 binding protein, 20 mM histidine / histidine-HCl, 180 mM sucrose, 15 mM L-methionine, and 0.02% polysorbate-80, wherein the composition is stored in a pre-filled syringe prior to administration. In an embodiment, disclosed herein is a method of administering a composition comprising 150 mg / mL of an anti-ILT7 binding protein, 20 mM histidine / histidine-HCl, 180 mM sucrose, 15 mM L-methionine, and 0.02% polysorbate-80 to a subject in need thereof, wherein the subject has a diagnosis of an autoimmune disease or condition; wherein the composition is stored in a pre-filled syringe prior to administration. In an embodiment, disclosed herein is a method of administering a composition comprising 150 mg / mL of an anti-ILT7 binding protein, 20 mM histidine / histidine-HCl, 180 mM sucrose, 15 mM L-methionine, and 0.02% polysorbate-80 to a subject in need thereof, wherein the subject has symptoms of an autoimmune disease or condition; wherein the composition is stored in a pre-filled syringe prior to administration.

[0235] Numbered Example

[0236] Notwithstanding the appended claims, the present disclosure sets forth the following numbered embodiments:

[0237] Example Group 1

[0238] Embodiment 1. A composition comprising: (i) about 100 mg / mL to about 350 mg / mL of immunoglobulin-like transcript 7 (ILT7) binding protein; (ii) about 50 to about 350 mM sucrose; (iii) about 0.001% to about 1% polysorbate-80; (iv) L-methionine; and (v) a buffer selected from a histidine buffer, a citrate buffer or a phosphate buffer.

[0239] Embodiment 2. A composition comprising: (i) about 100 mg / mL to about 165 mg / mL of immunoglobulin-like transcript 7 (ILT7) binding protein; (ii) about 150 to about 240 mM sucrose; (iii) about 0.003% to about 0.8% polysorbate-80; (iv) L-methionine; and (v) a buffer selected from a histidine buffer, a citrate buffer, or a phosphate buffer.

[0240] Embodiment 3. The composition of any one of embodiments 1-2, wherein the buffer is the histidine buffer.

[0241] Embodiment 4. The composition as described in any one of embodiments 1-2, wherein the buffer is a phosphate buffer.

[0242] Embodiment 5. The composition of any one of embodiments 1-2, wherein the buffer is a citrate buffer.

[0243] Embodiment 6. The composition of any one of embodiments 1-5, wherein the pH of the composition is acidic, as determined by a pH meter.

[0244] Embodiment 7. The composition of embodiment 6, wherein the acidic pH is from about 5 to about 7, as determined by a pH meter.

[0245] Embodiment 8. The composition of embodiment 7, wherein the acidic pH is about 6 as determined by a pH meter.

[0246] Embodiment 9. The composition of any one of embodiments 1-8, wherein the composition comprises about 5 mM to about 25 mM histidine / histidine-HCl.

[0247] Embodiment 10. The composition of embodiment 9, comprising about 20 mM histidine / histidine-HCl.

[0248] Embodiment 11. The composition of any one of embodiments 1-10, wherein the composition comprises about 5 mM to about 50 mM L-methionine.

[0249] Embodiment 12. The composition of embodiment 11, comprising about 15 mM L-methionine.

[0250] Embodiment 13. The composition of any one of embodiments 1-12, comprising about 0.02% polysorbate-80.

[0251] Embodiment 14. The composition of any one of embodiments 1-13, comprising up to about 150 mg / mL of the ILT7 binding protein.

[0252] Embodiment 15. The composition of any one of embodiments 1-14, comprising about 150 mg / mL of the ILT7 binding protein.

[0253] Embodiment 16. A composition as described in any of Embodiments 1-15, wherein the ILT7 binding protein comprises: i. VH, which comprises at least 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO: 1; ii. VL, which comprises at least 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO: 2; or iii.i. and ii.

[0254] Embodiment 17. The composition of any one of embodiments 1-16, wherein the ILT7 binding protein comprises: i. a VH comprising SEQ ID NO: 1; ii. a VL comprising SEQ ID NO: 2; or iii.i. and ii.

[0255] Embodiment 18. The composition of any one of embodiments 1-17, wherein the ILT7 binding protein comprises complementarity determining regions (CDRs) HCDR1, HDR2, HCDR3, LCDR1, LCDR2 and LCDR3, which comprise the sequences of SEQ ID NOs: 3, 4, 5, 6, 7 and 8, respectively.

[0256] Embodiment 19. The composition of any one of embodiments 1-18, wherein the composition comprises a viscosity of about 5 cP to about 50 cP as determined by a viscometer.

[0257] Embodiment 20. The composition of any one of embodiments 1-19, wherein the ILT7 binding protein is dastilimab.

[0258] Example 21. A composition comprising approximately: i. 150 mg / mL of immunoglobulin-like transcript 7 (ILT7) binding protein; ii. 20 mM histidine / histidine-HCl; iii. 180 mM sucrose; iv. 15 mM L-methionine; and v. 0.02% polysorbate-80.

[0259] Embodiment 22. A composition comprising approximately: i. 150 mg / mL of immunoglobulin-like transcript 7 (ILT7) binding protein; ii. 20 mM histidine / histidine-HCl; iii. 180 mM sucrose; iv. 15 mM L-methionine; and v. 0.02% polysorbate-80, wherein the ILT7 binding protein comprises: a VH comprising SEQ ID NO: 1 and a VL comprising SEQ ID NO: 2.

[0260] Embodiment 23. A composition comprising approximately: i. 150 mg / mL of immunoglobulin-like transcript 7 (ILT7) binding protein; ii. 20 mM histidine / histidine-HCl; iii. 180 mM sucrose; iv. 15 mM L-methionine; and v. 0.02% polysorbate-80, wherein the ILT7 binding protein comprises complementarity determining regions (CDRs) HCDR1, HDR2, HCDR3, LCDR1, LCDR2 and LCDR3, which respectively comprise the sequences of SEQ ID NOs: 3, 4, 5, 8, 7 and 8.

[0261] Embodiment 24. The composition of any one of embodiments 21-23, wherein the composition has a viscosity of about 5 to about 50 cP.

[0262] Embodiment 25. The composition of embodiment 24, wherein the viscosity does not exceed 20 cP.

[0263] Embodiment 26. The composition of any of embodiments 21-25, wherein the aggregation rate is reduced as compared to an otherwise comparable composition lacking the L-methionine as determined by size exclusion chromatography at 40°C.

[0264] Embodiment 27. The composition of any one of embodiments 21-26, wherein the aggregation rate is 0.5% to 1% per month as determined by size exclusion chromatography at 40°C.

