Drug solutions of anti-N3pGlu A [beta] antibodies and uses thereof

Abstract

The present disclosure relates to pharmaceutical solutions of certain anti-N3pGlu A [beta] antibodies. Also disclosed are uses of such pharmaceutical solutions, including in the treatment of Alzheimer's disease.

Description

[0001] Public content area

[0002] The present disclosure relates to pharmaceutical solutions of certain anti-N3pGlu Aβ antibodies and uses thereof, including use in the treatment of Alzheimer's disease.

[0003] Numerous antibodies have been studied for their therapeutic efficacy, including but not limited to antibodies administered to patients (eg, human patients) for treatment or prevention of disease. Treatment of disease using antibody therapeutics generally involves administering a pharmaceutical formulation of the antibody to a subject in need thereof.

[0004] It is recognized in the art that formulating a therapeutic antibody into a pharmaceutical formulation suitable for administration to a subject (including, but not limited to, subcutaneous, intramuscular, intravenous, and / or intraperitoneal administration) can be challenging and unpredictable, at least in part due to the numerous properties that a pharmaceutical formulation must possess to be therapeutically viable. These properties include, but are not limited to, formulations suitable for manufacture, distribution, and storage.

[0005] Each individual component, its concentration, its ratio relative to other components, and / or its properties can affect the suitability of the formulation for manufacture, distribution, and / or storage (among other functional properties necessary for therapeutic function). Thus, while specific adjustments may provide a beneficial effect on a given aspect of a formulation, the same adjustments may also negatively affect other aspects of the formulation. As just one example, while surfactants can impart beneficial properties to the formulation of an antibody, including surfactants (e.g., polyoxyethylene (20) sorbitan monooleate) in a pharmaceutical formulation of an antibody can also result in the formation of antibody aggregates, which is undesirable.

[0006] There is little to no correlation for predicting the effects of modifying individual components (or their concentrations and / or their ratios relative to other components) on the pharmaceutical formulation properties of antibodies. Further adding to the challenge is the fact that an almost infinite number of different formulation components (e.g., buffers and excipients) and their concentrations are possible.

[0007] Overview

[0008] The inventors of the present application have identified unique and unexpected properties of the anti-N3pGlu antibodies discussed herein, including that lyophilized antibody formulations of the antibodies are unsuitable for manufacture, distribution and storage due to unacceptable levels of protein aggregation, whereas aqueous pharmaceutical solutions of non-lyophilized antibodies are surprisingly suitable for manufacture, distribution and storage, and maintain the necessary functional properties of the antibodies for therapeutic use.

[0009] Lyophilization is often used to ensure the stability of protein drug products and their suitability for manufacture, distribution and storage, especially for therapeutic antibodies delivered at high doses and antibodies with proven challenging stability properties (including cloud point, aggregation and discoloration). Lyophilization of protein drug products is generally a more stable presentation, wherein, for example, lyophilized drug products are more resistant to stress experienced during the distribution process of pharmaceutical drug products (e.g., during the packaging, transportation and / or storage of pharmaceutical drug products). In fact, lyophilization has been described as "a method of choice for long-term storage of monoclonal antibodies because lyophilized antibodies are much more stable than they are in solution". See Johnson, M., "Antibody Storage and Antibody Shelf Life," Mater. Methods 2012, 2: 120 (available online at labome.com; DOI: / / dx.doi.org / 10.13070 / mm.en.2.120). However, when the inventors prepared lyophilized formulations of the humanized anti-N3pGlu antibodies discussed herein and subjected them to physical stresses designed to simulate a global distribution shipping environment (e.g., the ISTA 3A shipping assessment, the details of which are known to those of ordinary skill in the art and available through the International Safe Transit Association at ista.org), it was found that the lyophilized formulations exhibited certain undesirable properties such as protein aggregation and instability of the lyophilized cake.

[0010] In an exemplary experiment, a vial containing a lyophilized formulation of an anti-N3pGlu antibody discussed herein was prepared. The vial initially contained a complete lyophilized cake, and there was no powder at the vial shoulder. After being subjected to the physical stress designed to simulate a global distribution transportation environment, these vials showed shrunken lyophilized cake and / or broken lyophilized cake and powder at the vial shoulder, which is considered as an undesirable property.

[0011] In another exemplary experiment, the lyophilized formulation of the anti-N3pGlu antibody discussed herein was prepared and placed in a vial, and the vial was subjected to a physical stress designed to simulate a global distribution transportation environment. The vials were stored at -20°C, 5°C, 25°C and 40°C, and samples were regularly obtained, reconstituted with water for injection, and analyzed for sub-visible particles (SVP) by microfluidic imaging (MFI). Relative to samples from vials that were not subjected to physical stress, samples from vials subjected to physical stress designed to simulate a global distribution transportation environment consistently displayed higher levels of SVP (particle size greater than or equal to 2 μm to 5 μm) after 1 month (and all subsequent measured time points). Again, these properties are considered undesirable. In addition, samples of lyophilized formulations confirmed aggregation, a problem that is usually aggravated by one or more of, for example, transportation stress, freeze-thaw stress and solubility constraints.

[0012] The properties discussed above make lyophilized formulations undesirable for several important reasons. For example, potential changes to the drug material due to reduced cake stability or increased aggregation may affect the solubility of the drug, which in turn affects the accuracy and consistency of the dose delivered to the patient. Such issues present significant challenges to delivering the intended therapeutic dose to the patient.

[0013] Therefore, there is a need for a pharmaceutical composition comprising an antibody of the present disclosure, which provides improved stability suitable for manufacture, distribution, storage and administration to patients for the expected therapeutic benefit. The present disclosure meets this need by providing a pharmaceutical solution of an anti-N3pGlu Aβ antibody with improved properties. For example, various aspects of the present disclosure relate to the development of a pharmaceutical solution comprising an antibody, which exhibits improved stability over time during storage. The improved stability over time during storage is a surprising result associated with the disclosed embodiments of the pharmaceutical solution. In fact, the art teaches that sufficient stability of biomolecules is often not achieved in a liquid state. See Langford, A., et al., "Drying Technologies for Biotechnology and Pharmaceutical Applications" (Introduction), Wiley (2020). For example, it was previously believed that freeze-drying rather than aqueous solution formulations was the method of choice for long-term storage of monoclonal antibodies because freeze-dried antibodies were much more stable than they were in solution. See Johnson, M., "Antibody Storage and Antibody Shelf Life," Mater. Methods 2012, 2: 120. In addition, Langford et al. explain that in aqueous solution, water acts as a medium that causes significant molecular mobility and conformational perturbations, and acts as a catalyst for chemical degradation that can promote instability during storage and transportation. Therefore, contrary to conventional wisdom in the art, aspects of the present disclosure are directed to pharmaceutical solutions that exhibit improved stability, including improved stability over a period of weeks, months, or years when stored at 5°C to 35°C, such as at 5°C, 25°C, or 35°C. Aspects of the present disclosure also relate to pharmaceutical solutions suitable for administration to human patients for the treatment or prevention of diseases, including but not limited to Alzheimer's disease.

[0014] Accordingly, aspects of the present disclosure relate to pharmaceutical solutions comprising antibodies of the present disclosure, buffers, tonicity agents, surfactants, and optional excipients. Aspects of the present disclosure also relate to pharmaceutical solutions comprising antibodies of the present disclosure, buffers, tonicity agents, surfactants, and optional excipients that exhibit improved antibody stability, improved solution stability, improved solution purity, improved antibody solubility, and suitability for an expected therapeutic benefit, one or more.

[0015] Aspects of the present disclosure also relate to pharmaceutical solutions comprising an antibody of the present disclosure, a buffer, a tonicity agent, a surfactant, and an optional excipient, which are suitable as a drug product for administration to a patient. Aspects of the present disclosure also relate to pharmaceutical solutions comprising an antibody of the present disclosure, one or more buffers, one or more tonicity agents, one or more surfactants, and one or more optional excipients, wherein the pharmaceutical solution exhibits one or more of reduced hydrolysis of polyoxyethylene (20) sorbitan monooleate, reduced oxidation of polyoxyethylene (20) sorbitan monooleate, reduced levels of free oleic acid and / or total oleic acid, and reduced levels of free radicals.

[0016] Pharmaceutical solutions of the antibodies disclosed herein can be used to treat diseases characterized by Aβ deposition, including but not limited to diseases such as Alzheimer's disease (AD) (including but not limited to preclinical AD, prodromal AD, mild AD, moderate AD and severe AD), Down syndrome and cerebral amyloid angiopathy. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1A Depicted are the changes in the percentage of the main peak from the initial time, as measured by size exclusion chromatography (SEC), for different exemplary drug solutions.

[0019] Figure 1B Depicted are the changes in the percentage of high molecular weight species (% HMW) from an initial time, as measured by size exclusion chromatography, for different exemplary drug solutions.

[0020] FIG. 1C depicts the variation in the percentage of low molecular weight species (%LMW) as measured by size exclusion chromatography for different exemplary drug solutions.

[0021] Figure 2A Depicted are the differences (Δ) in % donetumab as measured by non-reducing capillary electrophoresis-sodium dodecyl sulfate (CE-SDS) for different exemplary drug solutions.

[0022] Figure 2B Depicted are the differences (Δ) in maximum % related species ("RS") as measured by non-reducing CE-SDS chromatography for different exemplary drug solutions.

[0023] Figure 3 Depicted are the differences (Δ) in purity as measured by reducing capillary electrophoresis-sodium dodecyl sulfate (CE-SDS) for different exemplary drug solutions as a function of temperature and time.

[0024] Figure 4A Depicted are the results for particles ≥ 10 μm in particles / mL as measured by light obscuration for various exemplary drug solutions.

[0025] Figure 4B Depicted are the results for particles ≥ 25 μm in particles / mL as measured by light obscuration for various exemplary drug solutions.

[0026] Figure 5A Depicted are the % main peak (monomer) results from freeze-thaw experiments for different exemplary drug solutions with various amounts of polysorbate, as measured by size exclusion chromatography (SEC).

[0027] Figure 5B Depicted are the % high molecular weight species (% HMW) results from freeze-thaw experiments for different exemplary drug solutions with various amounts of polysorbate, as measured by size exclusion chromatography (SEC).

[0028] Figure 5C Depicted are the % low molecular weight species (% LMW) results from freeze-thaw experiments for different exemplary drug solutions with various amounts of polysorbate, as measured by size exclusion chromatography (SEC).

[0029] Fig. 6A Depicted are the results of particles ≥ 10 μm from freeze-thaw experiments for different exemplary drug solutions with various amounts of polysorbate, as measured by light obscuration.

[0030] Figure 6B Depicted are the results of particles ≥ 25 μm from freeze-thaw experiments for different exemplary drug solutions with various amounts of polysorbate, as measured by light obscuration.

[0031] Fig. 7A Depicted are the % main peak (monomer) results from agitation experiments for different exemplary drug solutions with various amounts of polysorbate, as measured by size exclusion chromatography (SEC).

[0032] Figure 7B Depicted are the % high molecular weight species (% HMW) results from agitation experiments for different exemplary drug solutions with various amounts of polysorbate, as measured by size exclusion chromatography (SEC).

[0033] Figure 7C Depicted are the % low molecular weight species (% LMW) results from agitation experiments for different exemplary drug solutions with various amounts of polysorbate, as measured by size exclusion chromatography (SEC).

[0034] Figure 8 Depicted are the % intact donetumab results from agitation experiments for different exemplary drug solutions with various amounts of polysorbate as measured by non-reducing capillary electrophoresis-sodium dodecyl sulfate (CE-SDS) data.

[0035] Fig. 9 Depicted are the % purity as measured by reducing capillary electrophoresis-sodium dodecyl sulfate (CE-SDS) from agitation experiments for different exemplary drug solutions with various amounts of polysorbate.

[0036] Fig. 10A Depicted are the results of particles ≥ 10 μm from agitation experiments for different exemplary drug solutions with various amounts of polysorbate, as measured by light obscuration.

[0037] Fig. 10B Depicted are the results of particles ≥ 25 μm from agitation experiments for different exemplary drug solutions with various amounts of polysorbate, as measured by light obscuration.

[0038] Fig.11A A sample of an exemplary drug solution at initial time zero is depicted.

[0039] Fig. 11B Depicted is the storage at -5°C for 24 hours. Fig.15 A sample of an exemplary drug solution.

[0040] Fig. 12A Depicted are size exclusion chromatography (SEC) data (monomer content) for various exemplary drug solutions.

[0041] Fig. 12B Depicted are size exclusion chromatography (SEC) data (total aggregate content) for different exemplary drug solutions.

[0042] Fig.13A Reducing CE-SDS data (% purity) for different exemplary drug solutions are depicted.

[0043] Fig. 13B Reducing CE-SDS data (% total aggregate) for different exemplary drug solutions are depicted.

[0044] Fig.14A Non-reducing CE-SDS data (% purity) for different exemplary drug solutions are depicted.

[0045] Fig. 14B Non-reducing CE-SDS data (% total aggregate) for different exemplary drug solutions are depicted.

[0046] Fig.15 Depicted are free oleic acid (%FOA) data as measured by HPLC-UV for various exemplary drug solutions.

[0047] Fig.16ADepicted are subvisible particles ≥ 2 μm results in particles / mL as measured by microfluidics imaging (MFI) for different exemplary drug solutions.

[0048] Fig. 16B Depicted are subvisible particles ≥ 5 μm results in particles / mL as measured by microfluidics imaging (MFI) for different exemplary drug solutions.

[0049] Fig.17A Depicted are subvisible particles ≥ 2 μm results in particles / mL as measured by light obscuration for various exemplary drug solutions.

[0050] Fig. 17B Depicted are subvisible particles ≥ 5 μm results in particles / mL as measured by light obscuration for various exemplary drug solutions.

[0051] Fig. 17C Particle matter ≥ 10 μm results in particles / mL as measured by light obscuration are depicted for different exemplary drug solutions.

[0052] Fig.17D Depicted are the >25 μm results in particles / mL as measured by light obscuration for various exemplary drug solutions.

[0053] Fig.18A Depicted are the >10 μm results as particles / container as measured by light obscuration for various exemplary drug solutions.

[0054] Fig.18B Depicted are the > 25 μm results as particles / container as measured by light obscuration for various exemplary drug solutions.

[0055] Fig.19A Depicted are subvisible particles ≥ 2 μm results in particles / mL as measured by microfluidics imaging (MFI) for various exemplary drug solutions subjected to ISTA-3A transport testing.

[0056] Fig.19B Depicted are subvisible particles ≥ 5 μm results in particles / mL as measured by microfluidics imaging (MFI) for various exemplary drug solutions subjected to ISTA-3A transport testing.

[0057] Fig. 20A Depicted are the results for particulate matter ≥ 10 μm in particles / mL as measured by light obscuration for various exemplary drug solutions subjected to ISTA-3A transport testing.

[0058] Fig. 20BDepicted are the results for particulate matter ≥ 25 μm in particles / mL as measured by light obscuration for various exemplary drug solutions subjected to ISTA-3A transport testing.

[0059] Fig.21A Depicted are the % monomer as measured by size exclusion chromatography (SEC) for various exemplary drug solutions subjected to ISTA-3A transport testing.

[0060] Fig.21B Depicted are the % total aggregates as measured by size exclusion chromatography data (SEC) for various exemplary drug solutions subjected to ISTA-3A transport testing.

[0061] Fig.22A Depicted are the % purity as measured by non-reducing capillary electrophoresis-sodium dodecyl sulfate (CE-SDS) for various exemplary drug solutions subjected to ISTA-3A transport testing.

[0062] Fig. 22B Depicted are the % total fragments as measured by non-reducing capillary electrophoresis-sodium dodecyl sulfate (CE-SDS) for various exemplary drug solutions subjected to ISTA-3A transport testing.

[0063] Fig. 22C Depicted are the % total aggregates as measured by non-reducing capillary electrophoresis-sodium dodecyl sulfate (CE-SDS) for various exemplary drug solutions subjected to ISTA-3A transport testing.

[0064] Fig.23A Depicted are the % monomer as measured by size exclusion chromatography (SEC) for various exemplary drug solutions.

[0065] Fig. 23B Depicted are the % total aggregates as measured by size exclusion chromatography (SEC) for various exemplary drug solutions.

[0066] Fig.24A Depicted are the % purity as measured by reducing CE-SDS for different exemplary drug solutions.

[0067] Fig. 24B Depicted are the % total fragments as measured by reducing CE-SDS for different exemplary drug solutions.

[0068] Fig.24C Depicted are the % total aggregates as measured by reducing CE-SDS for different exemplary drug solutions.

[0069] Fig.25ADepicted are the % purity as measured by non-reducing CE-SDS for different exemplary drug solutions.

[0070] Fig.25B Depicted are the % total fragments as measured by non-reducing CE-SDS for different exemplary drug solutions.

[0071] Fig.25C Depicted are the % total aggregates as measured by non-reducing CE-SDS for different exemplary drug solutions.

[0072] Fig.26A Depicted are the total oleic acid content as measured by HPLC-UV for different exemplary drug solutions.

[0073] Fig.26B Depicted are the free oleic acid content as measured by HPLC-UV for different exemplary drug solutions.

[0074] Fig.27A Depicted are subvisible particles ≥ 2 μm results in particles / mL as measured by microfluidics imaging (MFI) for different exemplary drug solutions.

[0075] Fig.27B Depicted are subvisible particles ≥ 5 μm results in particles / mL as measured by microfluidics imaging (MFI) for different exemplary drug solutions.

[0076] Fig.28A Depicted are subvisible particles ≥ 2 μm results in particles / mL as measured by light obscuration for various exemplary drug solutions.

[0077] Fig.28B Depicted are subvisible particles ≥ 5 μm results in particles / mL as measured by light obscuration for various exemplary drug solutions.

[0078] Fig.28C Particle matter ≥ 10 μm results in particles / mL as measured by light obscuration are depicted for various exemplary drug solutions.

[0079] Fig.28D Particle matter ≥ 25 μm results in particles / mL as measured by light obscuration are depicted for various exemplary drug solutions.

[0080] Fig.29A Particle matter ≥ 10 μm results as particles / container as measured by light obscuration are depicted for various exemplary drug solutions.

[0081] Fig.29BParticle matter ≥ 25 μm results as particles / container as measured by light obscuration are depicted for various exemplary drug solutions.

[0082] Details

[0083] The disclosed compositions and methods may be understood more readily by reference to the following detailed description taken in conjunction with the accompanying drawings which form a part of this disclosure.

[0084] According to the present disclosure, a pharmaceutical solution of an antibody is provided. As used herein, the term "drug" refers to a composition (e.g., solution) that is suitable for contact with tissues of a subject (e.g., a human being) within the scope of reasonable medical judgment, without excessive toxicity, stimulation, allergic response, and / or other problems or complications, commensurate with a reasonable benefit / risk ratio. In some embodiments of a pharmaceutical solution according to the present disclosure, the pharmaceutical solution comprises an aqueous medium. Exemplary aqueous media include water such as water for injection and saline. The aqueous medium may include one or more buffers as discussed elsewhere herein. In some embodiments of a pharmaceutical solution according to the present disclosure, the pharmaceutical solution contains undissolved particles.

[0085] In some embodiments, a pharmaceutical solution of an antibody comprises an antibody, a buffer, a tonicity agent, a surfactant, and optionally an excipient.

[0086] In some embodiments, the antibody is present in a pharmaceutical solution according to the present disclosure at a concentration of 0.1 mg / mL to 1,000 mg / mL, such as about 1 mg / mL to about 500 mg / mL, about 1 mg / mL to about 300 mg / mL, about 1 mg / mL to about 150 mg / mL, about 1 mg / mL to about 100 mg / mL, about 1 mg / mL to about 50 mg / mL, about 1 mg / mL to about 40 mg / mL, about 100 mg / mL to about 300 mg / mL (e.g., 200 mg / mL), about 150 mg / mL to about 250 mg / mL, about 125 mg / mL to about 275 mg / mL, about 5 mg / mL to about 75 mg / mL, about 5 mg / mL to about 50 mg / mL, about 10 As used herein, the term "about" refers to a difference of ±10% of the value in some embodiments, a difference of ±5% of the value in some embodiments, or a difference of ±1% of the value in some embodiments.

[0087] In some embodiments, the antibody is present in a pharmaceutical solution according to the present disclosure at a concentration of 16.0 mg / mL to 19.0 mg / mL. In some embodiments, the antibody is present in a pharmaceutical solution according to the present disclosure at a concentration of 16.28 mg / mL to 18.73 mg / mL. In some embodiments, the antibody is present in a pharmaceutical solution according to the present disclosure at a concentration of 16.63 mg / mL to 18.38 mg / mL.

