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

Abstract

Provided are immunoglobulin-like transcript 7 (ILT7) binding proteins and methods for making, using, and storing them. Also provided are improved formulations comprising anti-ILT7 binding proteins and devices comprising the disclosed formulations. The disclosed compositions and methods offer improvements over the state of the art and address limitations associated with existing manufacturing methods. Specifically, existing methods are limited by the occurrence of light-induced tryptophan oxidation in the complementarity-determining regions (CDRs) of antibodies, which adversely affects potency and shelf life.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application claims priority to U.S. Patent Application No. 63 / 369,567, filed July 27, 2022, which is incorporated herein by reference in its entirety for all purposes.

[0002] Electronic Sequence Listing Reference The contents of the electronic sequence listing (HOPA_037_01WO_SeqList_ST26.xml; size: 13,040 bytes; and creation date: July 14, 2023) are incorporated herein by reference in their entirety.

[0003] Field of Disclosure The disclosure provided relates to improved immunoglobulin-like transcript 7 (ILT7) binding proteins and methods for making, utilizing, and storing same. Also provided are devices comprising the described proteins and methods of using them to treat various diseases and conditions associated with ILT7-expressing cells. [Background technology]

[0004] Proteins can undergo various degradation processes, including aggregation, deamidation, isomerization, oxidation, disulfide bond scrambling, and truncation. These events can occur during fermentation, purification, formulation, manufacturing, and storage. The clinical usefulness and shelf life of proteins are compromised when degradation adversely affects the biological activity of the protein or induces immunogenicity. One of the most common degradation processes observed is oxidation of unstable amino acid residues.

[0005] Light-induced tryptophan oxidation in complementarity-determining regions (CDRs) negatively impacts 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. Furthermore, there is a need to eliminate or reduce the need for engineering controls, including, but not limited to, the need for illumination and nitrogen overlay during the manufacture of these proteins.

[0006] The present disclosure addresses these and many more limitations of the state of the art and provides a variety of improved compositions and methods. Summary of the Invention [Means for solving the problem]

[0007] The compositions and methods of the present disclosure offer improvements over the state of the art and address limitations associated with existing manufacturing methods, specifically those limited by the occurrence of light-induced tryptophan oxidation in the complementarity-determining regions (CDRs) of antibodies, which adversely affects potency and shelf life.

[0008] Additionally, 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. Indeed, the methods of the present disclosure provide improved formulations containing higher concentrations of ILT7 binding protein, allowing for higher doses and more convenient dosing regimens.

[0009] Additionally, the provided methods eliminate the need for engineering controls such as specific lighting conditions and the inclusion of a nitrogen overlay during production, thereby reducing manufacturing costs, labor costs, and overhead expenses associated with antibody production.

[0010] Provided herein is a composition 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.

[0011] Provided herein is a composition 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.

[0012] In embodiments, the buffer in the composition is a histidine buffer. In embodiments, the buffer is a phosphate buffer. In embodiments, the buffer is a citrate buffer. In embodiments, the pH of the composition is acidic as determined by a pH meter. In embodiments, the acidic pH is about 5 to about 7 as determined by a pH meter. In embodiments, the acidic pH of a composition of the present disclosure is about 6 as determined by a pH meter. In embodiments, the composition comprises about 5 mM to about 25 mM histidine / histidine-HCl. In embodiments, the composition comprises 20 mM histidine / histidine-HCl. In embodiments, the composition comprises about 5 mM to about 50 mM L-methionine. In embodiments, the composition comprises 15 mM L-methionine. In embodiments, the composition comprises 0.02% polysorbate 80. In embodiments, the composition comprises up to about 150 mg / mL of an ILT7 binding protein. In embodiments, the composition comprises about 150 mg / mL of the 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.i. and ii. In embodiments, the anti-ILT7 binding protein comprises: i. a VL comprising SEQ ID NO: 1; a VH comprising SEQ ID NO: 2; or iii.i. and ii. In embodiments, the anti-ILT7 binding protein comprises complementarity determining regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprising the sequences of SEQ ID NOs: 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 viscosimetry. In embodiments, the anti-ILT7 binding protein is daxdilimab, which is also known as HZN7734, VIB7734, or MEDI7734.

[0013] Provided is a composition comprising: i. about 150 mg / mL anti-immunoglobulin-like transcript 7 (ILT7) binding protein; ii. about 20 mM histidine / histidine-HCl; iii. about 180 mM sucrose; iv. about 15 mM L-methionine; and v. about 0.02% polysorbate 80.

[0014] Provided is a composition comprising: i. about 150 mg / mL anti-immunoglobulin-like transcript 7 (ILT7) binding protein; ii. about 20 mM histidine / histidine-HCl; iii. about 180 mM sucrose; iv. about 15 mM L-methionine; and v. about 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.

[0015] Provided is a composition comprising: i. about 150 mg / mL anti-immunoglobulin-like transcript 7 (ILT7) binding protein; ii. about 20 mM histidine / histidine-HCl; iii. about 180 mM sucrose; iv. about 15 mM L-methionine; and v. about 0.02% polysorbate 80, wherein the ILT7 binding protein comprises complementarity determining regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprising the sequences of SEQ ID NOs: 3, 4, 5, 6, 7, and 8, respectively.

[0016] In embodiments, the viscosity of the composition is about 5 to about 50 cP. In embodiments, the viscosity of the composition does not exceed 20 cP. In embodiments, the composition exhibits a reduced aggregation rate, as determined by size exclusion chromatography at 40°C, compared to an otherwise equivalent composition lacking L-methionine. In embodiments, the aggregation rate is 0.5% to 1% per month, as determined by size exclusion chromatography at 40°C. In embodiments, the composition exhibits a reduced oxidation level, as determined by peptide mapping of W102 or W104 of SEQ ID NO: 1 of the anti-ILT7 binding protein at room temperature, compared to an otherwise equivalent composition lacking L-methionine. In embodiments, the composition exhibits a reduced oxidation level, as determined by peptide mapping of W102 or W104 of SEQ ID NO: 1 of the anti-ILT7 binding protein at room temperature, compared to an otherwise equivalent composition lacking L-methionine. In embodiments, the composition exhibits a reduced percentage of oxidized species per day of 0.2% to 0.5% when exposed to 1600 to 1800 lux for 5 days. In embodiments, the composition is Fc oxidation-resistant.

[0017] Provided is a container containing a composition of the present disclosure in unit dose form. In embodiments, the container contains nitrogen. In embodiments, the container does not contain nitrogen.

[0018] Provided is a method for treating a disease, comprising administering an effective amount of a composition of the present disclosure to a subject in need thereof, thereby treating the disease. In embodiments, the administration is sufficient to reduce the symptoms of the disease in the subject in need thereof after administration. In embodiments, the symptoms are reduced by at least about 1-fold.

[0019] Provided is a method for treating an autoimmune disease, comprising administering an effective amount of a composition of the present disclosure to a subject in need thereof, thereby treating the autoimmune disease. In embodiments, 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 anemia, multiple sclerosis, rheumatic 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 embodiments, the autoimmune disease is alopecia areata. In embodiments, the autoimmune disease is systemic lupus erythematosus. In embodiments, the autoimmune disease is FSGS.

[0020] Provided is a method of treating alopecia areata, comprising administering an effective amount of a composition of the present disclosure to a subject in need thereof, thereby treating alopecia areata.

[0021] Provided is a method of treating FSGS, comprising administering an effective amount of a composition of the present disclosure to a subject in need thereof, thereby treating FSGS.

[0022] Provided is a method of treating systemic lupus erythematosus, comprising administering an effective amount of a composition of the present disclosure to a subject in need thereof, thereby treating systemic lupus erythematosus.

[0023] In embodiments, the compositions of the present disclosure are administered every 4 weeks. In embodiments, the compositions of the present disclosure are administered every 12 weeks. In embodiments, administration continues for at least about 2 administrations.

[0024] Provided is a method of treating myositis, comprising administering an effective amount of a composition of the present disclosure to a subject in need thereof, thereby treating myositis. In embodiments, the administration of the composition of the present disclosure is subcutaneous.

[0025] Provided is a composition comprising: i. about 150 mg / mL immunoglobulin-like transcript 7 (ILT7) binding protein; ii. about 20 mM histidine / histidine-HCl; iii. about 180 mM sucrose; iv. about 15 mM L-methionine; and v. about 0.02% polysorbate 80, wherein the anti-ILT7 binding protein comprises a sequence having at least 85% identity to a sequence in Table 1.

[0026] Provided is a composition comprising: i. about 150 mg / mL immunoglobulin-like transcript 7 (ILT7) binding protein; ii. about 20 mM histidine / histidine-HCl; iii. about 180 mM sucrose; iv. about 15 mM L-methionine; and v. about 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 a VH and a VL of SEQ ID NO: 1 and SEQ ID NO: 2, respectively.

[0027] Provided are methods of treating an autoimmune disease, comprising administering a composition comprising: i. about 150 mg / mL 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 complementarity-determining regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprising the sequences of SEQ ID NOs: 3, 4, 5, 6, 7, and 8, respectively; the dose of the anti-ILT7 binding protein comprises about 150 mg to about 450 mg; the administration is subcutaneous; and the dose is administered as 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 from about 150 mg to about 200 mg.

[0028] Provided is a delivery device comprising any of the compositions disclosed herein. In embodiments, the delivery device is an autoinjector.

[0029] Provided are kits that include the delivery devices disclosed herein and instructions for their use. In embodiments, the kits include multiple autoinjectors.

[0030] Provided are methods of treatment comprising administering daxudilimab to a subject in need thereof, wherein the administering comprises an auto-injector. In embodiments, the auto-injector of the present disclosure is contacted with the thigh, abdomen, or arm of a subject in need thereof in a manner sufficient to achieve administration of daxudilimab to the subject in need thereof.

[0031] Provided are methods of treating an autoimmune disease, wherein the treatment is for 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, rheumatic carditis, systemic lupus erythematosus, psoriasis, rheumatoid arthritis, chronic inflammation, Sjogren's syndrome, polymyositis, dermatomyositis, inclusion body myositis, juvenile myositis, IgG4-related disease (IgG4RD), and scleroderma. In embodiments, the methods disclosed herein provide for the treatment of a non-autoimmune disease or condition. In embodiments, the non-autoimmune disease or condition comprises an ILT7-expressing cell-mediated disease.

[0032] Provided are compositions comprising (i) an immunoglobulin-like transcript 7 (ILT7) binding protein and (ii) L-methionine, wherein when the composition is exposed to light at 1600-1800 lux for 5 days, the increase in the percentage of oxidized species of the ILT7 binding protein in the composition is at most about 1.0%. In embodiments, the increase in the percentage of oxidized species of the ILT7 binding protein in the composition is at most about 0.4%, 0.3%, 0.2%, or 0.1%.

[0033] Provided are compositions comprising (i) an immunoglobulin-like transcript 7 (ILT7) binding protein and (ii) L-methionine, wherein 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% when the composition is exposed to light at 1600-1800 lux. In embodiments, 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%.

[0034] Provided are compositions comprising about 100 mg / mL to about 450 mg / mL of an ILT7 binding protein. In embodiments, the ILT7 binding protein comprises complementarity determining regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprising the sequences of SEQ ID NOs: 3, 4, 5, 6, 7, and 8, respectively.

[0035] These and other embodiments are described herein.

[0036] The accompanying drawings, which are incorporated in and form a part of this specification, illustrate some, but not the only or exclusive, embodiments and / or features. It is intended that the embodiments and figures disclosed herein be considered illustrative rather than limiting. [Brief explanation of the drawings]

[0037] [Figure 1A] Figure 1A shows an exemplary nonfucosylated human IgG1λ anti-ILT7 mAb "anti-ILT7 mAb" (Figure 1A) and the percentage of oxidized species for a formulation containing 100 mg / mL anti-ILT7 mAb at pH 6.0, 20 mM histidine / histidine HCl, 240 mM sucrose, and 0.02% PS-80, plus 10 mM excipient L-methionine (L-Met) or a control (0 mM L-Met). Oxidized species were assessed at 5°C (Figure 1B) and RT (Figure 1C). The results show that L-Met reduced the rate of oxidized species. RT = room temperature. [Figure 1B] Same as above [Figure 1C] Same as above [Figure 2A] Figure 2 shows the percentage of aggregates for a formulation containing 100 mg / mL anti-ILT7 mAb at pH 6.0, 20 mM histidine / histidine HCl, 240 mM sucrose, and 0.02% PS-80, plus 10 mM L-methionine (L-Met) as an excipient, or a control (0 mM L-Met). Aggregation was assessed at 40°C (Figure 2A), RT (Figure 2B), and 5°C (Figure 2C). The results show that L-Met reduced the aggregation rate of anti-ILT7 mAb. RT = room temperature. [Figure 2B] Same as above [Figure 2C] Same as above [Figure 3A]Figure 3A shows the percentage of oxidation (Figure 3A) and aggregation (Figure 3B) per month rate for formulations containing 150 mg / mL anti-ILT7 mAb, 20 mM histidine / histidine HCl, 200 mM sucrose, and 0.02% PS-80 at pH 6.0, plus L-Met (0 mM, 5 mM, 10 mM, and 20 mM). Percent formation was measured at 5°C, RT, and 40°C. 15 mM L-Met provided suitable stabilization and robustness. RT = room temperature. [Figure 3B] Same as above [Figure 4A] The percentage of oxidative species formed per day is shown for a formulation containing 100 mg / mL anti-ILT7 mAb at pH 6.0, 20 mM histidine / histidine HCl, 240 mM sucrose, and 0.02% PS-80 (P2) or a formulation containing 150 mg / mL anti-ILT7 mAb at pH 6.0, 20 mM histidine / histidine HCl, 200 mM sucrose, and 0.02% PS-80 (P3) exposed to light (Figure 4A) and in the dark (Figure 4B). The effect of the presence of air, nitrogen (N), or 15 mM L-Met on oxidative species formation in the formulations under light or dark conditions was evaluated. Vials were kept in a light box at ambient room temperature, and light intensity was measured at 1600–1800 lux throughout the experiment. 15 mM L-Met minimized oxidative species formation when exposed to light for 5 days. [Figure 4B] Same as above [Figure 5A]Figure 5 shows the % oxidized variant formation as a function of time for formulations containing 10 mg / mL, 25 mg / mL, 50 mg / mL, 75 mg / mL, or 100 mg / mL of anti-ILT7 mAb at 40°C (Figure 5A), RT (Figure 5B), and 5°C (Figure 5C). The change in % oxidized variant formation at 40°C was measured at approximately 0, 0.25, 0.5, 1, 2, and 3 months. The change in % oxidized variant formation at RT was measured at approximately 0, 1, 2, 3, 6, 8, and 12 months. The change in % oxidized variant formation at 5°C was measured at approximately 0, 3, 6, 9, and 12 months. The % oxidized variant formation was measured using size exclusion chromatography (SEC). RT = room temperature. [Figure 5B] Same as above [Figure 5C] Same as above [Figure 6A] Figure 6 shows the change in % monomer as a function of time, container type (prefilled syringe [PFS] or vial), and volume (1 mL PFS or 2 mL PFS) at 40°C (Figure 6A), 25°C (Figure 6B), and 5°C (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). [Figure 6B] Same as above [Figure 6C] Same as above [Figure 7A]Figure 7 shows the % oxidized variant formation as a function of time, container type (prefilled syringe [PES] or vial), and volume (1 mL PFS or 2 mL PFS) at 40°C (Figure 7A), 25°C (Figure 7B), and 5°C (Figure 7C). The change in % oxidized variant formation at 40°C was measured at approximately 0, 0.5, 1, 2, and 3 months. The change in % oxidized variant formation at 25°C was measured at approximately 0, 1, 2, 3, and 6 months. The change in % oxidized variant formation at 5°C was measured at approximately 0, 3, 6, 9, 12, 16, and 20 months. The % oxidized variant formation was measured using size exclusion chromatography (SEC). [Figure 7B] Same as above [Figure 7C] Same as above DETAILED DESCRIPTION OF THE INVENTION

[0038] Provided are compositions containing anti-ILT7 binding proteins with enhanced potency and shelf life. Also provided are methods of making and using the same in the treatment of diseases, including, but not limited to, autoimmune indications. The compositions find particular use in improving the stability of antibodies having the sequence of SEQ ID NO: 1. Amino acid residues of this antibody are damaged by light and oxygen. Specifically described are tryptophan residues that are oxidized, asparagine residues that are deamidated, and portions of the Fc region that are oxidized. The disclosed compositions are particularly beneficial with respect to reducing oxidation and aggregation. Also provided are devices (e.g., autoinjectors) containing the disclosed compositions and methods of utilizing them.

[0039] In embodiments, anti-ILT7 mAb-containing compositions may 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 aggregation levels of anti-ILT7 mAb formulations, thereby resulting in improved formulations that confer an extended shelf life compared to existing formulations.

[0040] definition Although the following terms are believed to be well understood by those of ordinary skill in the art, the following definitions are provided to facilitate description of the presently disclosed subject matter.

[0041] All technical and scientific terms used herein, unless otherwise defined below, are intended to have the same meaning as commonly understood by one of ordinary skill in the art. References to technology used herein are intended to refer to technology as commonly understood in the art, including variations on those technologies and / or equivalent technology substitutions that would be apparent to one of ordinary skill in the art.

[0042] Any range recited herein is intended to be inclusive of the endpoints, for example, a range of 2 to 4 includes 2 and 4 and all values in between.

[0043] As used herein, the singular forms "a," "an," and "the" include plural referents unless the context clearly dictates otherwise.

[0044] The term "about" or "approximately," when immediately preceding a numerical value, refers to a range plus or minus 10% of that value. For example, unless the context of this disclosure dictates otherwise or contradicts such an interpretation, "about 50" can mean 45 to 55, "about 25,000" can mean 22,500 to 27,500, etc. In the context of a list of numerical values such as "about 49, about 50, about 55, ...," "about 50" refers to a range extending less than half the interval between the preceding and following values, e.g., greater than 49.5 to less than 52.5. Furthermore, the phrase "less than about" a value or "greater than about" a value should be understood in light of the definition of the term "about" provided herein.

[0045] When referring to nucleic acid or amino acid sequences, the term "identity" is used to indicate the similarity between two sequences. Unless otherwise indicated, percent identity described herein is determined using the BLAST algorithm, available on the world wide web at the following address: blast.ncbi.nlm.nih.gov / Blast.cgi, with default parameters.

[0046] As used herein, the term "subject" refers to any individual, e.g., a human or non-human mammal, for whom diagnosis, prognosis, or treatment is desired. The term "subject" can refer to a human or non-human mammal that is suffering from, may be suffering from, or is suspected of being suffering from a disease, e.g., an autoimmune disease or condition. The terms "subject" and "patient" are used interchangeably herein. While the anti-ILT7 binding protein compositions provided herein are primarily directed to compositions suitable for administration to humans, one of skill in the art will understand that such compositions are generally suitable for administration to any type of subject. In an embodiment, the subject is a mammal. Mammals include primates, such as humans, monkeys, chimpanzees, and apes, non-primates, such as domestic animals including laboratory animals (rabbits and rodents, e.g., guinea pigs, rats, or mice) and household pets and livestock (e.g., cats, dogs, pigs, cows, sheep, goats, horses, rabbits), and non-domestic animals, such as wildlife, birds, reptiles, fish, etc.

[0047] As used herein, the term "room temperature" or "RT" refers to a temperature of about 20° C. to about 25° C. RT can be 21° C., 22° C., 23° C., 24° C., or up to about 25° C. RT can be about 20° C. to 21° C., 21° C. to 22° C., 22° C. to 23° C., 23° C. to 24° C., or 24° C. to 25° C.