[0265] Embodiment 28. The composition of any one of embodiments 21-27, wherein the oxidation level is reduced as compared to an otherwise comparable composition lacking the L-methionine, as determined by peptide mapping analysis of W102 or W104 of SEQ ID NO: 1 or SEQ ID NO: 10 of the ILT7 binding protein at room temperature.

[0266] Embodiment 29. The composition of any one of embodiments 21-28, wherein when the composition is exposed to 1600-1800 lux of light for 5 days, the percentage of oxidized species of ILT7 binding protein in the composition increases to at most 0.5% as determined by size exclusion chromatography.

[0267] Embodiment 30. The composition of any one of embodiments 21-29, wherein the composition is resistant to Fc oxidation.

[0268] Embodiment 31. A container comprising the composition of any one of embodiments 1-30 in unit dosage form.

[0269] Embodiment 32. The container of Embodiment 31, wherein the container comprises nitrogen.

[0270] Embodiment 33. The container of Embodiment 31, wherein the container does not contain nitrogen.

[0271] Embodiment 34. A method of treating a disease, comprising administering an effective amount of the composition of any one of embodiments 1-30 to a subject in need thereof, thereby treating the disease.

[0272] Embodiment 35. The method of embodiment 34, wherein following the administering, the administering is sufficient to alleviate the symptoms of the disease in the subject in need thereof.

[0273] Embodiment 36. The method of embodiment 35, wherein the symptom is reduced by at least about 1-fold.

[0274] Embodiment 37. A method for treating an autoimmune disease, the method comprising administering an effective amount of the composition of any one of embodiments 1-30 to a subject in need thereof, thereby treating the autoimmune disease.

[0275] Embodiment 38. The method of embodiment 37, wherein the autoimmune disease is selected from the group consisting of: discoid lupus erythematosus (DLE), focal segmental glomerulosclerosis (FSGS), alopecia areata, myositis, diabetes, Hashimoto's disease, autoimmune adrenal insufficiency, pure red cell aplasia, lupus nephritis, multiple sclerosis, IgG4RD, rheumatoid carditis, systemic lupus erythematosus, psoriasis, rheumatoid arthritis, chronic inflammation, Sjögren's syndrome, polymyositis, dermatomyositis, inclusion body myositis, juvenile myositis and scleroderma.

[0276] Embodiment 39. The method of embodiment 38, wherein the autoimmune disease is alopecia areata.

[0277] Embodiment 40. The method of embodiment 38, wherein the autoimmune disease is systemic lupus erythematosus.

[0278] Embodiment 41. The method of embodiment 38, wherein the autoimmune disease is FSGS.

[0279] Embodiment 42. A method for treating alopecia areata, the method comprising administering to a subject in need thereof an effective amount of the composition of any one of embodiments 1-30, thereby treating the alopecia areata.

[0280] Embodiment 43. A method of treating focal segmental glomerulosclerosis (FSGS), the method comprising administering to a subject in need thereof an effective amount of the composition of any one of embodiments 1-30, thereby treating the FSGS.

[0281] Embodiment 44. A method for treating systemic lupus erythematosus, comprising administering an effective amount of the composition of any one of embodiments 1-30 to a subject in need thereof, thereby treating the systemic lupus erythematosus.

[0282] Embodiment 45. The method of embodiment 44, wherein the administering is performed every 4 weeks.

[0283] Embodiment 46. The method of embodiment 44, wherein the administering is performed every 12 weeks.

[0284] Embodiment 47. A method of treating myositis, comprising administering to a subject in need thereof an effective amount of the composition of any one of embodiments 1-30, thereby treating the myositis.

[0285] Embodiment 48. The method of any one of embodiments 37-47, wherein the administration is subcutaneous.

[0286] Embodiment 49. A composition comprising approximately: i. 150 mg / mL of immunoglobulin-like transcript 7 (ILT7) binding protein; ii. 20 mM histidine / histidine-HCl; iii. 180 mM sucrose; iv. 15 mM L-methionine; and v. 0.02% polysorbate-80, wherein the ILT7 binding protein comprises a sequence that is at least 85% identical to the sequence of Table 1.

[0287] Embodiment 50. A composition comprising approximately: i. 150 mg / mL of immunoglobulin-like transcript 7 (ILT7) binding protein; ii. 20 mM histidine / histidine-HCl; iii. 180 mM sucrose; iv. 15 mM L-methionine; and v. 0.02% polysorbate-80, wherein the ILT7 binding protein comprises a VH comprising SEQ ID NO: 1, a VL comprising SEQ ID NO: 2, or both a VH and a VL comprising SEQ ID NO: 1 and SEQ ID NO: 2, respectively.

[0288] Embodiment 51. A method for treating an autoimmune disease, the method comprising administering a composition comprising: i. about 150 mg / mL of immunoglobulin-like transcript 7 (ILT7) binding protein; ii. 20 mM histidine / histidine-HCl; iii. 180 mM sucrose; iv. 15 mM L-methionine; and v. 0.02% polysorbate-80, wherein the ILT7 binding protein comprises complementarity determining regions (CDRs) HCDR1, HDR2, HCDR3, LCDR1, LCDR2 and LCDR3, which respectively comprise the sequences of SEQ ID NO: 3, 4, 5, 6, 7 and 8, wherein the dose of the ILT7 binding protein comprises about 150 mg to about 350 mg; wherein the administration is subcutaneous, and wherein the dose is administered in a single injection.

[0289] Embodiment 52. The method of embodiment 51, wherein the dose of the ILT7 binding protein comprises about 150 mg to about 275 mg.

[0290] Embodiment 53. The method of embodiment 52, wherein the dose of the ILT7 binding protein comprises about 150 mg to about 200 mg.

[0291] Example Group 2

[0292] Embodiment 54. A composition comprising: (i) about 100 mg / mL to about 350 mg / mL of immunoglobulin-like transcript 7 (ILT7) binding protein; (ii) about 50 to about 350 mM sucrose; (iii) about 0.001% to about 1% polysorbate-80; (iv) L-methionine; and (v) a buffer selected from a histidine buffer, a citrate buffer, or a phosphate buffer.

[0293] Embodiment 55. A composition comprising: (i) about 100 mg / mL to about 165 mg / mL of immunoglobulin-like transcript 7 (ILT7) binding protein; (ii) about 150 to about 240 mM sucrose; (iii) about 0.003% to about 0.8% polysorbate-80; (iv) L-methionine; and (v) a buffer selected from a histidine buffer, a citrate buffer, or a phosphate buffer.