[0088] Humanized monoclonal anti-N3pGlu antibodies disclosed herein can be used to prepare pharmaceutical solutions of antibodies according to the present disclosure. In some embodiments, the pharmaceutical solution of the antibody is purified by the monoclonal anti-N3pGlu antibody prepared therefrom. In some embodiments, the pharmaceutical solution of the antibody is purified by the monoclonal anti-N3pGlu antibody prepared therefrom, and has been subjected to one or more purification schemes (i.e., schemes for purifying monoclonal antibodies) as described in the U.S. Department of Health and Human Services (USDepartment of Health and Human Services), the U.S. Food and Drug Administration (Food and Drug Administration), and the Center for Biologics Evaluation and Research (Center for Biologics Evaluation and Research) (February 28, 1997) "Points to Consider in the Manufacture and Testing of Monoclonal Antibody Products for Human Use". For example, in some embodiments, the purification scheme includes one or more of the following: (a) production techniques that prevent the introduction of and / or eliminate contaminants, including but not limited to animal proteins and materials, DNA, endotoxins, pyrogens, media components, components that may leach from the column, and viruses; (b) the incorporation of one or more steps known to remove or inactivate retroviruses in excess of the endogenous particle load (where applicable), including but not limited to one or more robust viral removal / inactivation procedures that have been shown to work well with a variety of monoclonal antibodies under a variety of conditions (e.g., pH or ionic strength of the column buffer) (e.g., low pH, heat, solvent and / or detergent treatment, and filtration); (c) confirmation of the ability of the purification scheme to remove adventitious agents and other contaminants by means of clearance studies; (d) pre-set limits on the number of times a purification component (e.g., a chromatography column) can be reused; (e) storage of retain samples from each production run so that side-by-side comparisons can be made to determine product comparability; and (f) a description of the design features of the cleanroom, HVAC, and other supporting systems, equipment, transfers, and personnel.

[0089] In some embodiments, the pharmaceutical solution of antibody from which the monoclonal anti-N3pGlu antibody is prepared has been purified to be free of non-immunoglobulin (Ig) contaminants or to contain less than 5% by weight of non-Ig contaminants, less than 4% by weight of non-Ig contaminants, less than 3% by weight of non-Ig contaminants, less than 2% by weight of non-Ig contaminants, or less than 1% by weight of non-Ig contaminants. In some embodiments, the pharmaceutical solution of antibody from which the monoclonal anti-N3pGlu antibody is prepared is not fragmented, not aggregated, and / or is not otherwise modified (e.g., by the loss of carbohydrate side chains).

[0090] In some embodiments, the pharmaceutical solution of the antibody from which the monoclonal anti-N3pGlu antibody is prepared has been subjected to tests for one or more of the following: (a) protein quantity; (b) potency; (c) purity (e.g., as determined by electrophoretic migration of the antibody in both native and reduced states on polyacrylamide gels, with comparison to a reference standard); (d) sterility; (e) one or more tests for endotoxin (e.g., Limulus amebocyte lysate (LAL) assay); (f) identity testing; (g) moisture, as appropriate; (h) preservatives, as appropriate; (i) excipients, as appropriate; and (j) pH, as appropriate.

[0091] In some embodiments, the monoclonal anti-N3pGlu antibody prepared by the pharmaceutical solution of the antibody has been subjected to one or more tests for stability. For example, in some embodiments, the monoclonal anti-N3pGlu antibody prepared by the pharmaceutical solution of the antibody has been subjected to a stability testing program, which includes tests on one or more of the following: (a) physicochemical integrity (e.g., fragmentation and / or aggregation), (b) efficacy, (c) sterility, (d) moisture (when appropriate); (e) pH (when appropriate); and (f) preservation stability (when appropriate). In some embodiments, the monoclonal anti-N3pGlu antibody prepared by the pharmaceutical solution of the antibody is subjected to one or more tests for ensuring biological activity (e.g., quantitative in vitro efficacy determination).

[0092] Antibodies against N3pGlu Aβ are known in the art and have applications in treating or preventing diseases. One of ordinary skill in the art will appreciate and recognize that anti-N3pGlu Aβ antibodies are identified and disclosed in U.S. Patent No. 8,679,498B2 (which is incorporated herein by reference in its entirety) (together with methods for preparing and using such antibodies). For example, Donetomab disclosed in U.S. Patent No. 8,679,498 is an antibody modified with pyroglutamate of the third amino acid of the amyloid protein β (N3pGlu Aβ) epitope present only in brain amyloid plaques. As used herein, "donetuzumab" refers to an anti-N3pGlu Aβ antibody comprising a light chain variable region (LCVR), wherein the LCVR comprises SEQ ID NO: 1, a heavy chain variable region (HCVR), wherein the HCVR comprises SEQ ID NO: 2, a light chain (LC), wherein the LC consists of SEQ ID NO: 3, a heavy chain (HC), wherein the HC consists of SEQ ID NO: 4, a light chain complementary determining region 1 (LCDR1) of SEQ ID NO: 5, a light chain complementary determining region 2 (LCDR2) of SEQ ID NO: 6, a light chain complementary determining region 3 (LC DR3) of SEQ ID NO: 7, a heavy chain complementary determining region 1 (HCDR 1) of SEQ ID NO: 8, a heavy chain complementary determining region 2 (HCDR2) of SEQ ID NO: 9, and a heavy chain complementary determining region 3 (HCDR3) of SEQ ID NO: 10.

[0093] In some embodiments, the antibody is an anti-N3pGlu Aβ IgG antibody with a kappa light chain. In some embodiments, the anti-N3pGlu Aβ antibody comprises a kappa light chain and an IgG heavy chain. In some embodiments, the anti-N3pGlu Aβ antibody is of human IgG 1 isotype. In some embodiments, the antibody is an anti-N3pGlu Aβ antibody comprising a LCVR and a HCVR, wherein the LCVR comprises LCDR 1 of SEQ ID NO: 5, LCDR2 of SEQ ID NO: 6, and LCDR3 of SEQ ID NO: 7, and the HCVR comprises HCDR 1 of SEQ ID NO: 8, HCDR2 of SEQ ID NO: 9, and HCDR3 of SEQ ID NO: 10. In some embodiments, the antibody comprises a LCVR, wherein the LCVR comprises SEQ ID NO: 1, and / or a HCVR, wherein the HCVR comprises SEQ ID NO: 2. In some embodiments, the antibody comprises a LC, wherein the LC comprises SEQ ID NO: 3, and / or a HC, wherein the HC comprises SEQ ID NO: 4. In some embodiments, the antibody comprises a LCVR, wherein the LCVR consists of SEQ ID NO: 1, and / or a HCVR, wherein the HCVR consists of SEQ ID NO: 2. In some embodiments, the antibody comprises a LC, wherein the LC consists of SEQ ID NO: 3, and / or a HC, wherein the HC consists of SEQ ID NO: 4.

[0094] In some embodiments of the pharmaceutical solution according to the present disclosure, the antibody is a humanized anti-N3pGlu antibody. For example, in one embodiment, a pharmaceutical solution comprising an anti-N3pGlu Aβ antibody, a buffer, a tonicity agent, a surfactant, and an optional excipient is disclosed herein. In addition, for example, in one embodiment, a pharmaceutical solution comprising an anti-N3pGlu Aβ antibody, a buffer, a tonicity agent, a surfactant, and an optional excipient is disclosed herein, wherein the pH is 5.0 to 7.5.

[0095] As used herein, an "optional excipient" is an agent that can be included in a pharmaceutical solution according to the present disclosure within the scope of reasonable judgment, wherein when included in the pharmaceutical solution, the agent is suitable for contact with the tissue of a subject (e.g., a human) without excessive toxicity, irritation, allergic response and / or other problems or complications, commensurate with a reasonable benefit / risk ratio, and wherein the agent has properties other than those of a "buffer", "tonicity agent" and / or "surfactant", but not necessarily excluding these properties, as these terms are defined elsewhere herein. Non-limiting examples of optional excipients include, for example, agents disclosed in Remington: The Science and Practice of Pharmacy, 22nd Edition, Lippincott Williams & Wilkins, Philadelphia, PA. (2013) and / or other versions thereof. For example, non-limiting examples of excipients include diluents, binders, disintegrants, controlled release agents, emulsifiers, encapsulating agents, and coating agents.

[0096] It should be understood that lyophilized antibodies can be used to prepare pharmaceutical solutions according to the present disclosure. However, it should also be understood that in some embodiments of pharmaceutical solutions according to the present disclosure, antibodies that are not lyophilized or have never been lyophilized are used to prepare pharmaceutical solutions. In some embodiments of pharmaceutical solutions according to the present disclosure, the antibodies in the pharmaceutical solutions are not reconstituted by lyophilized materials.

[0097] In some embodiments of the pharmaceutical solution according to the present disclosure, the total concentration of the buffer is 0.1 mM to 1,000 mM, for example, about 1 mM to about 1,000 mM, about 10 to about 1,000 mM, about 10 mM to about 100 mM, about 100 mM to about 250 mM, about 175 mM to about 225 mM, about 5 mM to about 50 mM, about 10 mM to about 75 mM, about 75 mM to about 175 mM, about 10 mM to about 250 mM, about 1 mM to about 100 mM, about 1 mM to about 50 mM, about 1 mM to about 40 mM, about 1 mM to about 30 mM (e.g., 10 mM), about 2.5 mM to about 100 mM (e.g., 5 mM), about 3 mM to about 75 mM, 3 mM to 50 mM, about 5 mM to about 25 mM, about 5 mM to about 15 mM, about 2.5 mM to about 25 mM, about 5 mM to about 10 mM, about 2.5 mM to about 15 mM, or about 3 mM to about 12 mM.

[0098] In some embodiments, the pharmaceutical solution of the present disclosure comprises an anti-N3pGlu Aβ antibody at a concentration of 1 to 40 mg / mL, the anti-N3pGlu Aβ antibody comprising (a) a light chain variable region (LCVR) comprising LCDR1 of SEQ ID NO: 5, LCDR2 of SEQ ID NO: 6, LCDR3 of SEQ ID NO: 7, and (b) a heavy chain variable region (HCVR) comprising HCDR1 of SEQ ID NO: 8, HCDR2 of SEQ ID NO: 9, and HCDR3 of SEQ ID NO: 10, a buffer in an amount of 1 mM to 30 mM, a tonicity agent in an amount of 1% to 20% by volume (w / v), a surfactant in an amount of 0.005% to 0.06% by volume, and optional excipients. In some embodiments, the LCVR of the anti-N3pGlu Aβ antibody comprises SEQ ID NO: 1, and / or the HCVR of the anti-N3pGlu Aβ antibody comprises SEQ ID NO: 2. In some embodiments, the anti-N3pGlu A[beta] antibody comprises a light chain (LC) comprising SEQ ID NO:3, and / or a heavy chain (HC) comprising SEQ ID NO:4.

[0099] As used herein, it is understood that a "buffer" is an agent that acts to regulate the pH of a composition, but a "buffer" may also provide other functions in the composition (e.g., affecting the tonicity of the composition). In some embodiments, a "buffer" may be a "buffer system". As used herein, the term "single buffer system" is understood to refer to an agent that acts to regulate the pH of a composition, wherein the agent comprises two or more components, such as an acidic compound and its conjugate base. A representative, non-limiting example of a single buffer system is benzoic acid, which may be present in solution as a combination of benzoic acid and a benzoate anion.

[0100] In some embodiments of the pharmaceutical solution according to the present disclosure, the buffer comprises an organic acid, an inorganic acid, an amino acid and a combination thereof. In some embodiments of the pharmaceutical solution according to the present disclosure, the buffer comprises an organic acid salt, an inorganic acid salt and an amino acid and a combination thereof. The non-limiting examples of organic acids include citric acid, acetic acid, ascorbic acid, carbonic acid, tartaric acid, gluconic acid, succinic acid, phthalic acid, fumaric acid, malic acid, maleic acid, glutamic acid, benzoic acid, salicylic acid, toluenesulfonic acid, methanesulfonic acid, stearic acid and lactic acid. The non-limiting examples of inorganic acids include hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid and sulfuric acid. The non-limiting examples of amino acids include arginine, lysine, histidine, ornithine, isoleucine, leucine, alanine, glycine, glutamic acid, aspartic acid. In some embodiments of the pharmaceutical solution according to the present disclosure, the buffer comprises citric acid or a salt thereof, acetic acid or a salt thereof, ascorbic acid or a salt thereof, carbonic acid or a salt thereof, tartaric acid or a salt thereof, gluconic acid or a salt thereof, succinic acid or a salt thereof, phosphoric acid or a salt thereof, phthalic acid or a salt thereof, arginine or a salt thereof, lysine or a salt thereof, histidine or a salt thereof, ornithine or a salt thereof, isoleucine or a salt thereof, leucine or a salt thereof, alanine or a salt thereof, glycine or a salt thereof, glutamic acid or a salt thereof and aspartic acid or a salt thereof. In some embodiments, the buffer comprises citric acid or a salt thereof and histidine or a salt thereof. In some embodiments, the buffer is a buffer system as the term is defined elsewhere herein.

[0101] In some embodiments of the pharmaceutical solutions according to the present disclosure, the total amount of one or more tonicity agents is from 0.01% w / v to about 30% w / v, e.g., from about 1% w / v to about 20% w / v, from about 1% w / v to about 15% w / v, from about 5% w / v to about 15% w / v (e.g., 8% w / v), from about 1% w / v to about 10% w / v, from about 5% w / v to about 10% w / v, or from about 3% w / v to about 10% w / v. In some embodiments of the pharmaceutical solutions according to the present disclosure, the total amount of one or more tonicity agents is from 0.01 mM to about 1,000 mM, for example, from about 1 mM to about 500 mM, from about 1 mM to about 300 mM, from about 1 mM to about 250 mM, from about 50 mM to about 300 mM, from about 50 mM to about 150 mM, from about 100 mM to about 200 mM, from about 50 mM to about 200 mM, from about 1 mM to about 25 mM, from about 50 mM to about 200 mM, from about 1 mM to about 25 mM, from about 50 mM to about 200 mM, from about 2.5 mM to about 15 mM, from about 2.5 mM to about 25 mM, or from about 75 mM to about 175 mM.

[0102] As used herein, it is understood that a "tonicity agent" is an agent that affects the osmotic pressure of a composition, although a "tonicity agent" may also provide other functions in the composition (eg, buffering the pH of the composition).

[0103] In some embodiments of the pharmaceutical solution according to the present disclosure, the tonicity agent is selected from sugar, amino acid, salt and combination thereof. In some embodiments, the tonicity agent is selected from monosaccharide, disaccharide, polysaccharide and combination thereof. In some embodiments, the tonicity agent is selected from sodium chloride, arginine or its salt, lysine or its salt, histidine or its salt, methionine or its salt, ornithine or its salt, isoleucine or its salt, leucine or its salt, alanine or its salt, glycine or its salt, glutamic acid, aspartic acid, sucrose, fructose, glucose, maltose, trehalose, galactose, mannose, sorbose, lactose, cellobiose, mannitol, lactitol, xylitol, sorbitol, maltitol and combination thereof. In some embodiments, the tonicity agent is sodium chloride. In some embodiments, the tonicity agent is sucrose. In some embodiments, the pharmaceutical solution of the antibody comprises a single tonicity agent.

[0104] As used herein, it is understood that a "surfactant" is an agent that reduces the surface tension of an aqueous composition, but a "surfactant" may also provide other functions in the composition (e.g., buffering the pH of the composition). In some embodiments of the pharmaceutical solution according to the present disclosure, the surfactant is selected from polyoxyethylene sorbitan esters, poloxamers, and combinations thereof. In some embodiments, the surfactant is selected from polyoxyethylene (20) sorbitan monolaurate, polyoxyethylene (20) sorbitan monopalmitate, polyoxyethylene (20) sorbitan monostearate, polyoxyethylene (20) sorbitan monooleate, poloxamer 188, and combinations thereof. In some embodiments, the surfactant is selected from polyoxyethylene (20) sorbitan monolaurate, polyoxyethylene (20) sorbitan monopalmitate, polyoxyethylene (20) sorbitan monostearate, polyoxyethylene (20) sorbitan monooleate, poloxamer, and combinations thereof. In some embodiments, the surfactant is polyoxyethylene (20) sorbitan monooleate.

[0105] In some embodiments of the pharmaceutical solution according to the present disclosure, the surfactant is present in an amount of about 0.001% by volume to about 10% by volume, for example, about 0.001% by volume to about 1% by volume, about 0.005% by volume to about 0.03% by volume (e.g., 0.005% by volume to 0.030% by volume), about 0.005% by volume to about 0.1% by volume, about 0.01% by volume to about 0.5% by volume, about 0.01% by volume to about 0.25% by volume, about 0.01% by volume to about 0.20% by volume, about 0.01% by volume In some embodiments of the pharmaceutical solution of the present disclosure, the surfactant is present in an amount of about 0.04% by volume.

[0106] In some embodiments, the pharmaceutical solution according to the present disclosure does not include one or more of sodium chloride, trehalose, and mannitol. In some embodiments, the pharmaceutical solution according to the present disclosure does not include one or more of glycine, poloxamer (e.g., poloxamer 188), and polyoxyethylene (20) sorbitan monolaurate.

[0107] In some embodiments of the pharmaceutical solution according to the present disclosure, the pH of the solution is 4.0 to 10.0, for example 5.0 to 9.0, 5.0 to 8.0, 5.0 to 7.5, 5.0 to 7.0, 5.2 to 6.4, 5.3 to 6.3, 5.5 to 7.5, 5.5 to 6.5, 5.75 to 6.25, 5.8 to 6.2, or 5.9 to 6.1. In some embodiments, the pH of the solution is 4.0, 4.5, 5.0, 5.5, 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5, or 10.0. In some embodiments, the pH of the solution is 5.3, 5.4, 5.5, 5.6, 5.7, 5.8, 5.9, 6.0, 6.1, 6.2, 6.3, 6.4, or 6.5.

[0108] In some embodiments of the pharmaceutical solution according to the present disclosure, the pH of the solution is about 4.0 to about 10.0, such as about 5.0 to about 9.0, about 5.0 to about 7.5, about 5.0 to about 7.0, about 5.2 to about 6.4, about 5.5 to about 7.5, about 5.5 to about 6.5, about 5.75 to about 6.25, about 5.8 to about 6.2, or about 5.9 to about 6.1. In some embodiments, the pH of the solution is about 4.0, about 4.5, about 5.0, about 5.5, about 6.0, about 6.5, about 7.0, about 7.5, about 8.0, about 8.5, about 9.0, about 9.5, or about 10.0. In some embodiments, the pH of the solution is about 5.3, about 5.4, about 5.5, about 5.6, about 5.7, about 5.8, about 5.9, about 6.0, about 6.1, about 6.2, about 6.3, about 6.4, or about 6.5.

[0109] In some embodiments, the pH of a pharmaceutical solution according to the present disclosure is maintained at one or more pH values ​​or ranges described herein using one or more buffers described herein.

[0110] In some embodiments, the present disclosure encompasses a pharmaceutical solution comprising an anti-N3pGlu Aβ antibody at a concentration of 1 to 40 mg / mL, the anti-N3pGlu Aβ antibody comprising (a) a light chain variable region (LCVR) comprising LCDR1 of SEQ ID NO: 5, LCDR2 of SEQ ID NO: 6, LCDR3 of SEQ ID NO: 7, and (b) a heavy chain variable region (HCVR) comprising HCDR1 of SEQ ID NO: 8, HCDR2 of SEQ ID NO: 9, and HCDR3 of SEQ ID NO: 10, a buffer in an amount of 1 mM to 30 mM, a tonicity agent in an amount of 1% to 20% by volume, a surfactant in an amount of 0.005% to 0.06% by volume, and optional excipients.

[0111] In some embodiments, the present disclosure encompasses a pharmaceutical solution comprising an anti-N3pGluAβ antibody at a concentration of 17.5 mg / mL, a buffer comprising citric acid or a salt thereof in an amount of 10 mM; a tonicity agent comprising sucrose in an amount of 8% w / v; and a surfactant comprising polyoxyethylene (20) sorbitan monooleate in an amount of 0.02% w / v; wherein the anti-N3pGluAβ comprises the LCVR of SEQ ID NO: 1 and / or the HCVR of SEQ ID NO: 2; wherein, optionally, the anti-N3pGluAβ comprises the LC of SEQ ID NO: 3 and / or the HC of SEQ ID NO: 4.