[0048] As used herein, "treating" or "treat" describes the management and care of a subject for the purpose of combating a disease, condition, or disorder, and includes administering an 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. Thus, the term "treat" or "treating" refers to both therapeutic and prophylactic or preventative measures, the goal being to prevent, slow (alleviate), or ameliorate the progression of a disease (e.g., an autoimmune disease). Beneficial or desired clinical results include, but are not limited to, alleviation of symptoms, diminishment of the extent of the disease, stabilization (i.e., not worsening) of the disease state, delaying or slowing the progression of the disease, improvement or palliation of the disease state, and reversing the disease (whether partial or total). The term "treating" can also include treatment of cells in vitro or in an animal model.

[0049] 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 may be used interchangeably herein. In embodiments, an anti-ILT7 binding protein used in the methods described herein binds to full-length ILT7. In embodiments, an 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, either an ILT7 binding protein or an ILT7 binding molecule may refer to an anti-ILT7 binding protein (e.g., an antibody).

[0050] Compositions Comprising Anti-ILT7 Binding Proteins Immunoglobulin-like transcript 7 (ILT7) binding protein In embodiments, provided are anti-ILT7 binding proteins. In embodiments, the anti-ILT7 binding proteins bind to any mammalian ILT7. In embodiments, the anti-ILT7 binding proteins bind to human ILT7 or a fragment thereof, e.g., the extracellular portion of human ILT7. In embodiments, the anti-ILT7 binding proteins disclosed herein bind to cynomolgus ILT7 or a fragment thereof, e.g., the extracellular portion of cynomolgus ILT7.

[0051] Exemplary sequences of anti-ILT7 binding proteins are described in PCT Publication No. WO 2017156298, U.S. Patent No. 8,084,585, and PCT Publication No. WO 2021113702, all of which are incorporated by reference in their entireties. Exemplary sequences of anti-ILT7 binding proteins are shown in Table 1. In embodiments, the ILT7 to which the anti-ILT7 binding protein binds is located on plasmacytoid dendritic cells (pDCs). In embodiments, clone 2 is provided in PCT Publication No. WO 2017 / 156298 and is further described in Table 1 below.

[0052] In embodiments, any one of the sequences from Table 1 may be modified. In embodiments, modifications to the sequences of Table 1 include one or more truncations, deletions, insertions, substitutions, and any combination of these modifications. Modifications may occur at any of the residues provided in Table 1 and at any number of residues from Table 1. In embodiments, modifications include 1 to 3, 1 to 5, 1 to 10, 5 to 20, 1 to 3, 1 to 5, 1 to 10, 1 to 20, 3 to 8, 3 to 10, 3 to 15, 5 to 8, 5 to 10, or 5 to 20 residues. In embodiments, modifications may occur at up to 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 20, 30, 40, 50 residues.

[0053] [Table 1]

[0054] Provided herein are compositions comprising an anti-ILT7 binding protein. In embodiments, the composition may comprise an effective amount of the anti-ILT7 binding protein. In embodiments, the polynucleotide encoding the anti-ILT7 binding protein, or at least a portion thereof, comprises at least about or up to about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99% identity, or up to about 100% identity, to any one of the sequences in Table 1 (SEQ ID NOS: 1-12). In embodiments, the polynucleotide encoding the anti-ILT7 binding protein, or at least a portion thereof, comprises any one of the sequences in Table 1.

[0055] In embodiments, the isolated ILT7 binding protein is an anti-ILT7 binding protein that can bind to the same ILT7 epitope as an antibody comprising a heavy chain variable region (VH) of SEQ ID NO: 1 and a light chain variable region (VL) of SEQ ID NO: 2. In embodiments, the isolated ILT7 binding protein is an anti-ILT7 binding protein that competitively inhibits the binding to ILT7 of an antibody comprising a VH of SEQ ID NO: 1 and a VL of SEQ ID NO: 2.

[0056] In embodiments, the isolated ILT7 binding protein is an anti-ILT7 binding protein comprising complementarity determining regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprising the sequences of SEQ ID NOs: 3, 4, 5, 6, 7, and 8, respectively.

[0057] In embodiments, the anti-ILT7 binding protein comprises a VH at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO: 1 and / or a VL at least 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% identical to SEQ ID NO:2.

[0058] 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 VL comprising SEQ ID NO: 2.

[0059] In embodiments, the ILT7 binding protein comprises a light chain (LC) and a heavy chain (HC) that are at least 85%, 90%, 95%, 96%, 97%, 98% or 99% identical 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 with 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 with 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.

[0060] In embodiments, compositions 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 on the C- or N-terminus of a protein. In embodiments, the modification comprises at least a portion of a CDR region. In embodiments, the modification comprises at least a portion of a fragment crystallizable (Fc) region. In embodiments, the modification is reversible. In embodiments, the modification is irreversible. Exemplary modifications include phosphorylation, glycosylation, ubiquitination, nitrosylation, methylation, acetylation, lipidation, and proteolysis.

[0061] In embodiments, the ILT7 binding protein comprises an antibody or antigen-binding fragment thereof. In embodiments, the antibody or antigen-binding fragment thereof is non-fucosylated.

[0062] 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 ILT7.

[0063] In embodiments, the ILT7 binding protein inhibits the release of interferon (IFN) alpha from peripheral blood mononuclear cells (PBMCs). In embodiments, the ILT7 binding protein has ADCC activity against plasmacytoid dendritic cells (pDCs) in PBMCs.

[0064] In embodiments, the ILT7 binding protein comprises a murine, human, chimeric, humanized, or resurfaced antibody or antigen-binding fragment thereof. In embodiments, 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, intrabody, IgGΔCH2, minibody, F(ab')3, tetrabody, triabody, diabody, single-domain antibody, DVD-Ig, Fcab, mAb2, (scFv)2, or scFv-Fc. In embodiments, the ILT7 binding protein comprises a monoclonal antibody or antigen-binding fragment thereof.

[0065] In embodiments, the ILT7 binding protein comprises an 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 embodiments, the anti-ILT7 binding protein comprises an LC immunoglobulin constant domain selected from the group consisting of: (a) an Ig kappa constant domain; and (b) an Ig lambda constant domain. In embodiments, the anti-ILT7 binding protein comprises a human IgG1 constant domain and a human lambda constant domain.

[0066] In embodiments, provided herein are host cells that produce anti-ILT7 binding molecules.

[0067] In embodiments, provided herein is an isolated polynucleotide comprising a nucleic acid encoding a VH, wherein the VH comprises an amino acid sequence at least 85%, 90%, 95% identical to, or identical to, the VH of SEQ ID NO: 1. In embodiments, the polynucleotide comprises a sequence at least 85%, 90%, 95% identical to SEQ ID NO: 11. In embodiments, the polynucleotide comprises SEQ ID NO: 11.

[0068] In embodiments, provided herein is an isolated polynucleotide comprising a nucleic acid encoding a VL, wherein the VL comprises an amino acid sequence at least 85%, 90%, 95% identical to, or identical to, the VL of SEQ ID NO: 2. In embodiments, the polynucleotide comprises a sequence at least 85%, 90%, 95% identical to SEQ ID NO: 12. In embodiments, the polynucleotide comprises SEQ ID NO: 12.

[0069] In embodiments, the nucleic acid is operably linked to a regulatory sequence. In embodiments, an antibody or antigen-binding fragment thereof comprising the VH or VL encoded by this nucleic acid is capable of specifically binding to ILT7.

[0070] In embodiments, the polynucleotide encodes an anti-ILT7 binding molecule provided herein.

[0071] In embodiments, provided herein is a vector comprising this polynucleotide.

[0072] In embodiments, provided herein is a polypeptide encoded by the polynucleotide.

[0073] In embodiments, provided herein are host cells transformed with the polynucleotides provided herein (e.g., a polynucleotide comprising a nucleic acid encoding a VH and a polynucleotide comprising a nucleic acid encoding a VL).

[0074] In embodiments, provided herein are host cells comprising a polynucleotide provided herein (e.g., a polynucleotide comprising a nucleic acid encoding a VH and a polynucleotide comprising a nucleic acid encoding a VL), a vector provided herein, or a polypeptide provided herein. In embodiments, the host cell is a mammalian host cell. In embodiments, the host cell is an NS0 mouse myeloma cell, a PER.C6® human cell, or a Chinese hamster ovary (CHO) cell. In embodiments, the host cell lacks the enzyme α-1,6-fucosyltransferase.

[0075] In embodiments, the compositions of the present disclosure have a concentration of 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 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.

[0076] In embodiments, the composition may comprise from about 100 mg / mL to about 350 mg / mL of the anti-ILT7 binding protein. In embodiments, the composition may comprise from about 150 mg / mL to about 275 mg / mL of the anti-ILT7 binding protein. In embodiments, the composition may comprise from about 200 mg / mL to about 250 mg / mL of the anti-ILT7 binding protein. In embodiments, the composition may comprise from about 100 mg / mL to about 150 mg / mL of the anti-ILT7 binding protein. In embodiments, the composition may comprise from about 110 mg / mL to about 150 mg / mL of the anti-ILT7 binding protein. In embodiments, the composition may comprise from about 120 mg / mL to about 150 mg / mL of the anti-ILT7 binding protein. In embodiments, the composition may comprise from about 130 mg / mL to about 150 mg / mL of the anti-ILT7 binding protein.

[0077] sugar 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 a sugar. In embodiments, the compositions provided herein comprise a sugar. In embodiments, sugars for use with the compositions of the present disclosure include, but are not limited to, monosaccharides, disaccharides, and trisaccharides, or combinations thereof. In embodiments, the composition comprises a sugar, and the sugar may be, for example, sucrose, trehalose, raffinose, maltose, sorbitol, or mannitol, or combinations thereof. In embodiments, the sugar may be a sugar alcohol or an amino sugar. In embodiments, the sugar is sucrose.

[0078] In embodiments, a composition comprising an anti-ILT7 binding protein comprises a sugar. Any amount of sugar may be utilized. In embodiments, about, at least about, or at most about: 150 nM to about 240 mM sugar is utilized. In embodiments, the composition comprises about 160 nM to about 240 mM sugar. In embodiments, the composition comprises about 170 nM to about 240 mM sugar. In embodiments, the composition comprises about 180 nM to about 240 mM sugar. In embodiments, the composition comprises about 190 nM to about 240 mM sugar. In embodiments, the composition comprises about 200 nM to about 240 mM sugar. In embodiments, the composition comprises about 210 nM to about 240 mM sugar. In embodiments, the composition comprises about 220 nM to about 240 mM sugar. In embodiments, the composition comprises about 230 nM to about 240 mM sugar. In an embodiment, the composition comprises about 150 nM to about 200 mM sugar. In an embodiment, the composition comprises about 170 nM to about 190 mM sugar.

[0079] In embodiments, a composition comprising an anti-ILT7 binding protein comprises a sugar. Any amount of sugar may be utilized. In embodiments, about, at least about, or at most about: 150 mM to about 240 mM sugar is utilized. In embodiments, the composition comprises about 160 mM to about 240 mM sugar. In embodiments, the composition comprises about 170 mM to about 240 mM sugar. In embodiments, the composition comprises about 180 mM to about 240 mM sugar. In embodiments, the composition comprises about 190 mM to about 240 mM sugar. In embodiments, the composition comprises about 200 mM to about 240 mM sugar. In embodiments, the composition comprises about 210 mM to about 240 mM sugar. In embodiments, the composition comprises about 220 mM to about 240 mM sugar. In embodiments, the composition comprises about 230 mM to about 240 mM sugar. In an embodiment, the composition comprises about 150 mM to about 200 mM sugar. In an embodiment, the composition comprises about 170 mM to about 190 mM sugar.

[0080] In embodiments, a composition comprising an anti-ILT7 binding protein comprises sucrose. In embodiments, the composition may comprise any amount of sucrose. In embodiments, the composition may comprise sucrose in an amount of about, at least about, or at most about: 150 nM to about 240 mM. In embodiments, the composition comprises about 160 nM to about 240 mM sucrose. In embodiments, the composition comprises about 170 nM to about 240 mM sucrose. In embodiments, the composition comprises about 180 nM to about 240 mM sucrose. In embodiments, the composition comprises about 190 nM to about 240 mM sucrose. In embodiments, the composition comprises about 200 nM to about 240 mM sucrose. In embodiments, the composition comprises about 210 nM to about 240 mM sucrose. In embodiments, the composition comprises about 220 nM to about 240 mM sucrose. In embodiments, the composition comprises about 230 nM to about 240 mM sucrose. In embodiments, the composition comprises about 150 nM to about 200 mM sucrose. In embodiments, the composition comprises about 170 nM to about 190 mM sucrose.

[0081] In embodiments, a composition comprising an anti-ILT7 binding protein comprises about, at least about, or at most about: 150 mM, 155 mM, 160 mM, 165 mM, 170 mM, 175 mM, 180 mM, 185 mM, 190 mM, 195 mM, 200 mM, 205 mM, 210 mM, 215 mM, 220 mM, 225 mM, 230 mM, 235 mM, 240 mM, 245 mM, 250 mM sugar (e.g., sucrose). In embodiments, the composition comprises about 180 mM sucrose.

[0082] Polysorbate 80 In embodiments, compositions of the 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, compositions comprise an anti-ILT7 binding protein and PS-80. In embodiments, compositions comprise a solubility of 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%, 0.342% , 0.362%, 0.382%, 0.402%, 0.422%, 0.442%, 0.462%, 0.482%, 0.502%, 0.522%, 0.542%, 0.562%, 0.582%, 0.602%, 0.622%, 0.642%, 0.662%, 0.682%, 0.702%, 0.722%, 0.742%, 0.762%, 0.782%, or up to 0.8% PS-80. In embodiments, the composition comprises from about 0.002% to about 0.8% polysorbate 80. In embodiments, the composition comprises from about 0.01% to about 0.8% PS-80. In embodiments, the composition comprises from 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.

[0083] In embodiments, about 0.02% PS-80 is effective to reduce particle formation of the compositions provided herein under freeze / thaw (F / T) (e.g., exposure to temperatures above 30° C. / about 30° C.), under agitation stress, or both F / T and agitation stress. In embodiments, about 0.02% PS-80 is effective to reduce particle formation of the compositions provided herein under F / T, under agitation stress, or both F / T and agitation stress, compared to an otherwise equivalent composition lacking PS-80 or lacking about 0.02% PS-80. In embodiments, about 0.02% PS-80 is effective to reduce particle formation of the compositions provided herein under F / T, under agitation stress, or both F / T and agitation stress by at least about 1-fold, 5-fold, 10-fold, 30-fold, 50-fold, 100-fold, 150-fold, or 300-fold, compared to an otherwise equivalent composition lacking PS-80 or lacking about 0.02% PS-80. In embodiments, about 0.02% PS-80 is effective to reduce particle formation of the compositions provided herein under F / T, under agitation stress, or both F / T and agitation stress by at least about 3%, 10%, 20%, 40%, 60%, 80%, 100%, 150%, 200%, or about 300%, compared to an otherwise equivalent composition lacking PS-80 or lacking about 0.02% PS-80.

[0084] methionine In embodiments, a composition of the disclosure comprises an anti-ILT7 binding protein and a carrier. In embodiments, the carrier is a stabilizer. In embodiments, the stabilizer is an amino acid (e.g., methionine). In embodiments, a composition comprises an anti-ILT7 binding protein and methionine. In embodiments, the methionine is L-methionine. L-methionine is the L-enantiomer of methionine. In embodiments, a composition provided herein is L-methionine (i.e., (S)-2-amino-4-(methylmercapto)butyric acid, L-2-amino-4-(methylthio)butanoic acid). In embodiments, the methionine is D-methionine. In embodiments, a composition comprises L-methionine and D-methionine. In embodiments, a composition comprises an anti-ILT7 binding protein and L-methionine.

[0085] Any concentration of methionine can be utilized in the compositions. In embodiments, a composition comprising an anti-ILT7 binding protein comprises about, at least about, or at most about 5 nM to about 30 mM L-methionine. In embodiments, a composition comprising an anti-ILT7 binding protein comprises about, at least about, or at most about 1 nM to about 25 mM L-methionine. In embodiments, a composition comprising an anti-ILT7 binding protein comprises about, at least about, or at most about 15 nM to about 30 mM L-methionine. In embodiments, a composition comprising an anti-ILT7 binding protein comprises about, at least about, or at most about 20 nM to about 25 mM L-methionine. In embodiments, a composition comprising an anti-ILT7 binding protein comprises about, at least about, or at most about 15 nM to about 30 mM L-methionine. In embodiments, a composition comprising an anti-ILT7 binding protein comprises about, at least about, or at most about 10 nM to about 20 mM methionine (eg, L-methionine).

[0086] In embodiments, a composition comprising an anti-ILT7 binding protein comprises about 5 mM to about 10 mM, 5 mM to 20 mM, 8 mM to 15 mM, 8 mM to 20 mM, 10 mM to 20 mM, 12 mM to 25 mM, 15 mM to 30 mM, or 20 mM to 30 mM L-methionine. In embodiments, a composition comprising an anti-ILT7 binding protein comprises about, at least about, or at most about: 5 mM, 6 mM, 7 mM, 8 mM, 9 mM, 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, 35 mM, 40 mM, 45 mM, 50 mM, 55 mM, 60 mM, 65 mM, 70 mM, or 75 mM L-methionine. In embodiments, a composition comprising an anti-ILT7 binding protein comprises about, at least about, or at most about 15 mM methionine (e.g., L-methionine). In embodiments, a composition comprising an anti-ILT7 binding protein comprises about, at least about, or at most about 15 mM L-methionine.

[0087] buffer solution In embodiments, compositions provided herein comprise a buffer. In embodiments, compositions provided herein comprise an anti-ILT7 binding protein and a buffer. In embodiments, a composition comprising an anti-ILT7 binding protein and a buffer can be administered to a subject. In embodiments, a composition comprising an anti-ILT7 binding protein and a buffer can be administered to a subject in a dosage form.

[0088] In embodiments, the composition includes a buffer, which 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 embodiments, the buffer is a histidine buffer. In embodiments, the histidine buffer may include L-histidine hydrochloride. In embodiments, the buffer is a phosphate buffer. In embodiments, the buffer is a citrate buffer. In embodiments, the buffer is a citrate buffer. In embodiments, the buffer is citrate-free or includes reduced citrate. In embodiments, citrate buffers are not utilized because subjects may experience injection-related pain and / or discomfort associated with citrate. In embodiments, the buffer is citrate-free.

[0089] In embodiments, the buffers provided herein may be at any concentration. In embodiments, the buffer is at a concentration of about 10 mM to 40 mM. In embodiments, the buffer is at a concentration of about 15 mM to 40 mM. In embodiments, the buffer is at a concentration of about 20 mM to 40 mM. In embodiments, the buffer is at a concentration of about 25 mM to 35 mM. In embodiments, the buffer is at a concentration of about 20 mM to 30 mM. In embodiments, the buffer is at a concentration of about 20 mM to 25 mM. In embodiments, the buffer is a histidine buffer, such as histidine / histidine-HCl, at a concentration of about 15 mM to 40 mM. In embodiments, the buffer is a histidine buffer, such as histidine / histidine-HCl, at a concentration of about 15 mM to 25 mM. In embodiments, the buffer is a histidine buffer, such as histidine / histidine-HCl, at a concentration of about 18 mM to 22 mM.

[0090] 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 embodiments, the buffer is a histidine buffer, such as histidine / histidine-HCl, at a concentration of about 20 mM, 21 mM, 22 mM, 23 mM, 24 mM, 25 mM, 26 mM, 27 mM, 28 mM, 29 mM, or 30 mM. In embodiments, the buffer is a histidine buffer at a concentration of about, up to about, or at least about 20 mM. In embodiments, the buffer is histidine / histidine-HCl at a concentration of about, up to about, or at least about 20 mM. In embodiments, the buffer is histidine / histidine-HCl at a concentration of 20 mM.