[0294] Embodiment 56. The composition of any one of embodiments 54-55, wherein the buffer is the histidine buffer.

[0295] Embodiment 57. A composition as described in any of embodiments 54-55, wherein the buffer is a phosphate buffer.

[0296] Embodiment 58. A composition as described in any of embodiments 54-55, wherein the buffer is a citrate buffer.

[0297] Embodiment 59. The composition of any one of embodiments 54-58, wherein the pH of the composition is acidic as determined by a pH meter.

[0298] Embodiment 60. The composition of embodiment 59, wherein the acidic pH is about 5 to about 7, as determined by a pH meter.

[0299] Embodiment 61. The composition of embodiment 60, wherein the acidic pH is about 6 as determined by a pH meter.

[0300] Embodiment 62. The composition of any one of embodiments 54-62, wherein the composition comprises about 5 mM to about 25 mM histidine / histidine-HCl.

[0301] Embodiment 63. The composition of embodiment 62, comprising about 20 mM histidine / histidine-HCl.

[0302] Embodiment 64. The composition of any one of embodiments 54-63, wherein the composition comprises about 5 mM to about 50 mM L-methionine.

[0303] Embodiment 65. The composition of embodiment 64, comprising about 15 mM L-methionine.

[0304] Embodiment 66. The composition of any one of embodiments 54-65, comprising about 0.02% polysorbate-80.

[0305] Embodiment 67. The composition of any one of embodiments 54-66, comprising up to about 150 mg / mL of the ILT7 binding protein.

[0306] Embodiment 68. The composition of any one of embodiments 54-67, comprising about 150 mg / mL of the ILT7 binding protein.

[0307] Embodiment 69. A composition as described in any of Embodiments 54-68, wherein the ILT7 binding protein comprises: i. VH, which comprises at least 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO: 1; ii. VL, which comprises at least 95%, 96%, 97%, 98% or 99% identity with SEQ ID NO: 2; or iii.i. and ii.

[0308] Embodiment 70. A composition as described in any one of embodiments 54-69, wherein the ILT7 binding protein comprises: i. a VH comprising SEQ ID NO: 1; ii. a VL comprising SEQ ID NO: 2; or iii.i. and ii.

[0309] Embodiment 71. A composition as described in any of embodiments 54-70, wherein the ILT7 binding protein comprises complementarity determining regions (CDRs) HCDR1, HDR2, HCDR3, LCDR1, LCDR2 and LCDR3, which respectively comprise the sequences of SEQ ID NOs: 3, 4, 5, 6, 7 and 8.

[0310] Embodiment 72. The composition of any one of embodiments 54-71, wherein the composition comprises a viscosity of about 5 cP to about 50 cP as determined by a viscometer.

[0311] Embodiment 73. The composition of any one of embodiments 54-72, wherein the ILT7 binding protein is dastilimab.

[0312] Embodiment 74. A composition comprising approximately: i. 150 mg / mL of immunoglobulin-like transcript 7 (ILT7) binding protein; ii. 20 mM histidine / histidine-HCl; iii. 180 mM sucrose; iv. 15 mM L-methionine; and v. 0.02% polysorbate-80.

[0313] Embodiment 75. A composition comprising approximately: i. 150 mg / mL of immunoglobulin-like transcript 7 (ILT7) binding protein; ii. 20 mM histidine / histidine-HCl; iii. 180 mM sucrose; iv. 15 mM L-methionine; and v. 0.02% polysorbate-80, wherein the ILT7 binding protein comprises: a VH comprising SEQ ID NO: 1 and a VL comprising SEQ ID NO: 2.

[0314] Embodiment 76. A composition comprising approximately: i. 150 mg / mL of immunoglobulin-like transcript 7 (ILT7) binding protein; ii. 20 mM histidine / histidine-HCl; iii. 180 mM sucrose; iv. 15 mM L-methionine; and v. 0.02% polysorbate-80, wherein the ILT7 binding protein comprises complementarity determining regions (CDRs) HCDR1, HDR2, HCDR3, LCDR1, LCDR2 and LCDR3, which respectively comprise the sequences of SEQ ID NOs: 3, 4, 5, 8, 7 and 8.

[0315] Embodiment 77. The composition of any one of embodiments 54-76, wherein the viscosity of the composition is from about 5 to about 50 cP.

[0316] Embodiment 78. The composition of embodiment 77, wherein the viscosity does not exceed 20 cP.

[0317] Embodiment 79. The composition of any of embodiments 54-78, wherein the aggregation rate is reduced as compared to an otherwise comparable composition lacking the L-methionine as determined by size exclusion chromatography at 40°C.

[0318] Embodiment 80. The composition of any of embodiments 54-79, wherein the aggregation rate is 0.5% to 1% per month as determined by size exclusion chromatography at 40°C.

[0319] Embodiment 81. The composition of any one of embodiments 54-80, wherein the oxidation level is reduced as compared to an otherwise comparable composition lacking the L-methionine as determined by peptide mapping analysis of W102 or W104 of SEQ ID NO: 1 or SEQ ID NO: 10 of the ILT7 binding protein at room temperature.

[0320] Embodiment 82. The composition of any one of embodiments 54-81, wherein when the composition is exposed to 1600-1800 lux of light for 5 days, the percentage of oxidized species of ILT7 binding protein in the composition increases to at most 0.5% as determined by size exclusion chromatography.

[0321] Embodiment 83. The composition of any one of embodiments 54-82, wherein the composition is resistant to Fc oxidation.

[0322] Embodiment 84. A container comprising the composition of any one of embodiments 54-83 in unit dosage form.

[0323] Embodiment 85. The container of Embodiment 84, wherein the container comprises nitrogen.

[0324] Embodiment 86. The container of Embodiment 84, wherein the container does not contain nitrogen.

[0325] Embodiment 87. A method of treating a disease, comprising administering to a subject in need thereof an effective amount of the composition of any one of embodiments 54-83, thereby treating the disease.

[0326] Embodiment 88. The method of Embodiment 87, wherein following the administering, the administering is sufficient to alleviate the symptoms of the disease in the subject in need thereof.

[0327] Embodiment 89. The method of embodiment 88, wherein the symptom is reduced by at least about 1-fold.

[0328] Embodiment 90. A method of treating an autoimmune disease, comprising administering to a subject in need thereof an effective amount of the composition of any one of embodiments 54-83, thereby treating the autoimmune disease.