[0112] In some embodiments of the pharmaceutical solution according to the present disclosure, the pharmaceutical solution comprises no more than 0.12 EU / mg bacterial endotoxins as determined according to Chapter 2.6.32 of the European Pharmacopeia (Ph. Eur.).

[0113] In some embodiments of the pharmaceutical solution according to the present disclosure, the pharmaceutical solution has an osmotic pressure of not less than 255 mOsm / kg and not more than 345 mOsm / kg, as described in accordance with Chapter 2.2.35 of the European Pharmacopoeia (Ph. Eur.) and / or USP <785> Sure.

[0114] In some embodiments of the pharmaceutical solution according to the present disclosure, the pharmaceutical solution has a color that is not more intensely colored than color standard Y3, BY3 or B3, as determined according to Chapter 2.2.2 of the European Pharmacopoeia (Ph. Eur.).

[0115] In some embodiments of the pharmaceutical solution according to the present disclosure, the pharmaceutical solution has a transparency of no more than 60 NTU (nephelometric turbidity units), as determined according to Chapter 2.2.1 of the European Pharmacopoeia (Ph. Eur.).

[0116] In some embodiments, as used herein, the term "about" refers to any value within 10% of the stated value. In some embodiments, the term "about" refers to any value within 5% of the stated value. In some embodiments, the term "about" refers to any value within 1% of the stated value.

[0117] In some embodiments of the pharmaceutical solution according to the present disclosure, the pharmaceutical solution comprises an anti-N3pGlu Aβ antibody of the present disclosure present at a concentration of about 1 mg / mL to about 300 mg / mL (e.g., about 1 mg / mL to about 75 mg / mL, about 1 mg / mL to about 50 mg / mL, about 1 mg / mL to about 40 mg / mL, about 5 mg / mL to about 30 mg / mL, about 10 mg / mL to about 25 mg / mL, about 150 mg / mL to about 250 mg / mL), an anti-N3pGlu Aβ antibody of the present disclosure present at a concentration of about 1 A buffer present in a concentration of from about 1 mM to about 50 mM (e.g., from about 1 mM to about 30 mM or from about 5 mM to about 15 mM), a tonicity agent present in a total amount of from 1% w / v to 20% w / v (e.g., from about 5% w / v to about 15% w / v), a surfactant present in a total amount of from about 0.005% w / v to 0.1% w / v (e.g., from about 0.005% w / v to about 0.06% w / v or from about 0.01% w / v to about 0.04% w / v), and one or more optional excipients.

[0118] In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 35°C for 3 months, as measured by size exclusion chromatography, the pharmaceutical solution exhibits an antibody monomer content of at least 94% relative to the total antibody peak area. In the context of size exclusion chromatography, percentage refers to peak area percentage (% area). Size exclusion chromatography evaluates the total amount of high molecular weight species (HMW) (also referred to as aggregates) and low molecular weight (LMW) species (fragments) present in the sample. This evaluation is performed by the integration of the elution peak to represent the fractional ratio of each peak of interest to the total integrated peak area (when multiplied by 100, it obtains a percentage, e.g., % total aggregation). In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 25°C for 3 months, as measured by size exclusion chromatography, the pharmaceutical solution exhibits a total antibody monomer content of at least 94% relative to the total antibody peak area. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C for 3 months, the pharmaceutical solution exhibits an antibody monomer content of at least 94% relative to the total antibody peak area, as measured by size exclusion chromatography. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C for 3 months, the pharmaceutical solution exhibits an antibody monomer content of at least 95% relative to the total antibody peak area, as measured by size exclusion chromatography. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C for 3 months, the pharmaceutical solution exhibits an antibody monomer content of at least 96% relative to the total antibody peak area, as measured by size exclusion chromatography. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C for 3 months, the pharmaceutical solution exhibits a total antibody monomer content of at least 97% relative to the total antibody peak area, as measured by size exclusion chromatography. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C for 3 months, the pharmaceutical solution exhibits an antibody monomer content of at least 97.5% relative to the total antibody peak area, as measured by size exclusion chromatography. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C for 29 months, the pharmaceutical solution exhibits an antibody monomer content of at least 95% relative to the total antibody peak area, as measured by size exclusion chromatography. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C for 29 months, the pharmaceutical solution exhibits an antibody monomer content of at least 96% relative to the total antibody peak area, as measured by size exclusion chromatography. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C for 29 months, the pharmaceutical solution exhibits an antibody monomer content of at least 96.0% relative to the total antibody peak area, as measured by size exclusion chromatography.

[0119] In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 3 months, the pharmaceutical solution exhibits an antibody monomer content of at least 94% relative to the total antibody peak area, as measured by size exclusion chromatography. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 3 months, as measured by size exclusion chromatography, the pharmaceutical solution exhibits an antibody monomer content of at least 95% relative to the total antibody peak area. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 3 months, as measured by size exclusion chromatography, the pharmaceutical solution exhibits an antibody monomer content of at least 96% relative to the total antibody peak area. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 3 months, as measured by size exclusion chromatography, the pharmaceutical solution exhibits a total antibody monomer content of at least 97% relative to the total antibody peak area. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 3 months, the pharmaceutical solution exhibits an antibody monomer content of at least 97.5% relative to the total antibody peak area, as measured by size exclusion chromatography. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 29 months, the pharmaceutical solution exhibits an antibody monomer content of at least 95% relative to the total antibody peak area, as measured by size exclusion chromatography. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 29 months, the pharmaceutical solution exhibits an antibody monomer content of at least 96% relative to the total antibody peak area, as measured by size exclusion chromatography. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 29 months, the pharmaceutical solution exhibits an antibody monomer content of at least 96.0% relative to the total antibody peak area, as measured by size exclusion chromatography.

[0120] In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months, the pharmaceutical solution exhibits a total aggregate content of less than 6% relative to the total antibody peak area as measured by size exclusion chromatography. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months, the pharmaceutical solution exhibits a total aggregate content of less than 5% relative to the total antibody peak area as measured by size exclusion chromatography. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 25°C for 3 months, the pharmaceutical solution exhibits a total aggregate content of less than 4% relative to the total antibody peak area as measured by size exclusion chromatography. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C for 29 months, the pharmaceutical solution exhibits a total aggregate content of less than 3% relative to the total antibody peak area as measured by size exclusion chromatography. In some embodiments of the drug solution according to the present disclosure, the drug solution exhibits a total aggregate content of less than 2% relative to the total antibody peak area as measured by size exclusion chromatography after the drug solution has been stored at about 5°C for 3 months.

[0121] In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 29 months, the pharmaceutical solution exhibits a total aggregate content of less than 4% relative to the total antibody peak area as measured by size exclusion chromatography. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 29 months, the pharmaceutical solution exhibits a total aggregate content of less than 3% relative to the total antibody peak area as measured by size exclusion chromatography. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 3 months, the pharmaceutical solution exhibits a total aggregate content of less than 2% relative to the total antibody peak area as measured by size exclusion chromatography.

[0122] In some embodiments of the pharmaceutical solution according to the present disclosure, the pharmaceutical solution comprises polyoxyethylene (20) sorbitan monooleate, and after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months, the pharmaceutical solution exhibits a total oleic acid content of less than 0.03% by volume as measured by high performance liquid chromatography with UV detection (HPLC-UV) using an internal standard. In some embodiments of the pharmaceutical solution according to the present disclosure, the pharmaceutical solution comprises polyoxyethylene (20) sorbitan monooleate, and after the pharmaceutical solution has been stored at about 5°C for 29 months, the pharmaceutical solution exhibits a total oleic acid content of less than 0.03% by volume as measured by high performance liquid chromatography with UV detection (HPLC-UV) using an internal standard. In some embodiments of the pharmaceutical solution according to the present disclosure, the pharmaceutical solution comprises polyoxyethylene (20) sorbitan monooleate, and after the pharmaceutical solution has been stored at about 5° C., about 25° C., or about 35° C. for 3 months, the pharmaceutical solution exhibits a total oleic acid content of 0.01% by volume to 0.03% by volume as measured by high performance liquid chromatography with UV detection (HPLC-UV) using an internal standard. In some embodiments of the pharmaceutical solution according to the present disclosure, the pharmaceutical solution comprises polyoxyethylene (20) sorbitan monooleate, and after the pharmaceutical solution has been stored at about 5° C. for 29 months, the pharmaceutical solution exhibits a total oleic acid content of about 0.01% by volume to about 0.03% by volume as measured by high performance liquid chromatography with UV detection (HPLC-UV) using an internal standard. In some embodiments of the pharmaceutical solution according to the present disclosure, the pharmaceutical solution comprises polyoxyethylene (20) sorbitan monooleate, and after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months, the pharmaceutical solution exhibits a total free oleic acid content of less than about 0.015% by volume as measured by high performance liquid chromatography with UV detection (HPLC-UV) using an internal standard. In some embodiments of the pharmaceutical solution according to the present disclosure, the pharmaceutical solution comprises polyoxyethylene (20) sorbitan monooleate, and after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 29 months, the pharmaceutical solution exhibits a total free oleic acid content of less than about 0.015% by volume as measured by high performance liquid chromatography with UV detection (HPLC-UV) using an internal standard. In some embodiments of the pharmaceutical solution according to the present disclosure, the pharmaceutical solution comprises polyoxyethylene (20) sorbitan monooleate, and the pharmaceutical solution exhibits a total free oleic acid content of less than about 0.005% by weight by volume after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months, as measured by high performance liquid chromatography with UV detection (HPLC-UV) using an internal standard.In some embodiments of the pharmaceutical solution according to the present disclosure, the pharmaceutical solution comprises polyoxyethylene (20) sorbitan monooleate, and after the pharmaceutical solution has been stored at about 5° C. for 29 months, the pharmaceutical solution exhibits a total free oleic acid content of less than 0.0025% by volume as measured by high performance liquid chromatography with UV detection (HPLC-UV) using an internal standard. In some embodiments of the pharmaceutical solution according to the present disclosure, the pharmaceutical solution comprises polyoxyethylene (20) sorbitan monooleate, and after the pharmaceutical solution has been stored at 2-8° C. for 29 months, the pharmaceutical solution exhibits a total free oleic acid content of less than 0.0025% by volume as measured by high performance liquid chromatography with UV detection (HPLC-UV) using an internal standard. In some embodiments of the pharmaceutical solution according to the present disclosure, the pharmaceutical solution comprises polyoxyethylene (20) sorbitan monooleate, and after the pharmaceutical solution has been stored at about 5° C. for 3 months, the pharmaceutical solution exhibits a total free oleic acid content of less than 0.0025% by volume as measured by high performance liquid chromatography with UV detection (HPLC-UV) using an internal standard. In some embodiments of the pharmaceutical solution according to the present disclosure, the pharmaceutical solution comprises polyoxyethylene (20) sorbitan monooleate, and after the pharmaceutical solution has been stored at 2-8° C. for 3 months, the pharmaceutical solution exhibits a total free oleic acid content of less than 0.0025% by volume as measured by high performance liquid chromatography with UV detection (HPLC-UV) using an internal standard.

[0123] In some embodiments of the pharmaceutical solution according to the present disclosure, the pharmaceutical solution comprises polyoxyethylene (20) sorbitan monooleate, and after the pharmaceutical solution has been stored at about 5°C for 29 months, the pharmaceutical solution exhibits a total free oleic acid content of less than 0.001% by volume by weight as measured by high performance liquid chromatography with UV detection (HPLC-UV) using an internal standard. In some embodiments of the pharmaceutical solution according to the present disclosure, the pharmaceutical solution comprises polyoxyethylene (20) sorbitan monooleate, and after the pharmaceutical solution has been stored at about 5°C for 29 months, the pharmaceutical solution exhibits a total free oleic acid content of less than 0.005% by volume by weight as measured by high performance liquid chromatography with UV detection (HPLC-UV) using an internal standard. In some embodiments of the pharmaceutical solution according to the present disclosure, the pharmaceutical solution comprises polyoxyethylene (20) sorbitan monooleate, and the pharmaceutical solution exhibits a difference in the amount of total free oleic acid content of less than 0.0025% by volume weight when the pharmaceutical solution has been stored at about 5°C for 3 months compared to when the pharmaceutical solution has been stored at about 5°C for 29 months, as measured by high performance liquid chromatography with UV detection (HPLC-UV) using an internal standard.

[0124] In some embodiments, the drug solution of the anti-N3pGlu Aβ antibody comprises polyoxyethylene (20) sorbitan monooleate, and the drug solution exhibits a total free oleic acid content of less than 0.0025% by weight by volume after the drug solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months as measured by high performance liquid chromatography with UV detection (HPLC-UV) using an internal standard.

[0125] In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 6 months, the pharmaceutical solution exhibits a purity of at least 85 area % as measured by non-reducing capillary electrophoresis sodium dodecyl sulfate (CE-SDS). In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C or about 25°C for 6 months, the pharmaceutical solution exhibits a purity of at least 90 area % as measured by non-reducing CE-SDS. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C or about 25°C for 6 months, the pharmaceutical solution exhibits a purity of at least 90.5 area % as measured by non-reducing CE-SDS. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C or about 25°C for 6 months, the pharmaceutical solution exhibits a purity of at least 89.0 area % as measured by non-reducing CE-SDS. In some embodiments of the pharmaceutical solutions according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C for 6 months, the pharmaceutical solution exhibits a purity of at least 92 area % as measured by non-reducing CE-SDS. In some embodiments of the pharmaceutical solutions according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C for 6 months, the pharmaceutical solution exhibits a purity of at least 90.5 area % as measured by non-reducing CE-SDS. In some embodiments of the pharmaceutical solutions according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C for 6 months, the pharmaceutical solution exhibits a purity of at least 89.0 area % as measured by non-reducing CE-SDS.

[0126] In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months, the pharmaceutical solution exhibits a purity of at least 90 area % as measured by reduced CE-SDS. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months, the pharmaceutical solution exhibits a purity of at least 94 area % as measured by reduced CE-SDS. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months, the pharmaceutical solution exhibits a purity of at least 95 area % as measured by reduced CE-SDS. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 35°C for 3 months, the pharmaceutical solution exhibits a purity of at least 95 area % as measured by reduced CE-SDS. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 35° C. for 3 months, the pharmaceutical solution exhibits a purity of at least 94 area % as measured by reducing CE-SDS. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 35° C. for 3 months, the pharmaceutical solution exhibits a purity of at least 92 area % as measured by reducing CE-SDS.

[0127] In some embodiments of the pharmaceutical solutions according to the present disclosure, after the pharmaceutical solution has been stored at about 5° C. or about 25° C. for 3 months, the pharmaceutical solution exhibits a purity of at least 94 area % as measured by reducing CE-SDS. In some embodiments of the pharmaceutical solutions according to the present disclosure, after the pharmaceutical solution has been stored at about 5° C. or about 25° C. for 6 months, the pharmaceutical solution exhibits a purity of at least 94 area % as measured by reducing CE-SDS.

[0128] In some embodiments of the pharmaceutical solution according to the present disclosure, the pharmaceutical solution exhibits a purity of at least 96 area % as measured by reducing CE-SDS after the pharmaceutical solution has been stored at about 5°C for 3 months.

[0129] In some embodiments of the pharmaceutical solutions according to the present disclosure, the pharmaceutical solution exhibits a difference in purity of less than 5 area % as measured by reducing CE-SDS when the pharmaceutical solution has been stored at about 5°C for 3 months, compared to when the pharmaceutical solution has been stored at about 5°C for 6 months. In some embodiments of the pharmaceutical solutions according to the present disclosure, the pharmaceutical solution exhibits a difference in purity of less than 3 area % as measured by reducing CE-SDS when the pharmaceutical solution has been stored at about 5°C for 3 months, compared to when the pharmaceutical solution has been stored at about 5°C for 6 months.

[0130] In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C or about 25°C for 3 months, the pharmaceutical solution exhibits a total aggregate content of less than 4 area % as measured by reducing CE-SDS. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C or about 25°C for 6 months, the pharmaceutical solution exhibits a total aggregate content of less than 4 area % as measured by reducing CE-SDS. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C or about 25°C for 3 months, the pharmaceutical solution exhibits a total aggregate content of less than 3 area % as measured by reducing CE-SDS. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C or about 25°C for 6 months, the pharmaceutical solution exhibits a total aggregate content of less than 3 area % as measured by reducing CE-SDS. In some embodiments of the pharmaceutical solution according to the present disclosure, the pharmaceutical solution exhibits a total aggregate content of less than 5 area % as measured by reducing CE-SDS after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months.

[0131] In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 3 months, the pharmaceutical solution exhibits a total aggregate content of less than 4% relative to the total antibody peak area, as measured by size exclusion chromatography. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C for 3 months, the pharmaceutical solution exhibits a total aggregate content of less than 4% relative to the total antibody peak area, as measured by size exclusion chromatography. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 3 months, the pharmaceutical solution exhibits a total aggregate content of less than 2% relative to the total antibody peak area, as measured by size exclusion chromatography. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C for 3 months, the pharmaceutical solution exhibits a total aggregate content of less than 2% relative to the total antibody peak area, as measured by size exclusion chromatography. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 3 months, the pharmaceutical solution exhibits a total aggregate content of less than 1.5% relative to the total antibody peak area, as measured by size exclusion chromatography. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C for 3 months, the pharmaceutical solution exhibits a total aggregate content of less than 1.5% relative to the total antibody peak area, as measured by size exclusion chromatography. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 3 months, the pharmaceutical solution exhibits a total aggregate content of less than 1% relative to the total antibody peak area, as measured by size exclusion chromatography. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C for 3 months, the pharmaceutical solution exhibits a total aggregate content of less than 1% relative to the total antibody peak area, as measured by size exclusion chromatography.

[0132] In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 3 months, the pharmaceutical solution exhibits a total aggregate content of less than 9 area % as measured by non-reducing CE-SDS. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 3 months, the pharmaceutical solution exhibits a total aggregate content of less than 8.5 area % as measured by non-reducing CE-SDS. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 3 months, the pharmaceutical solution exhibits a total aggregate content of less than 7.5 area % as measured by non-reducing CE-SDS. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 3 months, the pharmaceutical solution exhibits a total aggregate content of less than 4 area % as measured by non-reducing CE-SDS. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C for 3 months, the pharmaceutical solution exhibits a total aggregate content of less than 4 area % as measured by non-reducing CE-SDS. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 3 months, the pharmaceutical solution exhibits a total aggregate content of less than 2 area % as measured by non-reducing CE-SDS. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C for 3 months, the pharmaceutical solution exhibits a total aggregate content of less than 2 area % as measured by non-reducing CE-SDS. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 3 months, the pharmaceutical solution exhibits a total aggregate content of less than 1.5 area % as measured by non-reducing CE-SDS. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C for 3 months, the pharmaceutical solution exhibits a total aggregate content of less than 1.5 area % as measured by non-reducing CE-SDS. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 3 months, the pharmaceutical solution exhibits a total aggregate content of less than 1 area % as measured by non-reducing CE-SDS. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C for 3 months, the pharmaceutical solution exhibits a total aggregate content of less than 1 area % as measured by non-reducing CE-SDS.

[0133] In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months, the pharmaceutical solution contains less than 10,000 particles / ml as measured using microfluidic imaging, wherein the size of the particles is greater than 2 μm. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C or about 25°C for 6 months, the pharmaceutical solution contains less than 6,000 particles / ml as measured using microfluidic imaging, wherein the size of the particles is greater than 2 μm. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C or about 25°C for 6 months, the pharmaceutical solution contains less than 2,000 particles / ml as measured using microfluidic imaging, wherein the size of the particles is greater than 2 μm.

[0134] In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months, the pharmaceutical solution contains less than 2,000 particles / ml as measured using microfluidic imaging, wherein the size of the particles is greater than 5 μm. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C or about 25°C for 6 months, the pharmaceutical solution contains less than 2,000 particles / ml as measured using microfluidic imaging, wherein the size of the particles is greater than 5 μm. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C or about 25°C for 6 months, the pharmaceutical solution contains less than 1,000 particles / ml as measured using microfluidic imaging, wherein the size of the particles is greater than 5 μm. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C or about 25°C for 29 months, the pharmaceutical solution contains less than 1,000 particles / ml as measured using microfluidic imaging, wherein the size of the particles is greater than 5 μm.

