WO2024020470A1

WO2024020470A1 - PHARMACEUTICAL SOLUTIONS OF ANTI-N3pGlu Aβ ANTIBODIES AND USES THEREOF

Info

Publication number: WO2024020470A1
Application number: PCT/US2023/070540
Authority: WO
Inventors: Vincent John Corvari; Nicole H. DURBIN; Anant Navanithan Sharma
Original assignee: Eli Lilly And Company
Priority date: 2022-07-21
Filing date: 2023-07-20
Publication date: 2024-01-25

Abstract

The present disclosure relates to pharmaceutical solutions of certain anti-N3pGlu Aβ antibodies. Uses of such pharmaceutical solutions, including use in the treatment of Alzheimer's disease, are also disclosed.

Description

PHARMACEUTICAL SOLUTIONS OF ANTI-N3pGlu Ap ANTIBODIES AND USES THEREOF

FIELD OF THE DISCLOSURE

The disclosure relates to pharmaceutical solutions of certain anti-N3pGlu Ap antibodies and to uses thereof, including use in the treatment of Alzheimer’s disease.

Numerous antibodies have been studied for their therapeutic effects, including, but not limited to, antibodies administered to patients (e g., human patients) for the treatment or prevention of a disease. Treatment of a disease using an antibody therapeutic typically comprises administering a pharmaceutical formulation of the antibody to a subject in need thereof.

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

Each individual component, concentration thereof, ratio thereof relative to other components, and/or characteristic thereof can affect the suitability of the formulation for manufacturing, distribution, and/or storage (among other functional characteristics essential for therapeutic function). Thus, while a specific adjustment may provide a beneficial impact to a given aspect of the formulation, the same adjustment may also negatively impact other aspects of the formulation. As merely one example, although surfactants may impart beneficial properties to a formulation of an antibody, including a surfactant (such as polyoxyethylene (20) sorbitan monooleate) in a pharmaceutical formulation of an antibody can also lead to the formation of antibody aggregates, which is undesirable.

There remains little-to-no correlation for predicting the impact that modifying an individual component (or the concentration thereof and/or ratio thereof relative to other components) will have on the properties of a pharmaceutical formulation of an antibody. Further adding to the challenge is the fact that a nearly limitless number of different formulation components (e.g., buffers and excipients) and concentrations thereof are possible.

SUMMARY

The inventors of the present application identified unique and unexpected properties of the anti-N3pGlu antibodies discussed herein, including that lyophilized antibody preparations of antibodies were unsuitable for manufacturing, distribution, and storage due to unacceptable levels of protein aggregation, whereas the aqueous pharmaceutical solutions of the non-lyophilized antibodies were surprisingly suitable for manufacturing, distribution, and storage as well as maintaining the essential functional characteristics of the antibodies for therapeutic use.

Lyophilization is often used to ensure the stability of a protein drug product and its suitability for manufacturing, distribution, and storage, especially for therapeutic antibodies delivered in high doses and antibodies that have demonstrated challenging stability characteristics including cloud point, aggregation, and discoloration. Lyophilization of a protein drug product is generally a more stable presentation, wherein, e g., the lyophilized drug product is more resistant to stresses experienced during distribution of a pharmaceutical drug product (e.g., during packing, transporting, and/or storage of the pharmaceutical drug product). Indeed, lyophilization has been described as “the 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 present 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., an ISTA 3A shipping evaluation, the details of which are known to persons having ordinary skill in the art and are 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 lyophilized cake instability.

In an exemplary experiment, vials were prepared that contained a lyophilized formulation of the anti-N3pGlu antibodies discussed herein. The vials initially contained an intact lyophilized cake with no powder present in the shoulder of the vial. After being subjected to physical stresses designed to simulate the global distribution shipping environment, those vials exhibited a shrunken lyophilized cake and/or a broken lyophilized cake and powder in the shoulder of the vial, properties that were deemed undesirable.

In another exemplary experiment, lyophilized formulations of the anti-N3pGlu antibodies discussed herein were prepared and placed into vials, and the vials were subjected to physical stresses designed to simulate the global distribution shipping environment. The vials were stored at -20°C, 5°C, 25°C, and 40°C, and samples were periodically taken, reconstituted with water for injection, and analyzed for subvisible particles (SVP) by microflow imaging (MFI). Samples from vials that were subjected to physical stresses designed to simulate the global distribution shipping environment consistently displayed higher levels of SVP (particles sized greater than or equal to 2 urn and 5 pm) after 1 month (and all subsequent timepoints measured) relative to samples from vials that were not subjected to those physical stresses. Again, these properties were deemed undesirable. Additionally, samples of lyophilized formulations demonstrated aggregation, a problem that is typically compounded by, for example, one or more of shipping stress, freeze-thaw stress, and solubility constraints.

The above discussed properties make the lyophilized formulation undesirable for several important reasons. For instance, potential changes to the drug material as a result of decreased cake stability or increased aggregation may affect the solubility of the drug, which in turn affects the accuracy and consistency of the doses delivered to patients. Such problems present significant challenges to delivering an intended therapeutic dose to the patient.

Thus, a need exists for a pharmaceutical composition comprising the antibodies of the present disclosure that provides improved stability suitable for manufacturing, distribution, storage, and administration to patients for intended therapeutic benefit. The present disclosure satisfies that need by providing pharmaceutical solutions of the anti-N3pGlu A|3 antibodies having improved properties. For example, aspects of the disclosure relate to the development of pharmaceutical solutions comprising antibodies that exhibit improved stability upon storage over time. The improved stability upon storage over time is a surprising result associated with embodiments of the disclosed pharmaceutical solutions. Indeed, the art teaches that sufficient stabilization of biomolecules often cannot be achieved in the liquid state. See Langford, A., et al., “Drying Technologies for Biotechnology and Pharmaceutical Applications” (Introduction), Wiley (2020). For instance, it was previously believed that lyophilization, and not aqueous solution formulation, is the 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. Additionally, Langford, et al., explain that, in an aqueous solution, water serves as a medium that results in significant molecular mobility and conformational perturbations and acts as a catalyst for chemical degradation that can promote instability during storage and shipping. Thus, contrary to the conventional wisdom of the art, aspects of the disclosure relate to pharmaceutical solutions that exhibit improved stability, including improved stability over a period of weeks, months, or years when stored at from 5°C to 35°C, such as at 5°C, 25°C, or 35°C. Aspects of the disclosure also relate to pharmaceutical solutions that are suitable for administration to human patients for the treatment or prevention of a disease, including, but not limited to, Alzheimer’s disease.

Accordingly, aspects of the disclosure relate to a pharmaceutical solution comprising an antibody of the disclosure, a buffer, a tonicity agent, a surfactant, and an optional excipient. Aspects of the disclosure also relate to pharmaceutical solutions comprising an antibody of the disclosure, a buffer, a tonicity agent, a surfactant, and an optional excipient that exhibit one or more of improved antibody stability, improved solution stability, improved solution purity, improved antibody solubility, and suitability for intended therapeutic benefit.

Aspects of the disclosure also relate to pharmaceutical solutions comprising an antibody of the disclosure, a buffer, a tonicity agent, a surfactant, and an optional excipient that are suitable as a drug product for administration to a patient. Aspects of the disclosure also relate to pharmaceutical solutions comprising an antibody of the 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 polyoxyethylene (20) sorbitan monooleate hydrolysis, reduced polyoxyethylene (20) sorbitan monooleate oxidation, reduced levels of free oleic acid and/or total oleic acid, and reduced levels of free radicals. Pharmaceutical solutions of antibodies disclosed herein are useful in treating diseases characterized by deposition of Ap, 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’s syndrome, and cerebral amyloid angiopathy.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 A depicts changes in the percentage of the main peak from an initial time, as measured by size-exclusion chromatography (SEC), for different exemplary pharmaceutical solutions.

FIG. 1 B depicts changes in the percentage of high molecular weight species (% HMW) from an initial time, as measured by size-exclusion chromatography, for different exemplary pharmaceutical solutions.

FIG. 1 C depicts changes in the percentage of low molecular weight species (% LMW), as measured by size-exclusion chromatography, for different exemplary pharmaceutical solutions.

FIG. 2A depicts differences (A) in % donanemab as measured by non-reducing capillary electrophoresis - sodium dodecyl sulfate (CE-SDS) for different exemplary pharmaceutical solutions.

FIG. 2B depicts differences (A) in the largest % related substance (“RS”) as measured by non-reducing CE-SDS chromatography for different exemplary pharmaceutical solutions.

FIG. 3 depicts differences (A) in purity, as measured by reducing capillary electrophoresis - sodium dodecyl sulfate (CE-SDS), for different exemplary pharmaceutical solutions as a function of temperature and time.

FIG. 4A depicts > 10 pm particulate matter results as measured by light obscuration in particles per mL for different exemplary pharmaceutical solutions.

FIG. 4B depicts > 25 pm particulate matter results as measured by light obscuration in particles per mL for different exemplary pharmaceutical solutions.

FIG. 5A depicts %main peak (monomer) results as measured by size exclusion chromatography (SEC) for different exemplary pharmaceutical solutions with varying amounts of polysorbate from freeze-thaw experiments. FIG. 5B depicts %high molecular weight species (%HMW) results as measured by size exclusion chromatography (SEC) for different exemplary pharmaceutical solutions with varying amounts of polysorbate from freeze-thaw experiments.

FIG. 5C depicts %low molecular weight species (%LMW) results as measured by size exclusion chromatography (SEC) for different exemplary pharmaceutical solutions with varying amounts of polysorbate from freeze-thaw experiments.

FIG. 6A depicts > 10 pm particulate matter results as measured by light obscuration for different exemplary pharmaceutical solutions with varying amounts of polysorbate from freeze-thaw experiments.

FIG. 6B depicts > 25 pm particulate matter results as measured by light obscuration for different exemplary pharmaceutical solutions with varying amounts of polysorbate from freeze-thaw experiments.

FIG. 7 A depicts %main peak (monomer) results as measured by size exclusion chromatography (SEC) for different exemplary pharmaceutical solutions with varying amounts of polysorbate from agitation experiments.

FIG. 7B depicts %high molecular weight species (%HMW) results as measured by size exclusion chromatography (SEC) for different exemplary pharmaceutical solutions with varying amounts of polysorbate from agitation experiments.

FIG. 7C depicts %low molecular weight species (%LMW) results as measured by size exclusion chromatography (SEC) for different exemplary pharmaceutical solutions with varying amounts of polysorbate from agitation experiments.

FIG. 8 depicts %intact donanemab results as measured by non-reducing capillary electrophoresis - sodium dodecyl sulfate (CE-SDS) data for different exemplary pharmaceutical solutions with varying amounts of polysorbate from agitation experiments.

FIG. 9 depicts %purity as measured by reducing capillary electrophoresis - sodium dodecyl sulfate (CE-SDS) for different exemplary pharmaceutical solutions with varying amounts of polysorbate from agitation experiments.

FIG. 10A depicts > 10 pm particulate matter results as measured by light obscuration for different exemplary pharmaceutical solutions with varying amounts of polysorbate from agitation experiments.

FIG. 10B depicts > 25 pm particulate matter results as measured by light obscuration for different exemplary pharmaceutical solutions with varying amounts of polysorbate from agitation experiments. FIG. 11 A depicts a sample of an exemplary pharmaceutical solution at an initial time zero.

FIG. 11 B depicts the sample of an exemplary pharmaceutical solution of FIG. 15A after storage at -5°C for 24 hours.

FIG. 12A depicts size exclusion chromatography (SEC) data (monomer content) for different exemplary pharmaceutical solutions.

FIG. 12B depicts size exclusion chromatography (SEC) data (total aggregates content) for different exemplary pharmaceutical solutions.

FIG. 13A depicts reducing CE-SDS data (% purity) for different exemplary pharmaceutical solutions.

FIG. 13B depicts reducing CE-SDS data (% total aggregates) for different exemplary pharmaceutical solutions.

FIG. 14A depicts non-reducing CE-SDS data (% purity) for different exemplary pharmaceutical solutions.

FIG. 14B depicts non-reducing CE-SDS data (% total aggregates) for different exemplary pharmaceutical solutions.

FIG. 15 depicts free oleic acid (%FOA) data as measured by HPLC-UV for different exemplary pharmaceutical solutions.

FIG. 16A depicts subvisible particles > 2 pm results as measured by microflow imaging (MFI) in particles per mL for different exemplary pharmaceutical solutions. FIG. 16B depicts subvisible particles > 5 pm results as measured by microflow imaging (MFI) in particles per mL for different exemplary pharmaceutical solutions. FIG. 17A depicts subvisible particles > 2 pm results as measured by light obscuration in particles per mL for different exemplary pharmaceutical solutions.

FIG. 17B depicts subvisible particles > 5 pm results as measured by light obscuration in particles per mL for different exemplary pharmaceutical solutions.

FIG. 17C depicts particulate matter > 10 pm results as measured by light obscuration in particles per mL for different exemplary pharmaceutical solutions.

FIG. 17D depicts > 25 pm results as measured by light obscuration in particles per mL for different exemplary pharmaceutical solutions.

FIG. 18A depicts > 10 pm results as measured by light obscuration in particles per container for different exemplary pharmaceutical solutions.

FIG. 18B depicts > 25 pm results as measured by light obscuration in particles per container for different exemplary pharmaceutical solutions. FIG. 19A depicts subvisible particles > 2 pm results as measured by microflow imaging (MFI) in particles per mL for different exemplary pharmaceutical solutions subjected to an ISTA-3A shipping test.

FIG. 19B depicts subvisible particles 2 5 pm results as measured by microflow imaging (MFI) in particles per mL for different exemplary pharmaceutical solutions subjected to an ISTA-3A shipping test.

FIG. 20A depicts > 10 pm particulate matter results as measured by light obscuration in particles per mL for different exemplary pharmaceutical solutions subjected to an ISTA-3A shipping test.

FIG. 20B depicts > 25 pm particulate matter results as measured by light obscuration in particles per mL for different exemplary pharmaceutical solutions subjected to an ISTA-3A shipping test.

FIG. 21A depicts %monomer as measured by size exclusion chromatography (SEC) for different exemplary pharmaceutical solutions subjected to an ISTA-3A shipping test.

FIG. 21 B depicts %total aggregates as measured by size exclusion chromatography data (SEC) for different exemplary pharmaceutical solutions subjected to an ISTA-3A shipping test.

FIG. 22A depicts %purity as measured by non-reduced capillary electrophoresis - sodium dodecyl sulfate (CE-SDS) for different exemplary pharmaceutical solutions subjected to an ISTA-3A shipping test.

FIG. 22B depicts %total fragments as measured by non-reduced capillary electrophoresis - sodium dodecyl sulfate (CE-SDS) for different exemplary pharmaceutical solutions subjected to an ISTA-3A shipping test.

FIG. 22C depicts %total aggregates as measured by non-reduced capillary electrophoresis - sodium dodecyl sulfate (CE-SDS for different exemplary pharmaceutical solutions subjected to an ISTA-3A shipping test.

FIG. 23A depicts %monomer as measured by size exclusion chromatography (SEC) for different exemplary pharmaceutical solutions.

FIG. 23B depicts %total aggregates as measured by size exclusion chromatography (SEC) for different exemplary pharmaceutical solutions.

FIG. 24A depicts %purity as measured by reduced CE-SDS for different exemplary pharmaceutical solutions. FIG. 24B depicts %total fragments as measured by reduced CE-SDS for different exemplary pharmaceutical solutions.

FIG. 24C depicts %total aggregates as measured by reduced CE-SDS for different exemplary pharmaceutical solutions.

FIG. 25A depicts %purity as measured by non-reduced CE-SDS for different exemplary pharmaceutical solutions.

FIG. 25B depicts %total fragments as measured by non-reduced CE-SDS for different exemplary pharmaceutical solutions.

FIG. 25C depicts %total aggregates as measured by non-reduced CE-SDS for different exemplary pharmaceutical solutions.

FIG. 26A depicts total oleic acid content as measured by HPLC-UV for different exemplary pharmaceutical solutions.

FIG. 26B depicts free oleic acid content as measured by HPLC-UV for different exemplary pharmaceutical solutions.