[0329] Embodiment 91. The method of embodiment 90, wherein the autoimmune disease is selected from the group consisting of: discoid lupus erythematosus (DLE), focal segmental glomerulosclerosis (FSGS), alopecia areata, myositis, diabetes, Hashimoto's disease, autoimmune adrenal insufficiency, pure red cell aplasia, lupus nephritis, multiple sclerosis, IgG4RD, rheumatoid carditis, systemic lupus erythematosus, psoriasis, rheumatoid arthritis, chronic inflammation, Sjögren's syndrome, polymyositis, dermatomyositis, inclusion body myositis, juvenile myositis and scleroderma.

[0330] Embodiment 92. The method of embodiment 91, wherein the autoimmune disease is alopecia areata.

[0331] Embodiment 93. The method of embodiment 91, wherein the autoimmune disease is systemic lupus erythematosus.

[0332] Embodiment 94. The method of embodiment 91, wherein the autoimmune disease is FSGS.

[0333] Embodiment 95. A method of treating alopecia areata, the method comprising administering to a subject in need thereof an effective amount of the composition of any one of embodiments 54-83, thereby treating the alopecia areata.

[0334] Embodiment 96. A method of treating focal segmental glomerulosclerosis (FSGS), the method comprising administering to a subject in need thereof an effective amount of the composition of any one of embodiments 1-98, thereby treating the FSGS.

[0335] Embodiment 97. A method for treating systemic lupus erythematosus, the method comprising administering to a subject in need thereof an effective amount of the composition of any one of embodiments 54-83, thereby treating the systemic lupus erythematosus.

[0336] Embodiment 98. The method of embodiment 97, wherein the administering is performed every 4 weeks.

[0337] Embodiment 99. The method of embodiment 97, wherein the administering is performed every 12 weeks.

[0338] Embodiment 100. A method of treating myositis, comprising administering to a subject in need thereof an effective amount of the composition of any one of embodiments 54-83, thereby treating the myositis.

[0339] Embodiment 101. The method of any one of embodiments 90-100, wherein the administration is subcutaneous.

[0340] Embodiment 102. A composition comprising approximately: i. 150 mg / mL of immunoglobulin-like transcript 7 (ILT7) binding protein; ii. 20 mM histidine / histidine-HCl; iii. 180 mM sucrose; iv. 15 mM L-methionine; and v. 0.02% polysorbate-80, wherein the ILT7 binding protein comprises a sequence that is at least 85% identical to the sequence of Table 1.

[0341] Embodiment 103. A composition comprising approximately: i. 150 mg / mL of immunoglobulin-like transcript 7 (ILT7) binding protein; ii. 20 mM histidine / histidine-HCl; iii. 180 mM sucrose; iv. 15 mM L-methionine; and v. 0.02% polysorbate-80, wherein the ILT7 binding protein comprises a VH comprising SEQ ID NO: 1, a VL comprising SEQ ID NO: 2, or both a VH and a VL comprising SEQ ID NO: 1 and SEQ ID NO: 2, respectively.

[0342] Embodiment 104. A method for treating an autoimmune disease, the method comprising administering a composition comprising: i. about 150 mg / mL of immunoglobulin-like transcript 7 (ILT7) binding protein; ii. 20 mM histidine / histidine-HCl; iii. 180 mM sucrose; iv. 15 mM L-methionine; and v. 0.02% polysorbate-80, wherein the ILT7 binding protein comprises complementarity determining regions (CDRs) HCDR1, HDR2, HCDR3, LCDR1, LCDR2 and LCDR3, which comprise the sequences of SEQ ID NO: 3, 4, 5, 6, 7 and 8, respectively, wherein the dose of the ILT7 binding protein comprises about 150 mg to about 350 mg; wherein the administration is subcutaneous, and wherein the dose is administered in a single injection.

[0343] Embodiment 105. The method of embodiment 104, wherein the dose of the ILT7 binding protein comprises about 150 mg to about 275 mg.

[0344] Embodiment 106. The method of embodiment 105, wherein the dose of the ILT7 binding protein comprises about 150 mg to about 200 mg.

[0345] Embodiment 107. A delivery device comprising the composition of any one of embodiments 54-83 or 102-103.

[0346] Embodiment 108. The delivery device of Embodiment 107, wherein the device is an automatic injector.

[0347] Embodiment 109. A kit comprising a delivery device as described in any one of embodiments 107-108 and instructions for use thereof.

[0348] Embodiment 110. The kit of embodiment 109, comprising a plurality of automatic injectors.

[0349] Embodiment 111. A method of treatment comprising administering dastilimab to a subject in need thereof, wherein the administering comprises using an autoinjector.

[0350] Embodiment 112. The method of treatment of Embodiment 111, wherein the autoinjector is brought into contact with the thigh, abdomen, or arm of the subject in a manner sufficient to effect administration of the dastilimab in the subject in need thereof.

[0351] Embodiment 113. The method of any one of embodiments 111-112, wherein the treatment is treatment of an autoimmune disease or condition selected from the group consisting of: discoid lupus erythematosus (DLE), focal segmental glomerulosclerosis (FSGS), alopecia areata, lupus nephritis, myositis, diabetes, Hashimoto's disease, autoimmune adrenal insufficiency, pure red cell aplasia, multiple sclerosis, rheumatoid carditis, systemic lupus erythematosus, psoriasis, rheumatoid arthritis, chronic inflammation, Sjögren's syndrome, polymyositis, dermatomyositis, inclusion body myositis, juvenile myositis, IgG4-related disease (IgG4RD) and scleroderma.

[0352] Embodiment 114. The method of any one of Embodiments 111-112, wherein the treatment is treatment of a non-autoimmune disease or condition.

[0353] Embodiment 115. The method of embodiment 114, wherein the non-autoimmune disease or condition comprises a disease mediated by ILT7 expressing cells.

[0354] Embodiment 116. A composition comprising: (i) an immunoglobulin-like transcript 7 (ILT7) binding protein; and (ii) L-methionine; wherein when the composition is exposed to 1600-1800 lux of light for 5 days, the percentage of oxidized species of the ILT7 binding protein in the composition increases to at most about 1.0%, as determined by size exclusion chromatography.

[0355] Embodiment 117. The composition of embodiment 116, wherein the percentage of oxidized species of the ILT7 binding protein in the composition is increased to at most about 0.4%, 0.3%, 0.2% or 0.1%.

[0356] Embodiment 118. A composition comprising: (i) an immunoglobulin-like transcript 7 (ILT7) binding protein; and (ii) L-methionine; wherein when the composition is exposed to 1600-1800 lux of light, the daily rate of formation of new oxidized species of the ILT7 binding protein in the composition is at most about 0.1%-0.5%, as determined by size exclusion chromatography.