[0135] In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months, the pharmaceutical solution contains less than 3,000 particles / ml, wherein the size of the particles is greater than 2 μm, as measured by light obscuration using a high-precision liquid particle counter (HIAC). In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months, the pharmaceutical solution contains less than 1,500 particles / ml, wherein the size of the particles is greater than 2 μm, as measured by light obscuration using HIAC. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months, the pharmaceutical solution contains less than 1,000 particles / ml, wherein the size of the particles is greater than 2 μm, as measured by light obscuration using HIAC. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months, the pharmaceutical solution contains less than 750 particles / ml, as measured by light obscuration using HIAC, wherein the size of the particles is greater than 2 μm. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months, the pharmaceutical solution contains less than 500 particles / ml, wherein the size of the particles is greater than 2 μm, as measured by light obscuration using HIAC. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months, the pharmaceutical solution contains less than 250 particles / ml, wherein the size of the particles is greater than 2 μm, as measured by light obscuration using HIAC. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months, the pharmaceutical solution contains less than 100 particles / ml, wherein the size of the particles is greater than 2 μm, as measured by light obscuration using HIAC. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months, the pharmaceutical solution contains less than 75 particles / ml, wherein the size of the particles is greater than 2 μm, as measured by light obscuration using HIAC.

[0136] In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 3 months, as measured by light obscuration using HIAC, the pharmaceutical solution contains less than 3,000 particles / ml, wherein the size of the particles is greater than 2 μm. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 3 months, as measured by light obscuration using HIAC, the pharmaceutical solution contains less than 1,500 particles / ml, wherein the size of the particles is greater than 2 μm. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 3 months, as measured by light obscuration using HIAC, the pharmaceutical solution contains less than 1,000 particles / ml, wherein the size of the particles is greater than 2 μm. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 3 months, as measured by light obscuration using HIAC, the pharmaceutical solution contains less than 750 particles / ml, wherein the size of the particles is greater than 2 μm. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 3 months, as measured by light obscuration using HIAC, the pharmaceutical solution contains less than 500 particles / ml, wherein the size of the particles is greater than 2 μm. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 3 months, as measured by light obscuration using HIAC, the pharmaceutical solution contains less than 250 particles / ml, wherein the size of the particles is greater than 2 μm. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 3 months, as measured by light obscuration using HIAC, the pharmaceutical solution contains less than 100 particles / ml, wherein the size of the particles is greater than 2 μm. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 3 months, as measured by light obscuration using HIAC, the pharmaceutical solution contains less than 75 particles / ml, wherein the size of the particles is greater than 2 μm.

[0137] In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months, the pharmaceutical solution contains less than 800 particles / ml, wherein the size of the particles is greater than 5 μm, as measured by light obscuration using HIAC. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months, the pharmaceutical solution contains less than 500 particles / ml, wherein the size of the particles is greater than 5 μm, as measured by light obscuration using HIAC. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months, the pharmaceutical solution contains less than 200 particles / ml, wherein the size of the particles is greater than 5 μm, as measured by light obscuration using HIAC. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months, the pharmaceutical solution contains less than 200 particles / ml, wherein the size of the particles is greater than 5 μm, as measured by light obscuration using HIAC. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months, the pharmaceutical solution contains less than 100 particles / ml, wherein the size of the particles is greater than 5 μm, as measured by light obscuration using HIAC. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months, the pharmaceutical solution contains less than 75 particles / ml, wherein the size of the particles is greater than 5 μm, as measured by light obscuration using HIAC.

[0138] In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 3 months, the pharmaceutical solution contains less than 800 particles / ml, as measured by light obscuration using HIAC, wherein the size of the particles is greater than 5 μm. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 3 months, the pharmaceutical solution contains less than 500 particles / ml, as measured by light obscuration using HIAC, wherein the size of the particles is greater than 5 μm. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 3 months, the pharmaceutical solution contains less than 200 particles / ml, as measured by light obscuration using HIAC, wherein the size of the particles is greater than 5 μm. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 3 months, the pharmaceutical solution contains less than 200 particles / ml, as measured by light obscuration using HIAC, wherein the size of the particles is greater than 5 μm. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 3 months, the pharmaceutical solution contains less than 100 particles / ml, wherein the size of the particles is greater than 5 μm, as measured by light obscuration using HIAC. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at 2-8°C for 3 months, the pharmaceutical solution contains less than 75 particles / ml, wherein the size of the particles is greater than 5 μm, as measured by light obscuration using HIAC.

[0139] In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months, the pharmaceutical solution contains less than 125 particles / ml, as measured by light obscuration using HIAC, wherein the size of the particles is greater than 10 μm. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months, the pharmaceutical solution contains less than 50 particles / ml, as measured by light obscuration using HIAC, wherein the size of the particles is greater than 10 μm. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months, the pharmaceutical solution contains less than 25 particles / ml, as measured by light obscuration using HIAC, wherein the size of the particles is greater than 10 μm. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months, the pharmaceutical solution contains less than 20 particles / ml, as measured by light obscuration using HIAC, wherein the size of the particles is greater than 10 μm. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months, the pharmaceutical solution contains less than 15 particles / ml, wherein the size of the particles is greater than 10 μm, as measured by light obscuration using HIAC. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months, the pharmaceutical solution contains less than 5 particles / ml, wherein the size of the particles is greater than 10 μm, as measured by light obscuration using HIAC.

[0140] In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C or about 25°C for 6 months, the pharmaceutical solution contains less than 25 particles / ml, as measured by light obscuration using HIAC, wherein the size of the particles is greater than 10 μm. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C for 29 months, the pharmaceutical solution contains less than 25 particles / ml, as measured by light obscuration using HIAC, wherein the size of the particles is greater than 10 μm. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C or about 25°C for 6 months, the pharmaceutical solution contains less than 3 particles / ml, as measured by light obscuration using HIAC, wherein the size of the particles is greater than 10 μm. In some embodiments of the pharmaceutical solution according to the present disclosure, after the pharmaceutical solution has been stored at about 5°C for 29 months, the pharmaceutical solution contains less than 3 particles / ml, as measured by light obscuration using HIAC, wherein the size of the particles is greater than 10 μm.

[0141] In some embodiments, within 4 weeks of storage at 2-8°C, the pharmaceutical solution according to the present disclosure exhibits a change in UV absorbance at 550nm of less than ±3%. In some embodiments, within 4 weeks of storage at 2-8°C, the pharmaceutical solution according to the present disclosure exhibits a change in UV absorbance at 550nm of less than ±2%. In some embodiments, within 4 weeks of storage at 2-8°C, the pharmaceutical solution according to the present disclosure exhibits a change in UV absorbance at 550nm of less than ±1%. In some embodiments, within 4 weeks of storage at about 5°C, the pharmaceutical solution according to the present disclosure exhibits a change in UV absorbance at 550nm of less than ±3%. In some embodiments, within 4 weeks of storage at about 5°C, the pharmaceutical solution according to the present disclosure exhibits a change in UV absorbance at 550nm of less than ±2%. In some embodiments, within 4 weeks of storage at about 5°C, the pharmaceutical solution according to the present disclosure exhibits a change in UV absorbance at 550nm of less than ±1%.

[0142] In some embodiments, after storage at about 5° C. for 4 weeks, the pharmaceutical solution according to the present disclosure exhibits a protein content change of about 0.1% to about 25% as measured by UV absorbance at 280 nm, for example, 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%, about 10%, about 15%, about 20%, or about 25% protein content change as measured by UV absorbance at 280 nm after storage at about 5° C. for 4 weeks. In some embodiments, after storage at about 5° C. for 4 weeks, the pharmaceutical solution according to the present disclosure exhibits a protein content change of 0.4% to 25% as measured by UV absorbance at 280 nm. In some embodiments, after storage at about 5°C for 4 weeks, the pharmaceutical solutions according to the present disclosure exhibit a protein content change of about 0.4% to about 13% as measured by UV absorbance at 280 nm. In some embodiments, after storage at about 5°C for 4 weeks, the pharmaceutical solutions according to the present disclosure exhibit a protein content change of about 1% to about 13% as measured by UV absorbance at 280 nm. In some embodiments, after storage at 2-8°C for 4 weeks, the pharmaceutical solution according to the present disclosure exhibits a protein content change of 0.1% to 25% as measured by UV absorbance at 280nm, for example, 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%, about 15%, about 20%, or about 25% protein content change as measured by UV absorbance at 280nm after storage at 2-8°C for 4 weeks. In some embodiments, after storage at 2-8°C for 4 weeks, the pharmaceutical solution according to the present disclosure exhibits a protein content change of about 0.4% to about 25% as measured by UV absorbance at 280nm. In some embodiments, after storage at 2-8°C for 4 weeks, the pharmaceutical solutions according to the present disclosure exhibit a protein content change of about 0.4% to about 13% as measured by UV absorbance at 280 nm. In some embodiments, after storage at 2-8°C for 4 weeks, the pharmaceutical solutions according to the present disclosure exhibit a protein content change of about 1% to about 13% as measured by UV absorbance at 280 nm.

[0143] In some embodiments, after storage at 2-8°C for 4 weeks, when analyzed by size exclusion chromatography, the pharmaceutical solution according to the present disclosure has at least 92% of anti-N3pGlu antibodies appearing in the main chromatographic peak (monomer). In some embodiments, after storage at 2-8°C for 4 weeks, when analyzed by size exclusion chromatography, the pharmaceutical solution according to the present disclosure has at least 93% of anti-N3pGlu antibodies appearing in the main chromatographic peak (monomer). In some embodiments, after storage at 2-8°C for 4 weeks, when analyzed by size exclusion chromatography, the pharmaceutical solution according to the present disclosure has at least 94% of anti-N3pGlu antibodies appearing in the main chromatographic peak (monomer). In some embodiments, after storage at 2-8°C for 4 weeks, when analyzed by size exclusion chromatography, the pharmaceutical solution according to the present disclosure has at least 93.1%, 93.2%, 93.3%, 93.4%, 93.5%, 93.6%, 93.7%, 93.8% or 93.9% of anti-N3pGlu antibodies appearing in the main chromatographic peak (monomer). In some embodiments, after storage at 2-8°C for 4 weeks, when analyzed by size exclusion chromatography, the pharmaceutical solution according to the present disclosure has 93.3% to 93.8% of anti-N3pGlu antibodies appearing in the main chromatographic peak (monomer).

[0144] In some embodiments, after storage at about 5°C for 4 weeks, when analyzed by size exclusion chromatography, the pharmaceutical solution according to the present disclosure has at least 92% of anti-N3pGlu antibodies appearing in the main chromatographic peak (monomer). In some embodiments, after storage at about 5°C for 4 weeks, when analyzed by size exclusion chromatography, the pharmaceutical solution according to the present disclosure has at least 93% of anti-N3pGlu antibodies appearing in the main chromatographic peak (monomer). In some embodiments, after storage at about 5°C for 4 weeks, when analyzed by size exclusion chromatography, the pharmaceutical solution according to the present disclosure has at least 94% of anti-N3pGlu antibodies appearing in the main chromatographic peak (monomer). In some embodiments, after storage at about 5°C for 4 weeks, when analyzed by size exclusion chromatography, the pharmaceutical solution according to the present disclosure has at least 93.1%, 93.2%, 93.3%, 93.4%, 93.5%, 93.6%, 93.7%, 93.8% or 93.9% of the anti-N3pGlu antibodies appearing in the main chromatographic peak (monomer). In some embodiments, after storage at about 5°C for 4 weeks, when analyzed by size exclusion chromatography, the pharmaceutical solution according to the present disclosure has 93.3% to 93.8% of the anti-N3pGlu antibodies appearing in the main chromatographic peak (monomer).

[0145] In some embodiments, after the drug solution has been stored at 2-8°C for 4 weeks, the drug solution according to the present disclosure exhibits a decrease of no more than 15 area % in the amount of anti-N3pGlu antibodies, as measured by non-reducing CE-SDS. In some embodiments, after the drug solution has been stored at 2-8°C for 4 weeks, the drug solution according to the present disclosure exhibits a decrease of no more than 12.5 area % in the amount of anti-N3pGlu antibodies, as measured by non-reducing CE-SDS. In some embodiments, after the drug solution has been stored at 2-8°C for 4 weeks, the drug solution according to the present disclosure exhibits a decrease of no more than 11 area % in the amount of anti-N3pGlu antibodies, as measured by non-reducing CE-SDS. In some embodiments, after the drug solution has been stored at 2-8°C for 4 weeks, the drug solution according to the present disclosure exhibits a decrease of no more than 10 area % in the amount of anti-N3pGlu antibodies, as measured by non-reducing CE-SDS. In some embodiments, after the drug solution has been stored at 2-8°C for 4 weeks, as measured by non-reducing CE-SDS, the drug solution according to the present disclosure exhibits a decrease in the amount of anti-N3pGlu antibodies of no more than 10.0 area%, 10.1 area%, 10.2 area%, 10.3 area%, 10.4 area%, 10.5 area%, 10.6 area%, 10.7 area%, 10.8 area%, or 10.9 area%. In some embodiments, after the drug solution has been stored at 5°C for 4 weeks, as measured by non-reducing CE-SDS, the drug solution according to the present disclosure exhibits a decrease in the amount of anti-N3pGlu antibodies of no more than 15 area%. In some embodiments, after the drug solution has been stored at about 5°C for 4 weeks, as measured by non-reducing CE-SDS, the drug solution according to the present disclosure exhibits a decrease in the amount of anti-N3pGlu antibodies of no more than 12.5 area%. In some embodiments, after the drug solution has been stored at about 5°C for 4 weeks, as measured by non-reducing CE-SDS, the drug solution according to the present disclosure exhibits a decrease of no more than 11 area % in the amount of anti-N3pGlu antibodies. In some embodiments, after the drug solution has been stored at about 5°C for 4 weeks, as measured by non-reducing CE-SDS, the drug solution according to the present disclosure exhibits a decrease of no more than 10 area % in the amount of anti-N3pGlu antibodies. In some embodiments, after the drug solution has been stored at about 5°C for 4 weeks, as measured by non-reducing CE-SDS, the drug solution according to the present disclosure exhibits a decrease of no more than 10.0 area %, 10.1 area %, 10.2 area %, 10.3 area %, 10.4 area %, 10.5 area %, 10.6 area %, 10.7 area %, 10.8 area % or 10.9 area % in the amount of anti-N3pGlu antibodies.

[0146] In some embodiments of the pharmaceutical solution according to the present disclosure, the pharmaceutical solution comprises an anti-N3pGlu Aβ antibody, a buffer, a tonicity agent, a surfactant, and an optional excipient in an amount sufficient to combine to allow the pharmaceutical solution to exhibit one or more of the following:

[0147] (a) an antibody monomer content of at least 97% relative to the total antibody peak area as measured by size exclusion chromatography after the drug solution has been stored at 2-8°C for 3 months;

[0148] (b) less than 2% total aggregate content as measured by size exclusion chromatography after the drug solution has been stored at 2-8°C for 3 months;

[0149] (c) an antibody purity of at least 92% as measured by reducing capillary electrophoresis sodium dodecyl sulfate (CE-SDS) after the drug solution has been stored at about 35°C for 3 months;

[0150] (d) after the drug solution has been stored at 2-8° C. for 3 months, (i) less than 2% total aggregate content as measured by size exclusion chromatography, or (ii) less than 1.5% total aggregate content as measured by non-reducing CE-SDS;

[0151] (e) less than 500 particles / ml as measured by light obscuration using a high accuracy liquid particle counter (HIAC) after the drug solution has been stored at 2-8°C for 3 months, wherein the size of the particles is greater than 2 μm;

[0152] (f) less than 100 particles / ml as measured by light obscuration using a high accuracy liquid particle counter (HIAC) after the drug solution has been stored at 2-8°C for 3 months, wherein the size of the particles is greater than 5 μm;

[0153] (g) the UV absorbance at 550 nm changes by less than ±3% within 4 weeks of storage at 2-8°C;

[0154] (h) a change in protein content of about 1% to about 13% after storage at 2-8°C for 4 weeks as measured by UV absorbance at 280 nm;

[0155] (i) after storage at 2-8°C for 4 weeks, at least 93% of the anti-N3pGlu antibody appears in the main chromatographic peak (monomer) when analyzed by size exclusion chromatography;

[0156] (i) no more than about 11% decrease in the amount of anti-N3pGlu antibody as measured by non-reducing CE-SDS after the drug solution has been stored at 2-8°C for 4 weeks; and

[0157] (k) After the drug solution has been stored at 2-8°C for 4 weeks, no more than four particles have a size of 25 μm or less as measured by differential counts per milliliter.

[0158] In some embodiments of the foregoing pharmaceutical solutions, one or more of characteristics (a)-(k) are present before and after storage of the pharmaceutical solution.

[0159] In some embodiments of the pharmaceutical solution according to the present disclosure, the pharmaceutical solution comprises an anti-N3pGlu Aβ antibody, a buffer, a tonicity agent, a surfactant, and an optional excipient in an amount sufficient to combine to allow the pharmaceutical solution to exhibit one or more of the following:

[0160] (a) an antibody monomer content of at least 97% relative to the total antibody peak area as measured by size exclusion chromatography after the drug solution has been stored at about 5°C for 3 months;

[0161] (b) less than 2% total aggregate content as measured by size exclusion chromatography after the drug solution has been stored at about 5°C for 3 months;

[0162] (c) a change in UV absorbance at 550 nm of less than ±3% over 4 weeks of storage at about 5°C;

[0163] (d) a change in protein content of about 1% to about 13% after storage at about 5°C for 4 weeks as measured by UV absorbance at 280 nm;

[0164] (e) after storage at about 5° C. for 4 weeks, at least 93% of the anti-N3pGlu antibody appears in the main chromatographic peak (monomer) as analyzed by size exclusion chromatography;

[0165] (f) no more than an 11% decrease in the amount of anti-N3pGlu antibody as measured by non-reducing CE-SDS after the drug solution has been stored at about 5°C for 4 weeks; and

[0166] (g) After the drug solution has been stored at about 5°C for 4 weeks, no more than four particles have a size of 25 μm or less as measured by differential counts per milliliter.

[0167] In some embodiments of the foregoing pharmaceutical solutions, one or more of characteristics (a)-(g) are present before and after storage of the pharmaceutical solution.

[0168] In some embodiments of the pharmaceutical solution according to the present disclosure, the pharmaceutical solution comprises an anti-N3pGlu Aβ antibody, a buffer, a tonicity agent, a surfactant, and an optional excipient in an amount sufficient to combine to allow the pharmaceutical solution to exhibit one or more of the following:

[0169] (a) an antibody monomer content of at least 97.5% relative to the total antibody peak area as measured by size exclusion chromatography after the drug solution has been stored at 2-8°C for 3 months;

[0170] (b) a total aggregate content of less than 1.5% as measured by size exclusion chromatography after the drug solution has been stored at 2-8°C for 3 months;

[0171] (c) an antibody purity of at least 94% as measured by reducing CE-SDS after the drug solution has been stored at about 35° C. for 3 months;

[0172] (d) after storage at 2-8°C for 4 weeks, 93.3% to 93.8% of the anti-N3pGlu antibody appeared in the main chromatographic peak (monomer) as analyzed by size exclusion chromatography;

[0173] (e) No more than 6.9% decrease in the amount of anti-N3pGlu antibody as measured by reducing CE-SDS after the drug solution has been stored at 2-8°C for 4 weeks.

[0174] In some embodiments of the foregoing pharmaceutical solutions, one or more of characteristics (a)-(e) are present before and after storage of the pharmaceutical solution.

[0175] In some embodiments of the pharmaceutical solution according to the present disclosure, the pharmaceutical solution comprises an anti-N3pGlu Aβ antibody, a buffer, a tonicity agent, a surfactant, and an optional excipient in an amount sufficient to combine to allow the pharmaceutical solution to exhibit one or more of the following:

[0176] (a) an antibody monomer content of at least 97.5% relative to the total antibody peak area as measured by size exclusion chromatography after the drug solution has been stored at about 5°C for 3 months;

[0177] (b) a total aggregate content of less than 1.5% as measured by size exclusion chromatography after the drug solution has been stored at 5°C for 3 months;

[0178] (c) an antibody purity of at least 96% as measured by reducing CE-SDS after the drug solution has been stored at about 5°C for 3 months;

[0179] (d) after storage at about 5° C. for 4 weeks, 93.3% to 93.8% of the anti-N3pGlu antibodies appeared in the main peak as analyzed by size exclusion chromatography;

[0180] (e) no more than a 6.9% decrease in the amount of anti-N3pGlu antibody as measured by reducing CE-SDS after the drug solution has been stored at about 5° C. for 4 weeks;

[0181] (f) less than 500 particles / ml as measured by light obscuration using HIAC after the drug solution has been stored at about 5°C for 3 months, wherein the particles are greater than 2 μm in size; and

[0182] (g) less than 100 particles / ml as measured by light obscuration using HIAC after the drug solution has been stored at about 5°C for 3 months, wherein the particles are greater than 5 μm in size.

