Anti-plasma kallikrein antibody formulations

Abstract

Disclosed herein are formulations of antibodies directed against plasma kallikrein, e.g., anti-plasma kallikrein antibodies. The formulations include, for example, amino acids, sugars, and surfactants. The disclosed formulations are useful for administration to subjects to treat plasma kallikrein associated disorders such as hereditary angioedema (HAE).

Description

ANTI-PLASMA KALLIKREIN ANTIBODY FORMULATIONSCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims priority to and the benefit of U.S. Provisional Patent Application No. 63 / 661,877 filed June 19, 2024, the contents of which are incorporated by reference herein in their entirety.FIELD

[0002] The invention relates to the field of biopharmaceuticals, specifically to formulating biopharmaceuticals such as therapeutic antibodies, more specifically to formulating anti-plasma kallikrein (pKal) antibodies for use, e.g., in the treatment of plasma kallikrein associated disorders such as hereditary angioedema (HAE).BACKGROUND

[0003] Formulating biologic drugs, such as antibodies, presents a unique set of challenges due to the nature of protein-based therapeutics. Protein formulations, such as pharmaceutical formulations of antibodies, must be optimized to ensure the stability of the protein during manufacturing and storage during which the protein may be exposed to many different stresses including but not limited to temperature and pH changes, and exposure to light, oxidizing agents, and mechanical stress. Accordingly, excipients must be selected to control negative impacts on the long-term stability of the protein, e.g., an antibody.

[0004] Further, the formulation itself can impact the patient experience by directly affecting the safety, efficacy and convenience of administering the drug. Factors such as dosage form, route of administration, and dosing frequency may impact patient convenience and comfort. For example, protein formulations are usually administered intravenously or by injection. In the case of injections, for example, subcutaneous injections, the formulation must be optimized for such a route of administration, considering factors such as the viscosity of the formulation and concentration of the protein, both of which can impact the number of injections and / or duration of the injection and the type of administration device, e.g., needles or syringes, that can be used.

[0005] In addition, the formulation of an antibody plays a crucial role in minimizing adverse reactions and immunogenicity, thereby enhancing safety and reducing the likelihood of treatment interruptions or discontinuations due to side effects.

[0006] Hereditary angioedema (HAE) is caused by a rare autosomal dominant disorder causing a deficiency in functional Cl esterase inhibitor (Cl -INH), a serpin family protein that blocks the activity of plasma kallikrein (pKal). Insufficient inhibition of pKal results in the over production of bradykinin, a vasoactive inflammatory mediator that produces acute attacks of painful and unpredictable angioedema (swelling under the skin), as well as swelling (edema) in the face, limbs, abdomen, and airway (Zuraw B. L. et al., N Engl J Med 359, 1027-1036, 2008). Such attacks, often precipitated by unknown triggers, can have potentially-life threatening consequences.

[0007] Anti-plasma kallikrein (pKal) antibodies have been developed for the treatment of plasma kallikrein related disorders. For example, TAKHZYRO® (lanadelumab-flyo), a monoclonal anti-plasma kallikrein antibody was approved by the U.S. Food & Drug Administration in 2018 for prophylaxis to prevent hereditary angioedema (HAE) attacks. However, in Phase III trials for lanadelumab, more than 40% of patients reported experiencing injection site pain, the most commonly observed treatment-emergent adverse event. (Petkova et al., Drug Health Patient Saf. 2022;14: 195-210). STAR-0215 is a monoclonal antibody inhibitor of plasma kallikrein currently in development for the treatment hereditary angioedema.

[0008] Accordingly, there is a need for pharmaceutical formulations of antibodies, e.g. , anti-pKal antibodies, e.g., for use in treating plasma kallikrein associated disorders, such as HAE, that improve the patient experience through improved administration while also maintaining the long-term stability of the antibody.SUMMARY

[0009] Disclosed are liquid pharmaceutical compositions comprising anti-plasma kallikrein antibodies.

[0010] In certain aspects, the disclosure provides a liquid pharmaceutical composition comprising an anti-plasma kallikrein antibody, a buffer selected from histidine, acetate, succinate, or phosphate; and an anti-oxidant. The antibody may comprise ComplementarityDetermining Region Sequences (CDRs) of a heavy chain variable region having the amino acid sequence of SEQ ID NO: 7, and CDRs of a light chain variable region having the amino acid sequence of SEQ ID NO: 8, wherein the antibody further comprises a constant region comprising an M252Y, an S254T, and a T256E mutation as numbered according to the EU numbering index. In yet other examples, the anti-plasma kallikrein antibody may comprise an immunoglobulin heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7, and an immunoglobulin light chain variable region comprising the amino acid sequence of SEQ ID NO: 8, wherein the antibody further comprises a constant region comprising an M252Y, an S254T, and a T256E mutation as numbered according to the EU numbering index. In still other examples, the anti-plasma kallikrein antibody may comprise an immunoglobulin heavy chain comprising the amino acid sequence of SEQ ID NON and a light chain comprising the amino acid sequence of SEQ ID NO: 10. For example, the antiplasma kallikrein antibody may be navenibart (also known as STAR-0215). The anti-pKal antibody, e.g., navenibart, may be present in the composition at a concentration of 50-500 mg / mL. For example, the concentration may be 70-250 mg / mL in some instances, while in other instances the concentration may be 100-200 mg / mL. In yet other instances, the concentration 150-200 mg / mL. In yet further instances, the concentration may be 135-165 mg / mL. For example, the concentration is about 150 mg / mL. For example, the concentration is about 175 mg / mL.

[0011] In some examples, the buffer is histidine, e.g., histidine hydrochloride. Alternatively, the buffer may be a phosphate buffer, e.g., a phosphate salt, in some examples, while in other examples it may be a succinate buffer, e.g., a succinate salt. In still other examples, the buffer may be an acetate buffer, e.g. , an acetate salt. The buffer may be present in at a concentration of about 0.01 to about 500 mM. For example, in some instances the concentration is about 0.01 to about 200 mM, while in yet other instances, the concentration is about 5 to about 50 mM. In still other instances, the concentration is about 5 to 15 mM. For example, the concentration is about 10 mM.

[0012] The anti-oxidant may be, for example, methionine, cysteine, DTPA, DFOA, or EDTA. For example, the anti-oxidant is methionine, e.g., free methionine such as L- methionine. The concentration of antioxidant in the composition may be about 0.01 to about 500 mM. For example, in some instances the concentration is about 0.01 to about 200 mM, while in yet other instances, the concentration is about 5 to about 50 mM. In still otherinstances, the concentration is about 5 to 15 mM. In yet further instances, the concentration is about 8 to about 12 mM. For example, the concentration is about 10 mM.

[0013] In addition to including the aforementioned anti-pKal antibody, buffer and antioxidant, the composition may also include a sugar, e.g., a polyol, monosaccharide, or disaccharide. For example, the sugar may be sorbitol. In other instances, the sugar may be sucrose, trehalose, or mannitol. The concentration of sugar in the composition may be about 0.01 to about 500 mM. For example, in some instances the concentration is about 50 to about 300 mM, while in yet other instances, the concentration is about 250 to about 500 mM. In still other instances, the concentration is about 100 to about 200 mM. In still other instances, the concentration is about 50 to about 150 mM. For example, the concentration of the sugar, e.g. , sorbitol, may be about 60 mM or about 90 mM. For example, the concentration of the sugar, e.g., sorbitol, may be about 75 mM or about 150 mM. For example, the concentration of the sorbitol may be about 50 to about 300 mM.

[0014] In addition to including the aforementioned anti-pKal antibody, buffer and antioxidant, and optionally the sugars discussed above, the composition may also include one or more amino acids. Such amino acid(s) is in addition to any amino acid that may be present in the composition as, for example, a buffer or antioxidant. The amino acid(s) may be selected from, for example, alanine, arginine, aspartic acid, glycine, glutamic acid, isoleucine, leucine, lysine, and / or proline. In some instances, the amino acid(s) are selected from glycine, proline, and / or arginine. For example, in some instances, the composition comprises glycine. In other instances, the composition comprises arginine, while in yet other instances glycine and arginine are present. The glycine, if present, may be free glycine, e.g., L-glycine. The arginine, if present, may be, e.g., arginine hydrochloride. In some instances, the amino acid is proline alone or in combination with glycine and / or arginine. Each of the one or more amino acids may be present in the composition at a concentration of about 0.01 to about 500 mM. For example, the concentration of each amino acid present may be about 50 to about 300 mM. In yet other examples, each amino acid is present at a concentration of about 50 to about 150 mM, or even about 50 to about 100 mM. For example, each amino acid may be present in the amount of 75 mM. For example, glycine, e.g. , at about 75 mM is present either alone or in combination with arginine, e.g. at about 75 mM. For example, each amino acid, e.g. , glycine, proline, and / or arginine, may be present in the amount of 150 mM. For example, each amino acid, e.g., glycine, proline, and / or arginine, may be present in theamount of 75 mM. For example, glycine is present in an amount of 50 to about 300 mM or about 100 to about 300 mM, or even about 75 to about 150 mM., e.g., about 75 mM, or about 150 mM. For example, glycine is present in an amount of about 60 to about 90 mM. For example, arginine is present in an amount of 50 to about 300 mM or about 100 to about 300 mM, or even about 75 to about 150 mM., e.g., about 75 mM, or about 150 mM. For example, arginine is present in an amount of about 60 to about 90 mM. For example, glycine and arginine are each present in an amount of 50 to about 300 mM or about 100 to about 300 mM, or about 60 to about 90 mM, or even about 75 to about 150 mM., e.g., about 75 mM, or about 150 mM. For example, glycine, arginine, and / or proline are each present in an amount of 50 to about 300 mM or about 100 to about 300 mM, or even about 75 to about 150 mM., e.g., about 75 mM, or about 150 mM.

[0015] In addition to including the aforementioned anti-pKal antibody, buffer and antioxidant, and optionally the sugars and amino acids discussed above, the formulation may also include a surfactant. For example, the surfactant may be a polysorbate, e.g. , polysorbate 20 or polysorbate 80, or a poloxamer, e.g., poloxamer 188. In some instances, the polysorbate in the composition is polysorbate 20, while in others it is polysorbate 80. The surfactant, e.g., polysorbate 20 or 80, may be present in the composition in a range of about 0.01% to about 1% (w / v). In some instances, the surfactant, e.g., polysorbate 20 or 80, is present in an amount of about 0.01% to about 0.1%. In some instances, the surfactant, e.g., polysorbate 20 or 80, is present in an amount of about 0.02% to about 0.07%. In some instances, the surfactant, e.g, polysorbate 20 or 80, is present in an amount of about 0.02% to about 0.1%. In some instances, the surfactant, e.g., polysorbate 20 or 80, is present in an amount of about 0.03% to about 0.06%, e.g. about 0.05%.

[0016] The composition may have a pH of about 5.0 to about 6.5, for example, about 5.5. to about 6.0. In some instances, the pH is about 5.8. The composition may have a viscosity of about 15 cP, e.g., about 10 cP, for example, at room temperature, e.g., about 20°C to about 25°C. The composition may have an osmolality not exceeding 400 mOsm / kg, e.g., not exceeding about 350 mOsm / kg. The composition may further comprise water for injection (WFI).

[0017] In some instances, disclosed are pharmaceutical compositions of navenibart at about 150 mg / mL that also include about 10 mM histidine, about 10 mM methionine, about75 mM sorbitol, about 75 mM glycine, about 75 mM arginine, about 0.05% w / v polysorbate 80, and have a pH of about 5.8.

[0018] In some aspects, disclosed herein is a method of treating a plasma kallikrein dependent disorder in a subject by administering to the subject the pharmaceutical composition as disclosed herein. The subject may be a human subject. The subject may be suffering from a plasma kallikrein dependent disorder such as hereditary angioedema (HAE).

[0019] In other aspects, disclosed herein are drug delivery devices comprising the aforementioned liquid pharmaceutical compositions along with a syringe comprising a plunger and a barrel. The pharmaceutical composition is contained within the barrel and a surface of the barrel in contact with the pharmaceutical composition comprises a siliconized surface, e.g, a cross-linked silicone surface. The barrel may be fabricated from glass, e.g., the silicone is cross-linked to the glass.