[0357] Embodiment 119. The composition of embodiment 118, wherein the daily formation rate of new oxidized species of ILT7 binding protein in the composition is at most about 0.2%-0.4% or 0.1%-0.3%.

[0358] Embodiment 120. The composition of any one of embodiments 116-119, comprising about 100 mg / mL to about 450 mg / mL of the ILT7 binding protein.

[0359] Embodiment 121. A composition as described in any of embodiments 116-119, wherein the ILT7 binding protein comprises complementarity determining regions (CDRs) HCDR1, HDR2, HCDR3, LCDR1, LCDR2 and LCDR3, which respectively comprise the sequences of SEQ ID NOs: 3, 4, 5, 6, 7 and 8.

[0360] These and other embodiments are disclosed herein.

[0361] Examples

[0362] Light-induced tryptophan oxidation in the complementarity determining regions (CDRs) of some antibody-based therapeutics can affect potency and shelf life. In addition, there is a need to eliminate and / or reduce the need for engineering controls during manufacturing, including but not limited to lighting adjustments, and the need for nitrogen blankets.

[0363] To evaluate and improve existing formulations, anti-ILT7 binding proteins were used to evaluate ways to reduce and / or eliminate light-induced tryptophan oxidation of the CDRs that can affect antibody potency and shelf life, the need for engineering controls during manufacturing, the use of nitrogen blankets, and the use of syringes (e.g., prefilled syringes) as storage containers.

[0364] Additionally, formulations containing higher concentrations of anti-ILT7 binding proteins allow for administration of higher doses. Progress towards higher concentrations has previously been limited due to increases in aggregation rates and formulation viscosity.

[0365] Example 1. Preparation of oxidizing materials and rate evaluation

[0366] Preparation

[0367] Several problems were identified in existing formulations containing afucosylated human IgG1λ anti-ILT7 mAb; in particular, light-induced tryptophan oxidation, oxidation, deamidation, and isomerization of the antibody Fc portion ( Figures 1A-1C ). Previously, nitrogen blankets have been used to reduce oxidation of liquid formulations. However, nitrogen blankets add additional manufacturing complexity to liquid formulations. The formulations herein are modified to reduce or eliminate these problems. The disclosed compositions and methods illustrate that the provided compositions and methods solve the identified problems.

[0368] Evaluation of the formation and aggregation rate of L-methionine oxidative species on anti-ILT7 monoclonal antibody

[0369] To reduce or eliminate the need for engineering controls during manufacturing (eg, light exposure, nitrogen blanketing, and the like), a screen for improved formulations comprising anti-ILT7 monoclonal antibody (mAb) and excipient use was performed and evaluated for the presence of oxidative species formation.

[0370] The effect of excipient [10 mM L-methionine (L-Met)] on oxidation and aggregation rates was evaluated in a formulation of 100 mg / mL of an anti-ILT7 mAb comprising the sequences of Table 1 (SEQ ID NOs: 10 and 11), 20 mM histidine / histidine-HCl, 240 mM sucrose, and 0.02% PS-80 (pH 6.0). Aggregates were analyzed using size exclusion chromatography (SEC). In particular, the effect of excipient (10 mM L-Met) on oxidation species was evaluated at 5° C. and RT relative to control (0 mM L-Met) and aggregation was evaluated at 5° C., RT, and 40° C.

[0371] The results showed that L-Met reduced the rate of oxidation of substances at 5°C and RT (respectively Figure 1B and Figure 1C In addition, L-Met reduced the aggregation rate of anti-ILT7 mAb at all temperatures (40°C, RT and 5°C) ( Figure 2A , Figure 2B and Figure 2C ). In fact, the use of the provided compositions reduces Met oxidation in ILT7 mAb compositions, which is known to have adverse effects on proteins, including reduced stability and reduced biological activity. In addition, the observed reduced aggregation rate supports the use of L-Met in the composition to allow for increased antibody concentrations in the dosage form.

[0372] Example 2: Evaluation of L-methionine in anti-ILT7 mAb formulations under stress conditions

[0373] To evaluate whether L-methionine reduces or eliminates oxidation, isomerization and / or deamidation that can affect antibody potency and shelf life, the formulations were evaluated under stress conditions simulating long-term storage.

[0374] The effects of 10 mM L-Met or control (0 mM L-Met) on CDR modifications and Fc oxidation were assessed at 2 weeks and 1 month under stress conditions (40°C) and at 3 months under ambient (RT) conditions in a formulation containing 100 mg / mL of anti-ILT7 mAb, 20 mM histidine, 240 mM sucrose, and 0.02% PS-80 (pH 6.0). The effects on oxidation, isomerization, and deamidation levels are reported in Table 2.

[0375] The data show that inclusion of 10 mM L-Met reduces antibody oxidation of exemplary residues M257 and M433 of SEQ ID NO: 10. It should be noted that for stress conditions (40°C), CDR modifications of exemplary residues W102 / W104 of SEQ ID NO: 1 or SEQ ID NO: 10 were reduced by about 50%. Oxidation of Fc residues was also substantially reduced. These unexpected results support the use of the disclosed compositions and methods, particularly to provide improved antibody compositions with increased stability and long-term storage capabilities.

[0376] Table 2. Effects of L-Met on post-translational modifications (PTMs) at 40°C and room temperature (RT)

[0377]

[0378] T0 = ​​starting time point; 2W = 2 weeks; 1M = 1 month; 3M = 3 months

[0379] Example 3. Evaluation of the headspace of anti-ILT7 mAb formulations

[0380] The effect of headspace (nitrogen and air) of L-Met-free formulations on CDR modification and Fc oxidation of specific agents was evaluated in formulations containing 100 mg / mL of anti-ILT7 mAb, 20 mM histidine, 240 mM sucrose, and 0.02% PS-80 (pH 6.0).

[0381] The results in Example 2 show that the presence of 10 mM L-Met resulted in a lower percentage of oxidation at RT compared to the absence of L-Met (0 mM) for exemplary residues M257 and M433 of SEQ ID NO: 10. In contrast, the addition of a nitrogen blanket resulted in a lower percentage of oxidation for the same exemplary residues M257 and M433 of SEQ ID NO: 10 in the absence of L-Met (0 mM) compared to air.