[0183] In some embodiments of the foregoing pharmaceutical solutions, one or more of characteristics (a)-(g) are present before and after storage of the pharmaceutical solution.

[0184] Aspects of the present disclosure also relate to a vessel containing a pharmaceutical solution according to the present disclosure.In some embodiments, the vessel is a vial, a syringe (eg, a pre-filled syringe), a bag, or a tube.

[0185] Aspects of the present disclosure also relate to administering the drug solution of the present disclosure to a patient. The terms "subject" and "patient" are used interchangeably in the present disclosure. In some embodiments, a patient (or interchangeably "subject") is a person (also referred to as "human patient" or interchangeably "human subject"). The drug solution of the present disclosure can be administered to a subject by parenteral routes (parentalroutes) (e.g., subcutaneous, intravenous, intraperitoneal, intramuscular), and the subject is at risk of a disease or condition as described herein or exhibits a disease or condition as described herein. In some embodiments, administration is by subcutaneous and / or intravenous routes. In some embodiments, antibodies (e.g., anti-N3pGlu A β antibodies) are administered by intravenous infusion.

[0186] As used herein, the terms "treatment," "treating," or "treat," and the like include inhibiting, slowing, or stopping the progression or severity of an existing symptom, condition, disease, or disorder in a subject. In some embodiments, treatment comprises reduction of amyloid beta in the brain of a human patient.

[0187] As used herein, "method of treatment" also applies to the use of a composition (e.g., a composition that is a pharmaceutical solution according to the present disclosure) for treating a disease or condition described herein and / or the use of a composition (e.g., a composition that is a pharmaceutical solution according to the present disclosure) for and / or in the manufacture of a medicament for treating a disease or condition described herein.

[0188] As used herein, the term "prevention" refers to the prophylactic administration of an antibody to an asymptomatic subject or a subject with preclinical disease (eg, preclinical Alzheimer's disease) to prevent the onset or progression of the disease.

[0189] Aspects of the present disclosure relate to treating diseases characterized by amyloid β (Aβ) deposition and / or diseases characterized by amyloid β (Aβ) deposits. In some embodiments, the present disclosure relates to treating diseases characterized by amyloid β (Aβ) deposition and / or diseases characterized by amyloid β (Aβ) deposits by administering a therapeutically effective amount of a pharmaceutical solution according to the present disclosure to a patient in need thereof. As used herein, the terms "disease characterized by amyloid β (Aβ) deposition" or "disease characterized by amyloid β (Aβ) deposits" are used interchangeably and refer to diseases characterized by pathological Aβ deposits in the brain or cerebral blood vessels. This includes diseases such as Alzheimer's disease (AD), Down syndrome, and cerebral amyloid angiopathy. In some embodiments, Alzheimer's disease is preclinical AD, prodromal AD, mild AD, moderate AD, or severe AD. In some embodiments, a method of treating a disease characterized by amyloid β (Aβ) deposition and / or a disease characterized by amyloid β (Aβ) deposits according to the present disclosure comprises administering a pharmaceutical solution according to the present disclosure obtained from a vessel according to the present disclosure to a patient in need thereof.

[0190] In some embodiments, one or more dosages of a pharmaceutical solution according to the present disclosure are applied to a human patient in need thereof. For the avoidance of doubt, it should be understood that applying "dosage" refers to applying a certain amount of pharmaceutical solutions according to the present disclosure. However, "dosage" can be expressed according to the amount of the antibody rather than the amount of the pharmaceutical solution. For example, as will be understood by those of ordinary skill in the art, referring to applying a dosage of, for example, 100 mg of an antibody refers to applying a pharmaceutical solution of, for example, 10 mL of an antibody, wherein the pharmaceutical solution has a concentration of 10 mg of antibody per 1 mL of solution (also referred to as a concentration of 10 mg / mL), or applying a pharmaceutical solution of, for example, 5 mL of an antibody, wherein the pharmaceutical solution has a concentration of 20 mg of antibody per 1 mL of solution (also referred to as a concentration of 20 mg / mL). In addition, for the avoidance of doubt, it should be understood that referring to applying an antibody refers to applying a pharmaceutical solution of the antibody (according to the present disclosure).

[0191] In some embodiments, the method of treatment according to the present disclosure includes administering to the patient one or more doses of about 100 mg to about 10,000 mg of anti-N3pGlu Aβ antibody, such as 100 mg, 150 mg, 200 mg, 250 mg, 300 mg, 350 mg, 400 mg, 450 mg, 500 mg, 550 mg, 600 mg, 650 mg, 700 mg, 750 mg, 800 mg, 850 mg, 900 mg, 950 mg or 1,000 mg or more of the antibody. In some embodiments, the method of treatment according to the present disclosure includes administering to the patient one or more doses of anti-N3pGlu Aβ antibody that is not lyophilized.

[0192] In some embodiments, one or more first doses of the antibody are administered to the subject. In some embodiments, one or more first doses are administered to a human subject such that each first dose is administered once every four weeks. In some embodiments, the first dose is administered to the subject once. In some embodiments, the first dose is administered to the subject twice, wherein each first dose is administered once every four weeks. In some embodiments, the first dose is administered to the subject three times, wherein each first dose is administered once every four weeks.

[0193] In some embodiments, one or more second doses of the antibody are administered to the subject. In some embodiments, one or more second doses comprise an antibody (e.g., anti-N3pGlu Aβ antibody) greater than about 700mg to about 1400mg. In some embodiments, one or more second doses of an antibody (e.g., anti-N3pGlu Aβ antibody) greater than about 700mg to about 1400mg are administered to the subject, wherein each second dose is administered approximately once every 4 weeks. In some embodiments, the second dose is administered 4 weeks after one or more first doses.

[0194] Dosage can also be expressed in mg / kg. As used herein, "mg / kg" means the amount of an antibody or drug in milligrams administered to a subject based on its body weight in kilograms. One dose is given at a time. For example, for a patient weighing 70 kg, a 10 mg / kg dose of antibody will be a single 700 mg dose of antibody given in a single administration. Similarly, for a patient weighing 70 kg, a 20 mg / kg dose of antibody will be a 1400 mg dose of antibody given in a single administration. In some embodiments, the first dose is an antibody of about 1 mg / kg to about 10 mg / kg. In some embodiments, a first dose of up to three about 1 mg / kg to about 10 mg / kg is administered to the patient. In some embodiments, a first dose, two first doses, or three first doses of about 1 mg / kg to about 10 mg / kg are administered to the patient. In some embodiments, three first doses of about 10 mg / kg are administered to the patient once every four weeks. In some embodiments, the first dose is about 1 mg / kg, about 2 mg / kg, about 3 mg / kg, about 4 mg / kg, about 5 mg / kg, about 6 mg / kg, about 7 mg / kg, about 8 mg / kg, about 9 mg / kg, or about 10 mg / kg.

[0195] In some embodiments, the antibodies, methods, dosing regimens and / or uses of the present disclosure result in a reduction in the amyloid beta in the brain of a human patient. In some embodiments, the administration of a pharmaceutical solution according to the present disclosure results in a reduction in the amount of at least 5% of the amyloid beta in the brain of a human patient. In some embodiments, the administration of a pharmaceutical solution according to the present disclosure results in a reduction in the amount of about 5%, about 10%, about 15%, about 20%, about 25%, about 30%, about 35%, about 40%, about 45%, about 50%, about 55%, about 60%, about 65%, about 70%, about 75%, about 80%, about 85%, about 90%, about 95%, about 99% or more of the amyloid beta in the brain of a human patient. Example

[0196] Example 1: Study on preformulation of Donetuzumab

[0197] 1. Abbreviations and Definitions

[0198] API - Active Pharmaceutical Ingredient

[0199] CE-SDS-capillary electrophoresis-sodium dodecyl sulfate

[0200] DLS - Dynamic Light Scattering

[0201] BDS-Bulk API, raw materials for process (donezetimumab)

[0202] DSC - Differential Scanning Calorimetry

[0203] EP - European Pharmacopoeia

[0204] ISO-International Organization for Standardization

[0205] NF - National Formulary

[0206] PDS-Pharmaceutical Development Services

[0207] SDS-Sodium dodecyl sulfate

[0208] SEC - Size Exclusion Chromatography

[0209] TC-Thermocouple

[0210] USP - United States Pharmacopoeia

[0211] 2. Materials and Equipment

[0212] The materials used during the development process are summarized in Table 1.

[0213] Table 1. Materials used

[0214]

[0215] The equipment used during the development process is summarized in Table 2.

[0216] Table 2. Equipment used

[0217]

[0218] 3. Methods

[0219] Protein content: UV absorbance at 280 nm (calculated extinction coefficient = 1.48 mL·mg-1·cm-1)

[0220] Determine the turbidity of the solution by measuring the absorbance at 550 nm

[0221] Use Accusizer SIS, use USP <788> (Light Obstruction Method) Method to Monitor Particles

[0222] Thermal stability was monitored using microcalorimetric differential scanning calorimetry (DSC)

[0223] 4. Experimental Design

[0224] 4.1 pH study

[0225] Without wishing to be bound by theory, it is believed that the pH of the antibody solution affects the properties of the antibody in the solution, including but not limited to solubility. The solubility of the antibody in the solution is an important parameter, because it affects the amount of solution (i.e., dosage) that must be applied to the patient, so as to deliver a given amount of antibody and achieve the target biological effect in the patient. Without wishing to be bound by theory, it is also believed that the pH of the antibody solution affects the stability of the solution (e.g., the antibody in the solution is more rapidly degraded at a first pH than at a second different pH). In view of the importance of pH, a pH rate curve stability study was performed to check the solution pH conditions for donenezumab. The experimental design is presented in Table 3.

[0226] Thawed bulk drug substance (10mM citrate, 150mM NaCl, pH 6.5; 57.5mg / mL) was dialyzed against 10mM citrate buffer using a 30,000MWCO Slide-a-lyzers box. Dialysis was performed at 2-8°C and the buffer was changed every day. After the buffer was changed, the protein concentration in each solution was measured and diluted to a predetermined concentration (approximately 50mg / mL for F4 and 2mg / mL for the other solutions); the final solution was filtered using a 0.22μm syringe filter.

[0227] The filtered solution was filled into 20R glass vials, which were then stoppered and sealed. The vials of each solution were stored under defined storage conditions in the relevant stability chamber (e.g., 5±3°C, 25±2°C / 60±5%RH and 40±2°C / 75±5%RH). The test schedule is listed in Table 4.

[0228] Samples were tested for purity (SEC and CE-SDS reducing and non-reducing), protein content (UV at 280 nm), insoluble particulate matter (light obscuration and visual appearance), turbidity (A550), pH. Approximately 1 mL of each solution was shipped for thermal stability (calorimetry).

[0229] Table 3: pH rate curve stability study design

[0230]

[0231] Table 4: Test schedule for pH study

[0232]

[0233] X = sample and test; O = sample and test as needed

[0234] *Samples were analyzed by standard DSC and microcalorimetry.

[0235] 4.2 Freeze-thaw studies

[0236] The stability of the donetumab solution was evaluated after a maximum of 3 freeze-thaw cycles.

[0237] The solutions were subjected to three freeze-thaw cycles and analyzed as follows:

[0238] -Day 1 morning: T0 analysis; freeze vials at -70°C

[0239] - Day 1 afternoon: Thaw and T1 analysis at room temperature; freeze vials to -70°C

[0240] -Day 2 morning: Thaw and T2 analysis at room temperature; freeze vials to -70°C

[0241] - Day 2 afternoon: Thawing and T3 analysis at room temperature

[0242] After the bulk drug substance was dialyzed against the selected 10 mM citrate buffer at pH 6.0, polysorbate 80 was added at different concentrations (0.01, 0.02, 0.04 w / v%) and finally diluted to about 25 mg / mL. Dialysis was performed at 2-8°C and the buffer was changed after 4, 8 and 24 hours from the start of dialysis.

[0243] Samples were formulated as outlined in the study design in Table 5.

[0244] After 0.22 μm filtration, the solutions were dispensed into 10R vials, each filled with 5 mL of each solution, stoppered and sealed. The test schedule is as listed in Table 6.

[0245] Samples were tested for soluble aggregation (SEC), insoluble particulate matter (light obscuration and visual appearance), protein content (UV measurement at 280 nm), aggregation (DLS), turbidity (A550), and pH.

[0246] Table 5: Freeze-thaw and agitation study design

[0247]

[0248] Table 6. Test samples

[0249]

[0250] Note: X = sampled and tested; blank entry = not tested

[0251] 4.3 Agitation study

[0252] The stability of Donetomab was evaluated after stirring on a rotary shaker at 100 rpm for 24 and 48 hours at room temperature. This speed allows for a small oscillation of the solution inside the vial. Solutions with the same matrix and the same dialysis program as those in the freeze-thaw study were analyzed (see Table 5). After 0.22 μm filtration, the solution was dispensed into 10R vials, each of which was filled with 5 mL of each solution, plugged with a stopper and sealed. The test schedule is listed in Table 7.

[0253] Table 7. Test samples

[0254]

[0255] 4.4 Solubility studies

[0256] The solubility of donetumab was studied in 10 mM citrate buffer at pH 6 with 0.01% (w / v) polysorbate 80. Donetuzumab BDS was dialyzed into the appropriate buffer (following the same dialysis procedure for freeze-thaw and agitation studies) using Ultra 30K centrifugal filter devices were concentrated, filled into 5 mL glass vials, stoppered, sealed, and stored at -5°C on pre-cooled freeze drying racks. After 24 hours, the samples were visually observed for phase separation. If no phase separation occurred, the samples were subjected to additional physical stability testing at 5°C for 1 week. The testing schedule is listed in Table 8.

[0257] Table 8. Test samples

[0258] test Protein concentration, UV280 A550 undiluted pH Visual Appearance SEC Viscosity

[0259] NOTE: Comprehensive testing is only expected for one point in time

[0260] 5. Results

[0261] 5.1 pH study

[0262] The study was designed to investigate the stability of Donetazoma B at different pH values. Seven solutions (F1-F7) indicated in Table 3 were studied. The effects of sodium chloride and protein concentration were also examined at pH 6.0. A pH range of 5 to 7 was selected based on previous studies, which indicated maximum chemical and physical stability at pH 6.0. Tables A.1-A.9 of Appendix A present the tabulated results from this study.

[0263] Protein content, turbidity (Ab at 550 nm) and pH remained constant for all solutions throughout the study. After 4 weeks at 2°C-8°C, small amounts of particles were noted in all solutions (F1-F7). After 4 weeks at 40°C / 75%RH, small amounts of particles and filaments were noted in all solutions (Tables A.1 and A.2).

[0264] From the overall SEC data, the results obtained from the storage temperature of 40°C / 75%RH are considered to be more significant than the results obtained from the storage conditions of 2°C-8°C. The SEC chromatogram shows a shoulder peak after the main peak, which is identified as a fragment of donemab, and therefore it is included in the % low molecular weight species (%LMW) or fragment. After 4 weeks at 2-8°C, negligible aggregation / fragmentation differences were observed in all test samples. After 4 weeks at 40°C, the fragmentation phenomenon was more obvious in F7 (pH6.0, NaCl) and F6 (pH 5.0). On the contrary, aggregation was higher in F4 (pH 6.0, 50mg / m L), which may be due to higher protein concentrations. Solutions F1 (pH 7.0), F2 (pH 6.5), F3 (pH 6.0) and F5 (pH 5.5) showed a lower degree of fragmentation and / or aggregation. Figure 1 and Table A.3 of Appendix A provide additional SEC data for solutions at different pH.

[0265] Purity results by non-reducing CE-SDS were relatively unchanged over 4 weeks of storage at 5°C. After 4 weeks at 40°C, the lowest decrease in % donetumab was observed in the following solutions: F7 (pH 6.0 NaCl) and F5 (pH 5.5). % donetumab refers only to the % area of ​​the peak identified as intact monoclonal antibody.

[0266] Appendix A Figure 2A , Figure 2B and Table A.4 provide additional details on the pH studies.

[0267] After 4 weeks of storage, the overall % purity by reducing CE-SDS was reduced. The solution with the smallest change in purity after 4 weeks was F5 (pH 5.5), and the solution with the largest change in purity after 4 weeks was F1 (pH 7.0). Figure 3 Additional purity data are provided in Table A.5.

[0268] Differential Scanning Calorimetry (DSC) analysis was performed on the pH Study 1 samples and the data are reported in Table A.7. The results indicated that the Tm 1 transition was the highest energy transition.

[0269] Regarding subvisible particles, such as Figure 4A and Figure 4B As shown in , after one month of stability, the number of particles / mL for each solution was reduced for each size investigated.

[0270] Without wishing to be bound by theory, the foregoing results suggest that antibody stability in solution may be maximized by preparing the solution at a pH between 5.5 and 6.0, such as pH 5.5, 5.6, 5.7, 5.8, 5.9 or 6.0. Table A.9 of Appendix A provides a summary of results related to the pH studies.

[0271] 5.2 Freeze-thaw studies

[0272] This study was conducted on solutions containing 25 mg / mL donetumab at a pH of 6.0 (based on the output of the pH study) with different levels of polysorbate 80 (Table 5). The donetumab solutions were subjected to 3 freeze-thaw cycles as described above. The analytical results of all tabulations from the freeze-thaw study are summarized in Tables A.10-A.14 of Appendix A.

[0273] Throughout the study, small amounts of particles were noted in solutions F2 (0.01% polysorbate 80), F3 (0.02% polysorbate 80), and F4 (0.04% polysorbate 80). In contrast, solution F1 (no polysorbate 80) showed an increase in particles starting with the first freeze-thaw cycle. See Table A.10 in Appendix A.

[0274] For solutions F2 (0.01% polysorbate 80) and F3 (0.02% polysorbate 80), no significant changes in the UV measurement at 280 nm were noted. Solutions F1 (no polysorbate 80) and F4 (0.04% polysorbate 80) showed a slight decrease in the UV measurement at 280 nm. Refer to Appendix A Table A.11.

[0275] No pH changes were noted for all solutions (Table A.12 in Appendix A).

[0276] No significant changes in Ab at 550 nm were noted for solutions F1 (no polysorbate 80) and F2 (0.01% polysorbate 80), whereas a slight decrease in this parameter was observed for solutions F3 (0.02% polysorbate 80) and F4 (0.04% polysorbate 80).

[0277] The chromatogram obtained by SEC analysis shows a shoulder after the main peak, which is identified as a fragment of donemab, and therefore it is included in the % low molecular weight species (%LMW) or fragments. No significant changes in the SEC profiles were noted for solutions F2 (0.01% polysorbate 80) and F4 (0.04% polysorbate 80), while solution F1 (without polysorbate 80) showed a slight increase in the main peak and a simultaneous reduction in fragmentation. A reduction in the main peak and a simultaneous increase in fragmentation were observed in solution F3 (0.02% polysorbate 80).

[0278] No changes in the percentage of aggregation were detected throughout the study. For a graphical representation of the above considerations, refer to Table A.13 in Appendix A and Figure 5A , Figure 5B and Figure 5C .

[0279] Without wishing to be bound by theory, these results indicate that the presence of a small percentage of polysorbate (eg, 0.01% w / v) improves the physical properties of the bulk solution, for example by reducing the number of visible and subvisible particles in the solution.

[0280] After freeze-thaw treatment, soluble aggregates increased slightly in all samples. Fig. 6A and Figure 6B As shown in , after the third freeze-thaw cycle, the number of particles / mL generally increased for each solution at each size investigated.

[0281] Samples formulated without polysorbate 80 exhibited higher particle counts as measured by light obscuration. Refer to Appendix A, Table A.14.

[0282] Without wishing to be bound by theory, the foregoing results suggest the benefit of including 0.01% (w / v) polysorbate 80 in a solution comprising donetumab in protecting donetumab from physical instabilities associated with freeze-thaw.