FIG. 27A depicts subvisible particles > 2 pm results as measured by microflow imaging (MFI) in particles per mL for different exemplary pharmaceutical solutions. FIG. 27B depicts subvisible particles > 5 pm results as measured by microflow imaging (MFI) in particles per mL for different exemplary pharmaceutical solutions. FIG. 28A depicts subvisible particles > 2 pm results as measured by light obscuration in particles per mL for different exemplary pharmaceutical solutions.

FIG. 28B depicts subvisible particles > 5 pm results as measured by light obscuration in particles per mL for different exemplary pharmaceutical solutions.

FIG. 28C depicts particulate matter > 10 pm results as measured by light obscuration in particles per mL for different exemplary pharmaceutical solutions.

FIG. 28D depicts particulate matter > 25 pm results as measured by light obscuration in particles per mL for different exemplary pharmaceutical solutions.

FIG. 29A depicts particulate matter > 10 pm results as measured by light obscuration in particles per container for different exemplary pharmaceutical solutions.

FIG. 29B depicts particulate matter > 25 pm results as measured by light obscuration in particles per container for different exemplary pharmaceutical solutions. DETAILED DESCRIPTION

The disclosed compositions and processes may be understood more readily by reference to the following detailed description taken in connection with the accompanying figures, which form a part of this disclosure.

In accordance with the disclosure, there are provided pharmaceutical solutions of antibodies. As used herein, the term “pharmaceutical” refers to a composition (e.g., a solution) that is, within the scope of sound medical judgment, suitable for use in contact with the tissues of subjects (e.g., human beings) without excessive toxicity, irritation, 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 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 disclosure, the pharmaceutical solution contains undissolved particles.

In some embodiments, a pharmaceutical solution of an antibody comprises an antibody, a buffer, a tonicity agent, a surfactant, and an optional excipient.

In some embodiments, the antibody is present in a pharmaceutical solution according to the disclosure at a concentration of from 0.1 mg/mL to 1 ,000 mg/mL, such as from about 1 mg/mL to about 500 mg/mL, from about 1 mg/mL to about 300 mg/mL, from about 1 mg/mL to about 150 mg/mL, from about 1 mg/mL to about 100 mg/mL, from about 1 mg/mL to about 50 mg/mL, from about 1 mg/mL to about 40 mg/mL, from about 100 mg/mL to about 300 mg/mL (such as 200 mg/mL), from about 150 mg/mL to about 250 mg/mL, from about 125 mg/mL to about 275 mg/mL, from about 5 mg/mL to about 75 mg/mL, from about 5 mg/mL to about 50 mg/mL, from about 10 mg/mL to about 30 mg/mL, from about 10 mg/mL to about 25 mg/mL, or from about 15 mg/mL to about 20 mg/mL, such as 15 mg/mL, 15.5 mg/mL, 16 mg/mL, 16.5 mg/mL, 17 mg/mL, 17.5 mg/mL, 18 mg/mL, 18.5 mg/mL, 19 mg/mL, 19.5 mg/mL, or 20 mg/mL. The term “about,” as used herein, refers to a difference of ± 10% of the stated value in some embodiments, ± 5% of the stated value in some embodiments, or ± 1 % of the stated value in some embodiments. In some embodiments, the antibody is present in a pharmaceutical solution according to the disclosure at a concentration of from 16.0 mg/mL to 19.0 mg/mL. In some embodiments, the antibody is present in a pharmaceutical solution according to the disclosure at a concentration of from 16.28 mg/mL to 18.73 mg/mL. In some embodiments, the antibody is present in a pharmaceutical solution according to the disclosure at a concentration of from 16.63 mg/mL to 18.38 mg/mL.

Pharmaceutical solutions of antibodies according to the disclosure can be prepared using the humanized monoclonal anti-N3pGlu antibodies disclosed herein. In some embodiments, a monoclonal anti-N3pGlu antibody from which a pharmaceutical solution of an antibody is prepared has been purified. In some embodiments, a monoclonal anti-N3pGlu antibody from which a pharmaceutical solution of an antibody is prepared has been subjected to one or more purification schemes (/.e., a scheme for purifying a monoclonal antibody) as described in “Points to Consider in the Manufacture and Testing of Monoclonal Antibody Products for Human Use,” U.S. Department of Health and Human Services, Food and Drug Administration, Center for Biologies Evaluation and Research (Feb. 28, 1997). For example, in some embodiments, a purification scheme comprises one or more of the following: (a) production techniques that prevent the introduction of, and/or that eliminate, contaminants, including but not limited to animal proteins and materials, DNA, endotoxins, pyrogens, culture media constituents, components that may leach from columns, and viruses; (b) incorporation of one or more steps known to remove or inactivate retroviruses in excess of an endogenous particle load (where applicable), including, but not limited to, one or more robust virus removal/inactivation operations, which are those operations that have been shown to work well under a variety of conditions (e.g., pH or ionic strength of column buffers) with a variety of monoclonal antibodies (e.g., low pH, heat, solvent and/or detergent treatments, and filtration); (c) demonstration of the ability of the purification scheme to remove adventitious agents and other contaminants, by means of a clearance study; (d) limits that are prospectively set on the number of times a purification component (e.g., a chromatography column) can be reused; (e) saving of retention samples from each production so that side-by-side comparisons may be made to determine product comparability; and (f) a description of the design features of purification room(s), HVAC, and other support systems, equipment, transfers, and personnel. In some embodiments, a monoclonal anti-N3pGlu antibody from which a pharmaceutical solution of an antibody is prepared has been purified to be free of non-immunoglobulin (Ig) contaminants or to contain less than 5% non-lg contaminants by weight, less than 4% non-lg contaminants by weight, less than 3% non-lg contaminants by weight, less than 2% non-lg contaminants by weight, or less than 1 % non-lg contaminants by weight. In some embodiments, a monoclonal anti- N3pGlu antibody from which a pharmaceutical solution of an antibody is prepared is not fragmented, not aggregated, and/or otherwise not modified (e.g., by loss of carbohydrate side chains).

In some embodiments, a monoclonal anti-N3pGlu antibody from which a pharmaceutical solution of an 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 endotoxins (e.g., a Limulus Amebocyte Lysate (LAL) assay); (f) an identity test; (g) moisture, where appropriate; (h) preservative, where appropriate; (i) excipients, where appropriate; and (j) pH, where appropriate

In some embodiments, a monoclonal anti-N3pGlu antibody from which a pharmaceutical solution of an antibody is prepared has been subjected to one or more tests for stability. For example, in some embodiments, a monoclonal anti- N3pGlu antibody from which a pharmaceutical solution of an antibody is prepared has been subjected to a stability testing program that includes tests for one or more of (a) physico-chemical integrity (e.g., fragmentation and/or aggregation), (b) potency, (c) sterility, (d) moisture (where appropriate); (e) pH (where appropriate); and (f) preservative stability (where appropriate). In some embodiments, a monoclonal anti-N3pGlu antibody from which a pharmaceutical solution of an antibody is prepared is subjected to one or more tests for assuring biological activity (e.g., quantitative in vitro potency assays).

Antibodies to N3pGlu A0 are known in the art and have applications in treating or preventing disease. One of ordinary skill in the art will appreciate and recognize that anti-N3pGlu Ap antibodies are identified and disclosed (along with methods for making and using such antibodies) in U.S. Patent No. 8,679,498 B2 (which is hereby incorporated by reference in its entirety). For example, donanemab, which is disclosed in U.S. Patent No. 8,679,498, is an antibody directed at the pyroglutamate modification of the third amino acid of amyloid beta (N3pGlu Ap) epitope that is present only in brain amyloid plaques. As used herein, “donanemab” refers to an anti-N3pGlu Ap 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 complementarity determining region 1 (LCDR1 ) of SEQ ID NO: 5, a light chain complementarity determining region 2 (LCDR2) of SEQ ID NO: 6, a light chain complementarity determining region 3 (LCDR3) of SEQ ID NO: 7, a heavy chain complementarity determining region 1 (HCDR1 ) of SEQ ID NO: 8, a heavy chain complementarity determining region 2 (HCDR2) of SEQ ID NO: 9, and a heavy chain complementarity determining region 3 (HCDR3) of SEQ ID NO: 10.

In some embodiments, the antibody is an anti-N3pGlu Ap IgG antibody having a kappa light chain. In some embodiments, an anti-N3pGlu Ap antibody includes a kappa light chain and IgG heavy chain. In some embodiments, an anti-N3pGlu Ap antibody is of the human lgG1 isotype. In some embodiments, the antibody is an anti-N3pGlu Ap antibody comprising a LCVR and a HCVR, wherein said LCVR comprises a LCDR1 of SEQ ID NO: 5, a LCDR2 of SEQ ID NO: 6, and a LCDR3 of SEQ ID NO: 7, and said HCVR comprises a HCDR1 of SEQ ID NO: 8, a HCDR2 of SEQ ID NO: 9, and a HCDR3 of SEQ ID NO: 10. In some embodiments, said 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, said 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, said 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, said 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.

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

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

It is to be understood that a pharmaceutical solution according to the disclosure may be prepared using an antibody that has been lyophilized. Nevertheless, it is also to be understood that, in some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution is prepared using an antibody that has not been lyophilized or has never been lyophilized. In some embodiments of a pharmaceutical solution according to the disclosure, the antibody in the pharmaceutical solution is not reconstituted from lyophilized material.

In some embodiments of a pharmaceutical solution according to the disclosure, the total concentration of the buffer is from 0.1 mM to 1 ,000 mM, such as from about 1 mM to about 1 ,000 mM, from about 10 to about 1 ,000 mM, from about 10 mM to about 100 mM, from about 100 mM to about 250 mM, from about 175 mM to about 225 mM, from about 5 mM to about 50 mM, from about 10 mM to about 75 mM, from about 75 mM to about 175 mM, from about 10 mM to about 250 mM, from about 1 mM to about 100 mM, from about 1 mM to about 50 mM, from about 1 mM to about 40 mM, from about 1 mM to about 30 mM (such as 10 mM), from about 2.5 mM to about 100 mM (such as 5 mM), from about 3 mM to about 75 mM, from 3 mM to 50 mM, from about 5 mM to about 25 mM, from about 5 mM to about 15 mM, from about 2.5 mM to about 25 mM, from about 5 mM to about 10 mM, from about 2.5 mM to about 15 mM, or from about 3 mM to about 12 mM

In some embodiments, a pharmaceutical solution of the disclosure comprises an anti-N3pGlu Ap antibody at a concentration of from 1 to 40 mg/mL, the anti- N3pGlu Ap antibody comprising (a) a light chain variable region (LCVR) comprising an LCDR1 of SEQ ID NO: 5, an LCDR2 of SEQ ID NO: 6, an LCDR3 of SEQ ID NO: 7, and (b) a heavy chain variable region (HCVR) comprising an HCDR1 of SEQ ID NO: 8, an HCDR2 of SEQ ID NO: 9, and an HCDR3 of SEQ ID NO: 10, a buffer in an amount of from 1 mM to 30 mM, a tonicity agent in an amount of from 1 % to 20% weight by volume (w/v), a surfactant in an amount of from 0 005% weight by volume to 0.06% weight by volume, and an optional excipient. In some embodiments, the LCVR of the anti-N3pGlu Ap antibody comprises SEQ ID NO: 1 , and/or the HCVR of the anti-N3pGlu Ap antibody comprises SEQ ID NO: 2. In some embodiments, the anti-N3pGlu Ap antibody comprises a light chain (LC) comprising SEQ ID NO: 3, and/or a heavy chain (HC) comprising SEQ ID NO: 4.

As used herein, it is to be 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 a composition (e.g., affecting the tonicity of the composition). In some embodiments, a “buffer” may be a “buffer system.” The term “a single buffer system” as used herein is to be 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 acid compound and its conjugate base. A representative, non-limiting example of a single buffer system is benzoic acid, which can exist in solution as a combination of benzoic acid and benzoate anion.

In some embodiments of a pharmaceutical solution according to the disclosure, the buffer comprises an organic acid, an inorganic acid, an amino acid, and combinations thereof. In some embodiments of a pharmaceutical solution according to the disclosure, the buffer comprises a salt of an organic acid, a salt of an inorganic acid, and an amino acid, and combinations thereof. 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. Non-limiting examples of inorganic acids include hydrochloric acid, hydrobromic acid, phosphoric acid, nitric acid, and sulfuric acid. Non-limiting examples of amino acids include arginine, lysine, histidine, ornithine, isoleucine, leucine, alanine, glycine, glutamic acid, aspartic acid. In some embodiments of a pharmaceutical solution according to the 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 that term is defined elsewhere herein.

In some embodiments of a pharmaceutical solution according to the disclosure, the total amount of the one or more tonicity agents is from 0.01 % w/v to about 30% w/v, such as 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 (such as 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 a pharmaceutical solution according to the disclosure, the total amount of the one or more tonicity agents is from 0 01 mM to about 1 ,000 mM, such as 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 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.

As used herein, it is to be understood that a “tonicity agent” is an agent that affects the osmotic pressure of a composition, but a “tonicity agent” may also provide other functions in a composition (e.g., buffering the pH of the composition).

In some embodiments of a pharmaceutical solution according to the disclosure, the tonicity agent is selected from a sugar, an amino acid, a salt, and combinations thereof. In some embodiments, the tonicity agent is selected from a monosaccharide, a disaccharide, a polysaccharide, and combinations thereof. In some embodiments, the tonicity agent is chosen 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, aspartic acid, sucrose, fructose, glucose, maltose, trehalose, galactose, mannose, sorbose, lactose, cellobiose, mannitol, lactitol, xylitol, sorbitol, maltitol, and combinations 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 an antibody comprises a single tonicity agent.

As used herein, it is to be 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 a composition (e.g., buffering the pH of the composition). In some embodiments of a pharmaceutical solution according to the 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, a poloxamer, and combinations thereof. In some embodiments, the surfactant is polyoxyethylene (20) sorbitan monooleate.

In some embodiments of a pharmaceutical solution according to the disclosure, the surfactant is present in an amount of from about 0.001 % weight by volume to about 10% weight by volume, such as from about 0.001 % weight by volume to about 1 % weight by volume, from about 0.005% weight by volume to about 0.03% weight by volume (such from 0.005% weight by volume to 0.030% weight by volume), from about 0.005% weight by volume to about 0.1 % weight by volume, from about 0.01 % weight to about 0.5% weight by volume, from about 0.01 % weight by volume to about 0.25% weight by volume, from about 0.01 % weight by volume to about 0.20% weight by volume, from about 0.01 % weight by volume to about 0.03% weight by volume (such as from 0.010% weight by volume to 0.030% weight by volume), from about 0.10% weight by volume to about 0.30% weight by volume, from about 0.01 % weight by volume to about 0.05% weight by volume, from about 0.01 % weight by volume to about 0.03% weight by volume, from about 0.02% weight by volume to about 0.10% weight by volume, from about 0.02% weight by volume to about 0.08% weight by volume, from about 0.025% weight by volume to about 0.06% weight by volume, from about 0.02% weight by volume to about 0.04% weight by volume, or from about 0.03% weight by volume to about 0.05% weight by volume. In some embodiments of a pharmaceutical solution according to the disclosure, the surfactant is present in an amount of about 0.04% weight by volume.

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

In some embodiments of a pharmaceutical solution according to the disclosure, the pH of the solution is from 4 0 to 10.0, such as from 5.0 to 9.0, from 5.0 to 8.0, from 5.0 to 7.5, from 5.0 to 7.0, from 5.2 to 6.4, from 5.3 to 6.3, from 5.5 to

7.5, from 5.5 to 6.5, from 5.75 to 6.25, from 5.8 to 6.2, or from 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.

In some embodiments of a pharmaceutical solution according to the disclosure, the pH of the solution is from about 4.0 to about 10.0, such as from about 5.0 to about 9.0, from about 5.0 to about 7.5, from about 5.0 to about 7.0, from about 5.2 to about 6.4, from about 5.5 to about 7.5, from about 5.5 to about 6.5, from about 5.75 to about 6.25, from about 5.8 to about 6.2, or from 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.

In some embodiments, the pH of a pharmaceutical solution according to the disclosure is retained at one or more of the pH values or ranges described herein using one or more of the buffers described herein.