[0091] pH The compositions provided herein comprise a pH. In embodiments, the pH is acidic. In embodiments, the pH is neutral. In embodiments, the pH is basic. 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.

[0092] 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.

[0093] 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.

[0094] The pH can be determined using a pH meter or similar techniques known in the art.

[0095] Pharmaceutical compositions comprising anti-ILT7 binding proteins The present disclosure is also directed to pharmaceutical compositions comprising anti-ILT7 binding proteins as described herein. In embodiments, the present disclosure provides for the use of a pharmaceutical composition comprising an anti-ILT7 binding protein (e.g., a mAb) used in the methods described herein in the manufacture of a medicament for treating a subject.

[0096] In embodiments, pharmaceutical compositions of the present disclosure comprise an ILT7 binding protein disclosed herein and one or more pharmaceutically acceptable carriers, diluents, or excipients. In this regard, a "pharmaceutically acceptable carrier, diluent, or excipient" includes, but is not limited to, any adjuvant, carrier, excipient, glidant, sweetener, diluent, preservative, dye / colorant, flavor enhancer, surfactant, wetting agent, dispersing agent, suspending agent, stabilizer, isotonicity agent, solvent, or emulsifier that may or may not be approved by the United States Food and Drug Administration as acceptable for use in humans or domestic animals. In embodiments, carriers are known to those of skill in the art and include stabilizers, diluents, and buffers. In embodiments, stabilizers include polyanions, salts, chelating agents (e.g., EDTA), metal ions (e.g., Cu), and the like. 2+ , Zn 2+), carbohydrates (e.g., sorbitol, lactose, mannitol, starch, sucrose, dextran, glucose, etc.), polysorbates (PS; e.g., PS-20, PS-40, PS-60, PS-80), proteins (e.g., albumin or casein, etc.), and amino acids (e.g., arginine, aspartic acid, glutamic acid, lysine, proline, glycine, histidine, methionine). In embodiments, diluents may include, but are not limited to, saline, Hank's balanced salts, Ringer's solution, etc.

[0097] In embodiments, the composition is formulated into a pharmaceutical composition. In embodiments, 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 embodiments, 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 embodiments, the components of the formulation may range in amount from about 25%. Exemplary amounts are described herein.

[0098] In embodiments, the anti-ILT7 mAbs of the present disclosure and compositions comprising them may be used in vitro, ex vivo, or incorporated into pharmaceutical compositions. In embodiments, the anti-ILT7 mAbs of the present disclosure and compositions comprising them may be used in vitro, ex vivo, or incorporated into pharmaceutical compositions and administered to a subject (e.g., for treating, ameliorating, or preventing a disease, or a combination thereof). In embodiments, administration of a pharmaceutical composition is independent of formulation (e.g., dosage). In embodiments, administration of a pharmaceutical composition may be dependent on formulation (e.g., dosage). In embodiments, administration of a pharmaceutical composition of the present disclosure may be dependent on formulation (e.g., dosage) and a therapeutically effective amount for a subject (e.g., for treating, ameliorating, or preventing a disease, or a combination thereof). In embodiments, the pharmaceutical compositions of the present disclosure are formulated into preparations in solid, semi-solid, liquid, or gaseous forms, including, but not limited to, solutions, injectables, liquid compositions, microspheres, and aerosols. In embodiments, pharmaceutical compositions comprising anti-ILT7 binding proteins used in the methods described herein may be in solid or liquid form. In embodiments, the carrier is a liquid (e.g., an injectable liquid). In embodiments, the carrier (e.g., an injectable liquid) is used for administration (e.g., intravenous or subcutaneous).

[0099] Administration route In embodiments, any of the compositions comprising an anti-ILT7 binding protein of the present disclosure may be administered in any form. In embodiments, the anti-ILT7 binding protein is administered intravenously, subcutaneously, orally, intramuscularly, intrathecally, sublingually, rectally, vaginally, cutaneously, systemically, topically, transdermally, or by inhalation. In embodiments, the anti-ILT7 binding protein is administered intravenously. In embodiments, the anti-ILT7 binding protein is administered subcutaneously. In embodiments, the anti-ILT7 binding protein is administered subcutaneously via an autoinjector.

[0100] In embodiments, the disclosed compositions are formulated and loaded into a self-administerable delivery device. Exemplary devices are described herein, including exemplary devices such as an auto-injector. The auto-injector may allow for intramuscular or subcutaneous administration routes. Any site on a subject can be targeted for use with the auto-injector. In embodiments, the target site of the injector is selected from the group consisting of the thigh, buttocks, abdomen, arm, lower back, and combinations thereof. In embodiments, the injector is contacted with the thigh of the subject to effect delivery of the disclosed composition. In embodiments, the injector is contacted with the abdomen of the subject to effect delivery of the disclosed composition. In embodiments, the injector is contacted with the buttocks of the subject to effect delivery of the disclosed composition.

[0101] Alternatively, the disclosed compositions can be administered orally as a liquid, capsule, or tablet (e.g., chewable tablet). The oral route is the most convenient, usually the safest, and least expensive, and therefore the most frequently used. However, it has limitations due to the way drugs typically move through the digestive tract. For orally administered drugs, absorption can begin in the mouth and stomach. However, most drugs are typically absorbed from the small intestine. Drugs pass through the intestinal wall and travel to the liver, and are then transported to their target site via the bloodstream. The intestinal wall and liver chemically alter (metabolize) many drugs, reducing the amount of drug that reaches the bloodstream. As a result, these drugs are often administered in smaller doses when injected intravenously to achieve the same effect.

[0102] For the subcutaneous route, a needle is inserted into the fatty tissue just below the skin. After the drug is injected, it then travels to small blood vessels (capillaries) and is carried by the bloodstream. Alternatively, the drug reaches the bloodstream through lymphatic vessels. The intramuscular route is preferred over the subcutaneous route when larger amounts of medication are needed. A longer needle is used because the muscle is beneath the skin and fatty tissue. Drugs are usually injected into the muscles of the upper arm, thigh, or buttocks. The rate at which a drug is absorbed into the bloodstream depends in part on the blood supply to the muscle. The smaller the blood supply, the more time it takes for the drug to be absorbed. For the intravenous route, a needle is inserted directly into a vein. A solution containing the drug may be given as a single dose or by continuous infusion. For infusions, the solution moves by gravity (from a collapsible plastic bag) or, more commonly, by an infusion pump, through thin, flexible tubing into a tube (catheter) inserted into a vein, usually the forearm.

[0103] Timing of administration The pharmaceutical compositions of the present disclosure can be administered at any time. In embodiments, the compositions are administered before, during, or after symptoms of the described disease or condition are detected. In embodiments, the compositions are administered by a delivery device (e.g., an autoinjector). In embodiments, the compositions of the present disclosure are administered every 4 weeks, 5 weeks, 6 weeks, 8 weeks, 10 weeks, 20 weeks, 25 weeks, 30 weeks, or 50 weeks. In embodiments, the compositions of the present disclosure are administered monthly, every 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, yearly, 2 years, 3 years, 4 years, or 5 years.

[0104] In embodiments, the pharmaceutical compositions provided herein are administered via infusion or bolus injection. The infusion may occur over a period of time. For example, the infusion may involve administration of a pharmaceutical agent over a period of about 5 minutes to about 10 hours. The infusion may occur over a period of about 5 minutes, 10 minutes, 20 minutes, 30 minutes, 40 minutes, 50 minutes, 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 embodiments, intravenous administration is used to deliver a precise dose to the entire body in a rapid and well-controlled manner. When administered via subcutaneous or intramuscular injection, irritating solutions are used that can cause pain and tissue damage. When administered intravenously, drugs are delivered immediately to the bloodstream and tend to take effect more quickly than when administered by other routes. As a result, medical professionals closely monitor people who receive intravenous injections for signs that the drug is working or causing unwanted side effects. Additionally, the effects of drugs administered via this route tend to last for a shorter period of time. Therefore, to maintain consistent efficacy, some drugs must be administered via continuous infusion. In embodiments, infusion reactions may occur, including headache, nausea, drowsiness, difficulty breathing, fever, muscle pain, rash, or other symptoms. Potential risks associated with administration of anti-ILT7 binding proteins include infection, redness, swelling, pain, and induration at the administration site. Prior to each IV infusion, subjects may receive prophylaxis with IV methylprednisone, oral diphenhydramine, and oral acetaminophen, or equivalents, to reduce the risk or severity of potential reactions.

[0105] In some embodiments, medications are administered intrathecally. For intrathecal administration, a needle is inserted between two vertebrae in the lower spine and into the space surrounding the spinal cord. The medication is then injected into the spinal canal. A small amount of local anesthetic is often used to anesthetize the injection site. This route is used when a medication needs to act quickly or locally on the brain, spinal cord, or the layers of tissue covering them (meninges), for example, to treat infections of these structures. Medication administered by inhalation through the mouth can be atomized into smaller droplets than those administered via the nasal route, allowing the medication to pass through the trachea (bronchi) and enter the lungs. How deeply the droplets penetrate into the lungs depends on their size. Smaller droplets penetrate deeper, which increases the amount of medication absorbed. Once inside the lungs, they are absorbed into the bloodstream. Medications applied to the skin are typically 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 inert substance, and depending on the consistency of the inert substance, the formulation can be an ointment, cream, lotion, solution, powder, or gel.

[0106] In embodiments, the treatment regimen comprising the pharmaceutical composition can be administered according to the subject's weight. For subjects who are determined to be obese (BMI>35), it may be necessary to use practical body weight. In embodiments, the dosage can be calculated using body surface area.

[0107] formulation In embodiments, the pharmaceutical composition of the present disclosure is in the form of a liquid, e.g., a solution, emulsion, or suspension. In embodiments, pharmaceutical compositions intended to be administered by injection may include one or more of a surfactant, preservative, wetting agent, dispersing agent, suspending agent, buffer, stabilizer, and isotonic agent. In embodiments, the pharmaceutical composition of the present disclosure is administered intravenously to a subject in need thereof. In embodiments, the pharmaceutical composition of the present disclosure is administered by subcutaneous injection to a subject in need thereof. In embodiments, the pharmaceutical composition of the present disclosure is administered by subcutaneous injection via an autoinjector to a subject in need thereof.

[0108] In embodiments, liquid pharmaceutical compositions containing ILT7 binding proteins used in the methods described herein, whether in solution, suspension, or other similar form, may contain one or more of the following components: water for injection, saline solution, e.g., sterile diluents such as physiological saline, Ringer's solution, isotonic sodium chloride, fixed oils such as synthetic mono- or diglycerides, polyethylene glycol, glycerin, propylene glycol, or other solvents that may serve as solvents or suspending media; antibacterial agents such as benzyl alcohol or methylparaben; antioxidants such as ascorbic acid or sodium bisulfite; chelating agents such as ethylenediaminetetraacetic acid; buffers such as acetates, citrates, or phosphates, and agents for adjusting osmolality such as sodium chloride or dextrose. In embodiments, the preparations can be packaged in one or more ampoules, disposable syringes, or vials (e.g., made of glass or plastic). In embodiments, the preparations are packaged in one or more vials (e.g., made of glass or plastic). In embodiments, the preparations are packaged in one or more disposable syringes, e.g., pre-filled syringes (PFS). In embodiments, the preparation is packaged in an auto-injector. In embodiments, the preparation is packaged in a pen. In embodiments, the preparation is packaged in one or more vials (e.g., glass or plastic) prior to administration, which are then transferred to an auto-injector for administration to a subject. In embodiments, the preparation is packaged in one or more disposable syringes (e.g., PFS) prior to administration, which are then transferred to an auto-injector for administration to a subject. In embodiments, the injectable pharmaceutical composition is sterile and in accordance with GMP practices.

[0109] In embodiments, the anti-ILT7 binding proteins of the present disclosure and compositions comprising them may be used as pharmaceutical compositions and may be combined with a pharmaceutically acceptable carrier. In embodiments, the compositions may include the anti-ILT7 binding protein, a carrier, various diluents, fillers, salts, buffers, stabilizers, solubilizers, and other materials well known in the art. In embodiments, the characteristics of the carrier may depend on the route of administration. In embodiments, the pharmaceutical composition includes a histidine buffer (e.g., histidine / histidine-HCl). In embodiments, the pharmaceutical composition of the present disclosure includes a pharmaceutically acceptable, non-toxic, sterile carrier. In embodiments, the pharmaceutical composition of the present disclosure includes an anti-ILT7 binding protein disclosed herein and one or more pharmaceutically acceptable carriers, diluents, or excipients. In this regard, "pharmaceutically acceptable carrier, diluent, or excipient" includes, but is not limited to, any adjuvant, carrier, excipient, glidant, sweetener, diluent, preservative, dye / colorant, flavor enhancer, surfactant, wetting agent, dispersing agent, suspending agent, stabilizer, isotonic agent, solvent, or emulsifier, which may or may not be approved by the U.S. Food and Drug Administration as acceptable for use in humans or domestic animals. For example, suitable carriers are known to those skilled in the art and include stabilizers, diluents, and buffers. Exemplary stabilizers include carbohydrates (such as sorbitol, lactose, mannitol, starch, sucrose, dextran, and glucose) and proteins (e.g., albumin or casein). Exemplary diluents include physiological saline, Hank's balanced salts, and Ringer's solution. Exemplary buffers include alkali metal phosphates, alkali metal carbonates, or alkaline earth metal carbonates.

[0110] In embodiments, the pharmaceutical compositions of the present disclosure may include one or more auxiliary substances, such as one or more lipids, phospholipids, carbohydrates, and lipopolysaccharides. In embodiments, the pharmaceutical compositions of the present disclosure may include one or more additional active substances. In embodiments, the pharmaceutical compositions of the present disclosure include one or more additional therapeutically active substances. In embodiments, a therapeutically effective amount of the pharmaceutical composition of the present disclosure is administered to a subject in need thereof in combination with one or more additional therapeutically active substances. As used herein, "combination" refers to a combination comprising an anti-ILT7 binding protein provided herein and one or more additional therapeutically active substances, each of which may be administered sequentially (sequentially), concurrently, or simultaneously. In embodiments, the pharmaceutical compositions of the present disclosure may be administered at several intervals to maintain therapeutic levels. In embodiments, the pharmaceutical compositions of the present disclosure may be used in conjunction with other bactericidal or bacteriostatic methods.

[0111] In embodiments, pharmaceutical compositions suitable for administration can be sterile. Prevention of microbial action can be achieved by various antibacterial and antifungal agents. Suitable formulations for use in the therapeutic methods disclosed herein are described in Remington's Pharmaceutical Sciences (Mack Publishing Co.), 16th ed. (1980).

[0112] The therapeutically effective amount of the compositions of the present disclosure for treating diseases mediated by ILT7-expressing cells, such as certain types of autoimmune diseases, varies depending on many different factors, including the means of administration, the target site, the physiological condition of the subject, whether the subject is human or animal, other agents administered, and whether the treatment is prophylactic or therapeutic. In embodiments, the subject is a human. In embodiments, the subject is a non-human animal (e.g., a transgenic mammal). In embodiments, treatment dosages can be titrated to optimize safety and efficacy.

[0113] In embodiments, pharmaceutical compositions for use in the disclosed methods can be prepared by conventional methods. In embodiments, the pharmaceutical composition is provided in lyophilized form. In embodiments, the lyophilized pharmaceutical composition is dissolved in a suitable aqueous carrier, such as sterile water for injection or sterile buffered saline, prior to administration to a subject in need thereof. In embodiments, the pharmaceutical composition is prepared for infusion. In embodiments, the pharmaceutical composition is prepared for infusion, and albumin (e.g., human serum albumin [HSA]) or the subject's own heparinized blood is incorporated into the saline solution during formulation. The presence of excess such physiologically inactive proteins prevents loss of antibody due to adsorption to the walls of containers or tubing used with the infusion solution. In embodiments, the pharmaceutical composition is prepared for infusion, and albumin is used. In embodiments, the pharmaceutical composition is prepared for infusion, and albumin is used at a concentration of about 0.5 to about 4.5% by weight of the saline solution. Other formulations may include liquid or lyophilized formulations.

[0114] In embodiments, a lyophilizate of the present disclosure comprises an anti-ILT7 binding protein. In embodiments, a lyophilizate comprising an anti-ILT7 binding protein can be reconstituted to obtain an aqueous composition having a concentration of at least about 150 mg / mL of the anti-ILT7 binding protein. In embodiments, the lyophilizate can comprise, in addition to the anti-ILT7 binding protein, additional components, such as one or more of the following: (i) a sugar (e.g., sucrose); (ii) a buffer (e.g., histidine / histidine-HCl); (iii) PS-80; and (iv) methionine (e.g., L-methionine). Exemplary reconstitution components for a lyophilized binding protein (e.g., an antibody) include sterile water, a buffer, and / or a preservative. In embodiments, the lyophilizate comprises a buffer, and the reconstitution components comprise a buffer that may be the same as or different from the buffer of the lyophilizate. In embodiments, the lyophilizate comprises a buffer, and the reconstitution components do not comprise a buffer (e.g., sterile water for injection [WFI], saline). In embodiments, the reconstitution components include a pharmacological agent, such as a chemotherapeutic compound, that can facilitate co-delivery with a binding protein (e.g., an antibody). In embodiments, the reconstitution components include buffers, salts, stabilizers, glycerol, alcohol, preservatives, surfactants, etc. A thorough discussion of such pharmaceutical ingredients is available in Gennaro (2000) Remington: The Science and Practice of Pharmacy. 20th edition, ISBN: 0683306472.

[0115] In embodiments, pharmaceutical compositions of the present disclosure can be prepared by techniques known to those of skill in the art. General considerations in formulating and / or manufacturing pharmaceutical compositions can be found, for example, in Remington: The Science and Practice of Pharmacy 21st ed., Lippincott Williams & Wilkins, 2005 (incorporated herein by reference in its entirety). In embodiments, the anti-ILT7 binding protein or fragment thereof used in the methods described herein can be mixed with a carrier to form a solution, suspension, or emulsion. In embodiments, one or more of the additives discussed herein can be added to the carrier or added subsequently. In embodiments, pharmaceutical compositions of the present disclosure can be an aqueous solution, e.g., an emulsion or suspension, or can be a dried preparation. In embodiments, pharmaceutical compositions of the present disclosure can be dried or lyophilized, e.g., by freeze-drying or spray-drying, for storage or formulation purposes. In embodiments, dried or lyophilized pharmaceutical compositions can be reconstituted into a liquid composition by the addition of a liquid carrier. In embodiments, dried or lyophilized pharmaceutical compositions can be administered in a dry formulation using methods known to those of skill in the art. In embodiments, the anti-ILT7 binding proteins used in the methods described herein are stored as lyophilized powders and then reconstituted into liquid compositions prior to administration to a subject in need thereof. In embodiments, pharmaceutical compositions comprising anti-ILT7 binding proteins are stored as lyophilized powders and then reconstituted into liquid compositions prior to administration to a subject in need thereof.

[0116] Delivery Device The various compositions of the present disclosure can be loaded into a delivery device or preloaded and stored for future use. A drug delivery device, such as an injector, is used to deliver the liquid to a subject in need thereof. When activated, the drug delivery device can expel a drug (e.g., an anti-ILT7 antibody) stored in an internal reservoir of a primary container through a needle, cannula, or other delivery member into the subject.

[0117] Exemplary delivery devices include, but are not limited to, pen injectors, manual injectors, auto-injectors, and on-body devices. In embodiments, the delivery device delivers, e.g., an agent, composition, formulation, etc., by automated administration. In embodiments, the delivery device is a pen injector. In embodiments, the delivery device is an auto-injector. In embodiments, the delivery device is an on-body device. In embodiments, the delivery device is a manual injector. In embodiments, the delivery device and the storage device are the same. In embodiments, the delivery device delivers the anti-ILT7 binding protein or a pharmaceutical composition comprising the anti-ILT7 binding protein to a delivery site, e.g., through the skin of a subject in need thereof. In embodiments, the delivery device is wearable.