[0283] 5.3 Agitation

[0284] In parallel with freeze-thaw, a study was conducted to evaluate potential stability concerns associated with processing (mixing, pumping, filling, etc.) of donezumab solutions. The study was conducted on solutions containing 25 mg / mL protein concentration at a pH of 6.0 (based on the output of Study 1) and formulated as outlined in Table 5. Donezumab was subjected to agitation on a rotary shaker as described above. Tabulated results for the rotation samples are found in Tables A.15.-A.21.

[0285] Throughout the study, some particles were noted in solution F1 (no polysorbate 80), while a reduction in particles was observed in solutions F2 (0.01% polysorbate 80), F3 (0.02% polysorbate 80), and F4 (0.04% polysorbate 80). Refer to Appendix A, Table A.15.

[0286] No significant changes in the UV measurement at 280 nm were noted for solutions F1 (no polysorbate 80), F2 (0.01% polysorbate 80) and F3 (0.02% polysorbate 80). A slight decrease in the UV measurement at 280 nm was observed for solution F4 (0.04% polysorbate 80). Refer to Table A.15A in Appendix A.

[0287] No pH changes were noted for all solutions (Table A.16 in Appendix A).

[0288] No significant changes in Ab at 550 nm were noted for solutions F1 (no polysorbate 80), F2 (0.01% polysorbate 80) and F4 (0.04% polysorbate 80). A slight decrease in this parameter was observed in solution F3 (0.02% polysorbate 80). See Table A.16 in Appendix A.

[0289] The chromatogram obtained by SEC analysis shows a shoulder after the main peak, which is identified as a fragment of donemab, and therefore it is included in the % low molecular weight species (%LMW) or fragments. In solutions F1 (no polysorbate 80) and F2 (0.01% polysorbate 80), no significant changes in the SEC profile were observed. Solutions F3 (0.02% polysorbate 80) and F4 (0.04% polysorbate 80) show a reduction in the main peak and a simultaneous increase in fragmentation.

[0290] No changes in the percentage of aggregation were recorded throughout the study. For a graphical representation of the above considerations, refer to Table A.17 in Appendix A. Fig. 7A , Figure 7B and Figure 7C .

[0291] Non-reducing CE-SDS analysis showed a general increase in % donemab. See Table A.18 and Figure 8 .

[0292] A general increase in % purity was noted by reducing CE-SDS analysis in all solutions. Refer to Table A.19 and Fig. 9 .

[0293] Donezetumab was chemically stable after 2 days of rotation. Likewise, soluble aggregation was minimal for all samples after agitation. Solutions with polysorbate 80 had the fewest number of particles / mL relative to solutions without polysorbate 80, primarily 10 μm in size ( Fig. 10A and Fig. 10B ). Refer also to Table A.20 of Appendix A.

[0294] Without wishing to be bound by theory, the foregoing results suggest that including 0.01% (w / v) polysorbate 80 in a solution comprising donezumab protects donezumab from physical instabilities associated with mixing. For example, the foregoing results suggest that a solution comprising 10 mM citrate buffer, 0.01% (w / v) polysorbate 80, and at pH 6.0 provides a stable solution of donezumab. For a summary of the freeze-thaw and agitation study results, refer to Table A.21 of Appendix A.

[0295] 5.4 Solubility

[0296] In view of pH, freeze-thaw and agitation studies, the solubility of donezumab was studied in 10 mM citrate buffer at pH 6 and in the presence of 0.01% (w / v) polysorbate 80. The solution was concentrated after dialyzing against the selected citrate buffer. After the addition of polysorbate 80, the concentration was measured and showed to be ~125 mg / mL. The sample was stored at -5°C for 24 hours and the appearance of the solution was more milky than at time 0, but no phase separation occurred. Figures 11 A and Fig. 11B A snapshot of the sample is shown. This same sample was clarified after equilibration to room temperature.

[0297] The samples were stored at 2-8°C for 1 week before analysis. The donezumab solution maintained a yellow coloration throughout the study. No phase separation was observed after 24 hours of storage. After 1 week of storage at 2°C-8°C, the solution was clear with particles and filaments in solution. A slight reduction in UV determination was detected. Without wishing to be bound by theory, the absorbance (Ab) results at 550 nm have been affected by the yellow color of the solution. No pH changes were observed. The SEC results are consistent with those obtained in previous studies of donezumab solutions at lower concentrations.

[0298] The results are summarized in Table 9.

[0299] Table 9: Solubility study results

[0300]

[0301] 6. Conclusion

[0302] A series of preformulation studies were conducted to select the pH and reagents required to stabilize donezumab. These studies involved identifying a pH range of 5.0 to 7.0, studying the effects of polysorbate 80 on freeze-thaw and agitation, and the solubility of donezumab. The molecule demonstrated good chemical stability at pH 5.5 and pH 6.0. The pH 5.5 solution showed the lowest % purity reduction by reducing and non-reducing CE-SDS. The pH 6.0 solution showed a reduction in % purity by reducing and non-reducing CE-SDS.

[0303] Without wishing to be bound by theory, these results suggest that formulating donetumab at pH 6.0 provides benefits with respect to the stability of the solution.

[0304] The addition of 0.01% (w / v) polysorbate 80 surfactant was also investigated. Without wishing to be bound by theory, the results suggest that formulating donetumab with 0.01% (w / v) polysorbate 80 provides benefits with respect to the stability of the solution.

[0305] During solubility experiments, no phase separation was observed at a concentration of approximately 125 mg / mL.

[0306] Table 10 summarizes certain observations from the aforementioned preformulation studies.

[0307] Table 10

[0308]

[0309]

[0310]

[0311]

[0312]

[0313]

[0314]

[0315]

[0316]

[0317]

[0318]

[0319]

[0320]

[0321]

[0322]

[0323]

[0324]

[0325]

[0326]

[0327]

[0328]

[0329]

[0330]

[0331]

[0332]

[0333]

[0334]

[0335]

[0336]

[0337]

[0338]

[0339]

[0340] Example 2 - Further solution studies on Donetuzumab

[0341] 2.1 Study design

[0342] Initial prototype solution screening studies evaluated thirteen prototypes with various donetumab concentrations, tonicity agents, buffer systems, and surfactant levels.

[0343] Donetazomab solution was prepared and 20mL vials were filled with 14mL solution to provide the worst case for headspace and potential sensitivity to oxidation and agitation. The vials were stoppered, capped and sealed, and stored for 3 months under upright storage conditions at 5°C, 25°C and 35°C (except for the 'R2' and 'R13' solutions at 10 and 17.5mg / mL described in the next section, which were stored only at 5°C and 35°C due to material constraints). The vials were also subjected to ISTA 3A transport stress assessment. A subset of solutions of interest was selected based on 3 months of data, and the retained solution was tested after 29 months of storage.

[0344] Table 11 provides a summary of the solutions studied. P188 refers to Poloxamer 188. PS20 refers to Polysorbate 20 (polyoxyethylene (20) sorbitan monolaurate). PS80 refers to Polysorbate 80 (polyoxyethylene (20) sorbitan monooleate).

[0345] As discussed in Example 1, without wishing to be bound by theory, it is believed that the pH of the antibody solution affects the properties of the solution and / or the antibody in solution. Also as discussed in Example 1, without wishing to be bound by theory, the results of this Example suggest that antibody stability in solution can be maximized by preparing the solution at a pH of 5.5 to 6.0. Given this information, in this Example, solutions were prepared at a target pH of 6.0.

[0346]

[0347] Without wishing to be bound by theory, it is believed that the concentration of antibodies in the solution affects the stability of the solution. For example, without wishing to be bound by theory, it is believed that even a highly purified antibody sample will still contain trace impurities, such as enzymes (e.g., esterases). Without wishing to be bound by theory, it is believed that these impurities may promote (e.g., catalyze) the process that leads to solution degradation and / or particle formation. Accordingly, without wishing to be bound by theory, it is believed that higher concentrations of antibodies in the solution are associated with higher concentrations of trace impurities (e.g., enzymes), and therefore, are associated with a greater likelihood of solution degradation occurring and / or particle formation in the solution (each of which is undesirable). For example, in a solution containing polyoxyethylene (20) sorbitan monooleate, trace amounts of esterases may catalyze the hydrolysis of polyoxyethylene (20) sorbitan monooleate and generate free oleic acid, which in turn may cause the accumulation of particle matter.

[0348] At least for these reasons, it should be understood that antibody concentration is one of the many factors that affect solution stability. Therefore, antibody concentration is a variable examined in this study. Specifically, a Donenumab concentration range of 10 to 50 mg / mL was studied. It is estimated that a 50 mg / mL concentration (R3) provides the worst case of potential particle growth over time, because the lyophilized formulations examined earlier show a trend of particle growth according to the increased Donenumab concentration. The use of a 50 mg / mL Donenumab solution concentration can allow a single vial to be used for a clinical dose of 700 mg. 10 and 25 mg / mL concentrations are selected as the lower and upper limits of the range expected for a feasible solution formulation, to mitigate the risk of particle growth and provide an acceptable stability profile. 17.5 mg / mL concentration (R13) is selected as the midpoint between the lower and upper limits of the estimated acceptable solution range. At 17.5 mg / mL concentration, a clinical dose of 700 mg can be administered from two 20-mL drug product vials.

[0349] Without wishing to be bound by theory, it is believed that the buffer properties of the antibody solution can affect the stability of the solution and / or the antibody therein. For example, without wishing to be bound by theory, it is believed that when present in solution, polyoxyethylene (20) sorbitan monooleate is susceptible to oxidation. Without wishing to be bound by theory, it is believed that oxidation of polyoxyethylene (20) sorbitan monooleate generates free radical species that can attack the antibody and cause protein changes and / or degradation. Without wishing to be bound by theory, it is also believed that oxidation of polyoxyethylene (20) sorbitan monooleate leads to an increase in the amount of free oleic acid in the solution, which in turn causes an increase in particulate matter formation in the solution. Without wishing to be bound by theory, it is believed that certain buffers can reduce or prevent oxidation of polyoxyethylene (20) sorbitan monooleate. Accordingly, it is believed that the selection of one or more buffers used in the antibody solution can affect the stability of the antibody solution by reducing or preventing changes and / or degradation of the antibody and / or reducing or preventing particulate matter formation. In this study, several prototype solutions were evaluated with a 10 mM citrate buffer system to minimize antibody matrix changes between the lyophilized formulations examined earlier and the study solutions. 25 mg / mL donetumab solutions R5 (containing histidine / citrate at a 3:1 ratio) and R10 (containing all histidine) were also studied for comparison against R1 containing 10 mM citrate with 25 mg / mL donetumab.

[0350] Without wishing to be bound by theory, it is believed that the properties of one or more tonicity agents present in the antibody solution can affect the stability of the solution and / or the antibody therein. For example, without wishing to be bound by theory, it is believed that certain tonicity agents can act as cryoprotectants to prevent degradation of the antibody during freeze-thaw processes. Accordingly, it is believed that the selection of one or more buffers used in the antibody solution can affect the stability of the antibody solution. In this study, several solutions evaluated 10% w / v sucrose levels. Previous lyophilized formulations have utilized 8% w / v sucrose to provide isotonic conditions. Prototypes R4 and R6 evaluated glycine in combination with sucrose or mannitol, respectively, to provide an alternative to 10% w / v sucrose levels. Prototype R8 evaluated the addition of methionine to mitigate any potential oxidation-related chemical degradation observed in previous forced degradation studies. Solutions R7 and R9 evaluated trehalose and sodium chloride as alternative tonicity agents for sucrose. After storage at 5°C for 29 months, solution vial retention solutions for the lead prototype and selected prototypes from the initial study were evaluated. Based on the extended 5°C storage conditions and acceptable chemical and physical property data, the sucrose-based solution formulation was modified to provide isotonic conditions (reducing sucrose from 10% w / v to 8% w / v).

[0351] Without wishing to be bound by theory, it is believed that the nature and / or concentration of one or more surfactants present in the antibody solution can affect the stability of the solution and / or the antibody therein. For example, without wishing to be bound by theory, it is believed that in a solution containing polyoxyethylene (20) sorbitan monooleate (PS80), a higher concentration of PS80 is associated with a greater number of free radical species (which, as discussed above, are themselves formed by oxidation of PS80), while a lower concentration of PS80 is associated with a lower number of free radical species. As discussed above, without wishing to be bound by theory, it is believed that free radical species may attack the antibody and cause protein changes and / or degradation. Accordingly, without wishing to be bound by theory, it is believed that it is preferable to reduce the number of free radical species present in the antibody solution. Without wishing to be bound by theory, it is believed that one way to do this is by adjusting the concentration of the PS80 surfactant in the solution (e.g., identifying a concentration that is high enough to impart beneficial properties, but low enough to minimize or avoid the generation of free radical species). Previous lyophilized formulations utilized PS80 at 0.02% w / v. In this study, several solutions had a target PS80 concentration of 0.02% w / v, except for R11 which used 0.02% w / v polysorbate 20 (PS20) and R12 which contained 0.04% w / v poloxamer 188. Solutions R1 and R3 contained 0.20% w / v PS80.

[0352] In a separate study, prototype solution vials were also subjected to ISTA-3A shipping evaluation to understand if there was any sensitivity to particle growth due to shipping stress conditions. Particle generation has been observed after exposure of various lyophilized formulations to ISTA-3A shipping conditions.

[0353] 2.2 Research Results

[0354] When differences between solutions are discussed, reference is made to the corresponding figure (by figure number). When there is an associated potential specification for a chemical or physical property attribute, a line is shown on the figure to indicate the specification limit.

[0355] After 3 months storage at 35 °C, SEC monomer loss and corresponding aggregate growth were observed for all solutions ( Fig. 12A and Fig. 12B ). At 25°C, both the solution containing sodium chloride and the alternative surfactant with PS80 all showed higher monomer loss when compared to the other solutions. The solution containing sodium chloride also showed monomer loss after 3 months at 5°C storage. Without wishing to be bound by theory, these results suggest that the solution containing PS80 may provide improved stability over time compared to the solution containing PS20, and / or that the solution containing sodium chloride may experience reduced stability over time compared to the solution containing a different tonicity agent.

[0356] CE-SDS reductive data ( Fig.13A and Fig. 13B ) show that the two solutions containing glycine had a higher % purity loss and correspondingly higher levels of total aggregates / non-reducible species relative to all other solutions over 3 months of storage at 25°C and 35°C. All solutions had similar stability profiles with respect to total fragments. Without wishing to be bound by theory, these results suggest that including glycine in the solutions may have a detrimental effect on the long-term stability of the solutions.

[0357] Non-reducing CE-SDS data ( Fig.14A and Fig. 14B ) showed similar main peak purity and overall aggregate stability profiles for all solutions. The 10 mM histidine solution showed lower overall aggregates after 3 months at all temperature conditions relative to all other solutions. The solution containing 7.5 mM histidine showed less overall aggregate growth than the other solutions, but above the level of the 10 mM histidine formulation, providing evidence that the presence of increased histidine levels in the DP matrix may prevent aggregate formation.

[0358] Evaluation of the surfactant chemistry data showed that none of the PS80-based solutions showed any appreciable change in total oleic acid (TOA) over 3 months of storage. Fig.15 It was shown that free oleic acid (FOA) in solutions containing sodium chloride and 10 mM histidine was higher than all other solutions containing 0.02% w / v PS80 after 3 months storage at 25°C and 35°C. After 3 months at 25°C, greater than 25% of the TOA level was present as FOA in these solutions, suggesting a higher sensitivity of these solutions to PS80 hydrolysis.

[0359] Without wishing to be bound by theory, it is believed that esterases contained in the solution of the antibody may catalyze the hydrolysis of PS80 to yield free oleic acid. Without wishing to be bound by theory, it is believed that increased amounts of free oleic acid in the solution of the antibody result in the formation of more particulate material.

[0360] Solutions containing PS20 showed an increase in free lauric acid after 3 months at 25°C, approaching similar levels observed for 10 mM histidine-based solutions (approximately 25% of the total present in a free state). Solutions containing poloxamer showed no indication of loss over storage time at 5°C. Without wishing to be bound by theory, these results suggest that solutions containing PS20 and / or histidine may be less preferred than solutions containing PS80 due to the increase in free lauric acid observed in solutions containing PS20 or histidine.

[0361] Fig.16A , Fig. 16B , Fig.17A , Fig. 17B , Fig. 17C , Fig.17D , Fig.18A and Fig.18BParticle data (MFI and light obscuration) about the solution under investigation are depicted. For all solutions except glycine and histidine solutions, particle data remain low for all temperatures at a time point of 3 months. Compared with other solutions, solutions containing glycine, methionine and 10 mM histidine show slightly elevated 10 and 25 micron particle count light obscuration data. Without wishing to be bound by theory, these results suggest that, compared with solutions containing, for example, sucrose and / or trehalose, antibody solutions containing glycine, methionine and / or histidine cause an increase in the amount of particulate matter, and therefore, from the standpoint of reducing particulate matter and / or reducing particulate matter formation over time, solutions containing sucrose and / or trehalose may be preferred. When 29 months of 5°C data are compared with 3 months of stability data, there are few changes in chemical or physical properties from 3 months of 5°C data. SEC data show a slight increase in aggregates and a corresponding reduction in monomers. Compared to the differences observed between the 5°C and accelerated temperature data at 3 months, the changes between 3 and 29 months at 5°C storage were less pronounced.

[0362] The sample of the solution is subjected to the ISTA-3A test. As described elsewhere herein, the details of the ISTA-3A test are known to those of ordinary skill in the art and can be obtained at ista.org through the International Safe Transit Association. In short, the ISTA-3A test is used to check the effects of vibration, shock and other stresses that may be encountered during material handling and / or transit in a parcel distribution system. When testing, the test material is subjected to drops, vibrations and impacts. It is not desirable to be bound by theory, and it is believed that the damage to the test material is cumulative. In some test cases, an acceleration factor can be used. It is not desirable to be bound by theory, and it is believed that the use of the acceleration factor allows an increase in power in exchange for an increase in time. For example, it is not desirable to be bound by theory, and it is believed that subjecting the sample to the first vibration power for one hour results in the same effect on the sample as subjecting the sample to the second vibration power (whose intensity is one-fifth of the first vibration power) for five hours.

[0363] Fig.19A , Fig.19B , Fig. 20A , Fig. 20B , Fig.21A , Fig.21B , Fig.22A , Fig. 22B and Fig. 22CPresented in the ISTA-3A transport exposure data for the test solutions, including data on particles of various sizes as measured by microflow imaging (MFI), data on particles of various sizes as measured by light obscuration using a high accuracy liquid particle counter (HIAC), data on percentage monomer content as measured by size exclusion chromatography, data on total aggregate content as measured by size exclusion chromatography, data on purity as measured by non-reducing CE-SDS, data on percentage fragment content as measured by non-reducing CE-SDS, and data on percentage aggregates as measured by non-reducing CE-SDS. The data do not indicate substantial differences in chemical properties or particle counts between control samples of the solutions (which were not subjected to ISTA-3A transport testing) and samples subjected to ISTA-3A transport testing (except for solutions containing poloxamer). For example, Fig.23A and Fig. 23B As shown in, the solution containing poloxamer shows a several-fold increase of particles ≥2 μm and particles ≥5 μm, as measured by M FI. Without wishing to be bound by theory, these results suggest that solutions containing poloxamer as (or a kind of) surfactants may be less compliant with packaging and transportation. However, for all solutions except the solution containing poloxamer, the solution does not show any significant increase in particle formation. It is worth noting that this result is in contrast to the ISTA-3A transportation test results performed on the lyophilized formulations of antibodies, as discussed elsewhere herein, the lyophilized formulations show a continuous higher level of granular material after storage for one month and at subsequent time points. Without wishing to be bound by theory, these results suggest that antibody solutions similar or identical to the antibody solutions tested herein (e.g., containing citrate or histidine buffer, containing one or more tonicity agents selected from sucrose, trehalose, mannitol and glycine, and anti-N3pG1u A β antibody solutions containing PS20 and / or PS80 surfactants) may show properties (e.g., physicochemical properties) that make it compliant with packaging and transportation.

[0364] Without wishing to be bound by theory, the aforementioned chemical and stability performance data of the test solutions suggest that the presence of histidine, methionine, sodium chloride and / or glycine in the solution may have a negative impact on one or more chemical properties, particle growth, and / or solution and / or antibody stability. Without wishing to be bound by theory, the aforementioned data suggest that in a citrate buffer containing 10% w / v sucrose and 0.02% w / v PS80, a combination of 17.5 mg / mL anti-N3pGlu Aβ antibody concentration provides an ideal solution in terms of practicality and stability. For example, the chemical and particle data of the antibody solution containing this combination of ingredients are comparable to the freeze-dried antibody matrix examined earlier, but the antibody solution containing this combination shows better stability over time compared to the freeze-dried antibody matrix examined earlier.