[0020] The plunger of the syringe may comprise a stopper that in combination with the siliconized surface, e.g., cross-linked silicone surface, of the barrel and the composition produces a glide force sufficient to eject the pharmaceutical formulation from the syringe into a subject subcutaneously in 20 seconds or less. For example, the drug delivery device in combination with the pharmaceutical composition produces a break loose force that does not exceed 25 N. For example, the break loose force is from about 10 to about 20 N. In some instances, the drug delivery device in combination with the pharmaceutical composition produces a glide force that does not exceed 15 N. For example, the glide force is about 5 N to about 15 N. For example, the break loose and glide forces are determined when the pharmaceutical composition is in use in the device at about 20°C to about 25°C. In some instances, the drug delivery device of holds a volume of the pharmaceutical composition of about 2 m . The syringe may further include a needle, e.g., a 23-27 gauge needle, e.g., a 27 gauge needle. In some instances, the syringe is contained within an auto injection device. In some instances, the device comprising the pharmaceutical composition is stored and / or maintained at a temperature of about 20°C to about 25°C, while in other instances the device comprising the pharmaceutical composition is stored and / or maintained under refrigeration, e.g., at about 2-8°C. In certain instances, the pharmaceutical composition is administered at a temperature of about 20°C to about 25°C.BRIEF DESCRIPTION OF THE FIGURES

[0021] FIG. 1 is a graph showing the apparent viscosity (cP) of various STAR-0125 anti- pKal antibody formulations at differing concentrations (mg / mL) of the antibody. The graph also includes the % monomer content of each formulation at each concentration (mg / mL) of the antibody. As it shows, the viscosity of the sorbitol + glycine containing formulation had a reduced viscosity compared to the formulation containing sorbitol alone at increasing concentrations.

[0022] FIG. 2 is a table showing the excipients and conditions of the 20 formulations of STAR-0125 anti-pKal antibody in the viscosity studies in Example 2.

[0023] FIG. 3 is a bar graph showing the flow rate of the 20 formulations tested in the viscosity studies in Example 2 at a concentration of 70 mg / mL STAR-0215.

[0024] FIG. 4 is a series of single effect leverage plots showing the impact of the listed excipient on flow rate of the formulation of STAR-0215. The top row shows the results for 200 mg / mL of STAR-0215 and the bottom row shows the results for 70 mg / mL. Negative slope suggests that the excipient negatively impacts flow rate of the formulation (e.g., decreases flow rate and increases viscosity) whereas a positive slope suggests that the excipient positively impacts flow rate of the formulation (e.g., increases flow rate and decreases viscosity).

[0025] FIG. 5 is a bar graph showing the flow rate of the 20 formulations tested in the viscosity studies in Example 2 at a concentration of 200 mg / mL STAR-0215.

[0026] FIG. 6 is a viscosity versus concentration curve for different formulations of STAR-0215 at 25°C. Formulations containing sorbitol, sorbitol and glycine, or sorbitol, glycine and arginine were tested.

[0027] FIG. 7 is a viscosity versus temperature curve comparing two formulations (Formulation A and Formulation B) of STAR-0215 at 5°C, 10°C, 15°C, 20°C, and 25°C.

[0028] FIG. 8 is a series of graphs showing the aggregation behavior of STAR-0215 as determined by SEC in STAR-0215 formulations maintained at either 5°C, 25°C, or 40°C over time (T=0 months, 1 months, 2 months 3 months). The lower panel shows the percentage of high molecular weight monomers whereas the upper panel shows the purity of theformulation based on SEC main peak. GMP1 and GMP 2 are formulations of STAR-0215 according to Formulation A (150 mg / mL STAR-0215) and ENG5 is a formulation of STAR- 0215 according to Formulation C (182 mg / mL STAR-0215).

[0029] FIGS. 9A-B provide the United States Adopted Name (USAN) Council statement on navenibart published May 31, 2023, which provides the chemical name, structural formula and other identifying information for this monoclonal antibody. FIG. 9A is page 1 of the statement as published by USAN regarding navenibart and FIG. 9B is page 2 of the statement as published regarding navenibart.

[0030] FIGS. 10A-D provide Pareto Charts of Standardized Effects and Main Effects plots showing the impact of protein concentration, pH, Arginine HC 1 and Glycine HC1 on viscosity of the formulations tested at 25°C (FIG. 10A), 20°C (FIG. 10B), 15°C (FIG. 10C), and 5°C (FIG. 10D).

[0031] FIGS. 11A-B provide various statistical analyses of the size exclusion high performance liquid chromatography (SE-HPLC) data showing the impact of various factors on the monomer % in formulations Fl -Fl 1 after being stored at 40°C for 1 month. FIG. 11 A - left panel provides a Pareto chart of the standardized effects of factors (A = pH value, B = arginine HC1 concentration, C = methionine concentration, and D = PS80 concentration) that were varied in the formulations (pH, arginine HC1, Methionine, PS80); FIG. HA - right panel shows a main effects plot of data means and FIG. 11B provides residual plots for SEC monomer %.

[0032] FIGS. 12A-B provide various statistical analyses of the size exclusion high performance liquid chromatography (SE-HPLC) data showing the impact of various factors on the monomer % in formulations Fl -Fl 1 after being stored at 40°C for 3 months. FIG. HA - left panel provides a Pareto chart of the standardized effects of factors (A = pH value, B = arginine HC1 concentration, C = methionine concentration, and D = PS80 concentration) that were varied in the formulations (pH, arginine HC1, Methionine, PS80); FIG. 12A - right panel shows a main effects plot of data means and FIG. 12B provides residual plots for SEC monomer %.

[0033] FIGS. 13A-B provide various statistical analyses of the size exclusion high performance liquid chromatography (SE-HPLC) data showing the impact of various factorson the monomer % in formulations Fl-Fl 1 after being stored at 25°C for 3 months. FIG. 13A - left panel provides a Pareto chart of the standardized effects of factors (A = pH value, B = arginine HC1 concentration, C = methionine concentration, and D = PS80 concentration) that were varied in the formulations (pH, arginine HC1, Methionine, PS80); FIG. 13A - right panel shows a main effects plot of data means and FIG. 13B provides residual plots for SEC monomer %.

[0034] FIGS. 14A-B provide various statistical analyses of the imaged capillary isoelectric focusing (icIEF) data showing the impact of various factors on the icIEF main peak % in formulations Fl -Fl 1 after being stored at 40°C for 1 month. FIG. 14A - left panel provides a Pareto chart of the standardized effects of factors (A = pH value, B = arginine HC1 concentration, C = methionine concentration, and D = PS80 concentration) that were varied in the formulations (pH, arginine HC1, Methionine, PS80); FIG. 14A - right panel shows a main effects plot of data means and FIG. 14B provides residual plots for icIEF main peak %.

[0035] FIG. 15 provides various statistical analyses of the imaged capillary isoelectric focusing (icIEF) data showing the impact of various factors on the icIEF main peak % in formulations Fl-Fll after being stored at 40°C for 3 months. FIG. 15 - left panel provides a Pareto chart of the standardized effects of factors (A = pH value, B = arginine HC1 concentration, C = methionine concentration, and D = PS80 concentration) that were varied in the formulations (pH, arginine HC1, Methionine, PS80); FIG. 15 - right panel shows a main effects plot of data means.

[0036] FIGS. 16A-B provide various statistical analyses of the imaged capillary isoelectric focusing (icIEF) data showing the impact of various factors on the icIEF main peak % in formulations Fl-Fll after being stored at 25°C for 3 months. FIG. 16A - left panel provides a Pareto chart of the standardized effects of factors (A = pH value, B = arginine HC1 concentration, C = methionine concentration, and D = PS80 concentration) that were varied in the formulations (pH, arginine HC1, Methionine, PS80); FIG. 16A - right panel shows a main effects plot of data means and FIG. 16B provides residual plots for icIEF main peak %.DETAILED DESCRIPTION

[0037] Disclosed herein are pharmaceutical formulations of antibodies that bind plasma kallikrein, e.g. human plasma kallikrein, that can be used to treat plasma kallikrein dependentdisorders, such as hereditary angioedema (HAE), as well as pharmaceutical formulations containing anti-pKal antibodies.

[0038] The pharmaceutical formulations disclosed herein are designed in certain aspects to maintain or enhance the stability of the anti-pKal antibody during manufacture and / or storage. Accordingly, excipients used to formulate the pharmaceutical compositions disclosed herein may be selected based on their ability to maintain or enhance stability of the antibodies, such as thermal stability, conformational stability, and / or colloidal stability. Accordingly, excipients may be selected to reduce or eliminate, for example, degradation, fragmentation, aggregation, oxidation, deamidation, or isomerization of the antibody.

[0039] Further, the pharmaceutical compositions disclosed herein are designed in certain aspects to have optimal viscosity for administration by injection, e.g., subcutaneously or intramuscularly. The pharmaceutical compositions may be optimized for administration by injection from a syringe, for example.I. Definitions

[0040] To facilitate an understanding of the present invention, a number of terms and phrases are defined below.

[0041] As used herein, the term “antibody,” e.g., an anti -plasma kallikrein antibody, refers to a full length or intact antibody which contains two immunoglobulin heavy chains, each associated with an immunoglobulin light chain. The antibody is bivalent, but each binding site binds the same target, e.g., plasma kallikrein.

[0042] As used herein, the term “complementarity determining regions” or “CDRs” refers to the immunoglobulin hypervariable domains that determine specific antibody binding. CDRs are located within four framework regions (FRs). The CDRs are usually aligned by the framework regions, enabling binding to a specific epitope. In general, from N-terminal to C-terminal, both light and heavy chain variable domains comprise FR1, CDR1, FR2, CDR2, FR3, CDR3 and FR4. As used herein, “HCDR1,” HCDR2”, and “HCDR3” refer to CDR1, 2, or 3, respectively, of the heavy chain variable region, and “LCDR1,” LCDR2”, and “LCDR3” refer to CDR1, 2, or 3 respectively, of the light chain variable region.

[0043] The assignment of amino acids to each CDR is, generally, in accordance with the definitions of Kabat (see, e.g., Sequences of Proteins of Immunological Interest, Kabat, et al:, National Institutes of Health, Bethesda, Md.; 5thed.; NIH Publ. No. 91-3242 (1991); Kabat (1978) Adv. Prot. Chem., 32: 1-75; Kabat, et al., (1977) J. Biol. Chem., 252:6609-6616) orthe definitions of Chothia (see, e.g., Chothia, et al., (1987) J Mol. Biol., 196:901-917 or Chothia, et al., (1989) Nature, 342:878-883), although alternative definitions are known in the art, such as IMGT (See e.g., Lefranc (2005), Nucl. Acids Res., 33, D593-D597; Lefranc et al., (2003), Dev. Comp. Immunol., 27, 55-77; Lefranc et al., (2005), Dev. Comp. Immunol., 29, 185-203 (2005); Lefranc et al., (2005), Dev. Comp. Immunol., 2005, 29, 917-938) or AbM (see, e.g., Martin, et al., (1989) roc. Natl Acad. Sci. USA, 86, 9268-9272; Pedersen et al., (1992), Immunomethods, 1, 126; Rees et a , (1996) In Sternberg M.J.E. (ed.), Protein Structure Prediction. Oxford University Press, Oxford, 141-172). In addition to the Chothia and Kabat numbering schemes described above, the CDRs can be determined using other approaches known in the art, including for example, the Martin numbering scheme, the Gelfand numbering scheme, the IMGT numbering scheme, the Honneger numbering scheme, and the ABM numbering scheme (see, e.g., Dondelinger et al. (October 2018) Frontiers Immunol. 8, 2278, 1-15).

[0044] The term “disorder” refers to and is used interchangeably with, the terms “disease,” “condition,” or “illness.”