[0118] In embodiments, delivery devices, such as auto-injectors and manual injectors, include a needle and a needle shield extending forward from a housing. In embodiments, the needle shield protects the needle from exposure prior to delivery. In embodiments, the needle shield may be configured to move further into the housing along a longitudinal axis of the housing when the drug delivery device is pushed toward a delivery site. In embodiments, in the case of an auto-injector, this movement of the needle shield may actuate the drug delivery device to expel a drug through the needle.

[0119] Provided is an autoinjector preloaded with 150 mg / mL of anti-ILT7 antibody in 20 mM histidine, 15 mM methionine, 180 mM sucrose, 0.02% PS80, pH 6.0. In embodiments, the autoinjector is a single-use or disposable injector.

[0120] In embodiments, provided is a device comprising a drug delivery device subassembly, the subassembly comprising: a housing configured to accommodate a drug container structure from which a drug (e.g., an anti-ILT7 antibody) is expelled during use of the drug delivery device, the housing having a proximal end and a distal end; and a drive assembly comprising a plunger rod at the proximal end of the drive assembly, the plunger rod configured, upon actuation, to apply an actuation force to the drug container structure to expel the drug from the drug delivery device, the proximal end of the housing comprising an opening and the distal end comprising a sealable portion, the drive assembly being insertable into the housing at the proximal end to form the subassembly. In embodiments, the drug is expelled after contact with a target injection site (e.g., abdomen, thigh, and / or arm). In embodiments, the drug is expelled after actuation by a button.

[0121] Exemplary delivery devices (e.g., autoinjectors) and methods of utilizing same are described in WO 2023 / 016889, WO 2023 / 016893, WO 2023 / 016933, WO 2023 / 016888, WO 2022 / 212227, WO 2022 / 203830, and WO 2022 / 192100. Nos. 2022 / 192308, 2022 / 098593, 2022 / 098592, 2021 / 011716, 2021 / 011717, 2020 / 023220, and 2018 / 034784, which are incorporated by reference herein in their entireties. For example, in embodiments, a delivery device described in any of the aforementioned patent applications can be utilized to deliver the compositions of the present disclosure.

[0122] The device, assembly, component, subsystem, method, or drug delivery device may further comprise or be used in conjunction with a drug, including, but not limited to, the compositions described herein and any modifications thereof. In embodiments, the composition may be in liquid form, lyophilized form, or reconstituted from a lyophilized form.

[0123] Kit containing anti-ILT7 binding protein Disclosed herein are kits (i.e., articles of manufacture) useful for providing anti-ILT7 binding protein compositions, e.g., anti-ILT7 antibodies. Such kits may include an anti-ILT7 binding protein (e.g., in liquid or lyophilized form) or a pharmaceutical composition comprising an anti-ILT7 binding protein. In addition, such kits may include an anti-ILT7 binding protein packaged in a storage container (e.g., a syringe, a prefilled pen, a vial) or a pharmaceutical composition comprising an anti-ILT7 binding protein, a delivery device (e.g., an autoinjector, an on-body device, a pen injector), and instructions for use. These kits may also contain additional therapeutic agents for treating the autoimmune diseases described above, e.g., for delivery in combination with the packaged anti-ILT7 binding protein.

[0124] In embodiments, the kit includes multiple delivery devices. For example, the kit can include 1, 2, 3, 4, 5, 6, 7, 8, 9, or up to 10 delivery devices (e.g., autoinjectors). In embodiments, the kit includes a disposable autoinjector. In embodiments, the kit also includes instructions for its use. In embodiments, the kit also includes a means for disposing of the used autoinjector (e.g., a sharps disposal container).

[0125] In embodiments, provided is a kit comprising: a) a pre-filled auto-injector containing a pharmaceutical composition comprising an anti-ILT7 binding protein; and b) instructions for use thereof. In embodiments, the pre-filled auto-injector contains daxudilimab.

[0126] In embodiments, provided is a kit 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.

[0127] In embodiments, provided is a kit comprising: (a) a pharmaceutical composition comprising an anti-ILT7 binding protein composition for administration to a subject in need thereof, the subject having 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. Exemplary autoimmune diseases include, but are not limited to, focal segmental glomerulosclerosis (FSGS), alopecia areata, myositis, diabetes, Hashimoto's disease, autoimmune adrenal insufficiency, pure red cell aplasia, multiple sclerosis, IgG4RD, rheumatic carditis, systemic lupus erythematosus, psoriasis, rheumatoid arthritis, chronic inflammation, Sjogren's syndrome, polymyositis, dermatomyositis, inclusion body myositis, juvenile myositis, and scleroderma.

[0128] Provided are containers containing an anti-ILT7 binding protein (e.g., daxudilimab). In embodiments, provided herein are containers containing a composition in unit dose form.

[0129] In embodiments, the container is a vial. In embodiments, the vial is made of glass. In embodiments, the vial is made of plastic. In embodiments, the vial may contain a lyophilized dosage form of a composition provided herein.

[0130] In embodiments, a vial may contain a liquid dosage form of the composition provided herein. In embodiments, the container is a vial, and the liquid dosage form may be approximately 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, or 4.25 mL. , 4.5 mL, 4.75 mL, 5.0 mL, 5.25 mL, 5.5 mL, 5.75 mL, 6.0 mL, 6.25 mL, 6.5 mL, 6.75 mL, 7.0 mL, 7.25 mL, 7.5 mL, 7.75 mL, 8.0 mL, 8.25 mL, 8.5 mL, 8.75 mL, 9.0 mL, 9.25 mL, 9.5 mL, 9.75 mL, or about 10.0 mL of liquid dosage form. In an embodiment, the container is a vial 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 the liquid dosage form. In an embodiment, the container is a vial and contains about 1.0 mL of the liquid dosage form. In embodiments, the container is a vial and contains about 1.5 mL of the liquid dosage form. In embodiments, the container is a vial and contains about 2.0 mL of the liquid dosage form.

[0131] In embodiments, the container is a syringe (e.g., a PFS). In embodiments, the syringe is a PFS. In embodiments, a vial may contain a liquid dosage form of the composition provided herein. In embodiments, the container is a PFS and may contain approximately 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, Contains 4.5mL, 4.75mL, 5.0mL, 5.25mL, 5.5mL, 5.75mL, 6.0mL, 6.25mL, 6.5mL, 6.75mL, 7.0mL, 7.25mL, 7.5mL, 7.75mL, 8.0mL, 8.25mL, 8.5mL, 8.75mL, 9.0mL, 9.25mL, 9.5mL, 9.75mL, or about 10.0mL liquid dosage form. 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 the liquid dosage form. In an embodiment, the container is a PFS and contains about 1.0 mL of the liquid dosage form. In an embodiment, the container is a PFS and contains about 1.5 mL of the liquid dosage form. In an embodiment, the container is a PFS and contains about 2.0 mL of the liquid dosage form.

[0132] In embodiments, the formulation is stable, e.g., in liquid form, as a liquid formulation. In embodiments, the liquid form of the formulation facilitates ease of administration compared to an otherwise equivalent formulation that is not in liquid form. In embodiments, the liquid form of the formulation involves fewer manufacturing steps compared to an otherwise equivalent formulation that is not in liquid form.

[0133] In embodiments, provided is a kit comprising a delivery device. In embodiments, the delivery device is, for example, an injection device, an inhalation device, or a medical nebulizer. In embodiments, the delivery device is an autoinjector.

[0134] In embodiments, the kit includes a delivery device, wherein the delivery device is assembled prior to addition to the kit. In embodiments, the kit includes a delivery device, wherein the delivery device is partially assembled prior to addition to the kit. In embodiments, the kit includes a delivery device, wherein the delivery device is fully assembled prior to addition to the kit. In embodiments, the kit includes a delivery device, wherein the delivery device is assembled prior to administration. In embodiments, the kit includes a delivery device, wherein the delivery device is fully assembled prior to administration.

[0135] In embodiments, the kit includes a delivery device, where the delivery device is assembled as part of the kit's instructions. In embodiments, the anti-ILT7 binding protein or a pharmaceutical composition comprising the anti-ILT7 binding protein enclosed in a reservoir is combined with the delivery device prior to administration. In embodiments, the kit includes instructions, where the instructions describe how to combine the delivery device with the anti-ILT7 binding protein or a pharmaceutical composition comprising the anti-ILT7 binding protein enclosed in a reservoir. In embodiments, the kit includes instructions, where the instructions describe how to combine the delivery device with the anti-ILT7 binding protein or a pharmaceutical composition comprising the anti-ILT7 binding protein enclosed in a reservoir, thereby producing a fully assembled delivery device for delivery to a delivery site (e.g., through the skin of a subject in need thereof).

[0136] In embodiments, provided is a kit 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) a delivery device for delivery of the pharmaceutical composition to a subject in need thereof.

[0137] In embodiments, provided is a kit 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 autoinjector for delivery of the pharmaceutical composition to a subject in need thereof.

[0138] In embodiments, the formulations disclosed herein are utilized for subcutaneous administration. In embodiments, the volume of the formulations of the present disclosure administered subcutaneously is about 0.5 mL to about 2.5 mL. In embodiments, the volume of a formulation of the present 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 the formulation of the present 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.

[0139] In an embodiment, the volume of the formulation of the present disclosure administered subcutaneously is about 1.0 mL. In an embodiment, the volume of the formulation of the present disclosure administered subcutaneously is about 1.5 mL. In an embodiment, the volume of the formulation of the present disclosure administered subcutaneously is about 2.0 mL. In an embodiment, the volume of the formulation of the present disclosure administered subcutaneously is about 1.0 mL, and the formulation was 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 1.5 mL, and the formulation was 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 2.0 mL, and the formulation was 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 1.0 mL, and the formulation was stored in two or more syringes (e.g., a prefilled syringe; PFS) before administration. In an embodiment, the volume of the formulation of the present disclosure administered subcutaneously is about 1.5 mL, and the formulation is stored in two or more syringes (e.g., pre-filled syringes; PFS) before administration. In an embodiment, the volume of the formulation of the present disclosure administered subcutaneously is about 2.0 mL, and the formulation is stored in two or more syringes (e.g., pre-filled syringes; PFS) before administration.

[0140] In an embodiment, the volume of the formulation of the present disclosure to be administered subcutaneously is about 1.0 mL, and the formulation is stored in two or more syringes (e.g., pre-filled syringes; PFS) before administration, and the formulation is administered by a delivery device.In an embodiment, the volume of the formulation of the present disclosure to be administered subcutaneously is about 1.5 mL, and the formulation is stored in two or more syringes (e.g., pre-filled syringes; PFS) before administration, and the formulation is administered by a delivery device.In an embodiment, the volume of the formulation of the present disclosure to be administered subcutaneously is about 2.0 mL, and the formulation is stored in two or more syringes (e.g., pre-filled syringes; PFS) before administration, and the formulation is administered by a delivery device.

[0141] In an embodiment, the volume of the formulation of the present disclosure administered subcutaneously is about 1.0 mL, and the formulation is stored in two or more syringes (e.g., pre-filled syringes; PFS) before administration, and the formulation is administered by an auto-injector. In an embodiment, the volume of the formulation of the present disclosure administered subcutaneously is about 1.5 mL, and the formulation is stored in two or more syringes (e.g., pre-filled syringes; PFS) before administration, and the formulation is administered by an auto-injector. In an embodiment, the volume of the formulation of the present disclosure administered subcutaneously is about 2.0 mL, and the formulation is stored in two or more syringes (e.g., pre-filled syringes; PFS) before administration, and the formulation is administered by an auto-injector.

[0142] In embodiments, the formulations disclosed herein include a high protein concentration of a binding protein (e.g., an anti-ILT7 binding protein) while maintaining a viscosity level suitable for subcutaneous administration. In embodiments, the high protein concentration facilitates a higher dose that can be delivered in a single injection. In embodiments, the viscosity levels of the formulations disclosed herein range from about 1 cP to about 50 cP. In embodiments, the formulations of the present disclosure include a viscosity of about 0 cP, 2 cP, 4 cP, 6 cP, 8 cP, 10 cP, 12 cP, 14 cP, 16 cP, 18 cP, 20 cP, 22 cP, 24 cP, 26 cP, 28 cP, 30 cP, 32 cP, 34 cP, 36 cP, 38 cP, 40 cP, 42 cP, 44 cP, 46 cP, 48 cP, or up to about 50 cP. 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.

[0143] In embodiments, a single injection of any of the disclosed formulations is administered to a subject in need thereof. In embodiments, multiple injections of any of the disclosed formulations are administered to a subject in need thereof. In embodiments, multiple injections of any of the disclosed formulations may be administered as part of the methods of the present disclosure. In embodiments, a single injection of any of the disclosed compositions may be administered as part of the methods of the present disclosure. In embodiments, subcutaneous administration allows for fewer or single injections of the disclosed compositions.

[0144] In embodiments, the anti-ILT7 binding proteins of the present disclosure are administered at a schedule that provides optimal results. In embodiments, the anti-ILT7 binding protein is administered to a subject in need thereof 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 three 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. Any number of administrations can be provided to a subject in need thereof.

[0145] 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 embodiments, the anti-ILT7 binding protein is administered about every week, every 2 weeks, every 3 weeks, every 4 weeks, every 5 weeks, every 6 weeks, every 7 weeks, every 8 weeks, every 9 weeks, every 10 weeks, every 11 weeks, every 12 weeks, every 13 weeks, every 14 weeks, every 15 weeks, every 16 weeks, every 20 weeks, or about once a month, about every 2 months, about every 3 months, about every 4 months, or about every 6 months. In embodiments, the anti-ILT7 binding protein is administered at a dose 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 (i.e., every 3 months), about 200 mg to about 500 mg every 12 weeks (i.e., every 3 months), or about 300 mg to about 600 mg every 12 weeks (i.e., every 3 months). In embodiments, the anti-ILT7 binding protein is administered at a dose 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.

[0146] In embodiments, the anti-ILT7 binding proteins disclosed herein may be administered at a dose of about 150 mg to about 450 mg in a single injection of 1 mL to 2 mL. In embodiments, the anti-ILT7 binding protein is administered at a dose of about 300 mg in a single injection of 1 mL. In embodiments, the anti-ILT7 binding protein is administered at a dose of about 300 mg in a single injection of 1.5 mL. In embodiments, the anti-ILT7 binding protein is administered at a dose of about 300 mg in a single injection of 2 mL.

[0147] In embodiments, the compositions disclosed herein may be administered subcutaneously in a single injection of 1 mL to 2 mL at a dose of about 150 mg to about 450 mg. In embodiments, the compositions are administered in a single 1 mL injection at a dose of about 300 mg. In embodiments, the compositions are administered in a single 1.5 mL injection at a dose of about 300 mg. In embodiments, the compositions are administered in a single 2 mL injection at a dose of about 300 mg.

[0148] In embodiments, the formulations disclosed herein may be administered subcutaneously in a single injection of 1 mL to 2 mL at a dose of about 150 mg to about 450 mg. In embodiments, the formulations are administered in a single injection of 1 mL at a dose of about 300 mg. In embodiments, the formulations are administered in a single injection of 1.5 mL at a dose of about 300 mg. In embodiments, the formulations are administered in a single injection of 2 mL at a dose of about 300 mg.

[0149] method Use of the formulation In embodiments, formulations comprising anti-ILT7 binding proteins provided herein are effective to resolve one or more of the following: light-induced tryptophan oxidation, reduced potency, reduced shelf life, the need for a nitrogen overlay, and combinations thereof. In embodiments, the formulations do not utilize a nitrogen overlay or lack a nitrogen overlay in their method of production.

[0150] In embodiments, the formulations and methods disclosed herein reduce or eliminate the need for engineering controls, including, but not limited to, the need for light control and nitrogen overlay during manufacturing. In embodiments, the methods do not include light control. In embodiments, the methods do not include nitrogen overlay. In embodiments, the formulations are produced without the use of nitrogen overlay.

[0151] In embodiments, a 15 mM concentration of L-methionine is effective in reducing aggregation, reducing oxidation (e.g., light-induced tryptophan and / or methionine oxidation), or both reducing aggregation and reducing oxidation of the compositions provided herein. In embodiments, reduced oxidation may refer to reduced L-methionine oxidation. In embodiments, reduced oxidation may refer to any one of 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 in reducing and / or the rate of light-induced tryptophan oxidation in the CDRs of anti-ILT7 binding proteins. In embodiments, L-methionine is effective in reducing light-induced tryptophan oxidation in the CDRs of anti-ILT7 binding proteins (e.g., the CDRs of SEQ ID NO: 1).

[0152] The reduction of light-induced tryptophan oxidation can range from stabilizing affected or presumed affected residues in the disclosed compositions to eliminating oxidation. The level of oxidation of the composition can be determined at any time. In embodiments, oxidation is determined at the beginning, during an intermediate step, or at the end of the production of the disclosed compositions. In embodiments, oxidation can be determined at the end of production. In embodiments, oxidation can be determined relative to levels before and after the addition of L-methionine.

[0153] In embodiments, use of the provided methods is effective for stabilizing the level of oxidation in the compositions of the present disclosure. The various provided methods can be useful for maintaining the oxidation level of the provided compositions (e.g., compositions comprising a sequence in Table 1 or a composition having at least about 85% identity to a sequence in Table 1) throughout the manufacturing process and / or throughout transportation and subject administration. Maintaining oxidation can be useful for preserving the potency of the provided compositions. For example, the compositions of the present disclosure can have a stable level of oxidation of one or more residues after exposure to light. For example, compositions provided herein exposed to 1600-1800 lux light for 3 days have 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% or less of oxidized species. For example, compositions provided herein exposed to 1600-1800 lux light for 4 days have 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% or less of oxidized species. For example, compositions provided herein exposed to 1600-1800 lux light for 5 days have 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% or less of oxidized species. For example, compositions provided herein exposed to 1600-1800 lux light for 5 days 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 an oxidized species selected from the group consisting of M257 of SEQ ID NO: 10 and M433 of SEQ ID NO: 10.For example, compositions provided herein exposed to 1600-1800 lux light for 5 days 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 an oxidized 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. For example, compositions provided herein exposed to 1600-1800 lux light for 3-5 days 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 an oxidized 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.

[0154] In embodiments, use of the provided methods is effective for stabilizing the level of post-translational modification of CDR residues in the compositions of the present disclosure. The various provided methods can be useful for maintaining the PTM levels of the provided compositions (e.g., compositions comprising a sequence in Table 1 or a composition having at least about 85% identity to a sequence in Table 1) throughout the manufacturing process and / or throughout transportation and subject administration. Maintaining the PTMs can be useful for maintaining the potency of the provided compositions. For example, the compositions of the present disclosure can have a stable level of PTMs of one or more residues after exposure to light. For example, compositions provided herein exposed to 1600-1800 lux of light for 3 days have 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% or less of the modified species. For example, compositions provided herein exposed to 1600-1800 lux of light for 4 days have 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% or less of the modified species. For example, compositions provided herein exposed to 1600-1800 lux of light for 5 days have 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% or less of the modified species. For example, compositions provided herein exposed to 1600-1800 lux of light for 5 days 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 species selected from the group consisting of M257 of SEQ ID NO: 10 and M433 of SEQ ID NO: 10.For example, compositions provided herein exposed to 1600-1800 lux of light for 5 days 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 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. For example, compositions provided herein exposed to 1600-1800 lux light for 3-5 days 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 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. In embodiments, the composition binds to ILT7 and comprises complementarity determining regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprising the sequences of SEQ ID NOs: 3, 4, 5, 6, 7, and 8, respectively.

[0155] In embodiments, the methods described herein are effective in producing Fc oxidation-resistant compositions. For example, use of any of the disclosed compositions and methods can prevent oxidation of vulnerable residues compared to oxidation in an otherwise equivalent composition without the disclosed method or composition. In embodiments, the vulnerable residues are M257 and / or M433 of SEQ ID NO: 10.