[0365] 2.3 Further studies on tonicity agents and extended storage of solutions at 5°C

[0366] Two other solutions were prepared at 17.5 mg / mL Donetuzumab concentration in 5 mM citrate and containing 0.02% w / v PS80. In these solutions (labeled P1 and P2), sucrose was replaced by mannitol (5.3% w / v concentration) or trehalose (10% w / v concentration). Sample vials were filled to 20 mL fill volume and the solutions were stored. FIG. 23A to FIG. 29B The chemical and physical property data for the other two solutions and a solution (identified as R13) containing 17.5 mg / mL of donemab in 10 mM citrate containing 0.02% PS80 and 10% w / v sucrose are shown in the figure, the latter solution is shown for comparison with the other two solutions. Samples of solutions P1 and P2 were stored at 5°C for 1, 3, and 6 months, and at 25°C for 1, 3, and 6 months. Samples of solution R13 were stored at 5°C for 3 and 29 months, and at 35°C for 3 months. FIG. 23A to FIG. 29B The collected data shown in include percent monomer content as measured by size exclusion chromatography, percent total aggregate content as measured by size exclusion chromatography, purity as measured by reducing CE-SDS, percent fragment content as measured by reducing CE-SDS, percent aggregate as measured by reducing CE-SDS, purity as measured by non-reducing CE-SDS, percent fragment content as measured by non-reducing CE-SDS, percent aggregate as measured by non-reducing CE-SDS, total oleic acid, free oleic acid, particles of various sizes as measured by microflow imaging (MFI), and particles of various sizes as measured by light obscuration using a high accuracy liquid particle counter (HIAC).

[0367] Comparison of the 29-month and 6-month 5°C data for the chemical and physical properties of the three solutions (i.e., the solution containing sucrose, the solution containing mannitol, and the solution containing trehalose) did not reveal significant differences among the three solutions. In addition, the 3-month 35°C data did not indicate stability concerns about any of the three solutions. The increased SEC monomer loss and total aggregate increase, degree of total acidic variants, and reduction in the main peak observed upon high temperature storage were within expectations. Without wishing to be bound by theory, the foregoing data suggest that solutions containing a combination of donezumab (e.g., at a concentration of 17.5 mg / mL), PS80 (e.g., at a concentration of 0.02% w / v), and one or more of sucrose (e.g., at a concentration of 10% w / v), mannitol (e.g., at a concentration of 5.3% w / v), or trehalose (e.g., at a concentration of 10% w / v) in citrate (e.g., at a concentration of 5 mM or 10 mM) can exhibit acceptable stability over time (e.g., 3 months, 6 months, or 29 months at 5°C, 25°C, and / or 35°C) and / or improved stability over time (e.g., 3 months, 6 months, or 29 months at 5°C, 25°C, and / or 35°C), e.g., improved stability compared to solutions omitting one or more of citrate (e.g., 5 mM or 10 mM citrate), PS80 (e.g., 0.02% w / v), or trehalose (e.g., at a concentration of 10% w / v). PS80) and one or more of sucrose, mannitol and / or trehalose (e.g., sucrose at a concentration of 10% w / v, mannitol at a concentration of 5.3% w / v, or trehalose at a concentration of 10% w / v).

[0368] 2.4 Peptide mapping studies

[0369] After storage at 5°C for 29 months, peptide mapping by LC-MS was performed for selected solutions. Solutions at 10, 17.5 and 25 mg / mL in citrate matrix (R2, R13 and R8, respectively) and a histidine-based solution at 25 mg / mL (R10) were compared against a reference standard. The 25 mg / mL solution in citrate matrix (R8) also contained 5 mM methionine. Table 12 provides the peptide mapping results.

[0370] Table 12. LC-MS peptide mapping analysis of selected prototypes after storage at 5°C for 29 months

[0371]

[0372] The peptide mapping results for the three citrate-based solutions were comparable to the reference standard. It appears that the addition of methionine had no additional benefit in reducing oxidized species beyond the levels observed in the other citrate-based solutions. The histidine-based solutions showed an increase in oxidized species (HC M250) relative to the citrate solutions and the reference standard.

[0373] In the overall peptide map, the citrate-based solutions were considered comparable to the reference standard. All solutions had reduced levels of incomplete pyroglutamate and Des Gly amidated degradants compared to the reference standard.

[0374] Without wishing to be bound by theory, these peptide mapping results suggest that incorporating citrate buffer into a solution of anti-N3pGluAβ antibody confers a benefit in terms of reducing antibody degradation. Without wishing to be bound by theory, these results suggest that incorporating histidine into a solution of anti-N3pGluAβ antibody has a deleterious effect on antibody degradation. Furthermore, without wishing to be bound by theory, these peptide mapping results combined with the results discussed above for solutions containing sucrose, solutions containing mannitol, and solutions containing trehalose (e.g., lack of a significant increase in aggregates or particles when stored at 5°C for 29 months) further suggest that solutions containing citrate (e.g., at 5 mM or 1 mM) may have a beneficial effect on antibody degradation. 0 mM concentration), PS80 (e.g., at a concentration of 0.02%), and a combination of one or more of sucrose (e.g., at a concentration of 10% w / v), mannitol (e.g., at a concentration of 5.3% w / w), or trehalose (e.g., at a concentration of 10% w / v) exhibit acceptable stability over time (e.g., 3 months, 6 months, or 29 months at 5° C., 25° C., and / or 35° C.) and / or stability over time Improved stability in the past (e.g., 3 months, 6 months, or 29 months at 5°C, 25°C, and / or 35°C), for example, improved stability compared to solutions omitting one or more of: citrate (e.g., 5 mM or 10 mM citrate), PS80 (e.g., 0.02% w / v PS80), and one or more of sucrose, mannitol, and / or trehalose (e.g., sucrose at a concentration of 10% w / v, mannitol at a concentration of 5.3% w / v, or trehalose at a concentration of 10% w / v).

[0375] Table 13. Donezetimibe solution formulation

[0376]

[0377] Example 3 - Product Specifications

[0378] Complete specifications for the donetumab drug product are provided below.

[0379] Table 14. Specifications for Donezetimibe Drug Product

[0380]

[0381]

[0382] Abbreviations: CE-SDS = capillary electrophoresis with sodium dodecyl sulfate; CEX = cation exchange chromatography; HPLC-UV = high performance liquid chromatography-ultraviolet spectroscopy; icIEF = imaging capillary isoelectric focusing; SEC = size exclusion chromatography; UV = ultraviolet spectroscopy.

[0383] aCompliance with the reference standard indicates that the sample chromatogram compares more favorably with the reference standard in terms of main peak retention time and chromatogram.

[0384] b Identity was confirmed if the test sample exhibited a sigmoidal dose-response curve similar to that of the donetumab reference standard.

[0385] c This is equivalent to not less than 16.63 mg / mL and not more than 18.38 mg / mL.

[0386] d This is equivalent to not less than 16.28 mg / mL and not more than 18.73 mg / mL.

[0387] eConform to reference standard indicates that the sample electropherogram compares favorably to the reference standard, based on examples from the method and clinical experience, with no new peaks and / or no missing peaks.

[0388] fIn the context of these specifications, passing refers to initial test results that meet the passing specifications.

[0389] gIn the context of these specifications, end of shelf life refers to test results for the entire storage period up to and including 24 months which meets the end of shelf life specification.

[0390] Table 15. CEX method details

[0391]

[0392] MES = 2-(N-morpholino)ethanesulfonic acid, TRIS = tris(hydroxymethyl)aminomethane, HEPES = (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), CHES = N-cyclohexyl-2-aminoethanesulfonic acid, CAPS = N-cyclohexyl-3-aminopropanesulfonic acid

[0393] Table 16. UV method details

[0394]

[0395] Table 17. SEC Method

[0396]

[0397] Table 18. Cell-based potency assay details

[0398]

[0399] Table 19. CE-SDS reduction method

[0400]

[0401] Table 20. Method parameters for CE-SDS non-reducing

[0402]

[0403] Table 21. icIEF master mix composition and method details

[0404]

[0405] icIEF Method Details

[0406]

[0407] Table 22. Polysorbate 80 Method

[0408]

[0409] Sequence (underlined parts indicate CDR)

[0410] SEQ ID NO: 1; Light chain variable region (LCVR)

[0411]

[0412] SEQ ID NO: 2; Heavy chain variable region (HCVR)

[0413]

[0414] SEQ ID NO: 3; Light chain (LC)

[0415]

[0416] SEQ ID NO: 4; Heavy chain (HC)

[0417]

[0418] SEQ ID NO: 5; Light chain complementarity determining region 1 (LCDR1)

[0419] KSSQSLLYSRGKTYLN

[0420] SEQ ID NO: 6; Light chain complementarity determining region 2 (LCDR2)

[0421] AVSKLDS

[0422] SEQ ID NO: 7; Light chain complementarity determining region 3 (LCDR3)

[0423] VQGTHYPFT

[0424] SEQ ID NO: 8; Heavy chain complementarity determining region 1 (HCDR1)

[0425] GYDFTRYYIN

[0426] SEQ ID NO: 9; Heavy chain complementarity determining region 2 (HCDR2)

[0427] WINPGSGNTKYNEKFKG

[0428] SEQ ID NO: 10; Heavy chain complementarity determining region 3 (HCDR3)

[0429] EGITVY

[0430] SEQ ID NO: 11; Nucleotide sequence of SEQ ID NO: 1; Light chain variable region (LCVR)

[0431]

[0432] SEQ ID NO.12; Nucleotide sequence of SEQ ID NO:2; Heavy chain variable region (HCVR)

[0433]

[0434] SEQ ID NO.13; Nucleotide sequence related to SEQ ID NO:3; Light chain (LC)

[0435]

[0436] SEQ ID NO.14; Nucleotide sequence related to SEQ ID NO:4; Heavy chain (HC)

[0437]

Claims

1. A pharmaceutical solution comprising: An anti-N3pGluAβ antibody comprising (a) a light chain variable region (LCVR) comprising LCDR1 of SEQ ID NO: 5, LCDR2 of SEQ ID NO: 6, and LCDR3 of SEQ ID NO: 7, and (b) a heavy chain variable region (HCVR) comprising HCDR1 of SEQ ID NO: 8, HCDR2 of SEQ ID NO: 9, and HCDR3 of SEQ ID NO: 10, Buffer, Tonicity agents, Surfactants, and optional excipients; The amount is sufficient to combine to make the pharmaceutical solution exhibit one or more of the following: (a) an antibody monomer content of at least 95% relative to the total antibody peak area as measured by size exclusion chromatography after the drug solution has been stored at 2-8°C for 3 months; (b) a total aggregate content of less than 5% relative to the total antibody peak area as measured by size exclusion chromatography after the drug solution has been stored at 2-8°C for 3 months; (c) an antibody purity of at least 94 area % as measured by reducing capillary electrophoresis sodium dodecyl sulfate (CE-SDS) after the drug solution has been stored at 35°C for 3 months; (d) after the drug solution has been stored at 2-8° C. for 3 months, (i) a total aggregate content of less than 5% relative to the total antibody peak area as measured by size exclusion, or (ii) a total aggregate content of less than 8.5 area % as measured by non-reducing CE-SDS; (e) less than 500 particles / ml as measured by light obscuration using a high accuracy liquid particle counter (HIAC) after the drug solution has been stored at 2-8°C for 3 months, wherein the size of the particles is greater than 2 μm; (f) less than 100 particles / ml as measured by light obscuration using a high accuracy liquid particle counter (HIAC) after the drug solution has been stored at 2-8°C for 3 months, wherein the size of the particles is greater than 5 μm; (g) the UV absorbance at 550 nm changes by less than ±3% within 4 weeks of storage at 2-8°C; (h) a change in protein content of 1% to 13% after storage at 2-8°C for 4 weeks as measured by UV absorbance at 280 nm; (i) after storage at 2-8°C for 4 weeks, at least 93% of the anti-N3pGlu antibody appears in the main chromatographic peak (monomer) when analyzed by size exclusion chromatography; (j) no more than 11% decrease in the amount of anti-N3pGlu antibody as measured by non-reducing CE-SDS after the drug solution has been stored at 2-8°C for 4 weeks; and (k) After the drug solution has been stored at 2-8°C for 4 weeks, no more than four particles have a size of 25 μm or less as measured by differential counts per milliliter.

2. The pharmaceutical solution according to claim 1, comprising an amount of anti-N3pGluAβ antibody, a buffer, a tonicity agent, a surfactant and an optional excipient sufficient to combine to make the pharmaceutical solution exhibit one or more of the following: (a) an antibody monomer content of at least 95% relative to the total antibody peak area as measured by size exclusion chromatography after the drug solution has been stored at about 5°C for 3 months; (b) a total aggregate content of less than 5% relative to the total antibody peak area as measured by size exclusion chromatography after the drug solution has been stored at about 5°C for 3 months; (c) the change in UV absorbance at 550 nm is less than ±3% within 4 weeks of storage at 5°C; (d) a change in protein content of 1% to 13% after storage at about 5°C for 4 weeks as measured by UV absorbance at 280 nm; (e) after storage at about 5° C. for 4 weeks, at least 93% of the anti-N3pGlu antibody appears in the main chromatographic peak (monomer) as analyzed by size exclusion chromatography; (f) no more than an 11% decrease in the amount of anti-N3pGlu antibody as measured by non-reducing CE-SDS after the drug solution has been stored at about 5°C for 4 weeks; and (g) After the drug solution has been stored at about 5°C for 4 weeks, no more than four particles have a size of 25 μm or less as measured by differential counts per milliliter.

3. The pharmaceutical solution according to claim 1 or claim 2, comprising an amount of anti-N3pGlu Aβ antibody, a buffer, a tonicity agent, a surfactant and an optional excipient sufficient to combine to make the pharmaceutical solution exhibit one or more of the following: (a) an antibody monomer content of at least 96% relative to the total antibody peak area as measured by size exclusion chromatography after the drug solution has been stored at 2-8°C for 3 months; (b) a total aggregate content of less than 4% relative to the total antibody peak area as measured by size exclusion chromatography after the drug solution has been stored at 2-8°C for 3 months; (c) an antibody purity of at least 95 area % as measured by reducing CE-SDS after the drug solution has been stored at 35° C. for 3 months; (d) after storage at 2-8° C. for 4 weeks, 93.3% to 93.8% of the anti-N3pGlu antibody appeared in the main chromatographic peak (monomer) as analyzed by size exclusion chromatography; (e) No more than 6.9% decrease in the amount of anti-N3pGlu antibody as measured by reducing CE-SDS after the drug solution has been stored at 2-8°C for 4 weeks.

4. The pharmaceutical solution according to claim 2, comprising an amount of anti-N3pGluAβ antibody, a buffer, a tonicity agent, a surfactant and an optional excipient sufficient to combine to make the pharmaceutical solution exhibit one or more of the following: (a) an antibody monomer content of at least 96% relative to the total antibody peak area as measured by size exclusion chromatography after the drug solution has been stored at about 5°C for 3 months; (b) a total aggregate content of less than 4% relative to the total antibody peak area as measured by size exclusion chromatography after the drug solution has been stored at about 5°C for 3 months; (c) an antibody purity of at least 95 area % as measured by reducing CE-SDS after the drug solution has been stored at about 5°C for 3 months; (d) after storage at about 5° C. for 4 weeks, 93.3% to 93.8% of the anti-N3pGlu antibodies appeared in the main peak as analyzed by size exclusion chromatography; (e) no more than a 6.9% decrease in the amount of anti-N3pGlu antibody as measured by reducing CE-SDS after the drug solution has been stored at about 5° C. for 4 weeks; (f) less than 500 particles / ml as measured by light obscuration using HIAC after the drug solution has been stored at about 5°C for 3 months, wherein the particles are greater than 2 μm in size; and (g) less than 100 particles / ml as measured by light obscuration using HIAC after the drug solution has been stored at about 5°C for 3 months, wherein the particles are greater than 5 μm in size.

5. The pharmaceutical solution of any one of claims 1 to 4, wherein one or more of features (a)-(k) in claim 1 is present before and after storage, one or more of features (a)-(g) in claim 2 is present before and after storage, one or more of features (a)-(e) in claim 3 is present before and after storage, and / or one or more of features (a)-(g) in claim 4 is present before and after storage.

6. The pharmaceutical solution according to any preceding claim, wherein the LCVR of the anti-N3pGlu Aβ antibody comprises SEQ ID NO: 1, and / or the HCVR of the anti-N3pGlu Aβ antibody comprises SEQ ID NO:

2.

7. The pharmaceutical solution according to any preceding claim, wherein the anti-N3pGlu Aβ antibody comprises a light chain (LC) comprising SEQ ID NO: 3, and / or a heavy chain (HC) comprising SEQ ID NO:

4.

8. A pharmaceutical solution according to any preceding claim having a pH of 5.0 to 7.

5.

9. A pharmaceutical solution according to any preceding claim, comprising polyoxyethylene (20) sorbitan monooleate and exhibiting a total free oleic acid content of less than 0.0025% by volume weight as measured by high performance liquid chromatography with UV detection (HPLC-UV) using an internal standard after the pharmaceutical solution has been stored at 2-8°C for 3 months.

10. The pharmaceutical solution according to any one of claims 1 to 8, comprising polyoxyethylene (20) sorbitan monooleate and exhibiting a total free oleic acid content of less than 0.0025% by volume weight as measured by high performance liquid chromatography with UV detection (HPLC-UV) using an internal standard after the pharmaceutical solution has been stored at 2-8°C for 29 months.

11. The pharmaceutical solution according to any preceding claim, wherein the buffer comprises an organic acid salt, an inorganic acid salt, an amino acid, and combinations thereof.

12. The pharmaceutical solution according to any preceding claim, wherein the buffer comprises citric acid or a salt thereof, acetic acid or a salt thereof, ascorbic acid or a salt thereof, carbonic acid or a salt thereof, tartaric acid or a salt thereof, gluconic acid or a salt thereof, succinic acid or a salt thereof, phosphoric acid or a salt thereof, phthalic acid or a salt thereof, arginine or a salt thereof, lysine or a salt thereof, histidine or a salt thereof, ornithine or a salt thereof, isoleucine or a salt thereof, leucine or a salt thereof, alanine or a salt thereof, glycine or a salt thereof, glutamic acid or a salt thereof, aspartic acid or a salt thereof, and combinations thereof.

13. The pharmaceutical solution according to any preceding claim, wherein the buffer comprises citric acid or a salt thereof, histidine or a salt thereof, and combinations thereof.

14. The pharmaceutical solution according to any preceding claim, wherein the buffer is a single buffer system.

15. The pharmaceutical solution according to any preceding claim, wherein the tonicity agent is selected from a sugar, an amino acid, a salt or a combination thereof.

16. The pharmaceutical solution according to any preceding claim, wherein the tonicity agent is selected from the group consisting of monosaccharides, disaccharides, polysaccharides and combinations thereof.

17. The pharmaceutical solution according to any preceding claim, wherein the tonicity agent is selected from sodium chloride, arginine or a salt thereof, lysine or a salt thereof, histidine or a salt thereof, methionine or a salt thereof, ornithine or a salt thereof, isoleucine or a salt thereof, leucine or a salt thereof, alanine or a salt thereof, glycine or a salt thereof, glutamic acid or a salt thereof, aspartic acid or a salt thereof, sucrose, fructose, glucose, maltose, trehalose, galactose, mannose, sorbose, lactose, cellobiose, mannitol, lactitol, xylitol, sorbitol and maltitol, and combinations thereof.

18. The pharmaceutical solution according to any preceding claim, wherein the pharmaceutical solution comprises a single tonicity agent.

19. The pharmaceutical solution according to any preceding claim, wherein the surfactant is selected from the group consisting of polyoxyethylene sorbitan esters, poloxamers, and combinations thereof.

20. The pharmaceutical solution of any one of claims 1-10, wherein the pharmaceutical solution does not contain one or more of sodium chloride, trehalose, and mannitol.

21. The pharmaceutical solution according to any one of claims 1-10, wherein the pharmaceutical solution does not contain one or more of glycine, poloxamer and polyoxyethylene (20) sorbitan monolaurate.