[0045] As used herein, the term “hereditary angioedema” or “HAE” refers to the disease or disorder caused by a genetic deficiency or dysfunction of the Cl -inhibitor protein, for example, the human Cl -inhibitor protein (Cl-INH). HAE is generally characterized by excess pKal activation and bradykinin release. Type I and Type II HAE are both caused by a genetic mutation in the SERPING1 gene which codes for Cl-IHN, while Type I results in a deficiency of Cl-INH, whereas Type II results in dysfunctional Cl-INH. “HAE” as described herein also includes Type III HAE in which Cl-INH levels and function are normal, but where patients experience similar attacks of painful edema associated with pregnancy or estrogen intake (e.g., via oral contraceptives). Type III HAE may involve mutations in Factor XII, but not in all cases. In all types of HAE, unknown triggers cause painful edema (swelling) in the skin and / or mucosa, such as in the face, larynx, hands, feet, gastrointestinal tract and / or genitals. In some embodiments, HAE refers only to Type I and Type II HAE.

[0046] As used herein, the term “human plasma kallikrein” or “human pKal” refers to residues 391-638 shown in bold below of the human pre-Kallikrein protein (UNIPROT P03952, KLKB1) which has the following amino acid sequence:MILFKQATYF ISLFATVSCG CLTQLYENAF FRGGDVASMY TPNAQYCQMR CTFHPRCLLF SFLPASSIND MEKRFGCFLK DSVTGTLPKV HRTGAVSGHS LKQCGHQISA CHRDIYKGVD MRGVNFNVSK VSSVEECQKR CTNNIRCQFF SYATQTFHKA EYRNNCLLKY SPGGTPTAIK VLSNVESGFS LKPCALSEIG CHMNIFQHLA FSDVDVARVL TPDAFVCRTI CTYHPNCLFF TFYTNVWKIE SQRNVCLLKT SESGTPSSST PQENTISGYS LLTCKRTLPE PCHSKIYPGV DFGGEELNVT FVKGVNVCQE TCTKMIRCQF FTYSLLPEDC KEEKCKCFLRLSMDGSPTRI AYGTQGSSGY SLRLCNTGDN SVCTTKTSTR IVGGTNSSWGEWPWQVSLQV KLTAQRHLCG GSLIGHQWVL TAAHCFDGLP LQDVWRIYSG ILNLSDITKD TPFSQIKEII IHQNYKVSEG NHDIALIKLQ APLNYTEFQK PICLPSKGDT STIYTNCWVT GWGFSKEKGE IQNILQKVNI PLVTNEECQK RYQDYKITQR MVCAGYKEGG KDACKGDSGG PLVCKHNGMW RLVGITSWGE GCARREQPGV YTKVAEYMDW ILEKTQSSDG KAQMQSPA (SEQ ID NO: 24). The mature form of human pre-Kallikrein includes a signal peptide sequence of amino acid residues 1-19, which can be cleaved during its post-translation processing. Accordingly, the mature form of human prekallikrein comprises resides 20-638 of SEQ ID NO:24. Factor Xlla cleaves human pre-Kallikrein at R390 / 1391 to produce human plasma Kallikrein (pKal).

[0047] As used herein, the term “pharmaceutical composition” or “pharmaceutical formulation” or “formulation” refers to the combination of a pharmaceutically active agent, e.g., an antibody, such as an anti-plasma kallikrein antibody described herein, e.g., navenibart, with one or more pharmaceutically acceptable carriers, inert or active, making the composition especially suitable for diagnostic or therapeutic use in vivo or ex vivo.

[0048] As used herein, “pharmaceutically acceptable” or “pharmacologically acceptable” refers to molecular entities, compounds, compositions, materials and / or dosage forms that do not produce an adverse, allergic or other untoward reaction when administered to an animal, or to a human, as appropriate. For human administration, preparations should meet sterility, pyrogenicity, and general safety and purity standards as required by relevant regulatory authorities, e.g., the USFDA Office of Biologies standards. “Pharmaceutically acceptable” and “pharmacologically acceptable” can mean approved or approvable by a regulatoryagency of the federal or a state government or the corresponding agency in countries other than the United States, or that is listed in the U.S. Pharmacopoeia or other generally recognized pharmacopoeia for use in animals, and more particularly, in humans.

[0049] The term, “pharmaceutically acceptable carrier” includes any and all solvents, excipients, fillers, dispersion media, coatings, antibacterial and antifungal agents, isotonic and absorption delaying agents and the like involved in carrying or transporting a pharmaceutical agent from one organ, or portion of the body, to another organ, or portion of the body. Except insofar as any conventional media or agent is incompatible with the active ingredient, its use in the therapeutic compositions is contemplated. Supplementary active ingredients can also be incorporated into the compositions. For examples of carriers, stabilizers and adjuvants, see Remington s ’ Pharmaceutical Sciences, 18th ed. (Mack Publishing Company, 1990).

[0050] As used herein, “pharmaceutically acceptable excipient” refers to a substance that aids the administration of a pharmaceutically active agent, e.g., the anti -plasma kallikrein antibodies disclosed herein, e.g., navenibart, to and / or absorption by a subject without causing a significant adverse toxicological effect on the patient. Accordingly, a pharmaceutically active agent, e.g., the anti-plasma kallikrein antibodies disclosed herein, e.g., navenibart, are not excipients. Non-limiting examples of pharmaceutically acceptable excipients include water, NaCl, normal saline solutions, such as a phosphate buffered saline solution, emulsions (e.g., such as an oil / water or water / oil emulsions), lactated Ringer’s, normal sucrose, normal glucose, binders, fillers, disintegrants, lubricants, coatings, sweeteners, flavors, salt solutions (such as Ringer’s solution), alcohols, oils, gelatins, carbohydrates such as lactose, dextrose, amylose or starch, fatty acid esters, hydroxymethy cellulose, polyvinyl pyrrolidine, and colors, and the like. Such preparations can be sterilized and, if desired, mixed with auxiliary agents such as lubricants, preservatives, stabilizers, wetting agents, emulsifiers, salts for influencing osmotic pressure, buffers, coloring, and / or aromatic substances and the like that do not deleteriously react with the compositions disclosed herein. For examples of excipients, see Remington s ’ Pharmaceutical Sciences, 18th ed. (Mack Publishing Company, 1990).

[0051] As used herein, “pharmaceutically active agent,” “active pharmaceutical agent,” or “active agent” refers to the component or components of a drug formulation responsiblefor delivering a therapeutic effect. For example, the pharmaceutically active agent in formulations disclosed herein is an anti-plasma kallikrein antibody as disclosed herein, such as navenibart.

[0052] As used herein, “plasma kallikrein associated disorder” refers to conditions that are caused by the function or aberrant expression of plasma kallikrein. These conditions include, but are not limited to, hereditary angioedema (including Type I, II, or III, “HAE”), bradykinin dependent edema, diabetic macular edema, retinal edema, Factor Xll-associated cold autoinflammatory syndrome (FACAS), rheumatoid arthritis, gout, intestinal bowel disease, oral mucositis, neuropathic pain, inflammatory pain, spinal stenosis-degenerative spine disease, arterial or venous thrombosis, post-operative ileus, aortic aneurysm, osteoarthritis, vasculitis, edema, cerebral edema, pulmonary embolism, stroke, clotting induced by ventricular assistance devices or stents, head trauma or peri-tumor brain edema, sepsis, acute middle cerebral artery (MCA) ischemic event (stroke), restenosis (e.g, after angioplasty), systemic lupus erythematosus nephritis, Alzheimer’s disease and bum injury.

[0053] As used herein, the term “STAR-0215” or “STAR-215” refers to an anti -plasma kallikrein antibody having two heavy chains and two light chains. Each heavy chain comprises the amino acid sequence of SEQ ID NO:9 and each light chain comprises the amino acid sequence of SEQ ID NO: 10. STAR-0215 is a humanized IgGl kappa light chain monoclonal antibody. STAR-0215 is also known by the nonproprietary name “navenibart” adopted by the United States Adopted Name (USAN) Council and published on May 31, 2023. The USAN statement providing the identifying characteristics of navenibart is provided in FIGS. 9A-B. “STAR-0215” and “navenibart” are used interchangeably herein. “Navenibart” is also the international nonproprietary name assigned to STAR-0215 by The World Health Organization (WHO). “Navenibart” is defined in the WHO’s INN Recommended List 92 (Vol. 38, No. 3, 2024) published on November 17, 2024, and as INN Request No. 12991.

[0054] As used herein, the terms “subject” and “patient” are used interchangeably and refer to an organism to be treated by the methods and compositions, e.g., pharmaceutical formulations, of the present invention. Such organisms may be mammals (e.g. , human, mouse, rat, guinea pig, dog, cat, horse, cow, pig, or non-human primate, such as a monkey, chimpanzee, baboon, and rhesus). In certain instances, the subject or patient is a human, e.g.,a human suffering from a plasma kallikrein dependent disorder, e.g., HAE. A subject that is “in need thereof’ refers to a subject that has been identified as requiring treatment for the condition, e.g., a plasma kallikrein dependent disorder, such as HAE, that is to be treated and is treated with the specific intent of treating such condition. In some embodiments, a subject is an adult human subject, z.e., 18 years of age or older. In some embodiments, a subject is a pediatric human subject, z.e., ages 0-17 years of age. In some embodiments, the pediatric human subject is 6-17 years of age or 12-17 years of age. In some embodiments, the pediatric human subject is one, two, three, four, five, six, seven, eight, nine, ten, eleven, twelve, thirteen, fourteen, fifteen, or sixteen years of age, or older, or seventeen years of age.

[0055] As used herein, the terms “therapeutically effective amount”, “therapeutically effective dose” and “effective amount” refer to an amount of pharmaceutically active agent, e.g., an anti-plasma kallikrein antibody, that, when administered alone (or in combination with an additional therapeutic agent) to a cell, tissue, or subject, is effective to cause a measurable improvement in one or more symptoms of a disease or condition or the progression of such disease or condition, e.g. hereditary angioedema (HAE) or another plasma kallikrein dependent disorder. A “therapeutically effective dose” further refers to that amount of the antibody sufficient to result in at least partial amelioration of symptoms, e.g., treatment, healing, prevention or amelioration of the relevant medical condition, e.g., HAE or another plasma kallikrein dependent disorder, or an increase in rate of treatment, healing, prevention or amelioration of such conditions. When applied to an individual active ingredient administered alone, a therapeutically effective dose refers to that ingredient alone. When applied to a combination, a therapeutically effective dose refers to combined amounts of the active ingredients that result in the therapeutic effect, whether administered in combination, serially or simultaneously. An effective amount of a therapeutic may result in an improvement of a diagnostic measure or parameter by at least 10%; 20%; 30%; 40%, or 50%. An effective amount can also result in an improvement in a subjective measure in cases where subjective measures are used to assess disease severity. In some embodiments, an amount is a therapeutically effective amount if it is an amount that can be used to treat or prevent symptoms of a plasma kallikrein dependent disorder, e.g. , swelling / edema. For example, a therapeutically effective amount of an anti-plasma kallikrein antibody disclosed herein may reduce the frequency of edema caused by a plasma kallikrein dependent disorder, or of HAE attacks in a subject, and / or may reduce the severity and / or duration of an HAEattack in a subject, for example, the level and / or duration of edema experienced by the subject during an attack.

[0056] As used herein, “therapeutically effective inhibition of plasma kallikrein” refers to a level of inhibition of pKal in a subject that is effective to treat a plasma kallikrein dependent disorder, such as hereditary angioedema. For example, “therapeutically effective inhibition of plasma kallikrein” results from administration of a therapeutically effective amount of the anti-plasma kallikrein antibody disclosed herein.