In some embodiments, the present disclosure encompasses a pharmaceutical solution comprising an anti-N3pGlu A[3 antibody at a concentration of from 1 to 40 mg/mL, the anti-N3pGlu Ap antibody comprising (a) a light chain variable region (LCVR) comprising an LCDR1 of SEQ ID NO: 5, an LCDR2 of SEQ ID NO: 6, an LCDR3 of SEQ ID NO: 7, and (b) a heavy chain variable region (HCVR) comprising an HCDR1 of SEQ ID NO: 8, an HCDR2 of SEQ ID NO: 9, and an HCDR3 of SEQ ID NO: 10, a buffer in an amount of from 1 mM to 30 mM, a tonicity agent in an amount of from 1 % to 20% weight by volume, a surfactant in an amount of from 0.005% weight by volume to 0.06% weight by volume, and an optional excipient.

In some embodiments, the present disclosure encompasses a pharmaceutical solution comprising an anti-N3pGlu Ap 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-N3pGlu Ap comprises an LCVR of SEQ ID NO: 1 and/or an HCVR of SEQ ID NO: 2; wherein, optionally, the anti-N3pGlu Ap comprises an LC of SEQ ID NO: 3 and/or an HC of SEQ ID NO: 4.

In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution comprises not more than 0.12 EU/mg of bacterial endotoxins, as determined according to European Pharmacopeia (Ph. Eur.) Chapter 2.6.32.

In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution has an osmolality of not less than 255 mOsm/kg and not more than 345 mOsm/kg, as determined according to European Pharmacopeia (Ph. Eur.) Chapter 2.2.35 and/or USP <785>.

In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution has a color that is not more intensely colored than Color Standard Y3, BY3, or B3, as determined according to European Pharmacopeia (Ph. Eur.) Chapter 2.2.2.

In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution has a clarity that is not more than 60 NTU (Nephelometric Turbidity Units), as determined according to European Pharmacopeia (Ph. Eur.) Chapter 2.2.1 .

In some embodiments, the term “about,” as used herein, refers to any value that is within 10% of the recited value. In some embodiments, the term “about” refers to any value that is within 5% of the recited value. In some embodiments, the term “about” refers to any value that is within 1 % of the recited value.

In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution comprises an anti-N3pGlu A|3 antibody of the disclosure present in a concentration of from about 1 mg/mL to about 300 mg/mL (such as from about 1 mg/mL to about 75 mg/mL, from about 1 mg/mL to about 50 mg/mL, from about 1 mg/mL to about 40 mg/mL, from about 5 mg/mL to about 30 mg/mL, from about 10 mg/mL to about 25 mg/mL, from about 150 mg/mL to about 250 mg/mL), a buffer present in a concentration of from about 1 mM to about 50 mM (such as 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 (such as 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 (such as 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.

In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits an antibody monomer content, as measured by size exclusion chromatography, of at least 94% relative to total antibody peak area after the pharmaceutical solution has been stored at about 35°C for 3 months. In the context of size exclusion chromatography, percentages refer to the peak area percent (% area). Size exclusion chromatography assesses the total amount of high molecular weight species (HMW) (also referred to as aggregates) and low molecular weight (LMW) species (fragments) present in a sample. This assessment is performed by integration of the eluted peaks to express fractional ratios of each peak of interest over the total integrated peak area (which, when multiplied by 100, yields a percentage, e g., % total aggregation). In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits a total antibody monomer content, as measured by size exclusion chromatography, of at least 94% relative to total antibody peak area after the pharmaceutical solution has been stored at about 25°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits an antibody monomer content, as measured by size exclusion chromatography, of at least 94% relative to total antibody peak area after the pharmaceutical solution has been stored at about 5°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits an antibody monomer content, as measured by size exclusion chromatography, of at least 95% relative to total antibody peak area after the pharmaceutical solution has been stored at about 5°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits an antibody monomer content, as measured by size exclusion chromatography, of at least 96% relative to total antibody peak area after the pharmaceutical solution has been stored at about 5°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits a total antibody monomer content, as measured by size exclusion chromatography, of at least 97%> relative to total antibody peak area after the pharmaceutical solution has been stored at about 5°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits an antibody monomer content, as measured by size exclusion chromatography, of at least 97.5%> relative to total antibody peak area after the pharmaceutical solution has been stored at about 5°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits an antibody monomer content, as measured by size exclusion chromatography, of at least 95% relative to total antibody peak area after the pharmaceutical solution has been stored at about 5°C for 29 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits an antibody monomer content, as measured by size exclusion chromatography, of at least 96% relative to total antibody peak area after the pharmaceutical solution has been stored at about 5°C for 29 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits an antibody monomer content, as measured by size exclusion chromatography, of at least 96.0% relative to total antibody peak area after the pharmaceutical solution has been stored at about 5°C for 29 months.

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

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

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

In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution comprises polyoxyethylene (20) sorbitan monooleate and the pharmaceutical solution exhibits a total oleic acid content, as measured by high performance liquid chromatography with UV detection (HPLC-UV) using an internal standard, of less than 0.03% weight by volume after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution comprises polyoxyethylene (20) sorbitan monooleate and the pharmaceutical solution exhibits a total oleic acid content, as measured by high performance liquid chromatography with UV detection (HPLC-UV) using an internal standard, of less than 0.03% weight by volume after the pharmaceutical solution has been stored at about 5°C for 29 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution comprises polyoxyethylene (20) sorbitan monooleate and the pharmaceutical solution exhibits a total oleic acid content, as measured by high performance liquid chromatography with UV detection (HPLC-UV) using an internal standard, of from 0.01 % weight by volume to 0.03% weight by volume after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution comprises polyoxyethylene (20) sorbitan monooleate and the pharmaceutical solution exhibits a total oleic acid content, as measured by high performance liquid chromatography with UV detection (HPLC-UV) using an internal standard, of from about 0.01 % weight by volume to about 0 03% weight by volume after the pharmaceutical solution has been stored at about 5°C for 29 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution comprises polyoxyethylene (20) sorbitan monooleate and the pharmaceutical solution exhibits a total free oleic acid content, as measured by high performance liquid chromatography with UV detection (HPLC- UV) using an internal standard, of less than about 0.015% weight by volume after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution comprises polyoxyethylene (20) sorbitan monooleate and the pharmaceutical solution exhibits a total free oleic acid content, as measured by high performance liquid chromatography with UV detection (HPLC- UV) using an internal standard, of less than about 0.015% weight by volume after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 29 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution comprises polyoxyethylene (20) sorbitan monooleate and the pharmaceutical solution exhibits a total free oleic acid content, as measured by high performance liquid chromatography with UV detection (HPLC- UV) using an internal standard, of less than about 0.005% weight by volume after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution comprises polyoxyethylene (20) sorbitan monooleate and the pharmaceutical solution exhibits a total free oleic acid content, as measured by high performance liquid chromatography with UV detection (HPLC- UV) using an internal standard, of less than 0.0025% weight by volume after the pharmaceutical solution has been stored at about 5°C for 29 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution comprises polyoxyethylene (20) sorbitan monooleate and the pharmaceutical solution exhibits a total free oleic acid content, as measured by high performance liquid chromatography with UV detection (HPLC-UV) using an internal standard, of less than 0.0025% weight by volume after the pharmaceutical solution has been stored at 2-8°C for 29 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution comprises polyoxyethylene (20) sorbitan monooleate and the pharmaceutical solution exhibits a total free oleic acid content, as measured by high performance liquid chromatography with UV detection (HPLC-UV) using an internal standard, of less than 0.0025% weight by volume after the pharmaceutical solution has been stored at about 5°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution comprises polyoxyethylene (20) sorbitan monooleate and the pharmaceutical solution exhibits a total free oleic acid content, as measured by high performance liquid chromatography with UV detection (HPLC-UV) using an internal standard, of less than 0.0025% weight by volume after the pharmaceutical solution has been stored at 2-8°C for 3 months.

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

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

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

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

In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits a purity, as measured by reducing CE-SDS, of at least 94 area % after the pharmaceutical solution has been stored at about 5°C or about 25°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits a purity, as measured by reducing CE-SDS, of at least 94 area % after the pharmaceutical solution has been stored at about 5°C or about 25°C for 6 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits a purity, as measured by reducing CE-SDS, of at least 96 area % after the pharmaceutical solution has been stored at about 5°C for 3 months

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

In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits a total aggregate content, as measured by reducing CE-SDS, of less than 4 area % after the pharmaceutical solution has been stored at about 5°C or about 25°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits a total aggregate content, as measured by reducing CE-SDS, of less than 4 area % after the pharmaceutical solution has been stored at about 5°C or about 25°C for 6 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits a total aggregate content, as measured by reducing CE-SDS, of less than 3 area % after the pharmaceutical solution has been stored at about 5°C or about 25°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits a total aggregate content, as measured by reducing CE-SDS, of less than 3 area % after the pharmaceutical solution has been stored at about 5°C or about 25°C for 6 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits a total aggregate content, as measured by reducing CE-SDS, of less than 5 area % after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits a total aggregate content of less than 4% relative to total antibody peak area, as measured by size exclusion chromatography, after the pharmaceutical solution has been stored at 2-8°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits a total aggregate content of less than 4% relative to total antibody peak area, as measured by size exclusion chromatography, after the pharmaceutical solution has been stored at about 5°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits a total aggregate content of less than 2% relative to total antibody peak area, as measured by size exclusion chromatography, after the pharmaceutical solution has been stored at 2-8°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits a total aggregate content of less than 2% relative to total antibody peak area, as measured by size exclusion chromatography, after the pharmaceutical solution has been stored at about 5°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits a total aggregate content of less than 1.5% relative to total antibody peak area, as measured by size exclusion chromatography, after the pharmaceutical solution has been stored at 2-8°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits a total aggregate content of less than 1.5% relative to total antibody peak area, as measured by size exclusion chromatography, after the pharmaceutical solution has been stored at about 5°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits a total aggregate content of less than 1 % relative to total antibody peak area, as measured by size exclusion chromatography, after the pharmaceutical solution has been stored at 2-8°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits a total aggregate content of less than 1 % relative to total antibody peak area, as measured by size exclusion chromatography, after the pharmaceutical solution has been stored at about 5°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits a total aggregate content of less than 9 area %, as measured by non-reducing CE-SDS, after the pharmaceutical solution has been stored at 2-8°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits a total aggregate content of less than 8.5 area %, as measured by nonreducing CE-SDS, after the pharmaceutical solution has been stored at 2-8°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits a total aggregate content of less than 7.5 area %, as measured by non-reducing CE-SDS, after the pharmaceutical solution has been stored at 2-8°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits a total aggregate content of less than 4 area %, as measured by nonreducing CE-SDS, after the pharmaceutical solution has been stored at 2-8°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits a total aggregate content of less than 4 area %, as measured by non-reducing CE-SDS, after the pharmaceutical solution has been stored at about 5°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits a total aggregate content of less than 2 area %, as measured by nonreducing CE-SDS, after the pharmaceutical solution has been stored at 2-8°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits a total aggregate content of less than 2 area %, as measured by non-reducing CE-SDS, after the pharmaceutical solution has been stored at about 5°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits a total aggregate content of less than 1 .5 area %, as measured by nonreducing CE-SDS, after the pharmaceutical solution has been stored at 2-8°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits a total aggregate content of less than 1.5 area %, as measured by non-reducing CE-SDS, after the pharmaceutical solution has been stored at about 5°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits a total aggregate content of less than 1 area %, as measured by non- reducing CE-SDS, after the pharmaceutical solution has been stored at 2-8°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution exhibits a total aggregate content of less than 1 area %, as measured by non-reducing CE-SDS, after the pharmaceutical solution has been stored at about 5°C for 3 months.

In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 10,000 particulates per milliliter, wherein the particulates are sized greater than 2 pm, as measured using microflow imaging, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 6,000 particulates per milliliter, wherein the particulates are sized greater than 2 pm, as measured using microflow imaging, after the pharmaceutical solution has been stored at about 5°C or about 25°C for 6 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 2,000 particulates per milliliter, wherein the particulates are sized greater than 2 pm, as measured using microflow imaging, after the pharmaceutical solution has been stored at about 5°C or about 25°C for 6 months.

In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 2,000 particulates per milliliter, wherein the particulates are sized greater than 5 pm, as measured using microflow imaging, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 2,000 particulates per milliliter, wherein the particulates are sized greater than 5 pm, as measured using microflow imaging, after the pharmaceutical solution has been stored at about 5°C or about 25°C for 6 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 1 ,000 particulates per milliliter, wherein the particulates are sized greater than 5 pm, as measured using microflow imaging, after the pharmaceutical solution has been stored at about 5°C or about 25°C for 6 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 1 ,000 particulates per milliliter, wherein the particulates are sized greater than 5 pm, as measured using microflow imaging, after the pharmaceutical solution has been stored at about 5°C or about 25°C for 29 months.

In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 3,000 particulates per milliliter, wherein the particulates are sized greater than 2 pm, as measured by light obscuration using a high accuracy liquid particle counter (HIAC), after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 1 ,500 particulates per milliliter, wherein the particulates are sized greater than 2 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 1 ,000 particulates per milliliter, wherein the particulates are sized greater than 2 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 750 particulates per milliliter, wherein the particulates are sized greater than 2 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 500 particulates per milliliter, wherein the particulates are sized greater than 2 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 250 particulates per milliliter, wherein the particulates are sized greater than 2 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 100 particulates per milliliter, wherein the particulates are sized greater than 2 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 75 particulates per milliliter, wherein the particulates are sized greater than 2 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months.

In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 3,000 particulates per milliliter, wherein the particulates are sized greater than 2 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at 2- 8°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 1 ,500 particulates per milliliter, wherein the particulates are sized greater than 2 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at 2- 8°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 1 ,000 particulates per milliliter, wherein the particulates are sized greater than 2 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at 2- 8°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 750 particulates per milliliter, wherein the particulates are sized greater than 2 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at 2- 8°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 500 particulates per milliliter, wherein the particulates are sized greater than 2 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at 2- 8°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 250 particulates per milliliter, wherein the particulates are sized greater than 2 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at 2- 8°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 100 particulates per milliliter, wherein the particulates are sized greater than 2 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at 2- 8°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 75 particulates per milliliter, wherein the particulates are sized greater than 2 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at 2- 8°C for 3 months.

In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 800 particulates per milliliter, wherein the particulates are sized greater than 5 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 500 particulates per milliliter, wherein the particulates are sized greater than 5 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 200 particulates per milliliter, wherein the particulates are sized greater than 5 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 200 particulates per milliliter, wherein the particulates are sized greater than 5 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 100 particulates per milliliter, wherein the particulates are sized greater than 5 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 75 particulates per milliliter, wherein the particulates are sized greater than 5 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months.

In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 800 particulates per milliliter, wherein the particulates are sized greater than 5 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at 2- 8°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 500 particulates per milliliter, wherein the particulates are sized greater than 5 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at 2- 8°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 200 particulates per milliliter, wherein the particulates are sized greater than 5 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at 2- 8°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 200 particulates per milliliter, wherein the particulates are sized greater than 5 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at 2- 8°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 100 particulates per milliliter, wherein the particulates are sized greater than 5 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at 2- 8°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 75 particulates per milliliter, wherein the particulates are sized greater than 5 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at 2- 8°C for 3 months.

In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 125 particulates per milliliter, wherein the particulates are sized greater than 10 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 50 particulates per milliliter, wherein the particulates are sized greater than 10 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 25 particulates per milliliter, wherein the particulates are sized greater than 10 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 20 particulates per milliliter, wherein the particulates are sized greater than 10 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 15 particulates per milliliter, wherein the particulates are sized greater than 10 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 5 particulates per milliliter, wherein the particulates are sized greater than 10 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at about 5°C, about 25°C, or about 35°C for 3 months.

In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 25 particulates per milliliter, wherein the particulates are sized greater than 10 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at about 5°C or about 25°C for 6 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 25 particulates per milliliter, wherein the particulates are sized greater than 10 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at about 5°C for 29 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 3 particulates per milliliter, wherein the particulates are sized greater than 10 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at about 5°C or about 25°C for 6 months. In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution contains less than 3 particulates per milliliter, wherein the particulates are sized greater than 10 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at about 5°C for 29 months.