22. A pharmaceutical solution according to any preceding claim, comprising: anti-N3pGlu antibody at a concentration of 1 to 40 mg / mL; Buffer in an amount ranging from 1 mM to 30 mM; a tonicity agent in an amount of 1% to 20% by weight by volume; and The surfactant is present in an amount of 0.005% by volume to 0.06% by volume.

23. The pharmaceutical solution according to claim 22, comprising: anti-N3pGlu antibody at a concentration of 10 to 25 mg / mL; Buffer in an amount of 5 mM to 15 mM; a tonicity agent in an amount of 5% to 15% by volume; and The surfactant is present in an amount of 0.01% to 0.04% by volume.

24. The pharmaceutical solution according to claim 22 or 23, comprising a buffer selected from citric acid or a salt thereof, a tonicity agent which is sucrose and a surfactant which is polyoxyethylene (20) sorbitan monooleate.

25. The pharmaceutical solution according to claim 24, comprising: anti-N3pGlu antibody at a concentration of 17.5 mg / mL; 10 mM amount of citric acid or its salt; sucrose in an amount of 8% by weight (w / v); and Polyoxyethylene (20) sorbitan monooleate in an amount of 0.02% by volume.

26. The pharmaceutical solution according to any one of claims 22-25, having a pH of 5.0 to 7.

0.

27. The pharmaceutical solution of any one of claims 22-26, having a pH of 6.

0.

28. A method of preparing a pharmaceutical solution according to any preceding claim, the method comprising: An anti-N3pGlu A[beta] antibody, a buffer, a tonicity agent, a surfactant, and one or more optional excipients are combined.

29. The method of claim 28, wherein the anti-N3pGluA[beta] antibody is not reconstituted from lyophilized material.

30. A vessel comprising the pharmaceutical solution according to any one of claims 1-27.

31. A method of treating a disease characterized by amyloid beta (A[beta]) deposition, the method comprising administering to a patient in need thereof a therapeutically effective amount of the pharmaceutical solution of any one of claims 1-27.

32. The method of claim 31 comprising administering to a patient a pharmaceutical solution obtained from the vessel of claim 30.

33. The method of claim 31 or claim 32, comprising administering to the patient an anti-N3pGlu A[beta] antibody that has not been lyophilized.

34. The method according to any one of claims 31-33, wherein the disease is selected from Alzheimer's disease (AD), Down syndrome and cerebral amyloid angiopathy.

35. The method of claim 34, wherein the disease is selected from preclinical AD, prodromal AD, mild AD, moderate AD, and severe AD.

36. The method of any one of claims 31-35, comprising administering to the patient one or more doses of 100 mg to 10,000 mg of an anti-N3pGlu A[beta] antibody.

37. The pharmaceutical solution according to any one of claims 1-27, for use in the treatment of a disease characterized by amyloid beta (A[beta]) deposition.

38. The pharmaceutical solution for use according to claim 37, wherein the pharmaceutical solution is obtained from the vessel of claim 30.

39. The pharmaceutical solution for use according to claim 37 or claim 38, wherein the anti-N3pGlu A[beta] antibody is not lyophilized.

40. The pharmaceutical solution for use according to any one of claims 37 to 39, wherein the disease is selected from the group consisting of Alzheimer's disease (AD), Down syndrome and cerebral amyloid angiopathy.

41. The pharmaceutical solution for use according to claim 40, wherein the disease is selected from preclinical AD, prodromal AD, mild AD, moderate AD and severe AD.

42. The pharmaceutical solution for use according to any one of claims 37-41, wherein the treatment comprises administering to the patient one or more doses of 100 mg to 10,000 mg of anti-N3pGlu A[beta] antibody.

43. Use of the pharmaceutical solution of any one of claims 1-27 in the manufacture of a medicament for treating a disease characterized by amyloid beta (A[beta]) deposition.

44. Use of a pharmaceutical solution according to claim 43, wherein the pharmaceutical solution is obtained from the vessel of claim 30.

45. Use of a pharmaceutical solution according to claim 43 or claim 44, wherein the anti-N3pGlu A[beta] antibody is not lyophilized.

46. ​​Use of a pharmaceutical solution according to any one of claims 43 to 45, wherein the disease is selected from Alzheimer's disease (AD), Down syndrome and cerebral amyloid angiopathy.

47. Use of the pharmaceutical solution according to claim 46, wherein the disease is selected from preclinical AD, prodromal AD, mild AD, moderate AD and severe AD.

48. Use of a pharmaceutical solution according to any one of claims 43-47, wherein the treatment comprises administering to the patient one or more doses of 100 mg to 10,000 mg of an anti-N3pGlu A[beta] antibody.

49. A method of reducing amyloid beta (A[beta]) in a patient in need thereof, the method comprising administering to the patient the pharmaceutical solution of any one of claims 1-27.

50. The method of claim 49, wherein the administration results in a reduction in the amount of amyloid beta by at least 5%.

51. A pharmaceutical solution comprising: an anti-N3pGlu Aβ antibody at a concentration of 1 to 40 mg / mL, the anti-N3pGlu Aβ antibody comprising (a) a light chain variable region (LCVR) comprising LCDR1 of SEQ ID NO: 5, LCDR2 of SEQ ID NO: 6, and LCDR3 of SEQ ID NO: 7, and (b) a heavy chain variable region (HCVR) comprising HCDR1 of SEQ ID NO: 8, HCDR2 of SEQ ID NO: 9, and HCDR3 of SEQ ID NO: 10, 1mM to 30mM amount of buffer, A tonicity agent in an amount of 1% to 20% by volume weight, A surfactant in an amount of 0.005% by volume to 0.06% by volume, and Optional excipients.

52. The pharmaceutical solution of claim 51, wherein the LCVR of the anti-N3pGlu Aβ antibody comprises SEQ ID NO: 1, and / or the HCVR of the anti-N3pGlu Aβ antibody comprises SEQ ID NO:

2.

53. The pharmaceutical solution according to claim 51 or claim 52, wherein the anti-N3pGlu Aβ antibody comprises a light chain (LC) comprising SEQ ID NO: 3, and / or a heavy chain (HC) comprising SEQ ID NO:

4.

54. The pharmaceutical solution of any one of claims 51-53, having a pH of 5.0 to 7.

5.

55. The pharmaceutical solution of any one of claims 51-54, wherein the buffer comprises an organic acid salt, an inorganic acid salt, an amino acid, and combinations thereof.

56. The pharmaceutical solution of any one of claims 51-55, wherein the buffer comprises citric acid or a salt thereof, acetic acid or a salt thereof, ascorbic acid or a salt thereof, carbonic acid or a salt thereof, tartaric acid or a salt thereof, gluconic acid or a salt thereof, succinic acid or a salt thereof, phosphoric acid or a salt thereof, phthalic acid or a salt thereof, arginine or a salt thereof, lysine or a salt thereof, histidine or a salt thereof, ornithine or a salt thereof, isoleucine or a salt thereof, leucine or a salt thereof, alanine or a salt thereof, glycine or a salt thereof, glutamic acid or a salt thereof, aspartic acid or a salt thereof, and combinations thereof.

57. The pharmaceutical solution of any one of claims 51-56, wherein the buffer comprises citric acid or a salt thereof, histidine or a salt thereof, and combinations thereof.

58. The pharmaceutical solution of any one of claims 51-57, wherein the buffer is a single buffer system.

59. The pharmaceutical solution of any one of claims 51-58, wherein the tonicity agent is selected from a sugar, an amino acid, a salt, or a combination thereof.

60. The pharmaceutical solution of any one of claims 51-59, wherein the tonicity agent is selected from the group consisting of monosaccharides, disaccharides, polysaccharides, and combinations thereof.

61. The pharmaceutical solution of any one of claims 51-60, wherein the tonicity agent is selected from sodium chloride, arginine or a salt thereof, lysine or a salt thereof, histidine or a salt thereof, methionine or a salt thereof, ornithine or a salt thereof, isoleucine or a salt thereof, leucine or a salt thereof, alanine or a salt thereof, glycine or a salt thereof, glutamic acid or a salt thereof, aspartic acid or a salt thereof, sucrose, fructose, glucose, maltose, trehalose, galactose, mannose, sorbose, lactose, cellobiose, mannitol, lactitol, xylitol, sorbitol and maltitol, and combinations thereof.

62. The pharmaceutical solution of any one of claims 51-61, comprising a tonicity agent.

63. The pharmaceutical solution of any one of claims 51-62, wherein the surfactant is selected from the group consisting of polyoxyethylene sorbitan esters, poloxamers, and combinations thereof.

64. The pharmaceutical solution of any one of claims 51-62, wherein the pharmaceutical solution does not comprise one or more of sodium chloride, trehalose, and mannitol.

65. The pharmaceutical solution of any one of claims 51-62, wherein the pharmaceutical solution does not comprise one or more of glycine, poloxamer, and polyoxyethylene (20) sorbitan monolaurate.

66. The pharmaceutical solution according to any one of claims 51-65, comprising: anti-N3pGlu antibody at a concentration of 10 to 25 mg / mL; Buffer in an amount of 5 mM to 15 mM; a tonicity agent in an amount of 5% to 15% by volume; and The surfactant is present in an amount of 0.01% to 0.04% by volume.

67. The pharmaceutical solution according to any one of claims 51-66, comprising: anti-N3pGlu antibody at a concentration of 17.5 mg / mL; 10 mM amount of citric acid or its salt; Sucrose in an amount of 8% by volume; and Polyoxyethylene (20) sorbitan monooleate in an amount of 0.02% by volume.

68. The pharmaceutical solution of any one of claims 51-67, having a pH of 5.0 to 7.

0.

69. The pharmaceutical solution of any one of claims 51-68, having a pH of 6.

0.

70. The pharmaceutical solution according to any one of claims 51-69, comprising an amount of anti-N3pGlu Aβ antibody, a buffer, a tonicity agent, a surfactant, and an optional excipient sufficient to combine to allow the pharmaceutical solution to exhibit one or more of the following: (a) an antibody monomer content of at least 97% relative to the total antibody peak area as measured by size exclusion chromatography after the drug solution has been stored at 2-8°C for 3 months; (b) a total aggregate content of less than 2% relative to the total antibody peak area as measured by size exclusion chromatography after the drug solution has been stored at 2-8°C for 3 months; (c) an antibody purity of at least 92 area % as measured by reducing capillary electrophoresis sodium dodecyl sulfate (CE-SDS) after the drug solution has been stored at 35°C for 3 months; (d) after the drug solution has been stored at 2-8°C for 3 months, (i) less than 2% total aggregate content relative to the total antibody peak area as measured by size exclusion, or (ii) less than 1.5% total aggregate content as measured by non-reducing CE-SDS (e) less than 500 particles / ml as measured by light obscuration using a high accuracy liquid particle counter (HIAC) after the drug solution has been stored at 2-8°C for 3 months, wherein the size of the particles is greater than 2 μm; (f) less than 100 particles / ml as measured by light obscuration using a high accuracy liquid particle counter (HIAC) after the drug solution has been stored at 2-8°C for 3 months, wherein the size of the particles is greater than 5 μm; (g) the UV absorbance at 550 nm changes by less than ±3% within 4 weeks of storage at 2-8°C; (h) a change in protein content of 1% to 13% after storage at 2-8°C for 4 weeks as measured by UV absorbance at 280 nm; (i) after storage at 2-8°C for 4 weeks, at least 93% of the anti-N3pGlu antibody appears in the main chromatographic peak (monomer) when analyzed by size exclusion chromatography; (j) no more than 11% decrease in the amount of anti-N3pGlu antibody as measured by non-reducing CE-SDS after the drug solution has been stored at 2-8°C for 4 weeks; and (k) After the drug solution has been stored at 2-8°C for 4 weeks, no more than four particles have a size of 25 μm or less as measured by differential counts per milliliter.

71. The pharmaceutical solution of any one of claims 51-70, comprising an amount of anti-N3pGlu Aβ antibody, a buffer, a tonicity agent, a surfactant, and an optional excipient sufficient to combine to cause the pharmaceutical solution to exhibit one or more of the following: (a) an antibody monomer content of at least 97% relative to the total antibody peak area as measured by size exclusion chromatography after the drug solution has been stored at 5°C for 3 months; (b) a total aggregate content of less than 2% relative to the total antibody peak area as measured by size exclusion chromatography after the drug solution has been stored at 5°C for 3 months; (c) the change in UV absorbance at 550 nm is less than ±3% within 4 weeks of storage at 5°C; (d) a change in protein content of 1% to 13% after storage at 5°C for 4 weeks as measured by UV absorbance at 280 nm; (e) after storage at 5° C. for 4 weeks, at least 93% of the anti-N3pGlu antibody appears in the main chromatographic peak (monomer) as analyzed by size exclusion chromatography; (f) no more than 11% decrease in the amount of anti-N3pGlu antibody as measured by non-reducing CE-SDS after the drug solution has been stored at 5°C for 4 weeks; and (g) After the drug solution has been stored at 5°C for 4 weeks, no more than four particles have a size of 25 μm or less as measured by differential counts per milliliter.

72. The pharmaceutical solution of any one of claims 51-71, comprising an amount of anti-N3pGlu Aβ antibody, a buffer, a tonicity agent, a surfactant, and an optional excipient sufficient to combine to cause the pharmaceutical solution to exhibit one or more of the following: (a) an antibody monomer content of at least 97.5% relative to the total antibody peak area as measured by size exclusion chromatography after the drug solution has been stored at 2-8°C for 3 months; (b) a total aggregate content of less than 1.5% relative to the total antibody peak area as measured by size exclusion chromatography after the drug solution has been stored at 2-8°C for 3 months; (c) an antibody purity of at least 94 area % as measured by reducing CE-SDS after the drug solution has been stored at 35° C. for 3 months; (d) after storage at 2-8° C. for 4 weeks, 93.3% to 93.8% of the anti-N3pGlu antibody appeared in the main chromatographic peak (monomer) as analyzed by size exclusion chromatography; (e) No more than 6.9% decrease in the amount of anti-N3pGlu antibody as measured by reducing CE-SDS after the drug solution has been stored at 2-8°C for 4 weeks.

73. The pharmaceutical solution of any one of claims 51-72, comprising an amount of anti-N3pGlu Aβ antibody, a buffer, a tonicity agent, a surfactant, and an optional excipient sufficient to combine to cause the pharmaceutical solution to exhibit one or more of the following: (a) an antibody monomer content of at least 97.5% relative to the total antibody peak area as measured by size exclusion chromatography after the drug solution has been stored at 5°C for 3 months; (b) a total aggregate content of less than 1.5% relative to the total antibody peak area as measured by size exclusion chromatography after the drug solution has been stored at 5°C for 3 months; (c) an antibody purity of at least 96 area % as measured by reducing CE-SDS after the drug solution has been stored at 5°C for 3 months; (d) after storage at 5°C for 4 weeks, 93.3% to 93.8% of the anti-N3pGlu antibodies appeared in the main peak as analyzed by size exclusion chromatography; (e) no more than a 6.9% decrease in the amount of anti-N3pGlu antibodies as measured by reducing CE-SDS after the drug solution has been stored at 5° C. for 4 weeks; (f) less than 500 particles / ml as measured by light obscuration using HIAC after the drug solution has been stored at 5°C for 3 months, wherein the particles are greater than 2 μm in size; and (g) less than 100 particles / ml as measured by light obscuration using HIAC after the drug solution has been stored at 5°C for 3 months, wherein the particles are greater than 5 μm in size.

74. A pharmaceutical solution according to any one of claims 70-73, wherein one or more of features (a)-(k) of claim 69 is present before and after storage, one or more of features (a)-(g) of claim 70 is present before and after storage, one or more of features (a)-(e) of claim 71 is present before and after storage, and / or one or more of features (a)-(g) of claim 72 is present before and after storage.

75. The pharmaceutical solution of any one of claims 51-74, comprising polyoxyethylene (20) sorbitan monooleate and exhibiting a total free oleic acid content of less than 0.0025% by volume weight as measured by high performance liquid chromatography with UV detection (HPLC-UV) using an internal standard after the pharmaceutical solution has been stored at 2-8°C for 3 months.

76. The pharmaceutical solution of any one of claims 51-75, comprising polyoxyethylene (20) sorbitan monooleate and exhibiting a total free oleic acid content of less than 0.0025% by volume weight as measured by high performance liquid chromatography with UV detection (HPLC-UV) using an internal standard after the pharmaceutical solution has been stored at 2-8°C for 29 months.

77. A method for preparing a pharmaceutical solution according to any one of claims 51-76, the method comprising: An anti-N3pGlu A[beta] antibody, a buffer, a tonicity agent, a surfactant, and one or more optional excipients are combined.

78. The method of claim 77, wherein the anti-N3pGluA[beta] antibody is not reconstituted from lyophilized material.

79. A vessel comprising the pharmaceutical solution of any one of claims 51-76.

80. A method of treating a disease characterized by amyloid beta (A[beta]) deposition, the method comprising administering to a patient in need thereof a therapeutically effective amount of the pharmaceutical solution of any one of claims 51-76.

81. The method of claim 80, comprising administering to a patient a drug solution obtained from the vessel of claim 79.

82. The method of claim 80 or claim 81, comprising administering to the patient an anti-N3pGlu A[beta] antibody that has not been lyophilized.

83. The method of any one of claims 80-82, wherein the disease is selected from Alzheimer's disease (AD), Down syndrome, and cerebral amyloid angiopathy.

84. The method of claim 83, wherein the disease is selected from preclinical AD, prodromal AD, mild AD, moderate AD, and severe AD.

85. The method of any one of claims 80-84, comprising administering to the patient one or more doses of 100 mg to 10,000 mg of an anti-N3pGlu A[beta] antibody.

86. The pharmaceutical solution according to any one of claims 51-76, for use in treating a disease characterized by amyloid beta (A[beta]) deposition.

87. The pharmaceutical solution for use according to claim 86, wherein the pharmaceutical solution is obtained from the vessel of claim 79.

88. The pharmaceutical solution for use according to claim 86 or claim 87, wherein the anti-N3pGlu A[beta] antibody is not lyophilized.

89. The pharmaceutical solution for use according to any one of claims 86 to 88, wherein the disease is selected from the group consisting of Alzheimer's disease (AD), Down syndrome and cerebral amyloid angiopathy.

90. The pharmaceutical solution for use according to claim 89, wherein the disease is selected from preclinical AD, prodromal AD, mild AD, moderate AD and severe AD.

91. The pharmaceutical solution for use according to any one of claims 86-90, wherein the treatment comprises administering to the patient one or more doses of 100 mg to 10,000 mg of an anti-N3pGlu A[beta] antibody.

92. Use of the pharmaceutical solution of any one of claims 51-76 in the manufacture of a medicament for treating a disease characterized by amyloid beta (A[beta]) deposition.

93. The use according to claim 92, wherein the pharmaceutical solution is obtained from the vessel of claim 79.

94. The use according to claim 92 or claim 93, wherein the anti-N3pGlu A[beta] antibody is not lyophilized.

95. Use of a pharmaceutical solution according to any one of claims 92-94, wherein the disease is selected from Alzheimer's disease (AD), Down syndrome and cerebral amyloid angiopathy.

96. The use according to claim 95, wherein the disease is selected from preclinical AD, prodromal AD, mild AD, moderate AD and severe AD.

97. Use of a pharmaceutical solution according to any one of claims 92-96, wherein the treatment comprises administering to the patient one or more doses of 100 mg to 10,000 mg of an anti-N3pGlu A[beta] antibody.

98. A method of reducing amyloid beta (A[beta]) in a patient in need thereof, the method comprising administering to the patient the pharmaceutical solution of any one of claims 51-76.

99. The method of claim 98, wherein the administration results in a reduction in the amount of amyloid beta by at least 5%.

100. A pharmaceutical solution comprising: anti-N3pGlu Aβ antibody at a concentration of 17.5 mg / mL; a buffer containing citric acid or a salt thereof in an amount of 10 mM; a tonicity agent comprising sucrose in an amount of 8% by volume; and a surfactant comprising polyoxyethylene (20) sorbitan monooleate in an amount of 0.02% by volume; wherein the anti-N3pGlu Aβ antibody comprises (a) a light chain variable region (LCVR) comprising SEQ ID NO: 1, and / or (b) a heavy chain variable region (HCVR) comprising SEQ ID NO: 2; and Wherein the drug solution has a pH of 6.

0. 101 . The pharmaceutical solution of claim 100 , wherein the anti-N3pGlu Aβ antibody comprises (a) a light chain (LC) comprising SEQ ID NO: 3, and / or (b) a heavy chain (HC) comprising SEQ ID NO: 4.

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