[0057] As used herein, the terms “treat” or “treatment” includes inhibition, prevention, or postponement or prevention of the development of the symptoms associated with a disorder and / or a reduction in the severity and / or duration of the symptoms of such disorder, such as plasma kallikrein dependent disorder, e.g. , HAE. The terms further include ameliorating existing uncontrolled or unwanted symptoms, preventing additional symptoms, and ameliorating or preventing the underlying causes of such symptoms, e.g., plasma kallikrein activation that causes symptoms of a plasma kallikrein dependent disorder, e.g., HAE. For example, “treating” a plasma kallikrein dependent disorder, e.g., HAE, may include inhibiting, preventing or reducing the frequency of attacks and / or reducing the severity of attacks, and / or achieving a therapeutically effective inhibition of plasma kallikrein in a subject. In the context of HAE, treatment includes prophylactic measures taken to prevent HAE attacks, reduce the frequency and / or severity and / or duration of HAE attacks in a subject.

[0058] Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs.

[0059] The articles “a” and “an” are used in this disclosure to refer to one or more than one (i. e. , to at least one) of the grammatical object of the article, unless the context is inappropriate. By way of example, “an element” means one element or more than one element.

[0060] The term “and / or” is used in this disclosure to mean either “and” or “or” unless indicated otherwise. The expression “and / or” in connection with three or more recitedobjects should be understood to have the same meaning unless otherwise understood from the context.

[0061] It should be understood that the expression “at least one of’ includes individually each of the recited objects after the expression and the various combinations of two or more of the recited objects unless otherwise understood from the context and use.

[0062] The use of the term “include,” “includes,” “including,” “have,” “has,” “having,” “contain,” “contains,” or “containing,” including grammatical equivalents thereof, should be understood generally as open-ended and non-limiting, for example, not excluding additional unrecited elements or steps, unless otherwise specifically stated or understood from the context.

[0063] Where the use of the term “about” is before a quantitative value, the disclosure also includes the specific quantitative value itself, unless specifically stated otherwise. As used herein, the term “about” refers to a ±10% variation from the nominal value unless otherwise indicated or inferred. For example, “about 10” contemplates both 10 and 10± 10%.

[0064] The term “in combination with” as used herein means that the described agents can be administered to an animal or subject together in a mixture, concurrently as single agents, or sequentially as single agents in any order.

[0065] The use of any and all examples, or exemplary language herein, for example, “such as” or “including,” is intended merely to illustrate better the present invention and does not pose a limitation on the scope of the invention unless claimed. No language in the specification should be construed as indicating any non-claimed element as essential to the practice of the present invention.

[0066] As a general matter, compositions specifying a percentage are by weight unless otherwise specified. Further, if a variable is not accompanied by a definition, then the previous definition of the variable controls.

[0067] It should be understood that the order of steps or order for performing certain actions is immaterial so long as the present invention remain operable. Moreover, two or more steps or actions may be conducted simultaneously.

[0068] Throughout the description, where compositions are described as having, including, or comprising specific components, or where processes and methods are described as having, including, or comprising specific steps, it is contemplated that, additionally, there are compositions of the present invention that consist essentially of, or consist of, the recited components, and that there are processes and methods according to the present invention that consist essentially of, or consist of, the recited processing steps.

[0069] In the application, where an element or component is said to be included in and / or selected from a list of recited elements or components, it should be understood that the element or component can be any one of the recited elements or components, or the element or component can be selected from a group consisting of two or more of the recited elements or components.II. Anti-Plasma Kallikrein Antibodies

[0070] Disclosed herein are pharmaceutical formulations comprising anti-plasma kallikrein (anti-pKal) antibodies. The anti-plasma kallikrein antibodies disclosed herein that may be included in such pharmaceutical formulations are useful for treating plasma kallikrein dependent disorders, such as hereditary angioedema (HAE), and, for example, potently and specifically inhibit pKal activity and have long serum half-lives. The anti-pKal antibodies disclosed herein have features useful in treating such disorders including specifically inhibiting pKal activity (e.g., KD of 1.0 nM), having a lower affinity for prekallikrein (e.g., >1, 000-fold lower affinity), and exhibiting no measurable inhibitory activity against other serine proteases. Anti -plasma kallikrein antibodies disclosed herein invention contain a YTE- modified Fc domain (corresponding to M252Y, S254T, and T256E according to EU numbering) which enhances pH-dependent FcRn binding, resulting in a prolonged serum half-life (e.g, two to three months or longer). Anti-plasma kallikrein antibodies useful in treating plasma kallikrein dependent disorders, including HAE, are described in International Patent Application Publication No. WO 2022 / 165130, the contents of which are incorporated by reference herein for all purposes.

[0071] The pharmaceutical formulations disclosed herein may include anti-plasma kallikrein antibodies useful in treating plasma kallikrein dependent disorders, e.g., HAE, defined by their CDR sequences which are disclosed in Table 1 and Table 2 below using Kabat, Chothia, IMGT and ABM numbering schemes. It is contemplated that the CDRsequences can be identified using other numbering schemes known in the art (see, e.g., Dondelinger et al. (October 2018) Frontiers Immunol. 8, 2278, 1-15).

[0072] In some examples, the anti-plasma kallikrein antibody has a heavy chain (or heavy chain variable region) with a CDRH1 comprising the amino acid sequence of SEQ ID NO: 1, 11, 17, or 22; a CDRH2 comprising the amino acid sequence of SEQ ID NO:2, 12, 18, or 23; and a CDRH3 comprising the amino acid sequence of SEQ ID NO:3, 13, or 19.

[0073] In other examples, the anti-plasma kallikrein antibody has a light chain (or light chain variable region) with a CDRL1 comprising the amino acid sequence of SEQ ID NO:4, 14, or 20; a CDRL2 comprising the amino acid sequence of SEQ ID NO:5 or 15; and a CDRL3 comprising the amino acid sequence of SEQ ID NO:6, 16, or 21.

[0074] In yet other examples, the anti-plasma kallikrein antibody has a heavy chain (or heavy chain variable region) with a CDRH1 comprising the amino acid sequence of SEQ ID NO: 1, 11, 17, or 22; a CDRH2 comprising the amino acid sequence of SEQ ID NO:2, 12, 18, or 23; and a CDRH3 comprising the amino acid sequence of SEQ ID NO:3, 13, or 19; and a light chain (or light chain variable region) with a CDRL1 comprising the amino acid sequence of SEQ ID NO:4, 14, or 20; a CDRL2 comprising the amino acid sequence of SEQ ID NO:5 or 15; and a CDRL3 comprising the amino acid sequence of SEQ ID NO:6, 16, or 21.

[0075] In further examples, the anti-plasma kallikrein antibody has a heavy chain (or heavy chain variable region) with a CDRH1 comprising the amino acid sequence of SEQ ID NO: 1; a CDRH2 comprising the amino acid sequence of SEQ ID NO:2; and a CDRH3 comprising the amino acid sequence of SEQ ID NO:3; and a light chain (or light chain variable region) with a CDRL1 comprising the amino acid sequence of SEQ ID NON; a CDRL2 comprising the amino acid sequence of SEQ ID NO:5; and a CDRL3 comprising the amino acid sequence of SEQ ID NO6.

[0076] The CDRs of the anti-plasma kallikrein antibody may be defined according to the Kabat definition, in which case the antibody comprises the heavy chain CDRs and light chain CDRs defined by Kabat in Tables 1 and 2 above. The CDRs of the anti-plasma kallikrein antibody may be defined according to the Chothia definition, in which case the antibody comprises the heavy chain CDRs and light chain CDRs defined by Chothia in Tables 1 and 2 above. The CDRs of the anti -plasma kallikrein antibody may be defined according to the IMGT definition, in which case the antibody comprises the heavy chain CDRs and light chain CDRs defined by IMGT in Tables 1 and 2 above. The CDRs of the anti-plasma kallikrein antibody may be defined according to the ABM definition, in which case the antibody comprises the heavy chain CDRs and light chain CDRs defined by ABM in Tables 1 and 2 above.

[0077] Antibodies defined by their CDRs according to the aforementioned embodiments may contain in their heavy chains an IgGl constant region comprising an M252Y, an S254T, and a T256E mutation as numbered according to the EU numbering index. This series of mutations is also referred to as the “YTE” mutation, and is believed to enhance pH-dependent FcRn binding, resulting in a prolonged serum half-life of the antibody.

[0078] For example, formulations disclosed herein may include an anti-plasma kallikrein antibody for the treatment of plasma kallikrein dependent disorders, e.g. , HAE, having a heavy chain with a CDRH1 comprising the amino acid sequence of SEQ ID NO: 1; a CDRH2 comprising the amino acid sequence of SEQ ID NO:2; and a CDRH3 comprising the amino acid sequence of SEQ ID NO:3; and a light chain with a CDRL1 comprising the amino acid sequence of SEQ ID NO:4; a CDRL2 comprising the amino acid sequence of SEQ ID NO:5; and a CDRL3 comprising the amino acid sequence of SEQ ID NO:6. The heavy chain also has an IgGl constant region with mutations M252Y, S254T, and T256E mutation as numbered according to the EU numbering index.

[0079] For example, formulations disclosed herein may include an anti-plasma kallikrein antibody for the treatment of plasma kallikrein dependent disorders, e.g. , HAE, having Complementarity Determining Sequences (CDRs) of a heavy chain variable region having the amino acid sequence of SEQ ID NO: 7, and CDRs of a light chain variable region having the amino acid sequence of SEQ ID NO: 8. The antibody may further comprise a constant region comprising an M252Y, an S254T, and a T256E mutation as numbered according to the EU numbering index.

[0080] In some embodiments, the anti-plasma kallikrein antibody is defined by its heavy and / or light chain variable region sequences which are shown in Table 3 below.

[0081] The anti-pKal antibody may comprise the Complementarity Determining Sequences (CDRs) of a heavy chain variable region having the amino acid sequence of SEQ ID NO: 7, and CDRs of a light chain variable region having the amino acid sequence of SEQ ID NO: 8. Further, the heavy chain of the antibody has an IgGl constant region with mutations M252Y, S254T, and T256E mutation as numbered according to the EU numbering index.

[0082] In one embodiment, the anti-plasma kallikrein antibody has a heavy chain variable region sequence having the amino acid sequence of SEQ ID NO:7. In another embodiment, the anti-plasma kallikrein antibody has a light chain variable region sequence having the amino acid sequence of SEQ ID NO:8.

[0083] For example, in one embodiment, the anti-plasma kallikrein antibody has a heavy chain variable region having the amino acid sequence of SEQ ID NO:7 and a light chain variable region having the amino acid sequence of SEQ ID NO: 8.

[0084] In another embodiment, the anti-plasma kallikrein antibody has a heavy chain variable region having the amino acid sequence of SEQ ID NO:7 and a light chain variable region having the amino acid sequence of SEQ ID NO:8, and the heavy chain has an IgGl constant region with the mutations M252Y, S254T, and T256E as numbered according to the EU numbering index.

[0085] In some embodiments, the anti-plasma kallikrein antibody is defined by its full length heavy and / or light chain sequences which are shown in Table 4 below.

[0086] For example, in one embodiment, the anti-plasma kallikrein antibody has a heavy chain having the amino acid sequence of SEQ ID NO:9, which includes an IgGl constant region with mutations M252Y, S254T, and T256E as numbered according to the EU numbering index; the mutated residues are underlined in Table 4 above. In another embodiment, the anti-plasma kallikrein antibody has a light chain having the amino acid sequence of SEQ ID NO: 10.

[0087] In a further embodiment, the anti-plasma kallikrein antibody has a heavy chain having the amino acid sequence of SEQ ID NO: 9 and a light chain having the amino acid sequence of SEQ ID NO: 10, and the heavy chain sequence has an IgGl constant region with mutations M252Y, S254T, and T256E mutation as numbered according to the EU numbering index; the mutated residues are underlined in Table 4 above. For example, the antibody is STAR-0215, also known as navenibart.III. Pharmaceutical Compositions

[0088] The anti-plasma kallikrein antibodies disclosed herein can be formulated as pharmaceutical compositions or formulations, e.g., for administration to a subject, e.g., to treat a plasma-kallikrein related disorder, e.g. , HAE. As used herein, the term “pharmaceutical composition” or “pharmaceutical formulation” refers to the combination of an active agent, e.g., the anti -plasma kallikrein antibodies described herein, with a carrier, inert or active, making the composition especially suitable for diagnostic or therapeutic use in vivo or ex vivo. Accordingly, the present disclosure provides pharmaceutical formulations that comprise a therapeutically effective amount of an anti-pKal antibody disclosed herein. In addition to the pharmaceutically active agent, e.g., the anti-pKal antibody, the pharmaceutical formulations comprise one or more excipients and / or surfactants and is maintained at a certain pH. Non-limiting examples of an “excipient,” as used herein, include any non-therapeutic agent added to the formulation to impart a desired physical or chemicalproperty, for example, pH, osmolality, viscosity, clarity, color, isotonicity, odor, sterility, stability, rate of dissolution or release, adsorption, or penetration.