[0382] The results in Example 2 (Table 2) also show that for exemplary residues W102 / W104 (SEQ ID NOs: 1 and 10), the presence of 10 mM L-Met produced a lower percentage of CDR modifications at RT as compared to conditions in the absence of L-Met (0 mM). In contrast, for the same exemplary residues W102 / W104 (SEQ ID NOs: 1 and 10), the addition of a nitrogen blanket in the absence of L-Met (0 mM) produced a lower percentage of oxidized species as compared to air. CDR modifications (W102 / W104 of SEQ ID NO: 1 or SEQ ID NO: 10 and M257 / M433 of SEQ ID NO: 10) produced similarly lower percentages of oxidized species in the 10 mM L-Met (1.4%; Table 2) and nitrogen blanket (1.1%; Table 3) groups. These data show that the presence of L-Met in the formulations enhances their stability and avoids the need for a nitrogen blanket, thereby reducing the labor and cost of producing these formulations as compared to existing methods.

[0383] Results reporting the above effects of headspace on PTMs are provided in Table 3.

[0384] Table 3. Effect of headspace on exemplary post-translational modifications (PTMs) at 3 months at room temperature (RT)

[0385]

[0386] P2: 100 mg / mL HZN7734, 20 mM histidine, 240 mM sucrose, 0.02% PS-80 (pH 6.0); T0 = starting time point

[0387] Example 4. Evaluation of L-methionine oxidation and aggregation of 150 mg / mL formulations of anti-ILT7 mAbs

[0388] The effects of L-Met (0 mM, 5 mM, 10 mM, 15 mM and 20 mM) on oxidation ( Figure 3A ) and aggregation ( Figure 3B The results showed that 15 mM L-Met resulted in stabilization and robustness.

[0389] In addition, the effect of L-Met (0 mM, 10 mM and 20 mM) on CDR modification and Fc oxidation was evaluated at 3 months at RT. The results showed that L-Met reduced the FC oxidation level of exemplary residues M257 and M433 (SEQ ID NO: 10) at RT, and L-Met reduced CDR modification of exemplary residues W102 / W104 (SEQ ID NO: 1 and 10), see Table 4. In fact, the use of L-methionine provides reduced oxidation and aggregation, thereby supporting the use of L-methionine to achieve formulations with improved efficacy, stability and flexibility, thereby achieving higher dosing in the treatment regimen.

[0390] Table 4. Effect of L-Met on PTM at 3 months under RT

[0391]

[0392] T0 = ​​starting time point; 3M = 3 months.

[0393] Example 5. Evaluation of the Effect of L-Methionine on Oxidation of Anti-ILT7 mAb Formulations in Light and Dark Conditions

[0394] The effect of L-Met on the formation of oxidative species of formulations exposed to light was evaluated. In particular, the presence of air, nitrogen or L-Met (0 mM or 15 mM) was evaluated. These formulations contained 100 mg / mL of anti-ILT7 mAb, 20 mM histidine / histidine-HCl, 240 mM sucrose, 0.02% PS-80 (pH 6.0) (P2) or 150 mg / mL of anti-ILT7 mAb, 20 mM histidine, 200 mM sucrose and 0.02% PS-80 (pH 6.0) (P3). The vials were kept in a light box at ambient room temperature and throughout the study, the light intensity was measured at 1600-1800 lux ( Figure 4A The vials were kept in a dark box at room temperature as a control ( Figure 4B ).

[0395] It was observed that 15 mM L-Met minimized the formation of oxidative species when exposed to light for 5 days ( Figure 4A ). The results indicate that the use of L-methionine in the formulation is at least effective in reducing light-induced tryptophan oxidation of the CDRs of anti-ILT7 mAbs, which can affect potency and / or shelf life. These results provide a solution to existing manufacturing methods, which require the need for manufacturing and storage controls to reduce oxidation of antibody formulations.

[0396] Example 6. Evaluation of the Effect of Sucrose Concentration on Oxidation and Aggregation Rates of Anti-ILT7 Formulations

[0397] The effect of sucrose concentration on the oxidation and aggregation rates of formulations containing at least 150 mg / mL anti-ILT7 mAb was evaluated. The results in Table 5 show that no significant effect was observed for 150-240 mM sucrose.

[0398] Table 5. Effect of sucrose concentration on oxidation and aggregation rates

[0399]

[0400] a The samples were kept at 40°C for 3 months, at RT for 6 months, and at 5°C for 24 months.

[0401] In addition, the effect of reduced sucrose concentrations (150-200 mM) on CDR modification and Fc oxidation was evaluated at 40°C at 1 month in a formulation containing 150 mg / mL of anti-ILT7 mAb, 20 mM histidine / histidine-HCl, 15 mM L-methionine, 0.02% PS-80 (pH 6.0). Minimal effects of reduced sucrose concentrations were observed, see Table 6.

[0402] Table 6. Effect of sucrose concentration on PTM at 40°C for 1 month

[0403]

[0404] T0 = ​​starting time point; 1M = 1 month.

[0405] Example 7. Evaluation of the effect of anti-ILT7 mAb concentration on oxidation rate

[0406] The effect of anti-ILT7 mAb concentrations (10, 25, 50, 75 and 100 mg / ml) on formulations containing 20 mM histidine, 240 mM sucrose and 0.02% PS-80 (pH 6.0) was evaluated at 5°C, RT and 40°C.

[0407] At all temperatures, it was determined that the concentration of anti-ILT7 mAb did not affect the oxidation rate ( Figures 5A-5C). Therefore, there is no limitation to using different amounts of mAb concentrations in the formulation and the treatment regimen comprising ILT7 mAb can be adapted accordingly.

[0408] Example 8. Evaluation of the effect of container on aggregation and oxidation of anti-ILT7 mAb formulations

[0409] The effect of storage container (vial or prefilled syringe (PFS)) on aggregation and oxidation of 150 mg / mL anti-ILT7 mAb formulations containing 20 mM histidine, 15 mM methionine, 180 mM sucrose, and 0.02% PS-80 (pH 6.0) was evaluated at 5°C (up to 20 months), 25°C (up to 6 months), and 40°C (up to 3 months). The volume of the formulation (1 mL and 2 mL) was also tested in the PFS.

[0410] It was determined that the type of storage container (vial or PFS) of the anti-ILT7 mAb formulation did not affect the percentage of oxidative variant formation at all temperatures ( Figures 6A-6C ) or promote a decrease in the percentage of monomers (e.g., increase aggregation; Figures 7A-7C ). In addition, the volume of the anti-ILT7 mAb formulation in PFS (1 mL or 2 mL) did not affect the oxidation percentage or monomer percentage. These data indicate that PFS can be used as a storage container for 1 mL and 2 mL volumes of anti-ILT7 mAb formulations and avoids the engineering requirements of using vials as storage containers.

[0411] Thus, any provided storage container (such as a pre-filled auto-injector) can be used without including the properties of the disclosed ILT7 antibody compositions.