[0156] In embodiments, compositions provided herein that include L-methionine (e.g., about 15 mM L-methionine) have a reduced percentage of oxidized species. In embodiments, compositions provided herein that are exposed to 1600-1800 lux of light for about 3 to about 5 days have a lower percentage of oxidized species compared to an otherwise equivalent composition 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% compared to an otherwise equivalent composition lacking a formulation provided herein and / or lacking L-methionine. In embodiments, when the compositions provided herein are exposed to 1600-1800 lux light for about 5 days, the percentage of oxidized species ranges from 0.2% to about 0.5%. In embodiments, the percentage of oxidized species in the disclosed compositions is less than 0.5% when exposed to 1600-1800 lux light for 1, 2, 3, 4, 5, 6, 7, 8, 9, or up to 10 days. In embodiments, the percentage of oxidized species in the disclosed compositions is less than 0.4% when exposed to 1600-1800 lux light for 1, 2, 3, 4, 5, 6, 7, 8, 9, or up to 10 days. In embodiments, the percentage of oxidized species in the disclosed compositions is less than 0.3% when exposed to 1600-1800 lux light for 1, 2, 3, 4, 5, 6, 7, 8, 9, or up to 10 days. In embodiments, the percentage of oxidized species in the disclosed compositions is less than 0.2% when exposed to 1600-1800 lux light for 1, 2, 3, 4, 5, 6, 7, 8, 9 days, or up to 10 days.In embodiments, the percentage of oxidized species in the disclosed compositions is less than 0.1% when exposed to 1600-1800 lux light for 1, 2, 3, 4, 5, 6, 7, 8, 9 days, or up to 10 days.

[0157] In embodiments, a composition may be Fc oxidation-resistant or may have reduced Fc oxidation of vulnerable residues. Reduced Fc oxidation may refer to a slowing or reduction in the rate of oxidation when exposed to degradative elements such as light. For example, when a composition of the present disclosure is exposed to light at 1600-1800 lux for 3-5 days, the percentage of oxidized species of the ILT7 binding protein in the composition increases at a rate of only 0.2%-0.5% per day. In embodiments, when a composition comprising a sequence in Table 1, or a sequence having at least about 85% identity thereto, is exposed to light at 1600-1800 lux for 3-5 days, the percentage of oxidized species in the composition increases at a rate of no more than 0.2% per day. In embodiments, when a composition comprising a sequence in Table 1, or a sequence having at least about 85% identity thereto, is exposed to light at 1600-1800 lux for 3-5 days, the percentage of oxidized species in the composition increases at a rate of no more than 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 light at 1600-1800 lux for 3-5 days, the percentage of oxidized species in the composition increases at a rate of up to 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 light at 1600-1800 lux for 3-5 days, the percentage of oxidized species in the composition increases at a rate of up to 0.5% per day. In embodiments, the composition binds to ILT7 and comprises complementarity determining regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprising the sequences of SEQ ID NOs: 3, 4, 5, 6, 7, and 8, respectively.

[0158] In embodiments, about 15 mM L-methionine is effective to reduce aggregation or the rate of aggregation of the compositions provided herein compared to an equivalent composition otherwise lacking a formulation provided herein and / or lacking L-methionine (e.g., less than 15 mM L-methionine). In embodiments, about 15 mM L-methionine is effective to reduce aggregation of the compositions 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 compared to an equivalent composition otherwise lacking L-methionine (e.g., less than 15 mM L-methionine). In embodiments, about 15 mM L-methionine is effective to reduce aggregation of the compositions provided herein under stress conditions (e.g., 40° C.) compared to an equivalent composition otherwise lacking L-methionine (e.g., less than 15 mM L-methionine). In embodiments, about a 15 mM concentration of L-methionine is effective to reduce aggregation of the compositions provided herein under stress conditions (e.g., 40° C.) by at least about 1-fold, 5-fold, 10-fold, or 15-fold compared to an otherwise equivalent composition lacking L-methionine (e.g., less than 15 mM L-methionine).

[0159] In embodiments, the about 15 mM concentration of L-methionine provides a reduction in the amount 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%, 31%, 32%, 33%, 34%, 35%, 36%, 37%, 38%, 39%, 40%, 41%, 42%, 43%, 44%, 45%, 46%, 47%, 48%, 49%, 50%, 51%, 52%, 53%, 54%, 55%, 56%, 57%, 58%, 59%, 60%, 61%, 62%, 63%, 64%, 65%, 66%, 67%, 68%, 69%, 70%, 71%, 72%, 73%, 74%, 75%, 76%, 77%, 78%, 79%, 80%, 81%, 82%, 83%, 84%, 85%, 86%, 87%, 88%, 89%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99%, 100%, 101%, 102%, 103%, 104%, 105%, 106%, 107%, 108%, 109%, 110%, 111%, 112%, 113%, 114%, 115%, 116%, 117%, 118%, 119%, 120%, 121%, 122%, 123%, 124%, The compositions provided herein are effective in reducing aggregation, reducing oxidation, or both reducing aggregation and reducing oxidation, relative to an otherwise equivalent composition at a different concentration by 8%, 30%, 32%, 34%, 36%, 38%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or up to about 100%. In embodiments, oxidation can be determined using any assay known 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 rate of oxidation 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 embodiments, 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.

[0160] Aggregate and particle formation can be determined using any assay known in the art. In embodiments, aggregate and particle formation is determined using in vitro assays, including but not limited to size exclusion chromatography (SEC), microflow imaging (MFI), and combinations thereof. In embodiments, aggregate and particle formation is determined using SEC. In embodiments, aggregate and particle formation is determined using MFI.

[0161] In embodiments, a 15 mM concentration of L-methionine is effective in reducing discoloration of the compositions provided herein compared to an otherwise equivalent composition lacking L-methionine, lacking about 10-20 mM L-methionine, or lacking about 15 mM L-methionine. In embodiments, discoloration may result from stress conditions, such as elevated temperature, agitation, elevated pressure, or any combination thereof.

[0162] In embodiments, the composition is colorless. In embodiments, the composition is transparent. In embodiments, the composition does not contain visible particles. In embodiments, the composition may be milky white. In embodiments, the color change can be determined using any means, including, but not limited to, visual inspection, microscopy, colorimetry, turbidimetry, and combinations thereof.

[0163] In embodiments, a composition comprising an anti-ILT7 binding protein is more stable in a histidine buffer compared to an otherwise equivalent composition in a different buffer. In embodiments, a composition comprising an anti-ILT7 binding protein is more stable in a histidine buffer compared to an otherwise equivalent composition in a phosphate buffer or a citrate buffer. In embodiments, the histidine buffer is effective in reducing aggregation, reducing oxidation, or both reducing aggregation and reducing oxidation. In embodiments, reduced oxidation may refer to reduced oxidation of L-methionine residues, including, but not limited to, W102 and / or W104 of SEQ ID NO:1.

[0164] In embodiments, a composition comprising an anti-ILT7 binding protein is 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 a histidine buffer compared to an otherwise equivalent composition in a different buffer. In embodiments, a composition comprising an anti-ILT7 binding protein is 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 a histidine buffer compared to an otherwise equivalent composition in a different buffer. In embodiments, a composition comprising an anti-ILT7 binding protein is at least about 1-fold, 5-fold, or 10-fold more stable in a histidine buffer compared to an otherwise equivalent composition in a different buffer. In embodiments, a histidine buffer is 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 effective at reducing aggregation in a composition comprising an anti-ILT7 binding protein compared to an otherwise equivalent composition in a different buffer. In embodiments, a histidine buffer is at least about 1-fold, 5-fold, or 10-fold more effective at reducing aggregation in a composition comprising an anti-ILT7 binding protein compared to an otherwise equivalent composition in a different buffer.

[0165] The stability of an anti-ILT7 binding protein can be assessed using any means known in the art. In embodiments, assessing stability can include determining any one of specificity, binding affinity, purity, aggregation, degradation, and thermal stability. In embodiments, stability is determined by ELISA, Western blotting and affinity analysis, SPR / BIACORE™, all of which can be used to demonstrate retention of biological function (e.g., antigen binding, specificity, affinity, percent monomer) during conditions encountered during production / isolation and subsequent storage. In addition, circular dichroism (CD), nuclear magnetic resonance (NMR), and mass spectrometry can be used to determine antibody stability. In embodiments, stability is determined by an assay selected from the group consisting of size exclusion chromatography (e.g., SEC-HPLC, SEC-FPLC), ELISA, Western blot, BIACORE™, SDS-PAGE, dynamic light scattering (DLS), differential scanning calorimetry (DSC), analytical ultracentrifugation (AUC), differential scanning fluorimetry, differential scanning fluorimetry, and combinations thereof.

[0166] In embodiments, stability is determined. In embodiments, stability is determined at various temperatures. In embodiments, stability is determined under stress conditions (e.g., 40°C). In embodiments, stability is determined at room temperature. In embodiments, 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.

[0167] In embodiments, the anti-ILT7 binding protein or composition comprising same comprises an increased shelf life, hi embodiments, the anti-ILT7 binding protein or composition comprising same comprises an increased shelf life compared to an otherwise equivalent composition lacking a histidine buffer. In embodiments, the shelf life is increased 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 embodiments, the compositions provided herein have a shelf life of about 60 months. In embodiments, the compositions provided herein have a shelf life of about 36 months. In embodiments, the shelf life may be at a temperature of from about 2°C to about 8°C.

[0168] In embodiments, the histidine buffer is effective to reduce pain upon injection of the composition into a subject in need thereof. In embodiments, the histidine buffer is effective to reduce pain upon injection of the composition into a subject in need thereof compared to an otherwise equivalent composition using a different buffer (e.g., a citrate buffer). In embodiments, the histidine buffer is effective to reduce pain associated with subcutaneous injection of a composition provided herein (e.g., a composition comprising an anti-ILT7 binding protein). In embodiments, the subject can assess pain using a scale selected from the group consisting of a numeric rating scale, a visual analog scale, an adult nonverbal pain scale, a behavioral pain scale, a critical care pain observation tool, the Defense and Veterans Affairs Pain Rating Scale, the Pain Rating Scale in Advanced Dementia, a medical interview, or any combination thereof. In embodiments, the histidine buffer is effective to reduce pain associated with administration of a composition provided herein by at least about 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 points on the scale. In embodiments, the histidine buffer is effective to reduce pain associated with administration of a composition provided herein by at least about 1-2 points, 1-3 points, or 1-4 points.

[0169] The viscosity can be determined using any means. In embodiments, the viscosity is determined using a viscosity modifier (e.g., arginine, NaCl). In embodiments, the viscosity can be determined using a viscometer.

[0170] Alternative and complementary methods for reducing and eliminating degradative modifications (e.g., oxidation) of amino acid residues in the described compositions are also contemplated. For example, the purification methods described in PCT / US2016 / 022003, which is incorporated by reference in its entirety, are also contemplated. In embodiments, the provided methods can be combined with the purification methods of PCT / US2016 / 022003.

[0171] treatment Also provided herein are methods of using compositions comprising anti-ILT7 binding proteins. In embodiments, provided herein are methods of treating a subject having an autoimmune disease, comprising administering to the subject an effective amount of an anti-ILT7 binding protein. Also provided are methods of treating a subject in need thereof, including a disease or condition associated with ILT7-expressing cells. Also provided are methods of treatment comprising subcutaneous administration of the disclosed compositions by autoinjector.

[0172] In embodiments, the treatment comprises administering an anti-ILT7 binding protein as part of the methods described herein to a subject in need thereof or suspected of needing such treatment. In embodiments, the administration of an anti-ILT7 binding protein as part of the methods described herein isolates tissue, cell(s) from a subject, the subject having a disease, symptoms of a disease, or a predisposition to a disease (e.g., an autoimmune disease). In embodiments, a subject in need thereof or suspected of needing such treatment may have elevated pDC numbers or activity compared to a subject not in need thereof. In embodiments, a subject in need thereof or suspected of needing such treatment despite not having a formal diagnosis, e.g., a subject may or may not have systemic lupus erythematosus (SLE) or cutaneous lupus erythematosus (CLE), but exhibits symptoms, e.g., elevated pDC numbers or activity, compared to a subject not in need thereof. In embodiments, a subject suspected of needing such treatment has elevated baseline blood type I IFNGS levels. In embodiments, treatment comprises administration of a pharmaceutical composition comprising an anti-ILT7 binding protein used in the methods described herein to a subject in need thereof or suspected of being in need of such treatment. In embodiments, treatment comprises administration of a pharmaceutical composition comprising an anti-ILT7 binding protein as part of a method described herein to isolate tissue, cell(s) from a subject with a disease, symptoms of a disease, or a predisposition to a disease (e.g., an autoimmune disease).

[0173] Examples of autoimmune disorders that may 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), Sjogren's syndrome, inflammatory myositis (e.g., dermatomyositis, inclusion body myositis, juvenile myositis, and polymyositis), systemic sclerosis, diabetes, focal segmental glomerulosclerosis (FSGS), alopecia areata, Hashimoto's disease, autoimmune adrenal insufficiency, pure red cell aplasia, multiple sclerosis, rheumatic carditis, IgG4RD, psoriasis, psoriatic arthritis, rheumatoid arthritis, chronic inflammation, chronic rheumatoid arthritis, vitiligo, alopecia areata, hidradenitis suppurativa, celiac disease, graft-versus-host disease (GVHD), chronic GVHD, vascular inflammation, myocardial infarction, and type I interferonopathy. 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 Sjogren'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 includes FSGS. In embodiments, the autoimmune disease includes alopecia areata.

[0174] Without being bound by theory, the anti-ILT7 binding protein as part of the methods described herein can induce antibody-dependent cell-mediated cytotoxicity (ADCC) activity against plasmacytoid dendritic cells (pDCs), thereby reducing or depleting pDCs. In embodiments, anti-ILT7 binding protein-mediated ADCC causes a reduction in circulating pDCs. In embodiments, anti-ILT7 binding protein-mediated ADCC causes a reduction in local or tissue pDCs. In embodiments, tissues from which pDCs are reduced include, but are not limited to, skin cells, skin biopsies, kidney cells, lung cells, liver cells, heart cells, brain cells, neural tissue, thyroid cells, eye cells, skeletal muscle cells, cartilage, bone tissue, and cells from the respiratory tract. In embodiments, the tissue is a skin biopsy. In embodiments, administration of the anti-ILT7 binding protein results in a reduction in pDCs. In embodiments, administration of the anti-ILT7 binding protein results in a reduction in skin pDCs. pDCs are not normally present in skin tissue; immature pDCs are typically found only in blood, thymic lymphoid tissue, tonsils, and lung tissue. Thus, the presence of pDCs in a skin biopsy sample indicates an abnormal condition in which pDCs are recruited to the skin. In embodiments, the disclosed methods comprise administering an anti-ILT7 binding protein to a subject in need of treatment for a condition characterized by the presence of pDCs in the subject's skin. In embodiments, the disclosed methods comprise administering an anti-ILT7 binding protein to a subject in need of such treatment, thereby reducing pDC levels in the subject's skin.

[0175] In embodiments, the reduction in pDC levels in the subject is about 1% to about 100% compared to the pDC levels in the subject before administration of the anti-ILT7 binding protein, i.e., the subject's baseline levels. In embodiments, the reduction in pDC levels in the subject is 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 100% compared to the subject's baseline level of pDC levels. In embodiments, the reduction in pDC levels in the subject is at least about 50% compared to the subject's baseline level of pDC levels. In embodiments, administration of a therapeutically effective amount of an anti-ILT7 binding protein results in at least about a 10% reduction in the total number of pDCs in a subject. In embodiments, administration of a therapeutically effective amount of an anti-ILT7 binding protein results in at least about a 10% reduction in activated pDCs in a subject. In embodiments, pDC levels are measured in a test biological sample taken from the subject. In embodiments, administration of a therapeutically effective amount of an anti-ILT7 binding protein to a subject in need thereof as part of a method described herein results in a reduction in pDC levels in a test biological sample taken from the subject. In embodiments, the reduction in pDC levels in a test biological sample taken from the subject is at least about 10% compared to the pDC levels in the test biological sample before administration of the anti-ILT7 binding protein used as part of a method described herein. Whole blood, plasma, urine, saliva, tissue, cell, and serum samples can be collected as test biological samples for assessing pDC levels. In embodiments, the test biological sample is whole blood. In embodiments, the test biological sample is tissue, including, but not limited to, skin cells and skin biopsy specimens. In embodiments, the pDCs are circulating pDCs. In embodiments, the pDCs are pDCs in the skin. In embodiments, the reduction in pDCs is reversible.

[0176] In embodiments, a subject may have elevated or high levels of pDCs in their skin tissue before treatment. In embodiments, subjects with high levels of pDCs in their skin tissue before treatment are more likely to respond to treatment. In embodiments, subjects with high levels of pDCs in their skin tissue have at least about 50 pDCs / mm of skin tissue. 2 , at least about 60 pDC / mm of skin tissue 2 , at least about 70 pDC / mm of skin tissue 2 , at least about 80 pDC / mm of skin tissue 2 , at least about 90 pDC / mm of skin tissue 2 , at least about 100 pDC / mm of skin tissue 2 , at least about 110 pDC / mm of skin tissue 2 , at least about 120 pDC / mm of skin tissue 2 , at least about 125 pDC / mm of skin tissue 2 , at least about 150 pDC / mm of skin tissue 2 , at least about 175 pDC / mm of skin tissue 2 , at least about 200 pDC / mm of skin tissue 2 In embodiments, low pDC levels in skin tissue are about 10 pDC / mm of skin tissue or more. 2 In embodiments, the elevated pDC levels in skin tissue are at least about 100 pDC / mm of skin tissue. 2 It is thought that this is the case.

[0177] In embodiments, administration of a therapeutically effective amount of an anti-ILT7 binding protein used as part of the methods described herein to a subject in need thereof causes at least about a 10% reduction in pDCs in the subject about 3 hours, about 6 hours, about 12 hours, about 24 hours, or about 48 hours after administration of the anti-ILT7 binding protein. In embodiments, administration of a therapeutically effective amount of an anti-ILT7 binding protein used as part of the methods described herein to a subject in need thereof causes at least about a 10% reduction in pDC levels in a test biological sample taken from the subject 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.

[0178] In embodiments, the reduction in pDC levels persists 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 following administration of a therapeutically effective amount of an anti-ILT7 binding protein as part of the methods described herein to a subject in need thereof. In embodiments, the reduction in pDC levels persists for at least about 30 days following administration of a therapeutically effective amount of an anti-ILT7 binding protein as part of the methods described herein to a subject in need thereof. In embodiments, the reduction in pDC levels persists for at least about 60 days following administration of a therapeutically effective amount of an anti-ILT7 binding protein as part of the methods described herein to a subject in need thereof.

[0179] In embodiments, the methods of the present disclosure can be used to monitor the effectiveness of a treatment by monitoring type I interferon gene signatures (IFNGS) and / or pDC levels. As discussed above, autoimmune conditions are often characterized by elevated type I IFNGS and / or elevated pDCs. In embodiments, monitoring the effectiveness of a treatment administered to a subject in need thereof (e.g., having a diagnosis and / or symptoms of an autoimmune disease or condition) can include monitoring type I IFNGS and / or pDC levels.

[0180] In embodiments, the present disclosure provides a method of monitoring the effectiveness of a treatment for an autoimmune disorder or condition, comprising: (a) measuring type I IFNGS in a biological sample taken from the subject to obtain a baseline level of type I IFNGS; and (b) measuring type I IFNGS in the biological sample taken from the subject after administering a treatment, wherein the treatment comprises administering an anti-ILT7 binding protein; and wherein a decrease in type I IFNGS in (b) compared to the baseline level in (a) indicates that the treatment is effective in the subject.