[0089] For example, pharmaceutical compositions comprising anti-pKal antibodies according to the present disclosure may be formulated with pharmaceutically acceptable buffers (e.g., amino acid buffers, citrate buffers, succinate buffers, acetate buffers, phosphate buffers, etc.), stabilizers ((e.g., amino acids such as arginine, glycine, lysine, histidine, glutamic acid, aspartic acid, isoleucine, leucine, alanine, phenylalanine, tyrosine, tryptophane, methionine, serine, proline, or cysteine), or sugars (e.g., polyols, monosaccharides, disaccharides, or oligosaccharides, such as mannitol, sorbitol, glucose, fructose, mannose, sorbose, galactose, trehalose, maltose, raffinose, etc.)), tonicifiers (e.g., salts or sugars), surfactants (e.g., ionic surfactants (carboxylates, sulfates, sulfonates, phosphate esters) or non-ionic surfactants (e.g., polysorbates or polyoxyethylenes (Tweens), polaxamers, or sorbitans (Spans)), and diluents (e.g., sterile water, phosphate-buffered saline etc.). Other pharmaceutically acceptable excipients suitable for use in the formulations of antibodies may also be used.1. Anti-plasma Kallikrein Antibodies

[0090] The pharmaceutical formulations disclosed herein are designed to contain a sufficient quantity of the disclosed anti-pKal antibodies to enable efficiency of dosing to the patient. For example, formulations disclosed herein may be considered to carry “high” concentrations of the antibodies, e.g., greater than 50 mg / mL. High concentration formulations are desirable for several reasons including patient convenience and compliance due to reduced injection volumes and less frequent dosing which make them suitable for, e.g., self-administration. High concentration formulations may also achieve improved treatment efficacy because larger amounts of the antibody can be delivered to the subject, subject resulting in higher blood concentrations, even with infrequent dosing.

[0091] Accordingly, in some formulations of the anti-pKal antibodies disclosed herein, the antibody is present in the formulation at a concentration of about 50 mg / mL to about 500 mg / mL. The anti-pKal antibody may be, for example, an anti-pKal antibody having a heavy chain having the amino acid sequence of SEQ ID NO: 9, and a light chain having the amino acid sequence of SEQ ID NO: 10, e.g., the antibody is STAR-0215, also known as navenibart.

[0092] In some formulations, the anti-pKal antibody may be present in the formulation at a concentration of about 50 mg / mL to about 475 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 50 mg / mL to about 450 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 50 mg / mL to about 425 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 50 mg / mL to about 400 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 50 mg / mL to about 375 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 50 mg / mL to about 350 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 50 mg / mL to about 325 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 50 mg / mL to about 300 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 50 mg / mL to about 275 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 50 mg / mL to about 250 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 50 mg / mL to about 225 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 50 mg / mL to about 200 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 50 mg / mL to about 175 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 50 mg / mL to about 150 mg / mL. The antibody present in the formulation at the aforementioned concentrations may be, for example, an anti-plasma kallikrein antibody having a heavy chain having the amino acid sequence of SEQ ID NO:9, and a light chain having the amino acid sequence of SEQ ID NO: 10, e.g., the antibody is STAR-0215, also known as navenibart.

[0093] In some formulations, the anti-pKal antibody may be present in the formulation at a concentration of about 70 mg / mL to about 300 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 70 mg / mL to about 275 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 70 mg / mL to about 250 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 70 mg / mL to about 225 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration ofabout 70 mg / mL to about 200 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 70 mg / mL to about 175 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 70 mg / mL to about 150 mg / mL. The antibody present in the formulation at the aforementioned concentrations may be, for example, an anti-plasma kallikrein antibody having a heavy chain having the amino acid sequence of SEQ ID NO:9, and a light chain having the amino acid sequence of SEQ ID NO: 10, e.g., the antibody is STAR-0215, also known as navenibart.

[0094] In some formulations, the anti-pKal antibody may be present in the formulation at a concentration of about 75 mg / mL to about 300 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 75 mg / mL to about 275 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 75 mg / mL to about 250 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 75 mg / mL to about 225 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 75 mg / mL to about 200 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 75 mg / mL to about 175 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 75 mg / mL to about 150 mg / mL. The antibody present in the formulation at the aforementioned concentrations may be, for example, an anti-plasma kallikrein antibody having a heavy chain having the amino acid sequence of SEQ ID NO:9, and a light chain having the amino acid sequence of SEQ ID NO: 10, e.g., the antibody is STAR-0215, also known as navenibart.

[0095] In some formulations, the anti-pKal antibody may be present in the formulation at a concentration of about 100 mg / mL to about 300 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 100 mg / mL to about 275 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 100 mg / mL to about 250 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 100 mg / mL to about 225 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 100 mg / mL to about 200 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 100 mg / mL to about 175 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 100 mg / mL to about 150 mg / mL. The antibody present in theformulation at the aforementioned concentrations may be, for example, an anti-plasma kallikrein antibody having a heavy chain having the amino acid sequence of SEQ ID NO:9, and a light chain having the amino acid sequence of SEQ ID NO: 10, e.g. , the antibody is STAR-0215, also known as navenibart.

[0096] In some formulations, the anti-pKal antibody may be present in the formulation at a concentration of about 125 mg / mLto about 300 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 125 mg / mL to about 275 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 125 mg / mL to about 250 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 125 mg / mL to about 225 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 125 mg / mL to about 200 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 125 mg / mL to about 175 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 125 mg / mL to about 150 mg / mL. The antibody present in the formulation at the aforementioned concentrations may be, for example, an anti-plasma kallikrein antibody having a heavy chain having the amino acid sequence of SEQ ID NON, and a light chain having the amino acid sequence of SEQ ID NO: 10, e.g. , the antibody is STAR-0215, also known as navenibart.

[0097] In some formulations, the anti-pKal antibody, e.g., navenibart, may be present in the formulation at a concentration of about 135 mg / mL to about 275 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 135 mg / mL to about 250 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 135 mg / mLto about 225 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 135 mg / mL to about 200 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 135 mg / mL to about 175 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 135 mg / mL to about 165 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 135 mg / mL to about 150 mg / mL. The antibody present in the formulation at the aforementioned concentrations may be, for example, an anti-plasma kallikrein antibody having a heavy chain having the amino acid sequence of SEQ ID NON,and a light chain having the amino acid sequence of SEQ ID NO: 10, e.g. , the antibody is STAR-0215, also known as navenibart.

[0098] In some formulations, the anti-pKal antibody, e.g., navenibart, may be present in the formulation at a concentration of about 140 mg / mL to about 300 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 140 mg / mL to about 275 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 140 mg / mL to about 250 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 140 mg / mL to about 225 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 140 mg / mL to about 215 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 140 mg / mL to about 200 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 140 mg / mL to about 190 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 140 mg / mL to about 185 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 140 mg / mL to about 180 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 140 mg / mL to about 175 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 140 mg / mL to about 170 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 140 mg / mL to about 165 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 140 mg / mL to about 160 mg / mL. The antibody present in the formulation at the aforementioned concentrations may be, for example, an anti-plasma kallikrein antibody having a heavy chain having the amino acid sequence of SEQ ID NO:9, and a light chain having the amino acid sequence of SEQ ID NO: 10, e.g. , the antibody is STAR-0215, also known as navenibart.

[0099] In some formulations, the anti-pKal antibody, e.g., navenibart, may be present in the formulation at a concentration of about 160 mg / mL to about 180 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 170 mg / mL to about 180 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 170 mg / mL to about 190 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 170 mg / mLto about 210 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 175 mg / mL to about 200 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 175 mg / mL to about 225 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 175 mg / mL to about 250 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 175 mg / mL to about 275 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of 175-300 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 180 mg / mL to about 200 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 180 mg / mL to about 210 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 180 mg / mL to about 220 mg / mL. The antibody present in the formulation at the aforementioned concentrations may be, for example, an anti-plasma kallikrein antibody having a heavy chain having the amino acid sequence of SEQ ID NO:9, and a light chain having the amino acid sequence of SEQ ID NO: 10, e.g. , the antibody is STAR-0215, also known as navenibart.

[0100] In some formulations the anti-pKal antibody, e.g., navenibart, may be present in the formulation in an amount of about 50 mg / mL or greater. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 50 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 55 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 60 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 65 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 70 mg / mL. For example, the anti- pKal antibody may be present in the formulation at a concentration of about 75 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 80 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 85 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 90 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 95 mg / mL. For example, the anti- pKal antibody may be present in the formulation at a concentration of about 100 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about105 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 110 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 115 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 120 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 125 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 130 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 135 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 140 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 145 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 150 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 155 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 160 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 165 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 170 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 175 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 180 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 185 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 190 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 195 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 200 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 205 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 210 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 215 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 220 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 225 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 230 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 235 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 240 mg / mL. For example, the anti-pKal antibodymay be present in the formulation at a concentration of about 245 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 250 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 255 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 260 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 265 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 270 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 15 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 280 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 285 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 290 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 295 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 300 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 310 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 320 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 330 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 340 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 350 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 360 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 370 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 380 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 390 mg / mL. For example, the anti-pKal antibody may be present in the formulation at a concentration of about 400 mg / mL. The antibody present in the formulation at one of the aforementioned concentrations may be, for example, an anti-plasma kallikrein antibody having a heavy chain having the amino acid sequence of SEQ ID NO:9, and a light chain having the amino acid sequence of SEQ ID NOTO, e.g., the antibody is STAR-0215, also known as navenibart.2. Excipients and Conditions2.1. Diluents

[0101] Disclosed herein are liquid pharmaceutical compositions or formulations e.g., formulations that are a solution comprising an anti-pKal antibody, e.g., navenibart, and a pharmaceutically acceptable diluent or combinations thereof. For example, the diluent may be aqueous, e.g., containing water. Accordingly, formulations disclosed herein include aqueous pharmaceutical compositions, e.g., formulations that include water. For example, the diluent may be water, e.g., water for injection (“WFI”), or sterile water for injection (“SWFI”) or bacteriostatic water for injection (“BWFI”) that is suitably free of, e.g., bacterial, viral or other contamination, including pyrogens and / or organic carbons.

[0102] Other suitable diluents may include sterile normal saline, sterile ringer’s solution, sterile lactated Ringer’s solution, sterile propylene glycol or polyethylene glycol (PEG), phosphate buffered sale, or a dextrose solution. The diluent may be selected to ensure compatibility with other excipients in the formulation and the route of administration. The diluent may be selected to ensure compatibility with pharmacopeial guidelines (e.g., USP or EP).

[0103] The diluent, e.g., an aqueous diluent, such as water, may constitute the balance of the ingredients in the formulations disclosed herein such that the weight percentages of all ingredients in the formulations with the diluent total 100%. Accordingly, in certain formulations disclosed herein, the formulation is adjusted to a final volume or weight, with water, e.g., water for injection (“WFI”), or sterile water for injection (“SWFI”) or bacteriostatic water for injection (“BWFI”).2.2. Buffers

[0104] A “buffer” or “buffer system” refers to a solution composed of a weak acid and its conjugate base (or a weak base and its conjugate acid) that resists significant changes in pH when acid or base is added to it. As such, a buffer is used to keep a solution, such as a liquid pharmaceutical formulation, at a nearly constant pH value.