[0412] Incorporated by Reference

[0413] All references, articles, publications, patents, patent publications and patent applications cited herein are incorporated by reference in their entirety for all purposes. However, the reference to any reference, article, publication, patent, patent publication and patent application cited herein is not and should not be taken as an admission or any form of suggestion that they constitute valid prior art or form part of the common general knowledge in any country in the world.

[0414] International Patent Applications: PCT / US2016 / 022003, PCT / JP 2006 / 325391, PCT / US2017 / 021616, PCT / US2020 / 063396, and PCT / US2022 / 027620 are hereby incorporated by reference in their entirety for all intents and purposes.

Claims

1. A composition comprising: (i) about 100 mg / mL to about 450 mg / mL of an immunoglobulin-like transcript 7 (ILT7) binding protein; (ii) about 50 to about 350 mM sucrose; (iii) from about 0.001% to about 1% polysorbate 80; (iv) L-methionine; and (v) A buffer selected from a histidine buffer, a citrate buffer or a phosphate buffer.

2. A composition comprising: (i) about 100 mg / mL to about 165 mg / mL of an immunoglobulin-like transcript 7 (ILT7) binding protein; (ii) about 150 to about 240 mM sucrose; (iii) from about 0.003% to about 0.8% polysorbate 80; (iv) L-methionine; and (v) A buffer selected from a histidine buffer, a citrate buffer or a phosphate buffer.

3. The composition of any one of claims 1-2, wherein the buffer is the histidine buffer.

4. The composition of any one of claims 1-2, wherein the buffer is the phosphate buffer.

5. The composition of any one of claims 1-2, wherein the buffer is the citrate buffer.

6. The composition of any one of claims 1-5, wherein the pH of the composition is acidic, as determined by a pH meter.

7. The composition of claim 6, wherein the acidic pH is from about 5 to about 7, as determined by a pH meter.

8. The composition of claim 7, wherein the acidic pH is about 6 as determined by a pH meter.

9. The composition of any one of claims 1-8, wherein the composition comprises about 5 mM to about 25 mM histidine / histidine-HCl.

10. The composition of claim 9, comprising about 20 mM histidine / histidine-HCl.

11. The composition of any one of claims 1-10, wherein the composition comprises about 5 mM to about 50 mM L-methionine.

12. The composition of claim 11 comprising about 15 mM L-methionine.

13. The composition of any one of claims 1-12 comprising about 0.02% polysorbate-80.

14. The composition of any one of claims 1-13, comprising up to about 150 mg / mL of the ILT7 binding protein.

15. The composition of any one of claims 1-14, comprising about 150 mg / mL of the ILT7 binding protein.

16. The composition of any one of claims 1-15, wherein the ILT7 binding protein comprises: i. VH comprising at least 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 1; ii. a VL comprising at least 95%, 96%, 97%, 98% or 99% identity to SEQ ID NO: 2; or iii.i. and ii..

17. The composition of any one of claims 1-16, wherein the ILT7 binding protein comprises: i. a VH comprising SEQ ID NO: 1; ii. a VL comprising SEQ ID NO: 2; or iii.i. and ii..

18. The composition of any one of claims 1-17, wherein the ILT7 binding protein comprises complementarity determining regions (CDRs) HCDR1, HDR2, HCDR3, LCDR1, LCDR2 and LCDR3, which comprise the sequences of SEQ ID NOs: 3, 4, 5, 6, 7 and 8, respectively.

19. The composition of any one of claims 1-18, wherein the composition comprises a viscosity of about 5 cP to about 50 cP, as determined by a viscometer.

20. The composition of any one of claims 1-19, wherein the ILT7 binding protein is dastilimab.

21. A composition comprising about: i. 150 mg / mL of immunoglobulin-like transcript 7 (ILT7) binding protein; ii. 20 mM histidine / histidine-HCl; iii. 180 mM sucrose; iv. 15 mM L-methionine; and v.0.02% Polysorbate-80.

22. A composition comprising about: i. 150 mg / mL of immunoglobulin-like transcript 7 (ILT7) binding protein; ii. 20 mM histidine / histidine-HCl; iii. 180 mM sucrose; iv. 15 mM L-methionine; and v. 0.02% polysorbate-80, wherein the ILT7 binding protein comprises: a VH comprising SEQ ID NO: 1 and a VL comprising SEQ ID NO:

2.

23. A composition comprising about: i. 150 mg / mL of immunoglobulin-like transcript 7 (ILT7) binding protein; ii. 20 mM histidine / histidine-HCl; iii. 180 mM sucrose; iv. 15 mM L-methionine; and v.0.02% polysorbate-80, wherein the ILT7 binding protein comprises complementarity determining regions (CDRs) HCDR1, HDR2, HCDR3, LCDR1, LCDR2 and LCDR3, which comprise the sequences of SEQ ID NOs: 3, 4, 5, 8, 7 and 8, respectively.

24. The composition of any one of claims 21-23, wherein the composition has a viscosity of about 5 to about 50 cP.

25. The composition of claim 24, wherein the viscosity does not exceed 20 cP.

26. The composition of any one of claims 21-25, wherein the aggregation rate is reduced as compared to an otherwise comparable composition lacking the L-methionine as determined by size exclusion chromatography at 40°C.

27. The composition of any one of claims 21-26, wherein the aggregation rate is 0.5% to 1% per month as determined by size exclusion chromatography at 40°C.

28. The composition of any one of claims 21-27, wherein the oxidation level is reduced as compared to an otherwise comparable composition lacking the L-methionine as determined by peptide mapping analysis of W102 or W104 of SEQ ID NO: 1 of the ILT7 binding protein at room temperature.

29. The composition of any one of claims 21-28, wherein the percentage of oxidized species of ILT7 binding protein in the composition increases to at most 1.0% when the composition is exposed to 1600-1800 lux of light for 5 days as determined by size exclusion chromatography.

30. The composition of any one of claims 21-29, wherein the composition is resistant to Fc oxidation.

31. A container comprising the composition of any one of claims 1-30 in unit dosage form.

32. The container of claim 31 , wherein the container contains nitrogen.

33. The container of claim 31, wherein the container does not contain nitrogen.

34. A method of treating a disease, comprising administering an effective amount of the composition of any one of claims 1-30 to a subject in need thereof, thereby treating the disease.

35. The method of claim 34, wherein following the administering, the administering is sufficient to alleviate symptoms of the disease in the subject in need thereof.

36. The method of claim 35, wherein the symptom is reduced by at least about 1-fold.

37. A method of treating an autoimmune disease, comprising administering to a subject in need thereof an effective amount of the composition of any one of claims 1-30, thereby treating the autoimmune disease.