In some embodiments, a pharmaceutical solution according to the disclosure exhibits a UV absorbance at 550 nm that varies by less than ±3% over 4 weeks of storage for at 2-8°C. In some embodiments, a pharmaceutical solution according to the disclosure exhibits a UV absorbance at 550 nm that varies by less than ±2% over 4 weeks of storage for at 2-8°C. In some embodiments, a pharmaceutical solution according to the disclosure exhibits a UV absorbance at 550 nm that varies by less than ±1 % over 4 weeks of storage for at 2-8°C. In some embodiments, a pharmaceutical solution according to the disclosure exhibits a UV absorbance at 550 nm that varies by less than ±3% over 4 weeks of storage for at about 5°C. In some embodiments, a pharmaceutical solution according to the disclosure exhibits a UV absorbance at 550 nm that varies by less than ±2% over 4 weeks of storage for at about 5°C. In some embodiments, a pharmaceutical solution according to the disclosure exhibits a UV absorbance at 550 nm that varies by less than ±1 % over 4 weeks of storage for at about 5°C.

In some embodiments, a pharmaceutical solution according to the disclosure exhibits a change in protein content as measured by UV absorbance at 280 nm from about 0.1 % to about 25% after storage for 4 weeks at about 5°C, such as a change in protein content as measured by UV absorbance at 280 nm from 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% after storage for 4 weeks at about 5°C. In some embodiments, a pharmaceutical solution according to the disclosure exhibits a change in protein content as measured by UV absorbance at 280 nm of from 0.4% to 25% after storage for 4 weeks at about 5°C. In some embodiments, a pharmaceutical solution according to the disclosure exhibits a change in protein content as measured by UV absorbance at 280 nm from about 0.4% to about 13% after storage for 4 weeks at about 5°C. In some embodiments, a pharmaceutical solution according to the disclosure exhibits a change in protein content as measured by UV absorbance at 280 nm from about 1 % to about 13% after storage for 4 weeks at about 5°C. In some embodiments, a pharmaceutical solution according to the disclosure exhibits a change in protein content as measured by UV absorbance at 280 nm from 0.1 % to 25% after storage for 4 weeks at 2-8°C, such as a change in protein content as measured by UV absorbance at 280 nm from 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% after storage for 4 weeks at 2- 8°C. In some embodiments, a pharmaceutical solution according to the disclosure exhibits a change in protein content as measured by UV absorbance at 280 nm from about 0.4% to about 25% after storage for 4 weeks at 2-8°C. In some embodiments, a pharmaceutical solution according to the disclosure exhibits a change in protein content as measured by UV absorbance at 280 nm from about 0.4% to about 13% after storage for 4 weeks at 2-8°C. In some embodiments, a pharmaceutical solution according to the disclosure exhibits a change in protein content as measured by UV absorbance at 280 nm from about 1 % to about 13% after storage for 4 weeks at 2- 8°C.

In some embodiments, a pharmaceutical solution according to the disclosure has at least 92% of the anti-N3pGlu antibody appearing in a main chromatographic peak (monomer), when analyzed by size exclusion chromatography, after storage for 4 weeks at 2-8°C. In some embodiments, a pharmaceutical solution according to the disclosure has at least 93% of the anti-N3pGlu antibody appearing in a main chromatographic peak (monomer), when analyzed by size exclusion chromatography, after storage for 4 weeks at 2-8°C. In some embodiments, a pharmaceutical solution according to the disclosure has at least 94% of the anti- N3pGlu antibody appearing in a main chromatographic peak (monomer), when analyzed by size exclusion chromatography, after storage for 4 weeks at 2-8°C. In some embodiments, a pharmaceutical solution according to the 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 antibody appearing in a main chromatographic peak (monomer), when analyzed by size exclusion chromatography, after storage for 4 weeks at 2-8°C. In some embodiments, a pharmaceutical solution according to the disclosure has from 93.3% to 93.8% of the anti-N3pGlu antibody appearing in a main chromatographic peak (monomer), when analyzed by size exclusion chromatography, after storage for 4 weeks at 2-8°C. In some embodiments, a pharmaceutical solution according to the disclosure has at least 92% of the anti-N3pGlu antibody appearing in a main chromatographic peak (monomer), when analyzed by size exclusion chromatography, after storage for 4 weeks at about 5°C. In some embodiments, a pharmaceutical solution according to the disclosure has at least 93% of the anti-N3pGlu antibody appearing in a main chromatographic peak (monomer), when analyzed by size exclusion chromatography, after storage for 4 weeks at about 5°C. In some embodiments, a pharmaceutical solution according to the disclosure has at least 94% of the anti- N3pGlu antibody appearing in a main chromatographic peak (monomer), when analyzed by size exclusion chromatography, after storage for 4 weeks at about 5°C. In some embodiments, a pharmaceutical solution according to the 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 antibody appearing in a main chromatographic peak (monomer), when analyzed by size exclusion chromatography, after storage for 4 weeks at about 5°C. In some embodiments, a pharmaceutical solution according to the disclosure has from 93.3% to 93.8% of the anti-N3pGlu antibody appearing in a main chromatographic peak (monomer), when analyzed by size exclusion chromatography, after storage for 4 weeks at about 5°C.

In some embodiments, a pharmaceutical solution according to the disclosure exhibits not more than a 15 area % decrease in the amount of the anti-N3pGlu antibody, as measured by non-reducing CE-SDS, after the pharmaceutical solution has been stored for 4 weeks at 2-8°C. In some embodiments, a pharmaceutical solution according to the disclosure exhibits not more than a 12.5 area % decrease in the amount of the anti-N3pGlu antibody, as measured by non-reducing CE-SDS, after the pharmaceutical solution has been stored for 4 weeks at 2-8°C. In some embodiments, a pharmaceutical solution according to the disclosure exhibits not more than an 11 area % decrease in the amount of the anti-N3pGlu antibody, as measured by non-reducing CE-SDS, after the pharmaceutical solution has been stored for 4 weeks at 2-8°C. In some embodiments, a pharmaceutical solution according to the disclosure exhibits not more than a 10 area % decrease in the amount of the anti-N3pGlu antibody, as measured by non-reducing CE-SDS, after the pharmaceutical solution has been stored for 4 weeks at 2-8°C. In some embodiments, a pharmaceutical solution according to the disclosure exhibits not more than a 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 % decrease in the amount of the anti-N3pGlu antibody, as measured by non-reducing CE-SDS, after the pharmaceutical solution has been stored for 4 weeks at 2-8°C. In some embodiments, a pharmaceutical solution according to the disclosure exhibits not more than a 15 area % decrease in the amount of the anti-N3pGlu antibody, as measured by non-reducing CE-SDS, after the pharmaceutical solution has been stored for 4 weeks at 5°C. In some embodiments, a pharmaceutical solution according to the disclosure exhibits not more than a 12.5 area % decrease in the amount of the anti-N3pGlu antibody, as measured by non-reducing CE-SDS, after the pharmaceutical solution has been stored for 4 weeks at about 5°C. In some embodiments, a pharmaceutical solution according to the disclosure exhibits not more than an 11 area % decrease in the amount of the anti-N3pGlu antibody, as measured by non-reducing CE-SDS, after the pharmaceutical solution has been stored for 4 weeks at about 5°C. In some embodiments, a pharmaceutical solution according to the disclosure exhibits not more than a 10 area % decrease in the amount of the anti-N3pGlu antibody, as measured by non-reducing CE-SDS, after the pharmaceutical solution has been stored for 4 weeks at about 5°C. In some embodiments, a pharmaceutical solution according to the disclosure exhibits not more than a 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 % decrease in the amount of the anti-N3pGlu antibody, as measured by non-reducing CE-SDS, after the pharmaceutical solution has been stored for 4 weeks at about 5°C.

In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution comprises an anti-N3pGlu A|3 antibody, a buffer, a tonicity agent, a surfactant, and an optional excipient in amounts that are sufficient in combination for the pharmaceutical solution to exhibit one or more of:

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

(b) a total aggregate content of less than 2%, as measured by size exclusion chromatography, after the pharmaceutical solution has been stored at 2-8°C for 3 months; (c) an antibody purity of at least 92%, as measured by reducing capillary electrophoresis sodium dodecyl sulfate (CE-SDS), after the pharmaceutical solution has been stored at about 35°C for 3 months;

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

(e) less than 500 particulates per milliliter, wherein the particulates are sized greater than 2 pm, as measured by light obscuration using a high accuracy liquid particle counter (HIAC), after the pharmaceutical solution has been stored at 2-8°C for 3 months;

(f) less than 100 particulates per milliliter, wherein the particulates are sized greater than 5 pm, as measured by light obscuration using a high accuracy liquid particle counter (HIAC), after the pharmaceutical solution has been stored at 2-8°C for 3 months;

(g) a UV absorbance at 550 nm that varies by less than ±3% over 4 weeks of storage for at 2-8°C;

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

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

(j) not more than an about 11 % decrease in the amount of the anti-N3pGlu antibody, as measured by non-reducing CE-SDS, after the pharmaceutical solution has been stored for 4 weeks at 2-8°C; and

(k) not more than four particles having a size of 25 pm or less, as measured by differential counts per mL, after the pharmaceutical solution has been stored for 4 weeks at 2-8°C.

In some embodiments of the foregoing pharmaceutical solution, one or more of features (a)-(k) exist before and after storage of the pharmaceutical solution.

In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution comprises an anti-N3pGlu A|3 antibody, a buffer, a tonicity agent, a surfactant, and an optional excipient in amounts that are sufficient in combination for the pharmaceutical solution to exhibit one or more of: (a) an antibody monomer content of at least 97% relative to total antibody peak area, as measured by size exclusion chromatography, after the pharmaceutical solution has been stored at about 5°C for 3 months;

(b) a total aggregate content of less than 2%, as measured by size exclusion chromatography, after the pharmaceutical solution has been stored at about 5°C for 3 months;

(c) a UV absorbance at 550 nm that varies by less than ±3% over 4 weeks of storage at about 5°C;

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

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

(f) not more than an 11 % decrease in the amount of the anti-N3pGlu antibody, as measured by non-reducing CE-SDS, after the pharmaceutical solution has been stored for 4 weeks at about 5°C; and

(g) not more than four particles having a size of 25 pm or less, as measured by differential counts per mL, after the pharmaceutical solution has been stored for 4 weeks at about 5°C.

In some embodiments of the foregoing pharmaceutical solution, one or more of features (a)-(g) exist before and after storage of the pharmaceutical solution

In some embodiments of a pharmaceutical solution according to the disclosure, the pharmaceutical solution comprises an anti-N3pGlu Ap antibody, a buffer, a tonicity agent, a surfactant, and an optional excipient in amounts that are sufficient in combination for the pharmaceutical solution to exhibit one or more of:

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

(b) a total aggregate content of less than 1 .5%, as measured by size exclusion chromatography, after the pharmaceutical solution has been stored at 2- 8°C for 3 months;

(c) an antibody purity of at least 94%, as measured by reducing CE-SDS, after the pharmaceutical solution has been stored at about 35°C for 3 months; (d) from 93.3% to 93.8% of the anti-N3pGlu antibody appearing in a main chromatographic peak (monomer), as analyzed by size exclusion chromatography, after storage for 4 weeks at 2-8°C;

(e) not more than a 6.9% decrease in the amount of the anti-N3pGlu antibody, as measured by reducing CE-SDS, after the pharmaceutical solution has been stored for 4 weeks at 2-8°C.

In some embodiments of the foregoing pharmaceutical solution, one or more of features (a)-(e) exist before and after storage of the pharmaceutical solution

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

(b) a total aggregate content of less than 1 .5%, as measured by size exclusion chromatography, after the pharmaceutical solution has been stored at 5°C for 3 months;

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

(d) from 93.3% to 93.8% of the anti-N3pGlu antibody appearing in a main peak, as analyzed by size exclusion chromatography, after storage for 4 weeks at about 5°C;

(e) not more than a 6.9% decrease in the amount of the anti-N3pGlu antibody, as measured by reducing CE-SDS, after the pharmaceutical solution has been stored for 4 weeks at about 5°C;

(f) less than 500 particulates per milliliter, wherein the particulates are sized greater than 2 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at about 5°C for 3 months; and

(g) less than 100 particulates per milliliter wherein the particulates are sized greater than 5 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at about 5°C for 3 months. In some embodiments of the foregoing pharmaceutical solution, one or more of features (a)-(g) exist before and after storage of the pharmaceutical solution

Aspects of the disclosure also relate to a vessel comprising a pharmaceutical solution according to the disclosure. In some embodiments, the vessel is a vial, a syringe (e.g. , a pre-filled syringe), a bag, or a tube.

Aspects of the disclosure also relate to the administration of pharmaceutical solutions of the disclosure to patients. The terms “subject” and “patient” are used interchangeably in the present disclosure. In some embodiments, a patient (or, interchangeably, a “subject”) is a human (also referred to as a “human patient” or, interchangeably, a “human subject”). Pharmaceutical solutions of the disclosure may be administered to a subject at risk for, or exhibiting, diseases or disorders as described herein by parental routes (e.g., subcutaneous, intravenous, intraperitoneal, intramuscular). In some embodiments, administration is by a subcutaneous and/or intravenous route. In some embodiments, the antibody (e.g., the anti-N3pGlu Ap antibody) is administered by intravenous infusion.

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

As used herein, “methods of treatment” are equally applicable to use of a composition (e.g., a composition that is a pharmaceutical solution according to the disclosure) for treating the diseases or disorders described herein and/or compositions (e.g., compositions that are pharmaceutical solutions according to the disclosure) for use and/or uses in the manufacture of a medicaments for treating the diseases or disorders described herein.

As used herein, the term “prevention” means prophylactic administration of the antibody to an asymptomatic subject or a subject with pre-clinical disease (e.g., pre-clinical Alzheimer’s disease) to prevent onset or progression of the disease.

Aspects of the disclosure pertain to treating a disease characterized by deposition of amyloid beta (Ap) and/or a disease characterized by amyloid beta (Ap) deposits. In some embodiments, the disclosure pertains to a method of treating a disease characterized by deposition of amyloid beta (A ) and/or a disease characterized by amyloid beta (Ap) deposits by administering a therapeutically effective amount of a pharmaceutical solution according to the disclosure to a patient in need thereof. As used herein, the terms “disease characterized by deposition of amyloid beta (Ap)” or a “disease characterized by amyloid beta (A ) deposits” are used interchangeably and refer to a disease that is pathologically characterized by Ap deposits in the brain or in brain vasculature. This includes diseases such as Alzheimer’s disease (AD), Down’s syndrome, and cerebral amyloid angiopathy. In some embodiments, the 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 deposition of amyloid beta (AP) and/or a disease characterized by amyloid beta (AP) deposits according to the disclosure comprises administering a pharmaceutical solution according to the disclosure obtained from a vessel according to the disclosure to a patient in need thereof.

In some embodiments, a human patient in need thereof is administered one or more doses of a pharmaceutical solution according to the disclosure. For the avoidance of doubt, it is to be understood that administering a “dose” refers to administering a quantity of a pharmaceutical solution according to the disclosure. The “dose” may nevertheless be expressed in terms of the amount of antibody rather than the amount of the pharmaceutical solution. For example, as a person having ordinary skill in the art would understand, a reference to administering, for example, a dose of 100 mg of antibody refers to administering, for example, 10 mL of a pharmaceutical solution of antibody where the pharmaceutical solution has a concentration of 10 mg antibody per 1 mL solution (also referred to as a concentration of 10 mg/mL) or to administering, for example, 5 mL of a pharmaceutical solution of antibody where the pharmaceutical solution has a concentration of 20 mg antibody per 1 mL solution (also referred to as a concentration of 20 mg/mL). Also, for the avoidance of doubt, it is to be understood that references to administering an antibody refer to administering a pharmaceutical solution (according to the present disclosure) of that antibody.

In some embodiments, methods of treatment according to the disclosure comprise administering, to a patient, one or more doses of about 100 mg to about 10,000 mg of anti-N3pGlu Ap antibody, such as one or more doses of 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 antibody. In some embodiments, methods of treatment according to the disclosure comprise administering, to a patient, one or more doses of anti-N3pGlu A antibody that has not been lyophilized.

In some embodiments, the subject is administered one or more first doses of the antibody. In some embodiments, the one or more first doses are administered to the 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.