[0105] Pharmaceutical compositions comprising anti-pKal antibodies, e.g., navenibart, according to the present disclosure may be formulated with pharmaceutically acceptable buffers. Suitable buffers may include, for example, amino acid buffers, citrate buffers,succinate buffers, acetate buffers, carbonate buffers, or phosphate buffers. However, in some cases, the formulation may be unbuffered meaning that the formulation lacks a buffer. In some cases, the formulation includes only a single buffer. In other cases, the formulation includes multiple buffers, e.g., more than one buffer. In some cases, the buffer, in addition to acting as a buffer, serves one or more additional roles in the formulation such as, for example, as a stabilizer, a viscosity reducer, or as a tonicifier, for example.

[0106] Accordingly, some formulations of anti-pKal antibodies disclosed herein, e.g., navenibart, include an amino acid buffer, a citrate buffer, a succinate buffer, an acetate buffer, a carbonate buffer, or a phosphate buffer. In some formulations, the buffer is an amino acid buffer. In some formulations, the buffer is a citrate buffer. In some formulations, the buffer is a succinate buffer. In some formulations, the buffer is a succinate buffer. In some formulations, the buffer is an acetate buffer. In yet other formulations, the buffer is a carbonate buffer. In still other formulations, the buffer is a phosphate buffer.

[0107] In some formulations of anti-pKal antibodies disclosed herein, e.g., navenibart, a buffer is not included and the formulation relies on the inherent buffering capacity of the antibody, e.g., navenibart. In other words, the disclosure contemplates pharmaceutical compositions that exclude (do not include) an excipient with buffering capacity, e.g., buffering capacity within the pH range of the formulation.

[0108] Accordingly, the buffer may be present in the formulation of an anti-pKal antibody as disclosed herein, e.g., navenibart, at a concentration of 0 mM to about 500 mM. The buffer may be present in the formulation at a concentration of 0 mM to about 400 mM. The buffer may be present in the formulation at a concentration of 0 mM to about 300 mM. The buffer may be present in the formulation at a concentration of 0 mM to about 200 mM. For example, the buffer may be present in the formulation at a concentration of greater than 0 mM to about 200 mM. For example, the buffer may be present in the formulation at a concentration of greater than 0 mM to about 175 mM. For example, the buffer may be present in the formulation at a concentration of greater than 0 mM to about 150 mM. For example, the buffer may be present in the formulation at a concentration of greater than 0 mM to about 125 mM. For example, the buffer may be present in the formulation at a concentration of greater than 0 mM to about 100 mM. For example, the buffer may be present in the formulation at a concentration of about 5 mM to about 90 mM. For example, thebuffer may be present in the formulation at a concentration of about 5 mM to about 80 mM. For example, the buffer may be present in the formulation at a concentration of about 5 mM to about 70 mM. For example, the buffer may be present in the formulation at a concentration of about 5 mM to about 60 mM. For example, the buffer may be present in the formulation at a concentration of about 5 mM to about 50 mM. For example, the buffer may be present in the formulation at a concentration of about 5 mM to about 45 mM. For example, the buffer may be present in the formulation at a concentration of about 5 mM to about 40 mM. For example, the buffer may be present in the formulation at a concentration of about 5 mM to about 35 mM. For example, the buffer may be present in the formulation at a concentration of about 5 mM to about 20 mM. For example, the buffer may be present in the formulation at a concentration of about 5 mM to about 15 mM. For example, the buffer may be present in the formulation at a concentration of about 5 mM to about 10 mM. For example, the buffer may be present in the formulation at a concentration of about 8 mM to about 12 mM. For example, the buffer may be present in the formulation at a concentration of about 9 mM to about 11 mM. For example, the buffer may be present in the formulation at a concentration of about 10 mM to about 15 mM. For example, the buffer may be present in the formulation at a concentration of about 10 mM to about 20 mM. For example, the buffer may be present in the formulation at a concentration of about 10 mM to about 25 mM. For example, the buffer may be present in the formulation at a concentration of about 10 mM to about 30 mM. For example, the buffer may be present in the formulation at a concentration of about 10 mM to about 40 mM. For example, the buffer may be present in the formulation at a concentration of about 10 mM to about 45 mM. For example, the buffer may be present in the formulation at a concentration of about 10 mM to about 50 mM. For example, the buffer may be present in the formulation at a concentration of about 10 mM to about 60 mM. For example, the buffer may be present in the formulation at a concentration of about 10 mM to about 70 mM. For example, the buffer may be present in the formulation at a concentration of about 15 mM to about 25 mM. For example, the buffer may be present in the formulation at a concentration of about 15 mM to about 35 mM. For example, the buffer may be present in the formulation at a concentration of about 20 mM to about 30 mM. For example, the buffer may be present in the formulation at a concentration of about 20 mM to about 40 mM. For example, the buffer may be present in the formulation at a concentration of about 25 mM to about 50 mM. For example, the buffer may be present in the formulation at a concentration of about 30 mM to about 60 mM. For example, the buffer may be presentin the formulation at a concentration of about 40 mM to about 75 mM. For example, the buffer may be present in the formulation at a concentration of about 50 mM to about 85 mM. For example, the buffer may be present in the formulation at a concentration of about 60 mM to about 100 mM. For example, the buffer may be present in the formulation at a concentration of about 60 mM to about 150 mM. For example, the buffer may be present in the formulation at a concentration of about 100 mM to about 200 mM. For example, the buffer may be present in the formulation at a concentration of 0 mM. For example, the buffer is a histidine buffer. For example, the buffer is an acetate buffer. For example, the buffer is a succinate buffer. For example, the buffer is a phosphate buffer. For example, the buffer is selected from succinate, acetate or phosphate.

[0109] Some formulations of anti-pKal antibodies disclosed herein, e.g., navenibart, include an amino acid buffer, e.g., a free amino acid that is not part of a protein or peptide. For example, suitable amino acid buffers for such formulations may include histidine, arginine, alanine, phenylalanine, glycine, cysteine, serine, glutamic acid, or aspartic acid. In some formulations, the amino acid buffer is histidine. For example, the buffer is free histidine, e.g., L-histidine. In some formulations, the amino acid buffer is arginine (e.g., L- arginine, e.g., L-arginine hydrochloride, e.g., L-arginine hydrochloride monohydrate, e.g., arginine glutamate, e.g., arginine aspartate, e.g., arginine acetate, e.g., arginine sulfate, e.g., arginine lactobionate). In some formulations, the amino acid is alanine. In some formulations, the amino acid buffer is phenylalanine. In some formulations, the amino acid buffer is glycine (e.g., L-glycine, e.g., L-glycine hydrochloride, e.g., tris-glycine). In some formulations, the amino acid buffer is cysteine. In some formulations, the amino acid buffer is serine. In some formulations, the amino acid buffer is glutamic acid. For example, the amino acid buffer is aspartic acid. In such formulations, the amino acid buffer may be present in the formulation at a concentration of greater than 0 mM to about 200 mM. For example, the amino acid buffer may be present in the formulation at a concentration of greater than 0 mM to about 150 mM. For example, the amino acid buffer may be present in the formulation at a concentration of greater than 0 mM to about 100 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 5 mM to about 90 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 5 mM to about 80 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 5 mM to about 70 mM. For example,the amino acid buffer may be present in the formulation at a concentration of about 5 mM to about 60 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 5 mM to about 50 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 5 mM to about 45 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 5 mM to about 40 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 5 mM to about 35 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 5 mM to about 20 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 5 mM to about 15 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 5 mM to about 10 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 8 mM to about 12 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 9 mM to about 11 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 10 mM to about 15 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 10 mM to about 20 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 10 mM to about 25 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 10 mM to about 30 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 10 mM to about 40 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 10 mM to about 45 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 10 mM to about 50 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 10 mM to about 60 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 10 mM to about 70 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 15 mM to about 25 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 15 mM to about 35 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 20 mM to about 30 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 20 mM to about 40 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 25 mM to about 50 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 30 mM toabout 60 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 40 mM to about 75 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 60 mM to about 150 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 100 mM to about 200 mM.

[0110] In some instances, in the formulations of an anti-pKal antibody as disclosed herein, e.g, navenibart, the amino acid buffer, e.g., histidine, arginine, alanine, phenylalanine, glycine, cysteine, serine, glutamic acid, or aspartic acid) is present in the formulation at a concentration greater than 0 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 1 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 2 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 3 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 4 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 5 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 6 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 7 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 8 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 9 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 10 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 11 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 12 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 13 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 14 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 15 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 16 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 17 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 18 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 19 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 20 mM. For example, the amino acidbuffer may be present in the formulation at a concentration of about 21 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 22 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 23 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 24 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 25 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 26 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 27 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 28 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 29 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 30 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 31 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 32 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 33 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 34 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 35 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 36 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 37 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 38 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 39 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 40 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 41 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 42 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 43 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 44 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 45 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 46 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 47 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 48 mM. For example, the amino acid buffer may be present in theformulation at a concentration of about 49 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 50 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 55 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 60 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 65 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 70 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 75 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 80 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 85 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 90 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 95 mM. For example, the amino acid buffer may be present in the formulation at a concentration of about 100 mM.[oni] In certain formulations of anti-pKal antibodies disclosed herein, e.g., navenibart, the buffer is histidine, e.g. , free histidine that is not part of a protein or peptide. For example, the histidine may be L-histidine. For example, the histidine may be L-histidine hydrochloride (HC1), e.g., L-histidine hydrochloride monohydrate. For example, the histidine may be a zinc histidine salt.

[0112] For example, in certain formulations of anti-pKal antibodies disclosed herein, e.g., navenibart, the histidine buffer may be present in the formulation at a concentration of greater than 0 mM to about 100 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 5 mM to about 90 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 5 mM to about 80 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 5 mM to about 70 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 5 mM to about 60 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 5 mM to about 50 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 5 mM to about 45 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 5 mM to about 40 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 5 mM to about 35 mM.For example, the histidine buffer may be present in the formulation at a concentration of about 5 mM to about 20 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 5 mM to about 15 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 5 mM to about 10 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 8 mM to about 12 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 8 mM to about 15 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 9 mM to about 11 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 10 mM to about 15 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 10 mM to about 20 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 10 mM to about 25 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 10 mM to about 30 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 10 mM to about 40 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 10 mM to about 45 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 10 mM to about 50 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 10 mM to about 60 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 10 mM to about 70 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 15 mM to about 25 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 15 mM to about 35 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 20 mM to about 30 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 20 mM to about 40 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 25 mM to about 50 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 30 mM to about 60 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 40 mM to about 75 mM.

[0113] For example, in certain formulations of anti-pKal antibodies disclosed herein, e.g., navenibart, the histidine buffer may be present in the formulation at a concentration of about1 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 2 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 3 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 4 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 5 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 6 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 7 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 8 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 9 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 10 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 11 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 12 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 13 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 14 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 15 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 16 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 17 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 18 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 19 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 20 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 21 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 22 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 23 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 24 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 25 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 26 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 27 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 28 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 29 mM. For example, the histidine buffer may be present in the formulation at a concentration ofabout 30 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 31 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 32 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 33 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 34 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 35 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 36 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 37 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 38 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 39 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 40 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 41 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 42 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 43 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 44 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 45 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 46 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 47 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 48 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 49 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 50 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 55 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 60 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 65 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 70 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 75 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 80 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 85 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 90 mM. For example, the histidine buffer may be present in the formulation at aconcentration of about 95 mM. For example, the histidine buffer may be present in the formulation at a concentration of about 100 mM.