[0181] In embodiments, treatment results in a decrease in type I IFNGS compared to baseline levels. In embodiments, the decrease in type I IFNGS compared to baseline levels ranges from about 1% to about 99%. In embodiments, the decrease in type I IFNGS compared to baseline levels 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 decrease in type I IFNGS levels compared to baseline levels is at least about 30%. In embodiments, the decrease in type I IFNGS levels compared to baseline levels is at least about 50%.

[0182] In embodiments, the elevation of type I IFNGS in the test biological sample relative to a normal biological sample, or in a subject in need thereof relative to a normal subject, is a fold change of at least about 1.1 to about 1000. In embodiments, type I IFNGS is elevated by 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 fold in the test biological sample relative to a normal biological sample, or in a subject in need thereof relative to a normal subject. In embodiments, type I IFNGS levels are elevated by at least about 4 fold in the test biological sample relative to a normal biological sample, or in a subject in need thereof relative to a normal subject.

[0183] In embodiments, the reduction in type I IFNGS persists 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 following administration of a therapeutically effective amount of an anti-ILT7 binding protein as part of the methods described herein to a subject in need thereof. In embodiments, the reduction in type I IFNGS persists for up to about 30 days following administration of a therapeutically effective amount of an anti-ILT7 binding protein as part of the methods described herein to a subject in need thereof. In embodiments, the reduction in type I IFNGS persists for up to about 60 days following administration of a therapeutically effective amount of an anti-ILT7 binding protein as part of the methods described herein to a subject in need thereof.

[0184] In embodiments, the disclosed methods include administering an anti-ILT7 binding protein as part of the methods described herein to inhibit type I IFN release from pDCs regardless of the location of the pDCs. In embodiments, the disclosed methods include administering an anti-ILT7 binding protein to inhibit type I IFN release from blood or circulating pDCs. In embodiments, the disclosed methods include administering an anti-ILT7 binding protein to inhibit type I IFN release from local pDCs. In embodiments, the disclosed methods include administering an anti-ILT7 binding protein to inhibit type I IFN release from pDCs in the skin of a subject. In embodiments, the inhibited type I IFN is IFNα. In embodiments, anti-ILT7 binding protein-mediated inhibition of type I IFN release from pDCs causes a reduction in type I IFNs.

[0185] The present disclosure provides methods for treating an autoimmune disorder in a subject using an anti-ILT7 binding protein. In embodiments, the methods include treating an autoimmune disorder in a subject in need thereof, where the subject has been determined to have an elevated blood type I interferon gene signature (IFNGS) level. In embodiments, the present disclosure provides methods for reducing IFNGS in a subject in need thereof. In embodiments, the methods include administering a pharmaceutically effective amount of an anti-ILT7 binding protein to the subject. In embodiments, the anti-ILT7 binding protein is administered to a subject when type I IFNGS is elevated in the subject compared to type I IFNGS in normal subjects. In embodiments, for example, the anti-ILT7 binding protein is administered to a subject with elevated baseline type I IFNGS compared to type I IFNGS in normal subjects. In embodiments, a method comprises selecting subjects for treatment with an anti-ILT7 binding protein, the method comprising (i) determining a subject's baseline blood type I IFNGS level, and (ii) selecting one or more subjects with an elevated baseline blood type I IFNGS level for treatment with the ILT7 binding protein. In embodiments, the anti-ILT7 binding protein is an antibody specific for the ILT7 protein.

[0186] In certain diseases (e.g., autoimmune diseases), activated pDCs secrete significant amounts of type I and type III interferons (IFNs). Type I IFNs are 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 embodiments, the type I IFN that produces type I IFNGS is IFNα. Although type I IFN protein levels cannot be measured directly in a reliable manner, measurement of IFN-inducible genes serves as a powerful surrogate for type I IFN protein levels. In embodiments, expression levels of type I IFN-inducible genes can be measured in biological samples (e.g., blood, skin, skeletal muscle, etc.) and analyzed as a composite result called a "type I interferon gene signature" or "type I IFNGS" or "IFNGS."

[0187] In embodiments, type I IFN-inducible genes are determined by assaying the expression levels 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-inducible genes in a biological sample. In embodiments, determining type I IFN-inducible genes includes the collective expression levels of two or more type I IFN-inducible genes. In embodiments, the two or more type I interferon (IFN)-inducible genes include, but are not limited to, two or more genes selected from SPATS2L, EPSTI1, HERC5, IFI127, IFI44, IFI44L, IFI6, IFIT1, IFIT3, ISG15, LAMP3, LY6E, MX1, OAS1, OAS2, OAS3, PLSCR1, RSAD2, RTP4, SIGLEC1, and USP18. In embodiments, type I IFNGS are determined by assaying 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.

[0188] In embodiments, type I IFNGS is determined by assaying collective expression of genes, the collective expression comprising a 21-gene signature. In embodiments, type I IFNGS in a subject is elevated by at least 1.5-fold compared to a normal score before treatment. In embodiments, type I IFNGS in a subject is elevated by at least 2-fold compared to a normal score before treatment. In embodiments, subjects with elevated type I IFNGS before treatment are more likely to respond to treatment. In embodiments, type I IFNGS is at least about 4-fold, at least about 5-fold, at least about 6-fold, at least about 7-fold, at least about 8-fold, at least about 9-fold, at least about 10-fold, at least about 11-fold, or at least about 12-fold or greater compared to a normal score before treatment with an anti-ILT7 binding protein used as part of the methods described herein. In embodiments, tissue type I IFNGS is determined from a skin biopsy. In embodiments, tissue type I IFNGS is determined using an IFN-inducible myxovirus protein A (MxA) immunohistochemistry (IHC) test.

[0189] As used herein, the terms "high" or "elevated," when used in conjunction with IFNGS, refer to a fold change of at least about 1.1 to about 1000 in type I IFNGS compared to normal type I IFNGS levels. "Normal type I IFNGS" refers to type I IFNGS obtained from a normal subject. The terms "high" or "elevated," when used in conjunction with type I IFNGS, are used interchangeably. In embodiments, type I IFNGS is "high" or "elevated" when the type I IFNGS used as part of the methods 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 greater than type I IFNGS in a normal subject. In embodiments, the methods of treatment described herein are applied when type I IFNGS is elevated at least about four-fold compared to normal type I IFNGS.

[0190] The present disclosure provides a method of treating a subject with elevated type I IFNGS, comprising administering an anti-ILT7 binding protein described herein. The subject may exhibit elevated type I IFNGS if suffering from an autoimmune disorder. In embodiments, the present disclosure provides a method of treating an autoimmune disorder where the subject exhibits elevated type I IFNGS. In embodiments, the autoimmune disorder is otherwise asymptomatic. In embodiments, the method includes selecting a subject for treatment with an anti-ILT7 binding protein, the method comprising: (i) determining the subject's baseline blood type I IFNGS level; and (ii) selecting one or more subjects with elevated baseline blood type I IFNGS levels for treatment with the ILT7 binding protein.

[0191] In embodiments, the methods of the present disclosure can be used to monitor the effectiveness of treatment of a condition or disorder by monitoring the levels of type I IFNGS and / or activated pDCs. As described above, autoimmune conditions are often characterized by elevated type I IFNGS and / or elevated pDCs, and thus monitoring the effectiveness of treatment can include monitoring type I IFNGS and / or pDC levels. In embodiments, the present disclosure provides a method for monitoring the effectiveness of treatment of an autoimmune disorder or condition, comprising: (a) measuring a type I interferon gene signature (IFNGS) in a biological sample obtained from the subject to obtain a baseline level of type I IFNGS; and (b) measuring type I IFNGS in the biological sample obtained from the subject after administering a treatment, wherein the treatment comprises administering an anti-ILT7 binding protein; and a decrease in type I IFNGS in step (b) compared to the baseline level (a) indicates that the treatment is effective in the subject. In embodiments, the treatment results in a decrease in type I IFNGS compared to the baseline level. In embodiments, the reduction in type I IFNGS compared to baseline levels ranges from about 1% to about 99%. In embodiments, the reduction in type I IFNGS compared to baseline levels 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 levels is at least about 30%. In embodiments, the reduction in type I IFNGS compared to baseline levels is at least about 50%.

[0192] In embodiments, the disclosed methods may include reducing Cutaneous Lupus Erythematosus Disease Activity and Severity Index (CLASI) in a tissue of a subject in need thereof. The disclosed methods may include administering a pharmaceutically effective amount of an anti-ILT7 binding protein to a subject. As used herein, the term "CLASI" refers to Cutaneous Lupus Erythematosus Disease Activity and Severity Index. The CLASI is an effective tool for measuring the cutaneous manifestations of CLE. The CLASI has two scores: the first summarizes the inflammatory activity of the disease, and the second is a measure of the damage done by the disease. Activity scores include erythema (0-3), scale / hypertrophy (0-2), mucosal lesions (0-1), recent hair loss (0-1), and non-scarring hair loss (0-3). Damage scores include dyspigmentation (0-1), scarring / atrophy / panniculitis (0-2), and scalp scarring (0-6). Subjects are asked if their dyspigmentation has persisted for more than 12 months; if so, the dyspigmentation score is doubled. Each of the above parameters is measured at 13 different anatomical locations, particularly as they are most commonly involved in CLE. The most severe lesion in each area is measured. As used herein, the term "CLASI reduction" refers to a reduced level of CLASI Activity (CLASI-A) score in a subject or in a biological sample (e.g., skin tissue, skin cells, skin biopsy, etc.) obtained from the subject, or a reduced level of CLASI Damage (CLASI-D) score in a subject or in a biological sample obtained from the subject, or both. In embodiments, the methods of the present disclosure result in a reduced CLASI-A score in a subject. In embodiments, a decrease in a subject's CLASI-A score involves a decrease in the CLASI-A score by at least 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 points from the baseline value. In embodiments, a decrease in a subject's CLASI-A score involves a decrease in the CLASI-A score by at least 4 points from the baseline value.In embodiments, the reduction in the subject's CLASI-A score involves a reduction in the CLASI-A score by at least 7 points from the baseline value. In embodiments, the reduction in the subject's CLASI-A score involves a reduction in the CLASI-A score by at least 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, or 99% from the baseline value. In embodiments, the reduction in the subject's CLASI-A score involves a reduction in the CLASI-A score by at least 50% from the baseline value. In embodiments, the baseline value is the CLASI-A score value in the subject prior to treatment with an anti-ILT7 binding protein as part of the methods described herein. In embodiments, the methods of the present disclosure result in a reduced CLASI-D score in the subject. In embodiments, the methods of the present disclosure result in a reduced CLASI-A score and a reduced CLASI-D score in the subject.

[0193] The disclosed compositions can be administered using a variety of regimens, in embodiments, the compositions are administered hourly, daily, weekly, monthly, or yearly.

[0194] 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, every 2 days, every 3 days, every 4 days, every 5 days, every 6 days, or every 7 days. In embodiments, the pharmaceutical composition is administered every week, every 2 weeks, every 3 weeks, every 4 weeks, every 5 weeks, every 6 weeks, every 7 weeks, every 8 weeks, every 9 weeks, every 10 weeks, every 11 weeks, every 12 weeks, every 13 weeks, every 14 weeks, every 15 weeks, every 16 weeks, every 17 weeks, every 18 weeks, every 19 weeks, 20 weeks, 21 weeks, 22 weeks, 23 weeks, 24 weeks, 25 weeks, 26 weeks, 27 weeks, or every 28 weeks. every week, every 28 weeks, every 29 weeks, every 30 weeks, every 31 weeks, every 32 weeks, every 33 weeks, every 34 weeks, every 35 weeks, every 36 weeks, every 37 weeks, every 38 weeks, every 39 weeks, every 40 weeks, every 41 weeks, every 42 weeks, every 43 weeks, every 44 weeks, every 45 weeks, every 46 weeks, every 47 weeks, every 48 weeks, every 49 weeks, every 50 weeks, every 51 weeks, or every 52 weeks. In embodiments, the pharmaceutical composition is administered monthly, every 2 months, every 3 months, every 4 months, every 5 months, every 6 months, every 7 months, every 8 months, every 9 months, every 10 months, every 11 months, or every 12 months.

[0195] In embodiments, methods are provided for treating systemic lupus erythematosus, comprising administering an effective amount of a composition provided herein, wherein the administration occurs every four weeks. In embodiments, methods are provided for treating systemic lupus erythematosus, comprising administering an effective amount of a composition provided herein, wherein the administration occurs every twelve weeks.

[0196] According to the methods of the present disclosure, anti-ILT7 binding proteins, as defined elsewhere herein, are used to promote a positive therapeutic response with respect to an autoimmune response. By "positive therapeutic response" with respect to autoimmune treatment, it is intended an improvement in the disease associated with the activity of the anti-ILT7 binding protein. Exemplary positive therapeutic responses include, but are not limited to, a decrease in interferon-alpha levels, a decrease in plasmacytoid dendritic cell levels or activity, or a decrease in one or more symptoms associated with the disease. In embodiments, the improvement in the disease can be characterized as a complete response. By "complete response" is meant the absence of clinically detectable disease by normalizing any prior test results. In embodiments, such a response can persist for at least one month after administration according to the methods of the present disclosure. In embodiments, the improvement in the disease can be classified as a partial response. In addition to these positive therapeutic responses, subjects receiving therapy with an ILT7 binding protein can experience the beneficial effect of an improvement in symptoms associated with the disease.

[0197] In embodiments, methods 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 a subject's immunological reaction against their own cells, tissues, and / or organs. In embodiments, the autoimmune disease is systemic lupus erythematosus.

[0198] Clinical response can be assessed using screening techniques such as magnetic resonance imaging (MRI) scans, x-ray imaging, computed tomography (CT) scans, 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, etc.

[0199] In embodiments, provided herein are methods utilizing anti-ILT7 binding proteins to diagnostically monitor protein levels in tissues as part of a clinical testing procedure, e.g., to determine the effectiveness of a given treatment regimen. Detection can be facilitated, for example, 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; an example of a luminescent material includes luminol; examples of bioluminescent materials include luciferase, luciferin, and aequorin; exemplary radioactive materials include 125 I, 131 I, 35 S, or 3 H is one example.

[0200] In embodiments, disclosed herein are in vitro testing methods for selecting a subject for disease treatment, comprising determining whether the subject has an autoimmune disease provided herein. In embodiments, the in vitro method can be performed on a biological sample extracted from a subject (e.g., blood, cartilage, bone, serum, etc.) and can be used in determining a mode or course of treatment for a particular subject, for example, whether to administer an anti-ILT7 binding protein to the subject (alone or in combination with another compound).

[0201] In embodiments, disclosed herein are methods for administering an anti-ILT7 binding protein to a subject. In embodiments, disclosed herein are methods for administering an anti-ILT7 binding protein to a subject in need thereof. In embodiments, disclosed herein are methods for administering an anti-ILT7 binding protein to a subject in need thereof, wherein the subject has a diagnosis of an autoimmune disease or disorder. In embodiments, disclosed herein are methods for administering an anti-ILT7 binding protein to a subject in need thereof, wherein the subject has symptoms of an autoimmune disease or disorder.

[0202] In embodiments, disclosed herein are methods for administering a composition comprising an anti-ILT7 binding protein to a subject. In embodiments, disclosed herein are methods for administering a composition comprising an anti-ILT7 binding protein to a subject in need thereof. In embodiments, disclosed herein are methods for administering a composition comprising an anti-ILT7 binding protein to a subject in need thereof, wherein the subject has been diagnosed with an autoimmune disease or disorder. In embodiments, disclosed herein are methods for administering a composition comprising an anti-ILT7 binding protein to a subject in need thereof, wherein the subject has symptoms of an autoimmune disease or disorder.

[0203] In embodiments, disclosed herein are methods for administering a formulation comprising an anti-ILT7 binding protein to a subject. In embodiments, disclosed herein are methods for administering a formulation comprising an anti-ILT7 binding protein to a subject in need thereof. In embodiments, disclosed herein are methods for administering a formulation comprising an anti-ILT7 binding protein to a subject in need thereof, wherein the subject has been diagnosed with an autoimmune disease or disorder. In embodiments, disclosed herein are methods for administering a formulation comprising an anti-ILT7 binding protein to a subject in need thereof, wherein the subject has symptoms of an autoimmune disease or disorder.

[0204] In embodiments, disclosed herein are methods for administering a composition comprising an anti-ILT7 binding protein to a subject. In embodiments, disclosed herein are methods for administering a composition comprising an anti-ILT7 binding protein to a subject in need thereof. In embodiments, disclosed herein are methods for administering a composition comprising an anti-ILT7 binding protein to a subject in need thereof, wherein the subject has been diagnosed with an autoimmune disease or disorder. In embodiments, disclosed herein are methods for administering a composition comprising an anti-ILT7 binding protein to a subject in need thereof, wherein the subject has symptoms of an autoimmune disease or disorder.

[0205] In embodiments, disclosed herein are methods for administering a composition comprising an anti-ILT7 binding protein to a subject, wherein the composition is stored in a pre-filled syringe prior to administration. In embodiments, disclosed herein are methods for administering a composition comprising an anti-ILT7 binding protein to a subject in need thereof, wherein the composition is stored in a pre-filled syringe prior to administration. In embodiments, disclosed herein are methods for administering a composition comprising an anti-ILT7 binding protein to a subject in need thereof, wherein the subject has been diagnosed with an autoimmune disease or disorder, and the composition is stored in a pre-filled syringe prior to administration. In embodiments, disclosed herein are methods for administering a composition comprising an anti-ILT7 binding protein to a subject in need thereof, wherein the subject has symptoms of an autoimmune disease or disorder, and the composition is stored in a pre-filled syringe prior to administration.

[0206] In embodiments, disclosed herein are methods for 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 embodiments, disclosed herein are methods for 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 embodiments, disclosed herein are methods for 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 disorder. In embodiments, disclosed herein are methods for 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.

[0207] In embodiments, disclosed herein are methods for 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 embodiments, disclosed herein are methods for 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 embodiments, disclosed herein are methods for 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 disorder, and the composition is stored in a pre-filled syringe prior to administration. In embodiments, disclosed herein are methods for 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, and the composition is stored in a pre-filled syringe prior to administration.

[0208] Numbered Embodiments Notwithstanding the appended claims, the present disclosure presents the following numbered embodiments.

[0209] Embodiment Set 1 Embodiment 1. A composition comprising: (i) about 100 mg / mL to about 350 mg / mL of an 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.

[0210] Embodiment 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) 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.

[0211] Embodiment 3. The composition of any one of embodiments 1-2, wherein the buffer is a histidine buffer.

[0212] Embodiment 4. The composition of any one of embodiments 1-2, wherein the buffer is a phosphate buffer.

[0213] Embodiment 5. The composition of any one of embodiments 1-2, wherein the buffer is a citrate buffer.

[0214] Embodiment 6. The composition of any one of embodiments 1 to 5, wherein the pH of the composition is acidic when measured by a pH meter.

[0215] Embodiment 7. The composition of embodiment 6, wherein the acidic pH is about 5 to about 7 as determined by a pH meter.

[0216] Embodiment 8. The composition of embodiment 7, wherein the acidic pH is about 6 as determined by a pH meter.

[0217] Embodiment 9. The composition of any one of embodiments 1 to 8, wherein the composition comprises about 5 mM to about 25 mM histidine / histidine-HCl.

[0218] Embodiment 10. The composition of embodiment 9, comprising about 20 mM histidine / histidine-HCl.

[0219] Embodiment 11. The composition of any one of embodiments 1 to 10, wherein the composition comprises about 5 mM to about 50 mM L-methionine.

[0220] Embodiment 12. The composition of embodiment 11, comprising about 15 mM L-methionine.

[0221] Embodiment 13. The composition of any one of embodiments 1 to 12, comprising about 0.02% Polysorbate 80.