In some embodiments, the subject is administered one or more second doses of the antibody. In some embodiments, the one or more second doses comprise greater than about 700 mg to about 1400 mg of the antibody (e.g., of an anti-N3pGlu A|3 antibody). In some embodiments, the subject is administered one or more second doses of greater than about 700 mg to about 1400 mg of the antibody (e.g., of anti-N3pGlu A|3 antibody) wherein each second dose is administered once about every 4 weeks. In some embodiments, the second dose is administered 4 weeks after the one or more first doses.

A dose may also be expressed in terms of mg/kg. As used herein, “mg/kg” means an amount, in milligrams, of antibody or drug administered to a subject based on his or her bodyweight in kilograms. A dose is given at one time. For example, a 10 mg/kg dose of antibody for a patient weighing 70 kg would be a single 700 mg dose of antibody given in a single administration. Similarly, a 20 mg/kg dose of antibody for a patient weighing 70 kg would be a 1400 mg dose of antibody given at a single administration. In some embodiments, the first dose is from about 1 mg/kg to about 10 mg/kg of antibody. In some embodiments, the patient is administered up to three first doses of about 1 mg/kg to about 10 mg/kg. In some embodiments, the patient is administered one first dose, two first doses, or three first doses of about 1 mg/kg to about 10 mg/kg. In some embodiments, the patient is administered three first doses of about 10 mg/kg 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. In some embodiments, the antibodies, methods, dosing regimens, and/or uses of the present disclosure result in reduction of amyloid beta in the brain of a human patient. In some embodiments, administration of a pharmaceutical solution according to the disclosure results in a reduction in the amount of amyloid beta in the brain of a human patient of at least 5%. In some embodiments, administration of a pharmaceutical solution according to the disclosure results in a reduction in the amount of amyloid beta in the brain of a human patient 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.

EXAMPLES

Example 1 : Preformulation Studies on Donanemab

1. Abbreviations and Definitions

API - Active pharmaceutical ingredient

CE-SDS - Capillary Electrophoresis - Sodium Dodecyl Sulfate

DLS- Dynamic Light Scattering

BDS - Bulk Drug substance, starting material (donanemab) for the process DSC - Differential Scanning Calorimetry EP - European Pharmacopoeia

ISO - International Organization for Standardization

NF - National Formulary

PDS - Pharmaceutical Development Services

SDS - Sodium Dodecyl Sulfate

SEC - Size-Exclusion Chromatography

TC - Thermo Couples

USP - United States Pharmacopoeia

2. Materials and Equipment

Materials used during development are summarized in Table 1. Table 1. Materials Used

Equipment used during development are summarized in Table 2.

Table 2. Equipment Used

3. Methods

• Protein content: UV Absorbance at 280 nm (calculated extinction coefficient = 1 .48 mL-mg-1 cm-1 )

• Turbidity of the solution is determined by measuring the absorbance at 550 nm

• Particulate matter is monitored using USP <788> (light obscuration) method using Accusizer SIS

• Thermal stability is monitored using microcalorimetric differential scanning calorimetry (DSC)

4. Experimental Designs

4.1 pH Study

Without wishing to be bound by theory, it is believed that the pH of an antibody solution impacts properties including, but not limited to, the solubility of the antibody in the solution. The solubility of the antibody in the solution is an important parameter because it influences the amount of solution that must be administered to a patient (/.e., the dose) in order 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 an antibody solution affects the stability of the solution (e.g., that the antibody may degrade in the solution more rapidly at a first pH than at a second, different pH). Given the importance of pH, a pH rate-profile stability study was conducted to examine solution pH conditions for donanemab. The experimental design is presented in Table 3.

The thawed bulk drug substance (10mM citrate, 150 mM NaCI, pH 6.5; 57.5 mg/mL) was dialyzed against the 10mM citrate buffers using 30,000 MWCO Slide-a-lyzers cassettes. Dialysis was performed at 2-8°C and buffers were exchanged each day. Following buffer exchange, the protein concentration in each solution was measured and diluted to the pre-defined concentration (approximately 50 mg/mL for F4 and 2 mg/mL for the other solutions); final solutions were filtered using 0,22 m syringe filters.

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

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

Table 3: pH Rate-Profile Stability Study Design

Table 4: Testing Schedule for pH Study

X= pull sample and test; O= pull sample and test if needed

* Samples were analyzed with standard DSC and with micro calorimetry 4.2 Freeze Thaw Study

The stability of the donanemab solutions was assessed after freezing and thawing for up to 3 times.

The solutions were subjected to three freeze-thaw cycles and analyzed in the following way:

1 ^st day morning: TO analysis; freezing of vials to -70°C

1^st day afternoon: thawing at room temperature and T1 analysis; freezing of vials to -70°C

2^nd day morning: thawing at room temperature and T2 analysis; freezing of vials to -70°C

2^nd day afternoon: thawing at room temperature and T3 analysis

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 it was diluted to approximately 25 mg/mL. Dialysis was performed at 2-8°C and buffers were exchanged after 4, 8, and 24 hours from the beginning of dialysis.

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

After 0.22 pm filtration, the solutions were split into 10R vials filled each with 5 mL of each solution, stoppered and sealed. The testing schedule was as listed in Table 6.

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

Table 5: Freeze Thaw and Agitation Study Design

Table 6. Testing Samples

Note: X= pull sample and test; Blank entry = No test

4.3 Agitation Study

The stability of donanemab was assessed after agitating on a rotary shaker at 100 rpm at room temperature for 24 and 48 hours. This speed allowed a small oscillation of the solution inside the vials. The solutions with the same matrices and the same dialysis procedure as those in freeze thaw study were analyzed (see Table 5). After 0.22 pm filtration, the solutions were split into 10R vials filled each with 5 mL of each solution, stoppered and sealed. The testing schedule is listed in Table 7.

Table 7. Testing Samples

4.4 Solubility Study

Solubility of donanemab was studied in 10mM citrate buffer at pH 6 and with a Polysorbate 80 amount of 0.01 % (w/v). Donanemab BDS was dialyzed into appropriate buffers (same dialysis procedure followed for freeze thaw and agitation study), concentrated using Amicon® Ultra 30 K centrifugal filter units, filled in a 5 mL glass vial, stoppered, sealed, and stored at - 5°C on a pre-cooled lyophilizer shelf. After 24 hours, the sample was visually observed for phase separation. If no phase separation occurred, the sample was subjected to additional physical stability testing at 5°Cfor 1 week. The testing schedule was as listed in Table 8.

Table 8. Testing Samples

Note: Full testing foreseen only for one time point

5. Results

5.1 pH Study

The study was designed to investigate stability of donanemab at different pHs. The seven solutions (F1 -F7) indicated in Table 3 were studied. Sodium chloride and protein concentration effects were also examined at pH 6.0. The pH range of 5 to 7 was selected based on previous studies, which indicated maximal chemical and physical stability at pH 6.0. Tables A 1 - A.9 of Appendix A present the tabulated results from this study.

The protein content, turbidity (Abs at 550 nm) and pH values remained unchanged throughout the study for all solutions. Few particles were noted in all solutions (F1-F7) after 4 weeks at 2°C-8°C. After 4 weeks at 40°C/75% RH, few particles and filaments were noted in all solutions (Tables A 1 and A.2).

Looking at the overall SEC data, the results obtained from the storage temperature of 40°C / 75% RH were considered more significant than the ones obtained from the 2°C-8°C storage conditions. The SEC chromatograms showed a shoulder after the main peak which was identified as a fragment of donanemab and therefore it was included in the %low molecular weight species (% LMW) or fragments. After 4 weeks at 2-8°C, negligible differences in aggregation/fragmentation were observed in all test samples. After 4 weeks at 40°C fragmentation phenomena were more evident in F7 (pH 6.0, NaCI) and F6 (pH 5.0). On the contrary aggregation was higher in F4 (pH 6.0, 50 mg/mL), which may have been due to the higher protein concentration. The solutions F1 (pH 7.0), F2 (pH 6.5), F3 (pH 6.0) and F5 (pH 5.5) exhibited lesser degrees of fragmentation and/or aggregation. FIG.1 and Table A.3 of Appendix A provide additional SEC data for solutions at different pHs.

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

FIG. 2A, FIG. 2B, and Table A.4 of Appendix A provide additional details regarding the pH study.

After 4 weeks storage the overall % purity by reducing CE-SDS decreased. The solution with the smallest change in purity after 4 weeks was F5 (pH 5.5), and the solution with the greatest change in purity after 4 weeks was F1 (pH 7.0). FIG. 3 and Table A.5 of Appendix A provide additional purity data.

Differential Scanning Calorimetry (DSC) analyses were performed on pH Study 1 samples and data are reported in Table A.7. Results indicated that the Tm1 transition is the highest-energy transition. Regarding the subvisible particles, as shown in FIG. 4A and FIG. 4B, the number of particles/mL of each solution decreased for each investigated size after one month of stability.

Without wishing to be bound by theory, the foregoing results suggested that antibody stability in solution may be maximized by preparing the solution at a pH of from 5.5 to 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 study.

5.2 Freeze-Thaw Studies

This study was conducted on solutions containing 25 mg/mL of donanemab at pH of 6.0 (based on the output of the pH study) with varied Polysorbate 80 levels (Table 5). The donanemab solutions were subjected to 3 freeze and thaw cycles as described above. All tabulated analytical results from the freeze and thaw study are summarized in Tables A.10- A 14 of Appendix A.

Few particles were noted in the solutions F2 (0.01 % Polysorbate 80), F3 (0.02% Polysorbate 80), and F4 (0.04% Polysorbate 80) throughout the study On the contrary the solution F1 (no Polysorbate 80) showed an increase of particles from the first freeze thaw cycle on. Refer to Table A.10 in Appendix A.

No significant variations in UV assay at 280 nm was noted for F2 (0.01 % Polysorbate 80) and F3 (0.02% Polysorbate 80) solutions. Solutions F1 (no Polysorbate 80) and F4 (0.04% Polysorbate 80) showed a slight decrease of UV assay at 280 nm. Refer to Appendix A Table A.11 .

No pH variations were noted for all solutions (Table A 12 in Appendix A).

No significant variation of the Abs at 550 nm was noted for solutions F1 (no Polysorbate 80) and F2 (0.01 % Polysorbate 80), while a slight decrease of this parameter was observed for solutions F3 (0.02% Polysorbate 80) and F4 (0.04% Polysorbate 80). Refer to Appendix A Table A.12

The chromatograms obtained by SEC analysis showed a shoulder after the main peak, which was identified as a fragment of donanemab and therefore it was included in the %low molecular weight species (% LMW) or fragments. No significant variations of SEC profile were noted for solutions F2 (0.01 % Polysorbate 80) and F4 (0.04% Polysorbate 80), while solution F1 (no Polysorbate 80) showed a slight increase of main peak and concurrent decrease of fragmentation. A decrease of the main peak and concurrent increase of fragmentation was observed in solution F3 (0.02% Polysorbate 80).

No variation of the aggregation percentage was detected throughout the study. Refer to Table A 13 in Appendix A and to FIG. 5A, FIG 5B, and FIG. 50 for a graphical representation of the above considerations.

Without wishing to be bound by theory, these results indicated that the presence of a small percentage of Polysorbate (e.g., 0.01 % w/v) improved the physical properties of the overall solution, such as by reducing the number of visible particles and subvisible particles in the solution.

Soluble aggregates increased slightly in all samples after freeze and thaw treatment. As shown in FIG. 6A and FIG. 6B, after the third freeze / thaw cycle, the number of particles/mL increased generally for each solution at each investigated size.

Sample formulated without Polysorbate 80 exhibited higher particulate matter counts as measured by light obscuration. Refer to Appendix A Table A.14.

Without wishing to be bound by theory, the foregoing results suggested a benefit to including 0.01 % (w/v) of polysorbate 80 in solutions comprising donanemab to protect donanemab from physical instability associated with freezing and thawing.

5.3 Agitation

Concurrently with the freeze thaw, a study was conducted to assess potential stability concerns related to processing (mixing, pumping, filling, etc.) of donanemab solutions. The study was conducted on solutions containing a 25 mg/mL protein concentration at pH of 6.0 (based on the output of the study 1 ) and formulated as outlined in Table 5. Donanemab was subjected to agitation on a rotary shaker as described above. Tabulated results for rotated samples are found in Tables A.15. - A.21.

Some particles were noted in the solution F1 (no Polysorbate 80), and a decrease of particles was observed in solutions F2 (0.01 % Polysorbate 80), F3 (0.02% Polysorbate 80), and F4 (0.04% Polysorbate 80) throughout the study Refer to Appendix A Table A.15. No significant variations in UV assay at 280 nm were noted for F1 (no Polysorbate 80), F2 (0.01 % Polysorbate 80), and F3 (0.02% Polysorbate 80) solutions. A slight decrease of UV assay at 280 nm was observed for solution F4 (0.04% Polysorbate 80). Refer to Table A.15A in Appendix A.

No pH variations were noted for all solutions (Table A 16 in Appendix A).

No significant variation of the Abs at 550 nm was noted for solutions F1 (no Polysorbate 80), F2 (0.01 % Polysorbate 80), and F4 (0.04% Polysorbate 80). A slight decrease of this parameter was observed in solution F3 (0.02% Polysorbate 80). Refer to Table A.16 in Appendix A.

The chromatograms obtained by SEC analysis showed a shoulder after the main peak, which was identified as a fragment of donanemab and therefore it was included in the %low molecular weight species (% LMW) or fragments. No significant variation in SEC profile was observed in solutions F1 (no Polysorbate 80) and F2 (0.01 % Polysorbate 80). Solutions F3 (0.02% Polysorbate 80) and F4 (0.04% Polysorbate 80) showed a decrease of the main peak and a concurrent increase of fragmentation.

No variation of the aggregation percentage was registered throughout the study. Refer to Table A 17 in Appendix A, FIG. 7A, FIG. 7B, and FIG. 7C for a graphical representation of the above considerations.

The non-reducing CE-SDS analyses showed a general increase of % donanemab. Refer to Table A.18 in Appendix A and to FIG. 8

A general increase of % purity was noted by reducing CE-SDS analysis in all solutions. Refer to Table A.19 in Appendix A and to FIG. 9.

Donanemab was chemically stable after rotating for 2 days. Likewise, soluble aggregation was minimal following agitation for all samples. Solutions with Polysorbate 80 had the fewest number of particles/mL with respect to solutions without it, mainly for 10 pm size (FIG. 10A and FIG. 10B). Refer also to Table A.20 of Appendix A.

Without wishing to be bound by theory, the foregoing results suggested a benefit from including 0.01 % (w/v) polysorbate 80 in solutions comprising donanemab to protect donanemab from physical instability associated with mixing. For example, the foregoing results suggested that a solution comprising 10 mM citrate buffer, 0.01 % (w/v) polysorbate 80, and at pH 6.0 provides a stable solution of donanemab. Refer to Table A.21 of Appendix A for a summary of the freeze thaw and agitation study results.

5.4 Solubility

In view of the pH, freeze thaw, and agitation studies, the solubility of donanemab was studied in 10mM citrate buffer at pH 6 and in the presence of 0.01 % (w/v) Polysorbate 80. The solution after dialysis against the selected citrate buffer, was concentrated. After the addition of Polysorbate 80, the concentration was measured and was shown to be ~125 mg/mL. Sample was stored at - 5°Cfor 24 hrs and the appearance of the solution was more opalescent than at time 0 but no phase separation occurred. FIG. 11 A and FIG. 11 B show a snapshot of the samples. This same sample clarified upon equilibration to room temperature.

The sample was stored at 2-8°C for 1 week and then analyzed. The donanemab solution remained yellow colored throughout the study. No phase separation was observed after 24 h storage. After 1 week storage at 2°C - 8°C the solution was clear with particles and a filament in solution. A slight decrease of the UV assay was detected. Without wishing to be bound by theory, the result of the absorbance (Abs) at 550 nm may have been affected by the yellow color of the solution. No pH variation was observed. The SEC results were in line with the results obtained in the previous studies on less concentrated donanemab solutions.

Results are summarized in Table 9.