[0114] In some cases, combinations of buffers may be used. Accordingly, the anti-pKal antibody formulations, e.g., navenibart formulations, disclosed herein may include two or more buffers. For example, antibody formulations may include one or more amino acid buffers alone, or in combination with one or more of a citrate buffer, a succinate buffer, an acetate buffer, and / or a phosphate buffer. For example, antibody formulations may include two or more of an amino acid buffer, a citrate buffer, a succinate buffer, an acetate buffer, and / or a phosphate buffer. For example, antibody formulations may include two or more amino acid buffers. In such cases, the combination of buffers may be present in the formulation at a total concentration of greater than 0 mM to about 100 mM. For example, the combination of buffers may be present in the formulation at a total concentration of about 5 mM to about 90 mM. For example, the combination of buffers may be present in the formulation at a total concentration of about 5 mM to about 80 mM. For example, the combination of buffers may be present in the formulation at a total concentration of about 5 mM to about 70 mM. For example, the combination of buffers may be present in the formulation at a total concentration of about 5 mM to about 60 mM. For example, the combination of buffers may be present in the formulation at a total concentration of about 5 mM to about 50 mM. For example, the combination of buffers may be present in the formulation at a total concentration of about 5 mM to about 45 mM. For example, the combination of buffers may be present in the formulation at a total concentration of about 5 mM to about 40 mM. For example, the combination of buffers may be present in the formulation at a total concentration of about 5 mM to about 35 mM. For example, the combination of buffers may be present in the formulation at a total concentration of about 5 mM to about 20 mM. For example, the combination of buffers may be present in the formulation at a total concentration of about 5 mM to about 15 mM. For example, the combination of buffers may be present in the formulation at a total concentration of about 5 mM to about 10 mM. For example, the combination of buffers may be present in the formulation at a total concentration of about 8 mM to about 12 mM. For example, the combination of buffers may be present in the formulation at a total concentration of about 9 mM to about 11 mM. For example, the combination of buffers may be present in the formulation at a total concentration of about 10 mM to about 15 mM. For example, thecombination of buffers may be present in the formulation at a total concentration of about 10 mM to about 20 mM. For example, the combination of buffers may be present in the formulation at a total concentration of about 10 mM to about 25 mM. For example, the combination of buffers may be present in the formulation at a total concentration of about 10 mM to about 30 mM. For example, the combination of buffers may be present in the formulation at a total concentration of about 10 mM to about 40 mM. For example, the combination of buffers may be present in the formulation at a total concentration of about 10 mM to about 45 mM. For example, the combination of buffers may be present in the formulation at a total concentration of about 10 mM to about 50 mM. For example, the combination of buffers may be present in the formulation at a total concentration of about 10 mM to about 60 mM. For example, the combination of buffers may be present in the formulation at a total concentration of about 10 mM to about 70 mM. For example, the combination of buffers may be present in the formulation at a total concentration of about 15 mM to about 25 mM. For example, the combination of buffers may be present in the formulation at a total concentration of about 15 mM to about 35 mM. For example, the combination of buffers may be present in the formulation at a total concentration of about 20 mM to about 30 mM. For example, the combination of buffers may be present in the formulation at a total concentration of about 20 mM to about 40 mM. For example, the combination of buffers may be present in the formulation at a total concentration of about 25 mM to about 50 mM. For example, the combination of buffers may be present in the formulation at a total concentration of about 30 mM to about 60 mM. For example, the combination of buffers may be present in the formulation at a total concentration of about 40 mM to about 75 mM. For example, the combination of buffers may be present in the formulation at a total concentration of about 50 mM to about 85 mM. For example, the combination of buffers may be present in the formulation at a total concentration of about 60 mM to about 100 mM.2.3. Anti-oxidants

[0115] When amino acids capable of oxidation are present in the protein, e.g, antibody, being formulated, it is necessary to consider including an excipient that acts as an antioxidant, e.g., to inhibit oxidation, thereby preventing degradation of the protein over time and due to various stresses. For example, methionine and cysteine residues are liable to oxidize, resulting in degradation and destabilization of the antibody. Accordingly, formulations of theanti-pKal antibodies disclosed herein, e.g., navenibart, may contain an antioxidant. For example, the antioxidant may be methionine, e.g., free methionine, e.g., L-methionine. For example, the antioxidant may be EDTA (ethylenediaminetetraacetic acid). For example, the anti-oxidant may be cysteine, e.g., L-cysteine hydrocholoride, or cysteamine. For example, the anti-oxidant may be DTPA (diethylenetriaminepentaacetic acid or pentetic acid). For example, the anti-oxidant may be DFOA (desferrioxamine or deferoxamine). For example, the anti-oxidant may be DTT (dithiothreitol).

[0116] Accordingly, an anti-oxidant, e.g., methionine, EDTA, cysteine, cysteamine, DTPA, DFOA, or DTT, may be present in the formulation at a concentration of greater than 0 mM to about 100 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 5 mM to about 90 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 5 mM to about 80 mM. For example, the antioxidant may be present in the formulation at a concentration of about 5 mM to about 70 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 5 mM to about 60 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 5 mM to about 50 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 5 mM to about 45 mM. For example, the antioxidant may be present in the formulation at a concentration of about 5 mM to about 40 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 5 mM to about 35 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 5 mM to about 20 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 5 mM to about 15 mM. For example, the antioxidant may be present in the formulation at a concentration of about 5 mM to about 10 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 8 mM to about 12 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 9 mM to about 11 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 10 mM to about 15 mM. For example, the antioxidant may be present in the formulation at a concentration of about 10 mM to about 20 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 10 mM to about 25 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 10 mM to about 30 mM. For example, the antioxidant may be present in the formulation at a concentration of about 10 mM to about 40mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 10 mM to about 45 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 10 mM to about 50 mM. For example, the antioxidant may be present in the formulation at a concentration of about 10 mM to about 60 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 10 mM to about 70 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 15 mM to about 25 mM. For example, the antioxidant may be present in the formulation at a concentration of about 15 mM to about 35 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 20 mM to about 30 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 20 mM to about 40 mM. For example, the antioxidant may be present in the formulation at a concentration of about 25 mM to about 50 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 30 mM to about 60 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 40 mM to about 75 mM. For example, the antioxidant is EDTA. For example, the anti-oxidant is methionine.

[0117] For example, the anti-oxidant may be present in the formulation at a concentration of about 1 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 2 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 3 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 4 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 5 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 6 mM. For example, the antioxidant may be present in the formulation at a concentration of about 7 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 8 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 9 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 10 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 11 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 12 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 13 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 14 mM. For example, the anti-oxidantmay be present in the formulation at a concentration of about 15 mM. For example, the antioxidant may be present in the formulation at a concentration of about 16 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 17 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 18 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 19 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 20 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 21 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 22 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 23 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 24 mM. For example, the antioxidant may be present in the formulation at a concentration of about 25 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 26 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 27 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 28 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 29 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 30 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 31 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 32 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 33 mM. For example, the antioxidant may be present in the formulation at a concentration of about 34 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 35 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 36 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 37 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 38 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 39 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 40 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 41 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 42 mM. For example, the antioxidant may be present in the formulation at a concentration of about 43 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 44 mM. Forexample, the anti-oxidant may be present in the formulation at a concentration of about 45 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 46 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 47 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 48 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 49 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 50 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 55 mM. For example, the antioxidant may be present in the formulation at a concentration of about 60 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 65 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 70 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 75 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 80 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 85 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 90 mM. For example, the anti-oxidant may be present in the formulation at a concentration of about 95 mM. For example, the antioxidant may be present in the formulation at a concentration of about 100 mM. For example, the anti-oxidant is EDTA. For example, the anti-oxidant is methionine.

[0118] In some cases, the anti-oxidant included in the formulations of anti-pKal antibodies, e.g., navenibart, disclosed herein is methionine. For example, the methionine may be free methionine, e.g., L-methionine or, the methionine may be L-methionine HC1. For example, methionine may be present in the formulation at a concentration of greater than 0 mM to about 100 mM. For example, methionine may be present in the formulation at a concentration of about 5 mM to about 90 mM. For example, methionine may be present in the formulation at a concentration of about 5 mM to about 80 mM. For example, methionine may be present in the formulation at a concentration of about 5 mM to about 70 mM. For example, methionine may be present in the formulation at a concentration of about 5 mM to about 60 mM. For example, methionine may be present in the formulation at a concentration of about 5 mM to about 50 mM. For example, methionine may be present in the formulation at a concentration of about 5 mM to about 45 mM. For example, methionine may be present in the formulation at a concentration of about 5 mM to about 40 mM. For example,methionine may be present in the formulation at a concentration of about 5 mM to about 35 mM. For example, methionine may be present in the formulation at a concentration of about 5 mM to about 20 mM. For example, methionine may be present in the formulation at a concentration of about 5 mM to about 15 mM. For example, methionine may be present in the formulation at a concentration of about 5 mM to about 10 mM. For example, methionine may be present in the formulation at a concentration of about 8 mM to about 12 mM. For example, methionine may be present in the formulation at a concentration of about 9 mM to about 11 mM. For example, methionine may be present in the formulation at a concentration of about 10 mM to about 15 mM. For example, methionine may be present in the formulation at a concentration of about 10 mM to about 20 mM. For example, methionine may be present in the formulation at a concentration of about 10 mM to about 25 mM. For example, methionine may be present in the formulation at a concentration of about 10 mM to about 30 mM. For example, methionine may be present in the formulation at a concentration of about 10 mM to about 40 mM. For example, methionine may be present in the formulation at a concentration of about 10 mM to about 45 mM. For example, methionine may be present in the formulation at a concentration of about 10 mM to about 50 mM. For example, methionine may be present in the formulation at a concentration of about 10 mM to about 60 mM. For example, methionine may be present in the formulation at a concentration of about 10 mM to about 70 mM. For example, methionine may be present in the formulation at a concentration of about 15 mM to about 25 mM. For example, methionine may be present in the formulation at a concentration of about 15 mM to about 35 mM. For example, methionine may be present in the formulation at a concentration of about 20 mM to about 30 mM. For example, methionine may be present in the formulation at a concentration of about 20 mM to about 40 mM. For example, methionine may be present in the formulation at a concentration of about 25 mM to about 50 mM. For example, methionine may be present in the formulation at a concentration of about 30 mM to about 60 mM. For example, methionine may be present in the formulation at a concentration of about 40 mM to about 75 mM.

[0119] For example, the anti-oxidant in the anti-pkal antibody, e.g., navenibart, formulation may be methionine. For example, methionine may be present in the formulation at a concentration of about 1 mM. For example, methionine may be present in the formulation at a concentration of about 2 mM. For example, methionine may be present inthe formulation at a concentration of about 3 mM. For example, methionine may be present in the formulation at a concentration of about 4 mM. For example, methionine may be present in the formulation at a concentration of about 5 mM. For example, methionine may be present in the formulation at a concentration of about 6 mM. For example, methionine may be present in the formulation at a concentration of about 7 mM. For example, methionine may be present in the formulation at a concentration of about 8 mM. For example, methionine may be present in the formulation at a concentration of about 9 mM. For example, methionine may be present in the formulation at a concentration of about 10 mM. For example, methionine may be present in the formulation at a concentration of about 11 mM. For example, methionine may be present in the formulation at a concentration of about 12 mM. For example, methionine may be present in the formulation at a concentration of about 13 mM. For example, methionine may be present in the formulation at a concentration of about 14 mM. For example, methionine may be present in the formulation at a concentration of about 15 mM. For example, methionine may be present in the formulation at a concentration of about 16 mM. For example, methionine may be present in the formulation at a concentration of about 17 mM. For example, methionine may be present in the formulation at a concentration of about 18 mM. For example, methionine may be present in the formulation at a concentration of about 19 mM. For example, methionine may be present in the formulation at a concentration of about 20 mM. For example, methionine may be present in the formulation at a concentration of about 21 mM. For example, methionine may be present in the formulation at a concentration of about 22 mM. For example, methionine may be present in the formulation at a concentration of about 23 mM. For example, methionine may be present in the formulation at a concentration of about 24 mM. For example, methionine may be present in the formulation at a concentration of about 25 mM. For example, methionine may be present in the formulation at a concentration of about 26 mM. For example, methionine may be present in the formulation at a concentration of about 27 mM. For example, methionine may be present in the formulation at a concentration of about 28 mM. For example, methionine may be present in the formulation at a concentration of about 29 mM. For example, methionine may be present in the formulation at a concentration of about 30 mM. For example, methionine may be present in the formulation at a concentration of about 31 mM. For example, methionine may be present in the formulation at a concentration of about 32 mM. For example, methionine may be present in the formulation at a concentration of about 33 mM. For example, methionine may be presentin the formulation at a concentration of about 34 mM. For example, methionine may be present in the formulation at a concentration of about 35 mM. For example, methionine may be present in the formulation at a concentration of about 36 mM. For example, methionine may be present in the formulation at a concentration of about 37 mM. For example, methionine may be present in the formulation at a concentration of about 38 mM. For example, methionine may be present in the formulation at a concentration of about 39 mM. For example, methionine may be present in the formulation at a concentration of about 40 mM. For example, methionine may be present in the formulation at a concentration of about 41 mM. For example, methionine may be present in the formulation at a concentration of about 42 mM. For example, methionine may be present in the formulation at a concentration of about 43 mM. For example, methionine may be present in the formulation at a concentration of about 44 mM. For example, methionine may be present in the formulation at a concentration of about 45 mM. For example, methionine may be present in the formulation at a concentration of about 46 mM. For example, methionine may be present in the formulation at a concentration of about 47 mM. For example, methionine may be present in the formulation at a concentration of about 48 mM. For example, methionine may be present in the formulation at a concentration of about 49 mM. For example, methionine may be present in the formulation at a concentration of about 50 mM. For example, methionine may be present in the formulation at a concentration of about 55 mM. For example, methionine may be present in the formulation at a concentration of about 60 mM. For example, methionine may be present in the formulation at a concentration of about 65 mM. For example, methionine may be present in the formulation at a concentration of about 70 mM. For example, methionine may be present in the formulation at a concentration of about 75 mM. For example, methionine may be present in the formulation at a concentration of about 80 mM. For example, methionine may be present in the formulation at a concentration of about 85 mM. For example, methionine may be present in the formulation at a concentration of about 90 mM. For example, methionine may be present in the formulation at a concentration of about 95 mM. For example, methionine may be present in the formulation at a concentration of about 100 mM.2.4. Stabilizers