[0222] Embodiment 14. The composition of any one of embodiments 1 to 13, comprising up to about 150 mg / mL of an ILT7 binding protein.

[0223] Embodiment 15. The composition of any one of embodiments 1 to 14, comprising about 150 mg / mL of an ILT7 binding protein.

[0224] Embodiment 16. The composition of any one of embodiments 1-15, wherein the 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.i. and ii.

[0225] Embodiment 17. The composition of any one of embodiments 1 to 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.

[0226] Embodiment 18. The composition of any one of embodiments 1 to 17, wherein the ILT7 binding protein comprises complementarity determining regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprising the sequences of SEQ ID NOs: 3, 4, 5, 6, 7, and 8, respectively.

[0227] Embodiment 19. The composition of any one of embodiments 1 to 18, wherein the composition comprises a viscosity of about 5 cP to about 50 cP as determined by viscometer.

[0228] Embodiment 20. The composition of any one of embodiments 1 to 19, wherein the ILT7 binding protein is daxudilimab.

[0229] Embodiment 21. A composition comprising: i. about 150 mg / mL immunoglobulin-like transcript 7 (ILT7) binding protein; ii. about 20 mM histidine / histidine-HCl; iii. about 180 mM sucrose; iv. about 15 mM L-methionine; and v. about 0.02% polysorbate 80.

[0230] Embodiment 22. A composition comprising: i. about 150 mg / mL immunoglobulin-like transcript 7 (ILT7) binding protein; ii. about 20 mM histidine / histidine-HCl; iii. about 180 mM sucrose; iv. about 15 mM L-methionine; and v. about 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.

[0231] Embodiment 23. A composition comprising: i. about 150 mg / mL immunoglobulin-like transcript 7 (ILT7) binding protein; ii. about 20 mM histidine / histidine-HCl; iii. about 180 mM sucrose; iv. about 15 mM L-methionine; and v. about 0.02% polysorbate 80, wherein the ILT7 binding protein comprises complementarity determining regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprising the sequences of SEQ ID NOs: 3, 4, 5, 8, 7, and 8, respectively.

[0232] Embodiment 24. The composition of any one of embodiments 21 to 23, wherein the viscosity of the composition is from about 5 to about 50 cP.

[0233] Embodiment 25. The composition of embodiment 24, wherein the viscosity does not exceed 20 cP.

[0234] Embodiment 26. The composition of any one of embodiments 21 to 25, wherein the rate of aggregation is reduced compared to an otherwise equivalent composition lacking L-methionine, as determined by size exclusion chromatography at 40°C.

[0235] Embodiment 27. The composition of any one of embodiments 21 to 26, wherein the rate of aggregation is 0.5% to 1% per month as determined by size exclusion chromatography at 40°C.

[0236] Embodiment 28. A composition according to any one of embodiments 21 to 27, wherein the level of oxidation is reduced compared to an otherwise equivalent composition lacking L-methionine, as determined by peptide mapping of W102 or W104 of SEQ ID NO: 1 or SEQ ID NO: 10 of the ILT7 binding protein at room temperature.

[0237] Embodiment 29. The composition of any one of embodiments 21 to 28, wherein when the composition is exposed to light of 1600 to 1800 lux for 5 days, the percentage increase in oxidized species of the ILT7 binding protein in the composition is at most 0.5%, as determined by size exclusion chromatography.

[0238] Embodiment 30. The composition of any one of embodiments 21 to 29, wherein the composition is Fc oxidation resistant.

[0239] Embodiment 31. A container containing the composition of any one of embodiments 1 to 30 in unit dose form.

[0240] Embodiment 32. The container of embodiment 31, wherein the container contains nitrogen.

[0241] Embodiment 33. The container of embodiment 31, wherein the container is nitrogen-free.

[0242] Embodiment 34. A method for treating a disease, comprising administering an effective amount of a composition according to any one of embodiments 1 to 30 to a subject in need thereof, thereby treating the disease.

[0243] Embodiment 35. The method of embodiment 34, wherein the administration is sufficient to reduce symptoms of a disease in a subject in need thereof after administration.

[0244] Embodiment 36. The method of embodiment 35, wherein the symptoms are reduced by at least about 1-fold.

[0245] Embodiment 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 embodiments 1 to 30, thereby treating the autoimmune disease.

[0246] 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, rheumatic carditis, systemic lupus erythematosus, psoriasis, rheumatoid arthritis, chronic inflammation, Sjogren's syndrome, polymyositis, dermatomyositis, inclusion body myositis, juvenile myositis, and scleroderma.

[0247] Embodiment 39. The method of embodiment 38, wherein the autoimmune disease is alopecia areata.

[0248] Embodiment 40 The method of embodiment 38, wherein the autoimmune disease is systemic lupus erythematosus.

[0249] Embodiment 41 The method of embodiment 38, wherein the autoimmune disease is FSGS.

[0250] Embodiment 42. A method for treating alopecia areata, comprising administering to a subject in need thereof an effective amount of the composition of any one of embodiments 1 to 30, thereby treating alopecia areata.

[0251] Embodiment 43. A method of treating focal segmental glomerulosclerosis (FSGS), comprising administering to a subject in need thereof an effective amount of the composition of any one of embodiments 1 to 30, thereby treating FSGS.

[0252] Embodiment 44. A method for treating systemic lupus erythematosus, comprising administering to a subject in need thereof an effective amount of the composition of any one of embodiments 1 to 30, thereby treating systemic lupus erythematosus.

[0253] Embodiment 45. The method of embodiment 44, wherein administration is every 4 weeks.

[0254] Embodiment 46. The method of embodiment 44, wherein administration is every 12 weeks.

[0255] Embodiment 47. A method for treating myositis, comprising administering to a subject in need thereof an effective amount of a composition of any one of embodiments 1 to 30, thereby treating the myositis.

[0256] Embodiment 48. The method of any one of embodiments 37 to 47, wherein administration is subcutaneous.

[0257] Embodiment 49. A composition comprising: i. about 150 mg / mL immunoglobulin-like transcript 7 (ILT7) binding protein; ii. about 20 mM histidine / histidine-HCl; iii. about 180 mM sucrose; iv. about 15 mM L-methionine; and v. about 0.02% polysorbate 80, wherein the ILT7 binding protein comprises a sequence having at least 85% identity to a sequence in Table 1.

[0258] Embodiment 50. A composition comprising: i. about 150 mg / mL immunoglobulin-like transcript 7 (ILT7) binding protein; ii. about 20 mM histidine / histidine-HCl; iii. about 180 mM sucrose; iv. about 15 mM L-methionine; and v. about 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 VL of SEQ ID NO: 1 and SEQ ID NO: 2, respectively.

[0259] Embodiment 51. A method of treating an autoimmune disease, comprising administering a composition comprising: i. about 150 mg / mL 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, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprising the sequences of SEQ ID NOs: 3, 4, 5, 8, 7, and 8, respectively; wherein the dose of the ILT7 binding protein is about 150 mg to about 350 mg; the administration is subcutaneous; and the dose is administered in a single injection.

[0260] Embodiment 52. The method of embodiment 51, wherein the dose of the ILT7 binding protein comprises from about 150 mg to about 275 mg.

[0261] Embodiment 53. The method of embodiment 52, wherein the dose of the ILT7 binding protein comprises about 150 mg to about 200 mg.

[0262] Embodiment Set 2 Embodiment 54. A composition comprising: (i) about 100 mg / mL to about 350 mg / mL of an 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.

[0263] Embodiment 55. 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) 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.

[0264] Embodiment 56. The composition of any one of embodiments 54 to 55, wherein the buffer is a histidine buffer.

[0265] Embodiment 57. The composition of any one of embodiments 54 to 55, wherein the buffer is a phosphate buffer.

[0266] Embodiment 58. A composition according to any one of embodiments 54 to 55, wherein the buffer is a citrate buffer.

[0267] Embodiment 59. The composition of any one of embodiments 54 to 58, wherein the pH of the composition is acidic when measured by a pH meter.

[0268] Embodiment 60. The composition of embodiment 59, wherein the acidic pH is about 5 to about 7 as determined by a pH meter.

[0269] Embodiment 61. The composition of embodiment 60, wherein the acidic pH is about 6 as determined by a pH meter.

[0270] Embodiment 62. The composition of any one of embodiments 54 to 62, wherein the composition comprises about 5 mM to about 25 mM histidine / histidine-HCl.

[0271] Embodiment 63. The composition of embodiment 62, comprising about 20 mM histidine / histidine-HCl.

[0272] Embodiment 64. The composition of any one of embodiments 54 to 63, wherein the composition comprises about 5 mM to about 50 mM L-methionine.

[0273] Embodiment 65. The composition of embodiment 64, comprising about 15 mM L-methionine.

[0274] Embodiment 66. The composition of any one of embodiments 54 to 65, comprising about 0.02% Polysorbate 80.

[0275] Embodiment 67. The composition of any one of embodiments 54 to 66, comprising up to about 150 mg / mL of an ILT7 binding protein.

[0276] Embodiment 68. The composition of any one of embodiments 54 to 67, comprising about 150 mg / mL of an ILT7 binding protein.

[0277] Embodiment 69. The composition of any one of embodiments 54 to 68, wherein the 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.i. and ii.

[0278] Embodiment 70. The composition of any one of embodiments 54 to 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.

[0279] Embodiment 71. The composition of any one of embodiments 54 to 70, wherein the ILT7 binding protein comprises complementarity determining regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprising the sequences of SEQ ID NOs: 3, 4, 5, 6, 7, and 8, respectively.

[0280] Embodiment 72. The composition of any one of embodiments 54 to 71, wherein the composition comprises a viscosity of about 5 cP to about 50 cP as determined by viscometer.

[0281] Embodiment 73. The composition of any one of embodiments 54 to 72, wherein the ILT7 binding protein is daxudilimab.

[0282] Embodiment 74. A composition comprising: i. about 150 mg / mL immunoglobulin-like transcript 7 (ILT7) binding protein; ii. about 20 mM histidine / histidine-HCl; iii. about 180 mM sucrose; iv. about 15 mM L-methionine; and v. about 0.02% polysorbate 80.

[0283] Embodiment 75. A composition comprising: i. about 150 mg / mL immunoglobulin-like transcript 7 (ILT7) binding protein; ii. about 20 mM histidine / histidine-HCl; iii. about 180 mM sucrose; iv. about 15 mM L-methionine; and v. about 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.

[0284] Embodiment 76. A composition comprising: i. about 150 mg / mL immunoglobulin-like transcript 7 (ILT7) binding protein; ii. about 20 mM histidine / histidine-HCl; iii. about 180 mM sucrose; iv. about 15 mM L-methionine; and v. about 0.02% polysorbate 80, wherein the ILT7 binding protein comprises complementarity determining regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprising the sequences of SEQ ID NOs: 3, 4, 5, 6, 7, and 8, respectively.

[0285] Embodiment 77. The composition of any one of embodiments 54 to 76, wherein the viscosity of the composition is from about 5 to about 50 cP.

[0286] Embodiment 78. The composition of embodiment 77, wherein the viscosity does not exceed 20 cP.

[0287] Embodiment 79. The composition of any one of embodiments 54 to 78, wherein the rate of aggregation is reduced compared to an otherwise equivalent composition lacking L-methionine, as determined by size exclusion chromatography at 40°C.

[0288] Embodiment 80. The composition of any one of embodiments 54 to 79, wherein the rate of aggregation is 0.5% to 1% per month as determined by size exclusion chromatography at 40°C.

[0289] Embodiment 81. The composition of any one of embodiments 54 to 80, wherein the level of oxidation is reduced compared to an otherwise equivalent composition lacking L-methionine, as determined by peptide mapping of W102 or W104 of SEQ ID NO: 1 or SEQ ID NO: 10 of the ILT7 binding protein at room temperature.

[0290] Embodiment 82. The composition of any one of embodiments 54 to 81, wherein when the composition is exposed to light of 1600 to 1800 lux for 5 days, the percentage increase in oxidized species of the ILT7 binding protein in the composition is at most 0.5%, as determined by size exclusion chromatography.

[0291] Embodiment 83. The composition of any one of embodiments 54 to 82, wherein the composition is Fc oxidation resistant.

[0292] Embodiment 84. A container containing the composition of any one of embodiments 54 to 83 in unit dose form.

[0293] Embodiment 85. The container of embodiment 84, wherein the container contains nitrogen.

[0294] Embodiment 86. The container of embodiment 84, wherein the container does not contain nitrogen.

[0295] Embodiment 87. A method for treating a disease, comprising administering an effective amount of a composition described in any one of embodiments 54 to 83 to a subject in need thereof, thereby treating the disease.

[0296] Embodiment 88. The method of embodiment 87, wherein the administration is sufficient to reduce symptoms of a disease in a subject in need thereof after administration.

[0297] Embodiment 89. The method of embodiment 88, wherein the symptoms are reduced by at least about 1-fold.

[0298] Embodiment 90. A method for treating an autoimmune disease, comprising administering to a subject in need thereof an effective amount of the composition of any one of embodiments 54 to 83, thereby treating the autoimmune disease.

[0299] 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, rheumatic carditis, systemic lupus erythematosus, psoriasis, rheumatoid arthritis, chronic inflammation, Sjogren's syndrome, polymyositis, dermatomyositis, inclusion body myositis, juvenile myositis, and scleroderma.

[0300] Embodiment 92. The method of embodiment 91, wherein the autoimmune disease is alopecia areata.

[0301] Embodiment 93 The method of embodiment 91, wherein the autoimmune disease is systemic lupus erythematosus.

[0302] Embodiment 94. The method of embodiment 91, wherein the autoimmune disease is FSGS.

[0303] Embodiment 95. A method for treating alopecia areata, comprising administering to a subject in need thereof an effective amount of the composition of any one of embodiments 54 to 83, thereby treating alopecia areata.

[0304] Embodiment 96. A method for treating focal segmental glomerulosclerosis (FSGS), comprising administering to a subject in need thereof an effective amount of the composition of any one of embodiments 1 to 98, thereby treating FSGS.

[0305] Embodiment 97. A method for treating systemic lupus erythematosus, comprising administering to a subject in need thereof an effective amount of the composition of any one of embodiments 54 to 83, thereby treating systemic lupus erythematosus.

[0306] Embodiment 98. The method of embodiment 97, wherein administration is every 4 weeks.

[0307] Embodiment 99. The method of embodiment 97, wherein administration is every 12 weeks.

[0308] Embodiment 100. A method for treating myositis, comprising administering to a subject in need thereof an effective amount of the composition of any one of embodiments 54 to 83, thereby treating the myositis.

[0309] Embodiment 101. The method of any one of embodiments 90 to 100, wherein administration is subcutaneous.

[0310] Embodiment 102. A composition comprising: i. about 150 mg / mL immunoglobulin-like transcript 7 (ILT7) binding protein; ii. about 20 mM histidine / histidine-HCl; iii. about 180 mM sucrose; iv. about 15 mM L-methionine; and v. about 0.02% polysorbate 80, wherein the ILT7 binding protein comprises a sequence having at least 85% identity to a sequence in Table 1.

[0311] Embodiment 103. A composition comprising: i. about 150 mg / mL immunoglobulin-like transcript 7 (ILT7) binding protein; ii. about 20 mM histidine / histidine-HCl; iii. about 180 mM sucrose; iv. about 15 mM L-methionine; and v. about 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 VL of SEQ ID NO: 1 and SEQ ID NO: 2, respectively.

[0312] Embodiment 104. A method of treating an autoimmune disease, comprising administering a composition comprising: i. about 150 mg / mL 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, HCDR2, 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 ILT7 binding protein is about 150 mg to about 350 mg; the administration is subcutaneous; and the dose is administered in a single injection.

[0313] Embodiment 105. The method of embodiment 104, wherein the dose of the ILT7 binding protein comprises from about 150 mg to about 275 mg.

[0314] Embodiment 106. The method of embodiment 105, wherein the dose of the ILT7 binding protein comprises about 150 mg to about 200 mg.

[0315] Embodiment 107. A delivery device comprising the composition of any one of embodiments 54 to 83, or 102 to 103.

[0316] Embodiment 108. The delivery device of embodiment 107, wherein the device is an autoinjector.

[0317] Embodiment 109. A kit comprising a delivery device described in any one of embodiments 107 to 108 and instructions for its use.

[0318] Embodiment 110. The kit of embodiment 109, comprising a plurality of autoinjectors.

[0319] Embodiment 111. A method of treatment comprising administering daxudilimab to a subject in need thereof, wherein the administration comprises use of an autoinjector.

[0320] Embodiment 112. The method of treatment of embodiment 111, wherein the autoinjector is contacted with the thigh, abdomen, or arm of a subject in a manner sufficient to administer daxudilimab to a subject in need thereof.

[0321] Embodiment 113. The method of any one of embodiments 111-112, wherein the treatment is for 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, rheumatic carditis, systemic lupus erythematosus, psoriasis, rheumatoid arthritis, chronic inflammation, Sjogren's syndrome, polymyositis, dermatomyositis, inclusion body myositis, juvenile myositis, IgG4-related disease (IgG4RD), and scleroderma.

[0322] Embodiment 114. The method of any one of embodiments 111-112, wherein the treatment is for a non-autoimmune disease or condition.

[0323] Embodiment 115. The method of embodiment 114, wherein the non-autoimmune disease or condition comprises an ILT7-expressing cell-mediated disease.

[0324] 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 light at 1600 to 1800 lux for 5 days, the increase in the percentage of oxidized species of the ILT7 binding protein in the composition is up to about 1.0%, as determined by size exclusion chromatography.

[0325] Embodiment 117. The composition of embodiment 116, wherein the increase in the percentage of oxidized species of the ILT7 binding protein in the composition is up to about 0.4%, 0.3%, 0.2%, or 0.1%.

[0326] 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 light at 1600 to 1800 lux, the rate of formation of new oxidized species of the ILT7 binding protein in the composition per day is at most about 0.1% to 0.5%, as determined by size exclusion chromatography.

[0327] Embodiment 119. The composition of embodiment 118, wherein the rate of formation of new oxidized species of the ILT7 binding protein per day in the composition is at most about 0.2% to 0.4% or 0.1 to 0.3%.

[0328] Embodiment 120. The composition of any one of embodiments 116-119, comprising from about 100 mg / mL to about 450 mg / mL of an ILT7 binding protein.

[0329] Embodiment 121. The composition of any one of embodiments 116 to 119, wherein the ILT7 binding protein comprises complementarity determining regions (CDRs) HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 comprising the sequences of SEQ ID NOs: 3, 4, 5, 6, 7, and 8, respectively.

[0330] These and other embodiments are disclosed herein. [Example]

[0331] Light-induced tryptophan oxidation in the complementarity-determining regions (CDRs) of some antibody-based therapeutics can affect potency and shelf life. Additionally, there is a need to eliminate and / or reduce the need for engineering controls, including, but not limited to, lighting adjustments and the need for nitrogen overlays during manufacturing.

[0332] To evaluate and improve existing formulations, anti-ILT7 binding proteins were utilized to assess means to reduce and / or eliminate light-induced tryptophan oxidation of the CDRs, which can affect antibody potency and shelf life, the need for engineering controls, the use of nitrogen overlay during manufacturing, and the use of syringes (e.g., pre-filled syringes) as storage containers.

[0333] Furthermore, formulations containing higher concentrations of anti-ILT7 binding protein allow for the administration of higher doses, progress with respect to higher concentrations having previously been limited due to increased rates of aggregation and formulation viscosity.

[0334] Example 1. Formulation and evaluation of the proportion of oxidized species formulation Several problems have been identified with existing formulations containing nonfucosylated human IgG1λ anti-ILT7 mAb. Specifically, light-induced tryptophan oxidation, oxidation of the Fc portion of the antibody, deamidation, and isomerization (Figures 1A-1C). Previously, nitrogen overlays were used to reduce oxidation in liquid formulations. However, nitrogen overlays add manufacturing complexity to liquid formulations. To reduce or eliminate these problems, the formulations were modified herein. The disclosed compositions and methods demonstrate that the identified problems are solved by the provided compositions and methods.