Table 9: Solubility Study Results

6. Conclusions

A series of preformulation studies were conducted to select the pH and agents necessary to stabilize donanemab. These studies involved identifying a pH range of from 5.0 to 7.0, studying the effect of Polysorbate 80 on freeze thaw and agitation, as well as solubility of donanemab. The molecule demonstrated good chemical stability at pH 5.5 and pH 6.0. The pH 5.5 solution showed the lowest decrease of the % purity by reducing and non-reducing CE- SDS. The pH 6.0 solution showed a decrease of the % purity by reducing and non-reducing CE-SDS.

Without wishing to be bound by theory, these results suggested that formulating donanemab at a pH 6.0 provides benefits with respect to the stability of the solution

The addition of 0.01 % (w/v) Polysorbate 80 surfactant was also studied. Without wishing to be bound by theory, the results suggested that formulating donanemab with 0.01 % (w/v) polysorbate 80 provides benefits with respect to the stability of the solution.

During solubility experiments, phase separation was not observed at a concentration of approximately 125 mg/mL.

Table 10 summarizes certain observations from the foregoing preformulation studies.

Table 10

7. Example 1 - Appendix A

Table A.1. pH Study. Abs 550, pH, and Appearance Results

Table A.2. pH Study. UV Assay (Abs 280 nm) Results

Table A.3. pH Study. SEC Results

Table A.4. pH Study. CE-SDS Non-Reduced Results (Note: %donanemab corresponds to the intact donanemab)

Table A.5. pH Study. CE-SDS-Reduced Results (Note: % Purity includes HC and LC)

Table A.7. pH Study 1 : DSC Data.

Table A.8. pH Study 1: Sub Visible Particles Data

Table A.9. pH Study. Summary of results

Table A.10. Freeze thaw. Visual Appearance Results

Table A.11. Freeze and Thaw Study. UV Assay at 280 nm Results.

Table A.12. Freeze and Thaw Study. pH and Abs at 550 nm Results.

Table A.13. Freeze and Thaw Study. SEC Results.

Table A.14. Freeze and Thaw Study 2: Particulate Matter and DLS Results

Table A.15. Agitation Study. Visual Appearance Results

Table A.15A. Agitation Study. UV Assay at 280 nm Results

Table A.16. Agitation Study. pH and Abs at 550 nm Results

Table A.17. Agitation Study. SEC Results

Table A.18. Agitation Study. CE-SDS Non-Reduced Results (Note: %donanemab corresponds to the intact donanemab)

Table A.19. Agitation Study. SDS-Reduced Results

Table A.20. Agitation Study 3: Particulate Matter and DLS Results

Table A.21. Freeze Thaw and Agitation Studies. Summary of Results

Example 2 - Further Solution Studies on Donanemab

2.1 Study Design

The initial prototype solution screening study evaluated thirteen prototypes with various donanemab concentrations, tonicity agents, buffer systems, and surfactant levels.

Donanemab solutions were prepared, and 20 mL vials were filled with 14 mL of solution, to provide a worst-case scenario for headspace and potential susceptibility to oxidation and agitation. Vials were stoppered, capped, and sealed, and stored in the upright storage condition at 5°C, 25°C and 35°C conditions for 3 months (with the exception of ‘R2’ and ‘R13’ solutions at 10 and 17.5 mg/mL described in the next section, which were only stored at 5°C and 35°C due to material constraints). Vials were also subjected to an ISTA 3A shipping stress evaluation. A subset of the solutions of interest were selected based on the 3-month data and retains were tested after 29 months of storage.

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).

As discussed in Example 1 , without wishing to be bound by theory, it is believed that the pH of the antibody solution impacts properties of the solution and/or of the antibody in solution. As also discussed in Example 1 , without wishing to be bound by theory, the results of that Example suggested that antibody stability in solution may be maximized by preparing the solution at a pH of from 5.5 to 6.0 Taking that information into account, in the present Example, the solutions were prepared at a target pH of 6.0. Table 11. donanemab Initial Solution Prototype Screening Study

*AII solutions were prepared at a target pH of 6.0

Without wishing to be bound by theory, it is believed that the concentration of the antibody in solution affects the stability of the solution. For example, without wishing to be bound by theory, it is believed that even a highly purified sample of the antibody will nevertheless contain trace amounts of 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) processes that lead to solution degradation and/or the formation of particulate matter. Accordingly, without wishing to be bound by theory, it is believed that a higher concentration of the antibody in solution correlates to a higher concentration of trace impurities (e.g., enzymes) and, therefore, to a greater possibility that solution degradation occurs and/or that particulate matter forms in solution, each of which is undesirable. For example, in solutions 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 accumulation of particulate matter.

For at least these reasons, it is understood that antibody concentration is one of many factors that impacts solution stability. Thus, antibody concentration was a variable examined in the present study. Specifically, a donanemab concentration range of 10 to 50 mg/mL was studied. The 50 mg/mL concentration (R3) was expected to provide a worst-case for potential particulate growth over time, as an earlier-examined lyophilized formulation showed a trend of increased particulates growth as a function of donanemab concentration Use of a 50 mg/mL donanemab solution concentration could enable a single vial to be used for a clinical dose of 700 mg. The 10 and 25 mg/mL concentrations were selected as the lower and upper ends of the range expected for a feasible solution formulation, to mitigate the risk of particulate growth and provide an acceptable stability profile. The 17.5 mg/mL concentration (R13) was selected as a midpoint between the lower and upper ends of the expected acceptable solution range. At a 17.5 mg/mL concentration, a clinical dose of 700 mg could be administered from two, 20-mL drug product vials.

Without wishing to be bound by theory, it is believed that the nature of the buffer of the antibody solution can impact 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 the 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 alteration 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 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 may reduce or prevent oxidation of polyoxyethylene (20) sorbitan monooleate. Accordingly, it is believed that the choice of the one or more buffers used in the antibody solution can impact the stability of the antibody solution by reducing or preventing alteration and/or degradation of the antibody and/or reducing or preventing particulate matter formation. In the present study, several prototype solutions evaluated a 10 mM citrate buffer system to minimize antibody matrix changes between an earlier-examined lyophilized formulation and the studied solutions. 25 mg/mL donanemab solutions R5, containing histidine to citrate at a 3:1 ratio, and R10 containing all histidine, were also studied to compare against R1 containing 10 mM citrate with 25 mg/mL donanemab.

Without wishing to be bound by theory, it is believed that the nature of the one or more tonicity agents present in the antibody solution can impact 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 the degradation of the antibody during the freeze-thaw process. Accordingly, it is believed that the choice of the one or more buffers used in the antibody solution can impact the stability of the antibody solution. In the present study, several solutions evaluated a 10% w/v sucrose level. A previous lyophilized formulation had utilized sucrose at 8% w/v to provide isotonic conditions. Prototypes R4 and R6 evaluated glycine in combination with sucrose or mannitol, respectively, to provide an alternative to the 10% w/v sucrose level. Prototype R8 evaluated the addition of methionine to mitigate any potential oxidative-related chemical degradation observed in prior forced degradation studies. Solutions R7 and R9 evaluated trehalose and sodium chloride as alternative tonicity agents to sucrose. After 29 months of storage at 5°C, solution vial retains for the lead prototype and selected prototypes from the initial study were evaluated. Based on the extended 5°C storage condition and acceptable chemical and physical property data, the sucrose-based solution formulation was modified to provide isotonic conditions (reducing the sucrose from 10% w/v to 8% w/v).

Without wishing to be bound by theory, it is believed that the nature and/or concentration of the one or more surfactants present in the antibody solution can impact the stability of the solution and/or the antibody therein. For example, without wishing to be bound by theory, it is believed that, in solutions containing polyoxyethylene (20) sorbitan monooleate (PS80), a higher concentration of PS80 is associated with a greater number of free radical species (which are themselves formed by oxidation of PS80, as discussed above), whereas 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 alteration and/or degradation. Accordingly, without wishing to be bound by theory, it is believed to be preferable to reduce the number of free radical species present in the antibody solution. Without wishing to be bound by theory, it is believed one way to do so is by adjusting the concentration of PS80 surfactant in the solution (e.g., identifying a concentration that is sufficiently high to impart beneficial properties but low enough to minimize or avoid generation of free radical species). A prior lyophilized formulation utilized PS80 at 0.02% w/v. In the present study, several solutions had a target PS80 concentration of 0.02% w/v, with the exception of R11 , which used 0.02% w/v Polysorbate 20 (PS20) and R12, containing 0.04% w/v Poloxamer 188. Solutions R1 and R3 contained 0.20% w/v PS80.

In a separate study, prototype solution vials were also subjected to an ISTA-3A shipping evaluation to understand if there was any susceptibility to particulate growth as a result of shipping stress conditions. Generation of particulates had been observed after exposing various lyophilized formulations to ISTA-3A shipping conditions.

2 2 Study Results Where differences between solutions are discussed, reference to correspondence figures (by FIG. number) is made. Where there is an associated potential specification for a che ical or physical property attribute, a line is shown on the figure to indicate the specification limit

SEC monomer loss and corresponding aggregate growth was observed for all solutions at the 3 month, 35°C storage condition (FIG. 12A and FIG. 12B). At the 25°C condition, the solutions containing sodium chloride and both solutions with alternative surfactants to 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 the 5°C storage condition. Without wishing to be bound by theory, these results suggested that solutions containing PS80 may offer improved stability over time compared to solutions containing PS20 or and/or that solutions containing sodium chloride may experience decreased stability over time compared to solutions containing a different tonicity agent.

CE-SDS reduced data (FIG. 13A and FIG. 13B) show that the two solutions containing glycine had higher % purity losses and corresponding higher total aggregates/non-reducible species levels, relative to all other solutions, at the 3-month 25°C and 35°C storage conditions. All solutions had a similar stability profile for total fragments. Without wishing to be bound by theory, these results suggested that including glycine in solutions may have a deleterious effect on the long-term stability of the solution.

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

Evaluation of the surfactant chemical data shows that none of the PS80-based solutions showed any appreciable changes in total oleic acid (TOA), over the 3-month storage condition. Additionally, FIG. 15 shows that the free oleic acid (FOA) in solutions containing sodium chloride and 10 mM histidine was higher after 3 months of storage at the 25°C and 35°C temperature conditions, than all other solutions containing 0.02% w/v PS80. Greater than 25% of the TOA level was present as FOA in these solutions after 3 months at 25°C, suggesting a higher susceptibility of these solutions to PS80 hydrolysis.

Without wishing to be bound by theory, it is believed that esterases contained in solutions of the antibodies 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 solutions of the antibodies lead to the formation of more particulate materials.

The solution containing PS20 showed an increase in free lauric acid after 3 months at 25°C, approaching similar levels to those observed for the 10 mM histidine- based solution (approximately 25% of the total existing in the free state). The solution containing poloxamer showed no indication of losses over the storage time at 5°C. Without wishing to be bound by theory, these results suggested that solutions containing PS20 and/or histidine may be less preferable than solutions containing PS80 due to the increase in free lauric acid observed in the solutions containing PS20 or histidine.

FIG. 16A, FIG. 16B, FIG. 17A, FIG. 17B, FIG. 17C, FIG. 17D, FIG 18A, and FIG. 18B depict particulate data (MFI and light obscuration) for studied solutions. For all solutions with the exception of the glycine and histidine solutions, particulate data remained low at the 3-month timepoint for all temperatures. The solutions containing glycine, methionine, and 10 mM histidine showed slightly elevated 10- and 25-micron particle count light obscuration data, compared to other solutions. Without wishing to be bound by theory, these results suggested that the antibody solutions containing glycine, methionine, and/or histidine resulted in increased amounts of particulate matter compared to, e.g., solutions containing sucrose and/or trehalose and, therefore, that solutions containing sucrose and/or trehalose may be preferred from the standpoint of decreasing particulate matter and/or decreasing the formation of particulate matters over time. When comparing the 29-month 5°C data with the 3-month stability data, there was little change in chemical or physical property attributes from the 3-month 5°C data. The SEC data showed a slight increase in aggregates and corresponding decrease in monomer. The changes between 3 and 29 months at 5°C storage were less pronounced than the differences observed between the 5°C and accelerated temperature data at 3 months.

Samples of solutions were subjected to ISTA-3A testing. As explained elsewhere herein, the details of ISTA-3A testing are known to persons having ordinary skill in the art and are available through the International Safe Transit Association at ista.org. In brief, ISTA-3A testing is used to examine the effect of vibrations, shocks, and other stress that may be encountered during the handling and/or transportation of a material in a package distribution system. When tested, a test material is subjected to drops, vibrations, and impacts. Without wishing to be bound by theory, it is believed that damage to a test material is cumulative. In some instances of testing, an acceleration factor may be used. Without wishing to be bound by theory, it is believed that use of an acceleration factor enables trading an increase in power for an increase in time. For example, without wishing to be bound by theory, it is believed that subjecting a sample to a first vibration power for one-hour results in the same effect on a sample as subjecting the sample to a second vibration power that is one-fifth the intensity of the first vibration power for five hours.

ISTA-3A shipping exposure data for the tested solutions, including data regarding particulates of various sizes as measured by microflow imaging (MFI), regarding particulates of various sizes as measured by light obscuration using a high accuracy liquid particle counter (HIAC), regarding percent monomer content as measured by size exclusion chromatography, regarding total aggregate content as measured by size exclusion chromatography, regarding purity as measured by non-reducing CE-SDS, regarding percent fragment content as measured by non-reducing CE-SDS, and regarding percent aggregates as measured by non-reducing CE-SDS, are presented in FIG. 19A, FIG. 19B, FIG. 20A, FIG. 20B, FIG. 21A, FIG. 21 B, FIG. 22A, FIG. 22B, and FIG. 22C. The data did not indicate substantive differences in chemical attributes or particulate counts between control samples of the solutions (which were not subjected to the ISTA-3A shipping test) and samples that were subjected to the ISTA-3A shipping test, except for the solution containing poloxamer. For example, as shown in FIG. 23A and FIG. 23B, the solution containing poloxamer exhibited a several-fold increase in particles > 2 pm and particles > 5 pm, as measured by MFI. Without wishing to be bound by theory, these results suggested that the solutions containing poloxamer as the (or a) surfactant may be less amenable to packaging and shipping. However, for all of the solutions except the solution containing poloxamer, the solutions did not show any substantial increase in particle formation. Notably, this result stands in contrast to results of ISTA-3A shipping tests performed on lyophilized formulations of antibody, which, as discussed elsewhere herein, exhibited consistently higher levels of particulate materials after storage for one month and at subsequent timepoints. Without wishing to be bound by theory, these results suggested that antibody solutions similar or identical to those tested herein (e.g., anti-N3pGlu A antibody solutions containing citrate or histidine buffer, containing one or more tonicity agents chosen from sucrose, trehalose, mannitol, and glycine, and containing PS20 and/or PS80 surfactant) may exhibit properties (e.g., physicochemical properties) that make them amenable to packaging and shipping.

Without wishing to be bound by theory, the foregoing chemical and stability performance data of the tested solutions suggested 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, particulate growth, and/or solution and/or antibody stability Without wishing to be bound by theory, the foregoing data suggested that the combination of a 17.5 mg/mL anti-N3pGlu A antibody concentration, in citrate buffer containing 10% w/v sucrose and 0.02% w/v PS80, provided an ideal solution in terms of utility and stability. For example, the chemical and particulates data for the antibody solution comprising that combination of ingredients were comparable to an earlier- examined lyophilized antibody matrix, yet the antibody solution comprising that combination exhibited superior stability over time compared to that earlier-examined lyophilized antibody matrix.

2.3 Further Studies on Tonicity Agents and Extended Storage of Solutions at 5°C Two additional solutions were prepared at the 17.5 mg/mL donanemab concentration in 5 mM citrate and containing 0.02% w/v PS80. In these solutions (identified as P1 and P2), the sucrose was substituted for either mannitol (5.3% w/v concentration) or trehalose (10% w/v concentration). Sample vials were filed to a 20 mL filled volume, and the solutions were stored. Chemical and physical property data for the two additional solutions and for a solution (identified as R13) comprising 17.5 mg/mL donanemab in 10 mM citrate, containing 0 02% PS80, and containing 10% w/v sucrose, the latter solution being shown for comparison to the two additional solutions, are illustrated in FIG. 23A to FIG. 29B. 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. The collected data that are illustrated in FIG. 23A to FIG. 29B 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 aggregates 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 aggregates as measured by non-reducing CE-SDS, total oleic acid, free oleic acid, particulates of various sizes as measured by microflow imaging (MFI), and particulates of various sizes as measured by light obscuration using a high accuracy liquid particle counter (HIAC).