38. The method of claim 37, wherein the autoimmune disease is selected from the group consisting of discoid lupus erythematosus (DLE), focal segmental glomerulosclerosis (FSGS), alopecia areata, myositis, lupus nephritis, diabetes, Hashimoto's disease, autoimmune adrenal insufficiency, pure red cell aplasia, multiple sclerosis, rheumatoid carditis, systemic lupus erythematosus, psoriasis, rheumatoid arthritis, chronic inflammation, Sjögren's syndrome, polymyositis, dermatomyositis, inclusion body myositis, juvenile myositis, IgG4-related disease (IgG4RD) and scleroderma.

39. The method of claim 38, wherein the autoimmune disease is alopecia areata.

40. The method of claim 38, wherein the autoimmune disease is systemic lupus erythematosus.

41. The method of claim 38, wherein the autoimmune disease is FSGS.

42. A method of treating alopecia areata, the method comprising administering to a subject in need thereof an effective amount of the composition of any one of claims 1-30, thereby treating the alopecia areata.

43. A method of treating focal segmental glomerulosclerosis (FSGS), the method comprising administering to a subject in need thereof an effective amount of the composition of any one of claims 1-30, thereby treating the FSGS.

44. A method for treating systemic lupus erythematosus, the method comprising administering to a subject in need thereof an effective amount of the composition of any one of claims 1-30, thereby treating the systemic lupus erythematosus.

45. The method of claim 44, wherein the administering is performed every 4 weeks.

46. ​​The method of claim 44, wherein the administering is performed every 12 weeks.

47. A method of treating myositis, comprising administering to a subject in need thereof an effective amount of the composition of any one of claims 1-30, thereby treating the myositis.

48. The method of any one of claims 37-47, wherein the administration is subcutaneous.

49. A composition comprising about: i. 150 mg / mL of immunoglobulin-like transcript 7 (ILT7) binding protein; ii. 20 mM histidine / histidine-HCl; iii. 180 mM sucrose; iv. 15 mM L-methionine; and v. 0.02% polysorbate-80, wherein the ILT7 binding protein comprises a sequence that is at least 85% identical to the sequence of Table 1.

50. A composition comprising about: i. 150 mg / mL of immunoglobulin-like transcript 7 (ILT7) binding protein; ii. 20 mM histidine / histidine-HCl; iii. 180 mM sucrose; iv. 15 mM L-methionine; and v. 0.02% polysorbate-80, wherein the ILT7 binding protein comprises a VH comprising SEQ ID NO: 1, a VL comprising SEQ ID NO: 2, or both a VH and a VL of SEQ ID NO: 1 and SEQ ID NO: 2, respectively.

51. A method of treating an autoimmune disease, the method comprising administering a composition comprising: i. about 150 mg / mL of immunoglobulin-like transcript 7 (ILT7) binding protein; ii. 20 mM histidine / histidine-HCl; iii. 180 mM sucrose; iv. 15 mM L-methionine; and v.0.02% Polysorbate-80, wherein the ILT7 binding protein comprises complementarity determining regions (CDRs) HCDR1, HDR2, HCDR3, LCDR1, LCDR2 and LCDR3, which comprise the sequences of SEQ ID NOs: 3, 4, 5, 6, 7 and 8, respectively, wherein the dosage of the ILT7 binding protein comprises about 150 mg to about 450 mg; wherein the administration is subcutaneous, and wherein the dose is administered in a single injection.

52. The method of claim 51, wherein the dose of the ILT7 binding protein comprises about 150 mg to about 275 mg.

53. The method of claim 52, wherein the dose of the ILT7 binding protein comprises about 150 mg to about 200 mg.

54. A delivery device comprising the composition of any one of claims 1-30 or 49-50.

55. The delivery device of claim 54, wherein the device is an autoinjector.

56. A kit comprising the delivery device of any one of claims 54-55 and instructions for use thereof.

57. The kit of claim 56 comprising a plurality of automatic injectors.

58. A method of treatment comprising administering dastilimab to a subject in need thereof, wherein the administering comprises using an autoinjector.

59. The method of treatment of claim 58, wherein the autoinjector is brought into contact with the thigh, abdomen, or arm of the subject in a manner sufficient to effect administration of the dastilimab in the subject in need thereof.

60. The method of any one of claims 58-59, wherein the treatment is treatment of an autoimmune disease or condition selected from the group consisting of: discoid lupus erythematosus (DLE), focal segmental glomerulosclerosis (FSGS), alopecia areata, lupus nephritis, myositis, diabetes, Hashimoto's disease, autoimmune adrenal insufficiency, pure red cell aplasia, multiple sclerosis, rheumatoid carditis, systemic lupus erythematosus, psoriasis, rheumatoid arthritis, chronic inflammation, Sjögren's syndrome, polymyositis, dermatomyositis, inclusion body myositis, juvenile myositis, IgG4-related disease (IgG4RD) and scleroderma.

61. The method of any one of claims 58-59, wherein the treatment is treatment of a non-autoimmune disease or condition.

62. The method of claim 61, wherein the non-autoimmune disease or condition comprises a disease mediated by ILT7 expressing cells.

63. A composition comprising: (i) immunoglobulin-like transcript 7 (ILT7) binding protein; and (ii) L-methionine; wherein the percentage of oxidized species of ILT7 binding protein in the composition increases to at most about 1.0% when the composition is exposed to 1600-1800 lux of light for 5 days as determined by size exclusion chromatography.

64. The composition of claim 63, wherein the percentage of oxidized species of the ILT7 binding protein in the composition is increased to at most about 0.4%, 0.3%, 0.2% or 0.1%.

65. A composition comprising: (i) immunoglobulin-like transcript 7 (ILT7) binding protein; and (ii) L-methionine; wherein the rate of formation of new oxidized species of ILT7 binding protein in the composition per day is at most about 0.1%-0.5% when the composition is exposed to 1600-1800 lux of light, as determined by size exclusion chromatography.

66. The composition of claim 65, wherein the daily formation rate of new oxidized species of the ILT7 binding protein in the composition is at most about 0.2%-0.4% or 0.1%-0.3%.

67. The composition of any one of claims 63-66, comprising about 100 mg / mL to about 450 mg / mL of the ILT7 binding protein.

68. The composition of any one of claims 63-67, wherein the ILT7 binding protein comprises complementarity determining regions (CDRs) HCDR1, HDR2, HCDR3, LCDR1, LCDR2 and LCDR3, which comprise the sequences of SEQ ID NOs: 3, 4, 5, 6, 7 and 8, respectively.

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