[0335] Assessment of the rate of oxidative species formation and aggregation of L-methionine for anti-ILT7 monoclonal antibodies To reduce or eliminate the need for engineering controls during manufacturing (e.g., light exposure, nitrogen overlay, etc.), improved formulations and excipient use containing anti-ILT7 monoclonal antibodies (mAbs) were screened and evaluated for the presence of oxidative species formation.

[0336] The effect of excipient [10 mM L-methionine (L-Met)] on the rate of oxidation and aggregation relative to a control (0 mM L-Met) was evaluated in a formulation containing 100 mg / mL of an anti-ILT7 mAb containing a sequence from 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). Specifically, the effect of excipient [10 mM L-Met] relative to a control (0 mM L-Met) on oxidative species was evaluated at 5°C and RT, and aggregation was evaluated at 5°C, RT, and 40°C.

[0337] The results show that L-Met reduced the rate of oxidized species at 5°C and RT (Figures 1B and 1C, respectively). Furthermore, at all temperatures (40°C, RT, and 5°C), L-Met reduced the rate of aggregation for anti-ILT7 mAb (Figures 2A, 2B, and 2C, respectively). Indeed, utilization of the provided compositions reduced Met oxidation in ILT7 mAb compositions, which is known to have adverse effects on proteins, including reduced stability and reduced biological activity. Furthermore, the observed reduction in the rate of aggregation supports the use of L-Met in compositions to allow for increased antibody concentration in dosage forms.

[0338] Example 2: Evaluation of L-methionine in anti-ILT7 mAb formulations under stress conditions To assess whether L-methionine reduces or eliminates oxidation, isomerization, and / or deamidation, which can affect antibody potency and shelf life, the formulations were evaluated under stress conditions that mimic long-term storage.

[0339] The effects of 10 mM L-Met or control (0 mM L-Met) on CDR modification and Fc oxidation were evaluated under stress conditions (40°C) for 2 weeks and 1 month and under ambient (RT) conditions for 3 months in a formulation containing 100 mg / mL 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.

[0340] The data show that the inclusion of 10 mM L-Met reduced antibody oxidation at exemplary residues M257 and M433 of SEQ ID NO: 10. Notably, CDR modifications at exemplary residues W102 / W104 of SEQ ID NO: 1 or SEQ ID NO: 10 were reduced by approximately 50% under stress conditions (40°C). Oxidation of Fc residues was also substantially reduced. These surprising results support the utility of the disclosed compositions and methods, particularly in providing improved antibody compositions with increased stability and capacity for long-term storage.

[0341] [Table 2]

[0342] Example 3. Headspace evaluation of anti-ILT7 mAb formulations The effect of headspace (nitrogen and air) in L-Met-free formulations on specific species of CDR modification and Fc oxidation was evaluated in a formulation containing 100 mg / mL anti-ILT7 mAb, 20 mM histidine, 240 mM sucrose, and 0.02% PS-80 (pH 6.0).

[0343] The results in Example 2 showed that the presence of 10 mM L-Met resulted in a lower percentage of oxidation at RT compared to conditions lacking L-Met (0 mM) for exemplary residues M257 and M433 of SEQ ID NO: 10. In comparison, the addition of a nitrogen overlay in conditions lacking L-Met (0 mM) resulted in a lower percentage of oxidation compared to air for the same exemplary residues M257 and M433 of SEQ ID NO: 10.

[0344] The results in Example 2 (Table 2) also showed that the presence of 10 mM L-Met resulted in a lower percentage of CDR modifications at RT compared to conditions lacking L-Met (0 mM) for exemplary residues W102 / W104 (SEQ ID NOs: 1 and 10). In comparison, the addition of a nitrogen overlay in conditions lacking L-Met (0 mM) resulted in a lower percentage of oxidized species compared to air for the same exemplary residues W102 / W104 (SEQ ID NOs: 1 and 10). CDR modifications (W102 / W104 of SEQ ID NO: 1 or SEQ ID NO: 10 and M257 / M433 of SEQ ID NO: 10) resulted in a similar lower percentage of oxidized species in the groups with 10 mM L-Met (1.4%, Table 2) and nitrogen overlay (1.1%, Table 3). These data indicate that the presence of L-Met in the formulations enhances their stability and eliminates the need for a nitrogen overlay, thereby reducing the effort and cost of producing these formulations compared to existing methods.

[0345] Results reporting the above effects of headspace on PTM are provided in Table 3.

[0346] [Table 3]

[0347] Example 4. Evaluation of L-methionine on oxidation and aggregation of a 150 mg / mL formulation of anti-ILT7 mAb The effect of L-Met (0 mM, 5 mM, 10 mM, 15 mM, and 20 mM) on the rate of oxidation (Figure 3A) and aggregation (Figure 3B) in a formulation containing 150 mg / mL anti-ILT7 mAb, 20 mM histidine, 200 mM sucrose, and 0.02% PS-80 (pH 6.0) was evaluated at 5°C, RT, and 40°C. The results show that 15 mM L-Met provided stabilization and robustness.

[0348] Additionally, the effect of L-Met (0 mM, 10 mM, and 20 mM) on CDR modification and Fc oxidation was evaluated at RT for 3 months. Results show that L-Met reduced Fc oxidation levels at exemplary residues M257 and M433 (SEQ ID NO: 10) at RT, and L-Met reduced CDR modification at exemplary residues W102 / W104 (SEQ ID NOs: 1 and 10), see Table 4. Indeed, the use of L-methionine resulted in reduced oxidation and aggregation, thereby supporting its use to achieve formulations with improved potency, stability, and flexibility in achieving higher doses in treatment regimens.

[0349] [Table 4]

[0350] Example 5. Evaluation of the effect of L-methionine on the oxidation of anti-ILT7 mAb formulations under light and dark conditions The effect of L-Met on the formation of oxidative species in exposed formulations was evaluated. Specifically, the presence of air, nitrogen, or L-Met (0 mM or 15 mM) was evaluated. The formulations contained either 100 mg / mL anti-ILT7 mAb, 20 mM histidine / histidine-HCl, 240 mM sucrose, and 0.02% PS-80 (pH 6.0) (P2) or 150 mg / mL anti-ILT7 mAb, 20 mM histidine, 200 mM sucrose, and 0.02% PS-80 (pH 6.0) (P3). Vials were kept in a light box at ambient temperature, and light intensity was measured at 1600–1800 lux throughout the study (Figure 4A). A vial was kept in a dark box at room temperature as a control (Figure 4B).

[0351] We 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 effective in at least reducing light-induced tryptophan oxidation in the CDRs of anti-ILT7 mAbs, which can affect potency and / or shelf life. These results provide a solution to existing manufacturing methods that require production and storage controls to reduce oxidation of antibody formulations.

[0352] Example 6. Evaluation of the effect of sucrose concentration on the rate of oxidation and aggregation of anti-ILT7 formulations The effect of sucrose concentration on the rate of oxidation and aggregation for formulations containing at least 150 mg / mL of anti-ILT7 mAb was evaluated. The results in Table 5 show that no significant effect was observed between 150 and 240 mM sucrose.

[0353] [Table 5]

[0354] Additionally, the effect of decreasing sucrose concentration (150-200 mM) on CDR modification and Fc oxidation was evaluated in a formulation containing 150 mg / mL anti-ILT7 mAb, 20 mM histidine / histidine-HCl, 15 mM L-methionine, and 0.02% PS-80 (pH 6.0) at 40°C for 1 month. Minimal effect of decreasing sucrose concentration was observed (see Table 6).

[0355] [Table 6]

[0356] Example 7. Evaluation of the effect of anti-ILT7 mAb concentration on the rate of oxidation The effect of anti-ILT7 mAb concentrations (10 mg / ml, 25 mg / ml, 50 mg / ml, 75 mg / ml, 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.

[0357] We determined that the concentration of anti-ILT7 mAb did not affect the rate of oxidation at all temperatures (Figures 5A-5C). Therefore, there is no restriction to use various amounts of mAb concentrations in the formulation, and treatment regimens including ILT7 mAb can be adapted accordingly.

[0358] Example 8. Evaluation of the effect of containers on aggregation and oxidation of anti-ILT7 mAb formulations The effect of storage container (vial or prefilled syringe (PFS)) on aggregation and oxidation of a 150 mg / mL anti-ILT7 mAb formulation 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). Formulation volumes (1 mL and 2 mL) were also tested in PFS.

[0359] We determined that the type of storage container (vial or PFS) for anti-ILT7 mAb formulations at all temperatures did not affect the percent formation of oxidized variants (Figures 6A-6C) or result in a decrease in the percentage of monomer (e.g., no increase in aggregates; Figures 7A-7C). Furthermore, the volume of anti-ILT7 mAb formulation in the PFS (1 mL or 2 mL) did not affect either the percent oxidation or the percent monomer. These data demonstrate that PFS can be used as a storage container for both 1 mL and 2 mL volumes of anti-ILT7 mAb formulations, eliminating the need for engineering vials as storage containers.

[0360] Thus, any of the provided reservoirs, such as pre-filled autoinjectors, can be utilized without compromising the performance of the disclosed ILT7 antibody compositions.

[0361] Incorporation by Reference All references, articles, publications, patents, patent publications, and patent applications cited herein are incorporated by reference in their entirety for all purposes. However, no reference, article, publication, patent, patent publication, or patent application cited herein is, and should not be, taken as an admission or any form of suggestion that it constitutes valid prior art or forms part of the common general knowledge anywhere in the world.

[0362] International Patent Applications: PCT / US2016 / 022003, PCT / JP2006 / 325391, PCT / US2017 / 021616, PCT / US2020 / 063396, and PCT / US2022 / 027620 are all incorporated by reference herein in their entirety for all intents and purposes.

Claims

1. A composition, (i) Immunoglobulin-like transcript 7 (ILT7) binding protein in a concentration of approximately 100 mg / mL to approximately 450 mg / mL, (ii) Sucrose in a range of approximately 50 to 350 mM, (iii) Approximately 0.001% to approximately 1% polysorbate 80, (iv) L-methionine and, (v) A composition comprising a buffer selected from histidine buffer, citrate buffer, or phosphate buffer.

2. A composition, (i) Immunoglobulin-like transcript 7 (ILT7) binding protein in a concentration of approximately 100 mg / mL to approximately 165 mg / mL, (ii) Sucrose of approximately 150 to 240 mM, (iii) Approximately 0.003% to approximately 0.8% polysorbate 80, (iv) L-methionine and, (v) A composition comprising a buffer selected from histidine buffer, citrate buffer, or phosphate buffer.

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

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

5. The composition according to any one of claims 1 to 2, wherein the buffer solution is a citrate buffer solution.

6. The composition according to any one of claims 1 to 2, wherein the pH of the composition is acidic when determined by a pH meter, and the acidic pH is about 5 to about 7 when determined by a pH meter, or about 6 when determined by a pH meter.

7. The composition according to claim 3, wherein the composition comprises about 5 mM to about 25 mM histidine / histidine-HCl.

8. The composition according to claim 7, comprising approximately 20 mM histidine / histidine-HCl.

9. The composition according to any one of claims 1 to 2, wherein the composition comprises about 5 mM to about 50 mM of L-methionine.

10. The composition according to claim 9, comprising approximately 15 mM L-methionine.

11. A composition according to any one of claims 1 to 2, comprising approximately 0.02% polysorbate 80.

12. The composition according to any one of claims 1 to 2, comprising approximately 150 mg / mL of the ILT7-binding protein.

13. The aforementioned ILT7-binding protein i. VH containing sequence number 1, ii. VL containing SEQ ID NO: 2, or A composition according to any one of claims 1 to 2, comprising iii. i. and ii.

14. The composition according to any one of claims 1 to 2, wherein the ILT7-binding protein comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, which are complementarity-determining regions (CDRs) containing the sequences of SEQ ID NOs: 3, 4, 5, 6, 7, and 8, respectively.

15. The composition according to any one of claims 1 to 2, wherein the composition has a viscosity of about 5 cP to about 50 cP when determined by a viscometer.

16. The composition according to any one of claims 1 to 2, wherein the ILT7-binding protein is daxdirimab.

17. A composition, i. Immunoglobulin-like transcript 7 (ILT7) binding protein at approximately 150 mg / mL, ii. Approximately 20 mM histidine / histidine-HCl, iii. Approximately 180 mM sucrose, iv. Approximately 15 mM L-methionine, v. A composition comprising approximately 0.02% polysorbate 80.

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

2.

19. A composition, i. 150 mg / mL of immunoglobulin-like transcript 7 (ILT7) binding protein, ii. 20 mM histidine / histidine-HCl and iii. 180 mM sucrose and iv. 15 mM L-methionine and v. A composition comprising 0.02% polysorbate 80, wherein the ILT7-binding protein comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, which are complementarity-determining regions (CDRs) containing the sequences of SEQ ID NOs. 3, 4, 5, 8, 7, and 8, respectively.

20. A composition, i. 150 mg / mL of immunoglobulin-like transcript 7 (ILT7) binding protein, ii. 20 mM histidine / histidine-HCl and iii. 180 mM sucrose and iv. 15 mM L-methionine and v. A composition comprising 0.02% polysorbate 80, wherein the ILT7-binding protein comprises the heavy chain of SEQ ID NO: 10 and the light chain of SEQ ID NO:

9.

21. The composition according to any one of claims 17 to 20, wherein the viscosity of the composition is about 5 to about 50 cP.

22. The composition according to claim 21, wherein the viscosity does not exceed 20 cP.

23. The composition according to any one of claims 17 to 20, wherein the aggregation rate, when determined by size exclusion chromatography at 40°C, is reduced compared to equivalent compositions except in that they lack L-methionine, and the aggregation rate, when determined by size exclusion chromatography at 40°C, is 0.5% to 1% per month.

24. The composition according to any one of claims 17 to 20, wherein the level of oxidation is reduced compared to equivalent compositions, except in that it lacks L-methionine, when determined at room temperature by peptide mapping of W102 or W104 of SEQ ID NO: 1 of the ILT7-binding protein.

25. The composition according to any one of claims 17 to 20, wherein when the composition is exposed to light of 1600 to 1800 lux for 5 days, the increase in the percentage of oxidized species of ILT7-binding protein in the composition is at most 1.0%, as determined by size exclusion chromatography.

26. The composition according to any one of claims 17 to 20, wherein the composition is resistant to Fc oxidation.

27. A container comprising the composition according to any one of claims 1, 2, 17 to 20 in unit dose form.

28. The container according to claim 27, wherein the container contains nitrogen.

29. The container according to claim 27, wherein the container does not contain nitrogen.

30. A pharmaceutical composition for use in the treatment of a disease in a subject requiring treatment of a disease, comprising the composition according to any one of claims 1, 2, 17 to 20.

31. A pharmaceutical composition for use in the treatment of an autoimmune disease in a subject requiring treatment for an autoimmune disease, comprising the composition according to any one of claims 1, 2, 17 to 20.

32. The pharmaceutical composition according to claim 31, wherein the autoimmune disease is selected from the group consisting of discoid lupus erythematosus (DLE), cutaneous lupus erythematosus (CLE), focal segmental glomerulosclerosis (FSGS), alopecia areata, myositis, lupus nephritis, diabetes mellitus, Hashimoto's disease, autoimmune adrenal insufficiency, pure red cell aplasia, multiple sclerosis, rheumatic 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.

33. The pharmaceutical composition according to claim 32, wherein the autoimmune disease is alopecia areata.

34. The pharmaceutical composition according to claim 32, wherein the autoimmune disease is systemic lupus erythematosus.

35. The pharmaceutical composition according to claim 32, wherein the autoimmune disease is FSGS.

36. The pharmaceutical composition according to claim 32, wherein the autoimmune disease is dermatomyositis.

37. The pharmaceutical composition according to claim 32, wherein the autoimmune disease is CLE.

38. The pharmaceutical composition according to claim 32, wherein the use is every four weeks.

39. The pharmaceutical composition according to claim 32, wherein the use is every 12 weeks.

40. The pharmaceutical composition according to claim 32, wherein the use is subcutaneous.

41. A composition, i. Immunoglobulin-like transcript 7 (ILT7) binding protein at approximately 150 mg / mL, ii. Approximately 20 mM histidine / histidine-HCl, iii. Approximately 180 mM sucrose, iv. Approximately 15 mM L-methionine, v. A composition comprising approximately 0.02% polysorbate 80, wherein the ILT7 binding protein comprises a sequence having at least 85% identity with the sequence in Table 1.

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

43. A pharmaceutical composition for use in the treatment of autoimmune diseases, wherein the composition is: i. Immunoglobulin-like transcript 7 (ILT7) binding protein at approximately 150 mg / mL, ii. 20 mM histidine / histidine-HCl and iii. 180 mM sucrose and iv. 15 mM L-methionine and v. Contains 0.02% polysorbate 80, A pharmaceutical composition characterized in that the ILT7-binding protein comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3 of complementarity-determining regions (CDRs) containing sequences 3, 4, 5, 6, 7, and 8, respectively, the use comprises a dose of the ILT7-binding protein comprising about 150 mg to about 450 mg, the composition is for subcutaneous administration, and the composition is administered in a single injection dose.

44. The pharmaceutical composition according to claim 43, wherein the amount of the ILT7-binding protein comprises about 150 mg to about 275 mg.

45. The pharmaceutical composition according to claim 44, wherein the amount of the ILT7-binding protein is approximately 150 mg to approximately 200 mg.

46. A delivery device comprising the composition according to any one of claims 1, 2, 17-20, or 41-42.

47. The delivery device according to claim 46, wherein the device is an auto-injector.

48. A kit comprising the delivery device described in claim 47 and instructions for its use.

49. The kit according to claim 48, comprising a plurality of auto-injectors.

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

51. The composition according to claim 50, wherein the increase in the percentage of oxidized species of ILT7-binding protein in the composition is at most about 0.4%, 0.3%, 0.2%, or 0.1%.

52. A composition, (i) Immunoglobulin-like transcript 7 (ILT7) binding protein in a concentration of approximately 100 mg / mL to approximately 450 mg / mL, (ii) A composition comprising L-methionine, wherein when the composition is exposed to light of 1600 to 1800 lux, the daily rate of formation of new oxidized species of ILT7-binding protein in the composition is, as determined by size exclusion chromatography, at a maximum of about 0.1% to 0.5%, at a maximum of about 0.2% to 0.4%, or at a maximum of 0.1% to 0.3%.

53. The composition according to claim 52, wherein the ILT7-binding protein comprises HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, and LCDR3, which are complementarity-determining regions (CDRs) containing the sequences of SEQ ID NOs. 3, 4, 5, 6, 7, and 8, respectively.

54. The composition according to claim 52, wherein the ILT7 binding protein comprises VH containing SEQ ID NO: 1, VL containing SEQ ID NO: 2, or both VH and VL of SEQ ID NO: 1 and SEQ ID NO: 2, respectively.

55. The composition according to claim 52, wherein the ILT7 binding protein comprises HC of SEQ ID NO: 10 and LC of SEQ ID NO:

9.

56. A pharmaceutical composition for use in the treatment of an autoimmune disease, comprising the composition according to any one of claims 52 to 55.

57. The pharmaceutical composition according to claim 56, wherein the autoimmune disease is selected from the group consisting of discoid lupus erythematosus (DLE), cutaneous lupus erythematosus (CLE), focal segmental glomerulosclerosis (FSGS), alopecia areata, myositis, lupus nephritis, diabetes mellitus, Hashimoto's disease, autoimmune adrenal insufficiency, pure red cell aplasia, multiple sclerosis, rheumatic 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.

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