Comparing the 29-month and 6-month 5°C data for the chemical and physical properties of the three solutions (/.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 for any of the three solutions. The observed increases in SEC monomer loss and total aggregate increases at the elevated temperature storage, the extent of total acidic variants, and the reduction in main peak were within expectations. Without wishing to be bound by theory, the foregoing data suggested that solutions containing the combination of donanemab {e.g., at a concentration of 17.5 mg/mL) in citrate e.g., at a concentration of 5 mM or 10 mM), PS80 e.g., at a concentration of 0.02% w/v), and one or more of sucrose {e.g., at a 10% w/v concentration), mannitol (e.g., at a 5.3% w/v concentration), or trehalose (e.g., at a 10% w/v concentration) may exhibit acceptable stability over time (e.g., for 3 months, 6 months, or 29 months at 5°C, 25°C, and/or 35°C) and/or improved stability over time (e.g., for 3 months, 6 months, or 29 months at 5°C, 25°C, and/or 35°C), such as improved stability compared to solutions that omit 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 10% w/v concentration, mannitol at 5.3% w/v concentration, or trehalose at 10% w/v concentration).

2.4 Peptide Mapping Studies

Peptide mapping by LC-MS was performed for selected solutions after storage at 29 months storage at 5°C. The solutions in citrate matrix at 10, 17.5 and 25 mg/mL (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.

Table 12. LC-MS Peptide Mapping of Selected Prototypes after 29 Months of 5°C Storage

The peptide mapping results for the three citrate-based solutions were comparable to the reference standard. There appeared to be no additional benefit to addition of methionine in terms of reducing oxidative species beyond the levels observed in the other citrate-based solutions. The histidine-based solution showed elevated oxidative species (HC M250) relative to the citrate solutions and reference standard.

The citrate-based solutions were considered comparable to the reference standard in overall peptide map profiles. All solutions had reduced incomplete pyroglutamate and Des Gly Amidation degradant levels compared to the reference standard.

Without wishing to be bound by theory, these peptide mapping results suggested that incorporating a citrate buffer into the solution of anti-N3pGlu A|3 antibody imparts benefits in terms of reducing antibody degradation. Without wishing to be bound by theory, these results suggested that incorporating histidine into the solution of anti- N3pGlu Ap antibody had a deleterious effect on antibody degradation. Furthermore, these peptide mapping results, in combination with the results discussed above for the solution containing sucrose, the solution containing mannitol, and the solution containing trehalose (e.g., the lack of a significant increase in aggregates or particulates upon storage at 5°C for 29 months), without wishing to be bound by theory, further suggested that solutions containing the combination of donanemab (e.g., at a concentration of 17.5 mg/mL) in citrate (e.g., at a concentration of 5 mM or 10 mM), PS80 (e.g., at a concentration of 0.02%), and one or more of sucrose (e.g., at a 10% w/v concentration), mannitol (e g., at a 5.3% w/w concentration) or trehalose (e.g., at a 10% w/v concentration) exhibited acceptable stability over time (e.g., for 3 months, 6 months, or 29 months at 5°C, 25°C, and/or 35°C) and/or improved stability over time (e.g., for 3 months, 6 months, or 29 months at 5°C, 25°C, and/or 35°C), such as improved stability compared to solutions that omit 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 10% w/v concentration, mannitol at 5.3% w/v concentration, or trehalose at 10% w/v concentration).

Table 13. Donanemab Solution Formulation

Example 3 - Product specifications

Full specifications for the donanemab drug product are provided below.

Table 14. Specifications for Donanemab Drug Product

Abbreviations: CE-SDS = capillary electrophoresis with sodium dodecyl sulfate; CEX = cation exchange chromatography; HPLC-UV = high-performance liquid chromatography-ultraviolet spectroscopy; icIEF = imaged capillary isoelectric focusing; SEC = size-exclusion chromatography; UV = ultraviolet spectroscopy. ^a Conforms to reference standard indicates that the sample chromatographic profile compares favorably to the reference standard with respect to the main peak retention time and the chromatographic profile. ^D The identity is confirmed if the test sample exhibits a sigmoidal dose-response curve similar to the donanemab reference standard. ^c This is equivalent to not less than 16.63 mg/mL and not more than 18.38 mg/mL.

" This is equivalent to not less than 16.28 mg/mL and not more than 18.73 mg/mL. ^e Conforms with reference standard indicates that the sample electrophoretic profile compares favorably to the reference standard, with no new peaks and/or no absence of peaks based on examples in the methods and clinical experience. ^f In the context of these specifications, release refers to initial test results that meet the release specifications.

⁹ In the context of these specifications, end of shelf-life refers to test results throughout storage up to and including 24 months that meet the end-of-shelf-life specifications.

Table 15. CEX Method Details

MES = 2-(N-morpholino)ethanesulfonic acid, TRIS =

Tris(hydroxymethyl)aminomethane, HEPES = (4-(2-hydroxyethyl)-1- piperazineethanesulfonic acid), CHES - N-cyclohexy-2-aminoethanesulfonic acid, CAPS = N-cyclohexyl-3-aminopropanesulfonic acid

Table 16. UV Method Details

Table 17. SEC Method

Table 18. Cell Based Potency Assay Details

Table 19. CE-SDS Reduced Method

Table 20. Method Parameters for CE-SDS Non-Reduced

Table 21. icIEF Master Mix Composition and Method Details

Table 22. Polysorbate 80 Method

SEQUENCES (Underlined Portions Indicate CDRs)

SEQ ID NO: 1 ; Light Chain Variable Region (LCVR)

DIVMTQTPLSLSVTPGQPASISCKSSQSLLYSRGKTYLNWLLQKPGQSPQLLIYAVSKL DSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCVQGTHYPFTFGQGTKLEIK

SEQ ID NO: 2; Heavy Chain Variable Region (HCVR)

QVQLVQSGAEVKKPGSSVKVSCKASGYDFTRYYINWVRQAPGQGLEWMGWINPGS GNTKYNEKFKGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGIT\/YWGQGTTVTV SS

SEQ ID NO: 3; Light Chain (LC)

DIVMTQTPLSLSVTPGQPASISCKSSQSLLYSRGKTYLNWLLQKPGQSPQLLIYAVSKL DSGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCVQGTHYPFTFGQGTKLEIKRTVAA

PSVFIFPPSDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSK DSTYSLSSTLTLSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC

SEQ ID NO: 4; Heavy Chain (HC)

QVQLVQSGAEVKKPGSSVKVSCKASGYDFTRYYINWVRQAPGQGLEWIVIGWINPGS

GNTKYNEKFKGRVTITADESTSTAYMELSSLRSEDTAVYYCAREGITVYWGQGTTVTV SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAV LQSSGLYSLSSWTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPA

PELLGGPSVFLFPPKPKDTLMISRTPEVTCVWDVSHEDPEVKFNWYVDGVEVHNAKT KPREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQ VYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFF LYS KLTVD KS R WQ QGN VFS CS VM H E ALH N H YTQ KS LS LS PG

SEQ ID NO: 5; Light Chain Complementarity Determining Region 1 (LCDR1 ) KSSQSLLYSRGKTYLN

SEQ ID NO: 6; Light Chain Complementarity Determining Region 2 (LCDR2) AVSKLDS

SEQ ID NO: 7; Light Chain Complementarity Determining Region 3 (LCDR3) VQGTHYPFT

SEQ ID NO: 8; Heavy Chain Complementarity Determining Region 1 (HCDR1) GYDFTRYYIN

SEQ ID NO: 9; Heavy Chain Complementarity Determining Region 2 (HCDR2)

WINPGSGNTKYNEKFKG

SEQ ID NO: 10; Heavy Chain Complementarity Determining Region 3 (HCDR3)

EGITVY SEQ ID NO: 11 ; Nucleotide Sequence for SEQ ID NO: 1 ; Light Chain Variable Region (LCVR)

GATATTGTGATGACTCAGACTCCACTCTCCCTGTCCGTCACCCCTGGACAGCCGG C CTCCATCTCCTGCAAGTCAAGTCAGAGCCTCTTATATAGTCGCGGAAAAACCTAT TTGAATTGGCTCCTGCAGAAGCCAGGCCAATCTCCACAGCTCCTAATTTATGCGGT

GTCTAAACTGGACTCTGGGGTCCCAGACAGATTCAGCGGCAGTGGGTCAGGCACA G ATTTC AC ACTG AAAATCAG CAGG GTGGAG GC CG AAG ATGTTGG G GTTTATTACTG CGTGCAAGGTACACATTACCCATTCACGTTTGGCCAAGGGACCAAGCTGGAGATC AAA

SEQ ID NO. 12; Nucleotide Sequence for SEQ ID NO: 2; Heavy Chain Variable Region (HCVR)

CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGTCCTCAGTG

AAGGTTTCCTGCAAGGCATCTGGTTACGACTTCACTAGATACTATATAAACTGGGT

GCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATTAATCCTGGAAG CGGTAATACTAAGTACAATGAGAAATTCAAGGGCAGAGTCACCATTACCGC G GAC

GAATCCACGAGCACAGCCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACG GCCGTGTATTACTGTGCGAGAGAAGGCATCACGGTCTACTGGGGCCAAGGGACCA CGGTCACCGTCTCCTCA

SEQ ID NO. 13; Nucleotide Sequence for SEQ ID NO: 3; Light Chain (LC)

GATATTGTGATGACTCAGACTCCACTCTCCCTGTCCGTCACCCCTGGACAGCCGG CCTCCATCTCCTGCAAGTCAAGTCAGAGCCTCTTATATAGTCGCGGAAAAACCTAT TTGAATTGGCTCCTGCAGAAGCCAGGCCAATCTCCACAGCTCCTAATTTATGCGGT GTCTAAACTGGACTCTGGGGTCCCAGACAGATTCAGCGGCAGTGGGTCAGGCACA G ATTTC AC ACTG AAAATCAG CAGG GTGGAG GC CG AAG ATGTTGG G GTTTATTACTG CGTGCAAGGTACACATTACCCATTCACGTTTGGCCAAGGGACCAAGCTGGAGATC AAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCATCTGATGAGCAGTT GAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTATCCCAGAGAGG C CAAAGTAC AGTG G AAG GTGG ATAACG C C CTCCAATC G G GTAACTCCC AGG AG AG TGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGAC

GCTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCAT CAGGGCCTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGC

SEQ ID NO. 14; Nucleotide Sequence for SEQ ID NO: 4; Heavy Chain (HC)

CAGGTGCAGCTGGTGCAGTCTGGGGCTGAGGTGAAGAAGCCTGGGTCCTCAGTG

AAGGTTTCCTGCAAGGCATCTGGTTACGACTTCACTAGATACTATATAAACTGGGT

GCGACAGGCCCCTGGACAAGGGCTTGAGTGGATGGGATGGATTAATCCTGGAAG

CGGTAATACTAAGTACAATGAGAAATTCAAGGGCAGAGTCACCATTACCGCGGAC

GAATCCACGAGCACAGCCTACATGGAGCTGAGCAGCCTGAGATCTGAGGACACG

GCCGTGTATTACTGTGCGAGAGAAGGCATCACGGTCTACTGGGGCCAAGGGACCA

CGGTCACCGTCTCCTCAGCCTCCACCAAGGGCCCATCGGTCTTCCCGCTAGCACC CTCCTCCAAGAGCACCTCTGGGGGCACAGCGGCCCTGGGCTGCCTGGTCAAGGA CTACTTCCCCGAACCGGTGACGGTGTCGTGGAACTCAGGCGCCCTGACCAGCGG CGTGCACACCTTCCCGGCTGTCCTACAGTCCTCAGGACTCTACTCCCTCAGCAGC GTGGTGACCGTGCCCTCCAGCAGCTTGGGCACCCAGACCTACATCTGCAACGTGA ATCACAAGCCCAGCAACACCAAGGTGGACAAGAAAGTTGAGCCCAAATCTTGTGA

CAAAACTCACACATGCCCACCGTGCCCAGCACCTGAACTCCTGGGGGGACCGTCA GTCTTCCTCTTCCCCCCAAAACCCAAGGACACCCTCATGATCTCCCGGACCCCTGA GGTCACATGCGTGGTGGTGGACGTGAGCCACGAAGACCCTGAGGTCAAGTTCAAC TGGTACGTGGACGGCGTGGAGGTGCATAATGCCAAGACAAAGCCGCGGGAGGAG CAGTACAACAGCACGTACCGTGTGGTCAGCGTCCTCACCGTCCTGCACCAGGACT

GGCTGAATGGCAAGGAGTACAAGTGCAAGGTCTCCAACAAAGCCCTCCCAGCCCC CATC GAG AAAAC C ATCTC C AAAG CC AAAG G GCAGC CCC G AGAAC C ACAG GTGTAC ACCCTGCCCCCATCCCGGGACGAGCTGACCAAGAACCAGGTCAGCCTGACCTGC CTGGTCAAAGGCTTCTATCCCAGCGACATCGCCGTGGAGTGGGAGAGCAATGGG CAGCCGGAGAACAACTACAAGACCACGCCCCCCGTGCTGGACTCCGACGGCTCC

TTCTTCCTCTATAGCAAGCTCACCGTGGACAAGAGCAGGTGGCAGCAGGGGAACG TCTTCTCATGCTCCGTGATGCATGAGGCTCTGCACAACCACTACACGCAGAAGAG CCTCTCCCTGTCTCCGGGT

Claims

CLAIMS A pharmaceutical solution comprising: an anti-N3pGlu A0 antibody comprising (a) a light chain variable region (LCVR) comprising an LCDR1 of SEQ ID NO: 5, an LCDR2 of SEQ ID NO: 6, and an LCDR3 of SEQ ID NO: 7, and (b) a heavy chain variable region (HCVR) comprising an HCDR1 of SEQ ID NO: 8, an HCDR2 of SEQ ID NO: 9, and an HCDR3 of SEQ ID NO: 10, a buffer, a tonicity agent, a surfactant, and an optional excipient; in amounts that are sufficient in combination for the pharmaceutical solution to exhibit one or more of:

(a) an antibody monomer content of at least 95% relative to total antibody peak area, as measured by size exclusion chromatography, after the pharmaceutical solution has been stored at 2-8°C for 3 months;

(b) a total aggregate content of less than 5% relative to total antibody peak area, as measured by size exclusion chromatography, after the pharmaceutical 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 pharmaceutical solution has been stored at 35°C for 3 months;

(d) a total aggregate content of (i) less than 5% relative to total antibody peak area, as measured by size exclusion, or (ii) less than 8.5 area %, as measured by non-reducing CE-SDS, after the pharmaceutical solution has been stored at 2-8°C for 3 months;

(e) less than 500 particulates per milliliter, wherein the particulates are sized greater than 2 .m, as measured by light obscuration using a high accuracy liquid particle counter (HIAC), after the pharmaceutical solution has been stored at 2-8°C for 3 months; (f) less than 100 particulates per milliliter, wherein the particulates are sized greater than 5 pm, as measured by light obscuration using a high accuracy liquid particle counter (HIAC), after the pharmaceutical solution has been stored at 2-8°C for 3 months;

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

(j) not more than an 11 % decrease in the amount of the anti-N3pGlu antibody, as measured by non-reducing CE-SDS, after the pharmaceutical solution has been stored for 4 weeks at 2-8°C; and

(k) not more than four particles having a size of 25 pm or less, as measured by differential counts per mL, after the pharmaceutical solution has been stored for 4 weeks at 2-8°C. The pharmaceutical solution of claim 1 , comprising amounts of the anti-N3pGlu Ap antibody, the buffer, the tonicity agent, the surfactant, and the optional excipient that are sufficient in combination for the pharmaceutical solution to exhibit one or more of:

(a) an antibody monomer content of at least 95% relative to total antibody peak area, as measured by size exclusion chromatography, after the pharmaceutical solution has been stored at about 5°C for 3 months;

(b) a total aggregate content of less than 5% relative to total antibody peak area, as measured by size exclusion chromatography, after the pharmaceutical solution has been stored at about 5°C for 3 months;

(c) a UV absorbance at 550 nm that varies by less than ±3% over 4 weeks of storage at 5°C; (d) a change in protein content as measured by UV absorbance at 280 nm of from 1 % to 13% after storage for 4 weeks at about 5°C;

(g) not more than four particles having a size of 25 p or less, as measured by differential counts per mL, after the pharmaceutical solution has been stored for 4 weeks at about 5°C. The pharmaceutical solution of claim 1 or claim 2, comprising amounts of the anti-N3pGlu Ap antibody, the buffer, the tonicity agent, the surfactant, and the optional excipient that are sufficient in combination for the pharmaceutical solution to exhibit one or more of:

(a) an antibody monomer content of at least 96% relative to total antibody peak area, as measured by size exclusion chromatography, after the pharmaceutical solution has been stored at 2-8°C for 3 months;

(b) a total aggregate content of less than 4% relative to total antibody peak area, as measured by size exclusion chromatography, after the pharmaceutical 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 pharmaceutical solution has been stored at 35°C for 3 months;

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

(e) not more than a 6.9% decrease in the amount of the anti-N3pGlu antibody, as measured by reducing CE-SDS, after the pharmaceutical solution has been stored for 4 weeks at 2-8°C. The pharmaceutical solution of claim 2, comprising amounts of the anti-N3pGlu A[3 antibody, the buffer, the tonicity agent, the surfactant, and the optional excipient that are sufficient in combination for the pharmaceutical solution to exhibit one or ore of:

(a) an antibody monomer content, as measured by size exclusion chromatography, of at least 96% relative to total antibody peak area after the pharmaceutical solution has been stored at about 5°C for 3 months;

(b) a total aggregate content of less than 4% relative to total antibody peak area, as measured by size exclusion chromatography, after the pharmaceutical 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 pharmaceutical solution has been stored at about 5°C for 3 months;

(f) less than 500 particulates per milliliter, wherein the particulates are sized greater than 2 p.m, as measured by light obscuration using an HIAC, after the pharmaceutical solution has been stored at about 5°C for 3 months; and

(g) less than 100 particulates per milliliter wherein the particulates are sized greater than 5 |im, as measured by light obscuration using an HIAC, after the pharmaceutical solution has been stored at about 5°C for 3 months. The pharmaceutical solution according to any one of claims 1-4, wherein one or more of features (a)-(k) in claim 1 exist before and after storage, one or more of features (a)-(g) in claim 2 exist before and after storage, one or more of features (a)- (e) in claim 3 exist before and after storage, and/or one or more of features (a)-(g) in claim 4 exist before and after storage.

6. The pharmaceutical solution according to any preceding claim, wherein the LCVR of the anti-N3pGlu A3 antibody comprises SEQ ID NO: 1 , and/or the HCVR of the anti- N3pGlu A3 antibody comprises SEQ ID NO: 2.

7. The pharmaceutical solution according to any preceding claim, wherein the anti- N3pGlu A3 antibody comprises a light chain (LC) comprising SEQ ID NO: 3, and/or a heavy chain (HC) comprising SEQ ID NO: 4.

8. The pharmaceutical solution according to any preceding claim, having a pH of from 5.0 to 7.5.

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

10. The pharmaceutical solution according to any one of claims 1-8, comprising polyoxyethylene (20) sorbitan monooleate, and exhibiting a total free oleic acid content, as measured by high performance liquid chromatography with UV detection (HPLC-UV) using an internal standard, of less than 0.0025% weight by volume 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 a salt of an organic acid, a salt of an inorganic acid, 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. 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. The pharmaceutical solution according to any preceding claim, wherein the buffer is a single buffer system. The pharmaceutical solution according to any preceding claim, wherein the tonicity agent is selected from a sugar, an amino acid, a salt, or combinations thereof. The pharmaceutical solution according to any preceding claim, wherein the tonicity agent is selected from a monosaccharide, a disaccharide, a polysaccharide, and combinations thereof. 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. The pharmaceutical solution according to any preceding claim, wherein the pharmaceutical solution comprises a single tonicity agent. The pharmaceutical solution according to any preceding claim, wherein the surfactant is selected from polyoxyethylene sorbitan esters, poloxamers, and combinations thereof. The pharmaceutical solution according to any one of claims 1-10, wherein the pharmaceutical solution does not comprise one or more of sodium chloride, trehalose, and mannitol. The pharmaceutical solution according to any one of claims 1 -10, wherein the pharmaceutical solution does not comprise one or more of glycine, a poloxamer, and polyoxyethylene (20) sorbitan monolaurate. The pharmaceutical solution according to any preceding claim, comprising: the anti-N3pGlu antibody at a concentration of from 1 to 40 mg/mL; the buffer in an amount of from 1 mM to 30 mM; the tonicity agent in an amount of from 1 % to 20% weight by volume; and the surfactant in an amount of from 0 005% weight by volume to 0.06% weight by volume. The pharmaceutical solution according to claim 22, comprising: the anti-N3pGlu antibody at a concentration of from 10 to 25 mg/mL; the buffer in an amount of from 5 mM to 15 mM; the tonicity agent in an amount of from 5% to 15% weight by volume; and the surfactant in an amount of from 0 01 % weight by volume to 0.04% weight 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 that is sucrose, and a surfactant that is polyoxyethylene (20) sorbitan monooleate.

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

26. The pharmaceutical solution according to any one of claims 22-25, having a pH of from 5.0 to 7.0.

27. The pharmaceutical solution according to any one of claims 22-26, having a pH of 6.0.

28. A method of making the pharmaceutical solution according to any preceding claim, the method comprising: combining the anti-N3pGlu Ap antibody, the buffer, the tonicity agent, the surfactant, and the one or more optional excipients.

29. The method of claim 28, wherein the anti-N3pGlu Ap 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 deposition of amyloid beta (Ap), the method comprising administering to a patient in need thereof a therapeutically effective amount of the pharmaceutical solution according to any one of claims 1 -27.

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

33. The method according to claim 31 or claim 32, comprising administering to the patient an anti-N3pGlu A|3 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’s syndrome, and cerebral amyloid angiopathy.

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

36. The method according to any one of claims 31-35, comprising administering to the patient one or more doses of 100 mg to 10,000 mg of the anti-N3pGlu A|3 antibody.

37. A pharmaceutical solution according to any one of claims 1-27 for use in the treatment of a disease characterized by deposition of amyloid beta (A|3).

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|3 antibody has not been lyophilized.

40. The pharmaceutical solution for use according to any one of claims 37-39, wherein the disease is chosen from Alzheimer’s disease (AD), Down’s 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 the anti-N3pGlu A|3 antibody.

43. Use of a pharmaceutical solution according to any one of claims 1-27 in the manufacture of a medicament for the treatment of a disease characterized by deposition of amyloid beta (AP).

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

45. The use of a pharmaceutical solution according to claim 43 or claim 44, wherein the anti-N3pGlu Ap antibody has not been lyophilized.

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

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

48. The 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 the anti-N3pGlu Ap antibody.

49. A method of reducing amyloid beta (Ap) in a patient in need thereof, the method comprising administering to the patient a pharmaceutical solution according to 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 of at least 5%.

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

52. The pharmaceutical solution according to claim 51 , wherein the LCVR of the anti- N3pGlu AP antibody comprises SEQ ID NO: 1 , and/or the HCVR of the anti-N3pGlu Ap antibody comprises SEQ ID NO: 2.

53. The pharmaceutical solution according to claim 51 or claim 52, wherein the anti- N3pGlu Ap 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 according to any one of claims 51-53, having a pH of from 5.0 to 7.5.

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

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

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

60. The pharmaceutical solution according to any one of claims 51 -59, wherein the tonicity agent is selected from a monosaccharide, a disaccharide, a polysaccharide, and combinations thereof.

61 . The pharmaceutical solution according to 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 according to any one of claims 51 -61 , comprising one tonicity agent.

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

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

66. The pharmaceutical solution according to any one of claims 51 -65, comprising: the anti-N3pGlu antibody at a concentration of from 10 to 25 mg/ml_; the buffer in an amount of from 5 mM to 15 mM; the tonicity agent in an amount of from 5% to 15% weight by volume; and the surfactant in an amount of from 0 01 % weight by volume to 0.04% weight by volume.

67. The pharmaceutical solution according to any one of claims 51 -66, comprising: the anti-N3pGlu antibody at a concentration of 17.5 mg/ml_; the citric acid or a salt thereof in an amount of 10 mM; the sucrose in an amount of 8% weight by volume; and the polyoxyethylene (20) sorbitan monooleate in an amount of 0.02% weight by volume. The pharmaceutical solution according to any one of claims 51 -67, having a pH of from 5.0 to 7.0. The pharmaceutical solution according to any one of claims 51-68, having a pH of 6.0. The pharmaceutical solution according to any one of claims 51 -69, comprising amounts of the anti-N3pGlu A|3 antibody, the buffer, the tonicity agent, the surfactant, and the optional excipient that are sufficient in combination for the pharmaceutical solution to exhibit one or more of:

(b) a total aggregate content of less than 2% relative to total antibody peak area, as measured by size exclusion chromatography, after the pharmaceutical 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 pharmaceutical solution has been stored at 35°C for 3 months;

(d) a total aggregate content of (i) less than 2% relative to total antibody peak area, as measured by size exclusion, or (ii) less than 1.5 area %, as measured by non-reducing CE-SDS, after the pharmaceutical solution has been stored at 2-8°C for 3 months;

(g) a LIV absorbance at 550 nm that varies by less than ±3% over 4 weeks of storage for at 2-8°C;

(k) not more than four particles having a size of 25 pm or less, as measured by differential counts per mL, after the phar aceutical solution has been stored for 4 weeks at 2-8°C. The pharmaceutical solution according to any one of claims 51-70, comprising amounts of the anti-N3pGlu A|3 antibody, the buffer, the tonicity agent, the surfactant, and the optional excipient that are sufficient in combination for the pharmaceutical solution to exhibit one or more of:

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

(b) a total aggregate content of less than 2% relative to total antibody peak area, as measured by size exclusion chromatography, after the pharmaceutical solution has been stored at 5°C for 3 months; (c) a UV absorbance at 550 nm that varies by less than ±3% over 4 weeks of storage at 5°C;

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

(e) at least 93% of the anti-N3pGlu antibody appearing in a main chromatographic peak (monomer) as analyzed by size exclusion chromatography after storage for 4 weeks at 5°C;

(f) not more than an 11 % decrease in the amount of the anti-N3pGlu antibody as measured by non-reducing CE-SDS after the pharmaceutical solution has been stored for 4 weeks at 5°C; and

(g) not more than four particles having a size of 25 pm or less, as measured by differential counts per mL, after the pharmaceutical solution has been stored for 4 weeks at 5°C.

72. The pharmaceutical solution according to any one of claims 51-71 , comprising amounts of the anti-N3pGlu A antibody, the buffer, the tonicity agent, the surfactant, and the optional excipient that are sufficient in combination for the pharmaceutical solution to exhibit one or more of:

(b) a total aggregate content of less than 1 .5% relative to total antibody peak area, as measured by size exclusion chromatography, after the pharmaceutical 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 pharmaceutical solution has been stored at 35°C for 3 months;

(d) from 93.3% to 93.8% of the anti-N3pGlu antibody appearing in a main chromatographic peak (monomer) as analyzed by size exclusion chromatography after storage for 4 weeks at 2-8°C; (e) not more than a 6.9% decrease in the amount of the anti-N3pGlu antibody as measured by reducing CE-SDS after the pharmaceutical solution has been stored for 4 weeks at 2-8°C.

73. The pharmaceutical solution according to any one of claims 51 -72, comprising amounts of the anti-N3pGlu Ap antibody, the buffer, the tonicity agent, the surfactant, and the optional excipient that are sufficient in combination for the pharmaceutical solution to exhibit one or more of:

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

(b) a total aggregate content of less than 1 .5% relative to total antibody peak area, as measured by size exclusion chromatography, after the pharmaceutical 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 pharmaceutical solution has been stored at 5°C for 3 months;

(d) from 93.3% to 93.8% of the anti-N3pGlu antibody appearing in a main peak, as analyzed by size exclusion chromatography, after storage for 4 weeks at 5°C;

(e) not more than a 6.9% decrease in the amount of the anti-N3pGlu antibody, as measured by reducing CE-SDS, after the pharmaceutical solution has been stored for 4 weeks at 5°C;

(f) less than 500 particulates per milliliter, wherein the particulates are sized greater than 2 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at 5°C for 3 months; and

(g) less than 100 particulates per milliliter wherein the particulates are sized greater than 5 pm, as measured by light obscuration using a HIAC, after the pharmaceutical solution has been stored at 5°C for 3 months.

74. The pharmaceutical solution according to any one of claims 70-73, wherein one or more of features (a)-(k) in claim 69 exist before and after storage, one or more of features (a)-(g) in claim 70 exist before and after storage, one or more of features (a)-(e) in claim 71 exist before and after storage, and/or one or more of features (a)- (g) in claim 72 exist before and after storage. The pharmaceutical solution according to any one of claims 51-74, comprising polyoxyethylene (20) sorbitan monooleate and exhibiting a total free oleic acid content, as measured by high performance liquid chromatography with UV detection (HPLC-UV) using an internal standard, of less than 0.0025% weight by volume after the pharmaceutical solution has been stored at 2-8°C for 3 months. The pharmaceutical solution according to any one of claims 51 -75, comprising polyoxyethylene (20) sorbitan monooleate, and exhibiting a total free oleic acid content, as measured by high performance liquid chromatography with UV detection (HPLC-UV) using an internal standard, of less than 0.0025% weight by volume after the pharmaceutical solution has been stored at 2-8°C for 29 months. A method of making the pharmaceutical solution according to any one of claims 51-76, the method comprising: combining the anti-N3pGlu Ap antibody, the buffer, the tonicity agent, the surfactant, and the one or more optional excipients. The method of claim 77, wherein the anti-N3pGlu Ap antibody is not reconstituted from lyophilized material. A vessel comprising the pharmaceutical solution according to any one of claims 51 - 76. A method of treating a disease characterized by deposition of amyloid beta (AP), the method comprising administering to a patient in need thereof a therapeutically effective amount of the pharmaceutical solution according to any one of claims 51 - 76. The method according to claim 80, comprising administering to the patient a pharmaceutical solution obtained from the vessel of claim 79. The method according to claim 80 or claim 81 , comprising administering to the patient an anti-N3pGlu A|3 antibody that has not been lyophilized. The method according to any one of claims 80-82, wherein the disease is chosen from Alzheimer’s disease (AD), Down’s syndrome, and cerebral amyloid angiopathy. The method according to claim 83, wherein the disease is selected from preclinical AD, prodromal AD, mild AD, moderate AD, and severe AD. The method according to any one of claims 80-84, comprising ad inistering to the patient one or more doses of 100 mg to 10,000 mg of the anti-N3pGlu A|3 antibody. A pharmaceutical solution according to any one of claims 51 -76 for use in the treatment of a disease characterized by deposition of amyloid beta (A|3). The pharmaceutical solution for use according to claim 86, wherein the pharmaceutical solution is obtained from the vessel of claim 79. The pharmaceutical solution for use according to claim 86 or claim 87, wherein the anti-N3pGlu AfB antibody has not been lyophilized. The pharmaceutical solution for use according to any one of claims 86-88, wherein the disease is chosen from Alzheimer’s disease (AD), Down’s 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 the anti-N3pGlu A|3 antibody.

92. Use of the pharmaceutical solution according to any one of claims 51 -76 in the manufacture of a medicament for the treatment of a disease characterized by deposition of amyloid beta (AP).

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(3 antibody has not been lyophilized.

95. The use of a pharmaceutical solution according to any one of claims 92-94, wherein the disease is chosen from Alzheimer’s disease (AD), Down’s 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. The 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 the anti-N3pGlu A[3 antibody.

98. A method of reducing amyloid beta (A[B) in a patient in need thereof, the method comprising administering to the patient a pharmaceutical solution according to 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 of at least 5%.

100. A pharmaceutical solution comprising: an anti-N3pGlu Ap 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% weight by volume; and a surfactant comprising polyoxyethylene (20) sorbitan monooleate in an amount of 0 02% weight by volume; wherein the anti-N3pGlu A 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 pharmaceutical solution has a pH of 6.0.

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