[0120] A “stabilizer” or “stabilizing agent” refers to a component added to a formulation to maintain the structural integrity and activity of the protein, e.g., antibody, e.g., anti-pKalantibody in that formulation overtime (e.g., during manufacture and storage) and in light of stresses that the protein may face, such as freeze / thaw or other temperature stresses including heating or lyophilization, agitation, or exposure to light, which may lead to, e.g., fragmentation, degradation (e.g, side chain oxidation, hydrolysis, deamidation), aggregation, and conformational instability of the protein. Therefore, anti-pKal antibody, e.g., navenibart, formulations disclosed herein may include one or more stabilizers or stabilizing agents, e.g., to mitigate the impacts of stress on the protein in formulation. Stabilizers may also fulfill other roles in the formulation, e.g. , a stabilizer may act as both a stabilizer and a buffer, or as stabilizer and an anti-oxidant, or as a stabilizer and a viscosity-reducing agent, or the stabilizer may fulfdl multiple roles in the formulation.

[0121] Stabilizers may be included in the disclosed anti-pKal antibody, e.g., navenibart, pharmaceutical formulations such as amino acids, sugar polyols, monosaccharides, disaccharides, and oligosaccharides.

[0122] For example, amino acid stabilizers, e.g, free amino acids that are not part of a protein or peptide, that may be included in such formulations include alanine, arginine, aspartic acid, cysteine, glycine, glutamic acid, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, tryptophan, or tyrosine. In some instances, amino acids other than an amino acid present as a buffer or anti-oxidant, are not included in the pharmaceutical formulations of the invention. However, in some instances, other amino acids present in a histidine buffer and a methionine antioxidant, the formulation is free of free amino acids, e.g., free of amino acids that are not part of a protein or peptide, e.g., the anti- pKal antibody, e.g., navenibart.

[0123] Sugar stabilizers that may be included in such formulations also include sugar polyols such as mannitol, sorbitol, glycerol, erythritol, maltitol, or xylitol; monosaccharides such as glucose, fructose, galactose, mannose, or sorbose; and disaccharides such as trehalose, sucrose, maltose, and lactose. In some formulations disclosed herein, sugars, e.g., monosaccharides, disaccharides, polysaccharides, and polyols, are not used in the formulation, such that the formulation is free of sugars.

[0124] Salts, e.g., metal salts, may also be used as stabilizers in formulations of anti-pKal antibodies, e.g., navenibart, disclosed herein. For example, sodium chloride (NaCl) may be included as a stabilizer in the formulations disclosed herein. For example, potassium chloride(KC1), magnesium chloride (MgCh), zinc sulfate (ZnSO-i). or copper sulfate (CuSO-i) may be included in formulations disclosed herein. In some formulations disclosed herein, metal salts, e.g. , sodium chloride, are not used in the formulation, such that the formulation is free of metal salt, e.g., sodium chloride.

[0125] In some formulations of the anti-pKal antibodies, e.g., navenibart, disclosed herein, a stabilizer that is a cryoprotectant (e.g., stabilizes the formulation by acting against freeze / thaw and temperature induced stress) is included in the formulation. The aforementioned amino acid stabilizers, sugar polyols, and mono- and disaccharides may be included in the formulations of anti-pKal antibodies, e.g., navenibart, disclosed herein to provide stability, e.g. as cryoprotectants, to the formulation. For example, in certain formulations, sorbitol is present in the formulation, e.g., as a cryoprotectant. For example, in certain formulations, mannitol is present in the formulation, e.g., as a cryoprotectant.

[0126] In some formulations of the anti-pKal antibodies disclosed herein, more than one excipient that acts as a stabilizer is included. For example, the formulation may include one or more amino acids and / or one or more sugar polyols and / or one or more monosaccharides and / or one or more disaccharides. The amino acids and / or sugar stabilizers may, in some instances, act as stabilizers in addition to performing other functions in the formulation, such as buffering, or ensuring appropriate viscosity, tonicity or osmolality of the formulation.

[0127] Accordingly, the concentration of a polyol, a disaccharide, an amino acid, or a metal salt, such as one of the aforementioned polyols, monosaccharides, disaccharides, amino acids or metal salts, in the anti-pKal antibody, e.g., navenibart, formulations disclosed herein, e.g. , for use as a stabilizer, may be greater than 0 mM to about 500 mM. For example, the concentration may be about 10 to about 500 mM. For example, the concentration may be about 10 to about 450 mM. For example, the concentration may be about 10 to about 400 mM. For example, the concentration may be about 10 to about 350 mM. For example, the concentration may be about 10 to about 300 mM. For example, the concentration may be about 10 to about 275 mM. For example, the concentration may be about 10 to about 250 mM. For example, the concentration may be about 10 to about 225 mM. For example, the concentration may be about 10 to about 200 mM. For example, the concentration may be about 10 to about 175 mM. For example, the concentration may be about 10 to about 150 mM. For example, the concentration may be about 10 to about 125 mM. For example, theconcentration may be about 10 to about 100 mM. For example, the concentration may be about 10 to about 75 mM. For example, the concentration may be about 25 to about 400 mM. For example, the concentration may be about 25 to about 350 mM. For example, the concentration may be about 25 to about 300 mM. For example, the concentration may be about 25 to about 250 mM. For example, the concentration may be about 25 to about 200 mM. For example, the concentration may be about 25 to about 175 mM. For example, the concentration may be about 25 to about 150 mM. For example, the concentration may be about 25 to about 125 mM. For example, the concentration may be about 25 to about 100 mM. For example, the concentration may be about 25 to about 75 mM. For example, the concentration may be about 50 to about 400 mM. For example, the concentration may be about 50 to about 350 mM. For example, the concentration may be about 50 to about 300 mM. For example, the concentration may be about 50 to about 250 mM. For example, the concentration may be about 50 to about 200 mM. For example, the concentration may be about 50 to about 175 mM. For example, the concentration may be about 50 to about 150 mM. For example, the concentration may be about 50 to about 125 mM. For example, the concentration may be about 50 to about 100 mM. For example, the concentration may be about 75 to about 400 mM. For example, the concentration may be about 75 to about 350 mM. For example, the concentration may be about 75 to about 300 mM. For example, the concentration may be about 75 to about 250 mM. For example, the concentration may be about 75 to about 200 mM. For example, the concentration may be about 75 to about 175 mM. For example, the concentration may be about 75 to about 150 mM. For example, the concentration may be about 75 to about 125 mM. For example, the concentration may be about 75 to about 100 mM. For example, the concentration may be about 100 to about 150 mM. For example, the concentration may be about 100 to about 175 mM. For example, the concentration may be about 100 to about 200 mM. For example, the concentration may be about 100 to about 250 mM. For example, the concentration may be about 100 to about 300 mM. For example, the concentration may be about 150 to about 200 mM. For example, the concentration may be about 150 to about 250 mM. For example, the concentration may be about 150 to about 300 mM. For example, the concentration may be about 150 to about 350 mM. For example, the concentration may be about 150 to about 400 mM. For example, the concentration may be about 200 to about 400 mM. For example, the concentration may be about 200 to about 350 mM. For example, the concentration may be about 200 to about 300 mM. For example, the concentration may be about 200 to about 250 mM. For example, theconcentration may be about 250 to about 400 mM. For example, the concentration may be about 250 to about 350 mM. For example, the concentration may be about 250 to about 300 mM. For example, the concentration may be about 300 to about 400 mM. For example, the amino acid may be alanine, glycine, arginine, histidine, aspartic acid, proline, lysine, glutamic acid, or aspartic acid. For example, the disaccharide may be trehalose, sucrose, maltose, or lactose. For example, the polyol may be sorbitol or mannitol.

[0128] In some formulations of anti-pKal antibodies, e.g., navenibart, disclosed herein, sorbitol is included. In such cases, the concentration of sorbitol may be about 10 to about 500 mM. For example, the concentration of sorbitol may be about 10 to about 450 mM. For example, the concentration of sorbitol may be about 10 to about 400 mM. For example, the concentration of sorbitol may be about 10 to about 350 mM. For example, the concentration of sorbitol may be about 10 to about 300 mM. For example, the concentration of sorbitol may be about 10 to about 275 mM. For example, the concentration of sorbitol may be about 10 to about 250 mM. For example, the concentration of sorbitol may be about 10 to about 225 mM. For example, the concentration of sorbitol may be about 10 to about 200 mM. For example, the concentration of sorbitol may be about 10 to about 175 mM. For example, the concentration of sorbitol may be about 10 to about 150 mM. For example, the concentration of sorbitol may be about 10 to about 125 mM. For example, the concentration of sorbitol may be about 10 to about 100 mM. For example, the concentration of sorbitol may be about 10 to about 75 mM. For example, the concentration of sorbitol may be about 25 to about 400 mM. For example, the concentration of sorbitol may be about 25 to about 350 mM. For example, the concentration of sorbitol may be about 25 to about 300 mM. For example, the concentration of sorbitol may be about 25 to about 250 mM. For example, the concentration of sorbitol may be about 25 to about 200 mM. For example, the concentration of sorbitol may be about 25 to about 175 mM. For example, the concentration of sorbitol may be about 25 to about 150 mM. For example, the concentration of sorbitol may be about 25 to about 125 mM. For example, the concentration of sorbitol may be about 25 to about 100 mM. For example, the concentration of sorbitol may be about 25 to about 75 mM. For example, the concentration of sorbitol may be about 50 to about 400 mM. For example, the concentration of sorbitol may be about 50 to about 350 mM. For example, the concentration of sorbitol may be about 50 to about 300 mM. For example, the concentration of sorbitol may be about 50 to about 250 mM. For example, the concentration of sorbitol may be about 50 to about200 mM. For example, the concentration of sorbitol may be about 50 to about 175 mM. For example, the concentration of sorbitol may be about 50 to about 150 mM. For example, the concentration of sorbitol may be about 50 to about 125 mM. For example, the concentration of sorbitol may be about 50 to about 100 mM. For example, the concentration of sorbitol may be about 75 to about 400 mM. For example, the concentration of sorbitol may be about 75 to about 350 mM. For example, the concentration of sorbitol may be about 75 to about 300 mM. For example, the concentration of sorbitol may be about 75 to about 250 mM. For example, the concentration of sorbitol may be about 75 to about 200 mM. For example, the concentration of sorbitol may be about 75 to about 175 mM. For example, the concentration of sorbitol may be about 75 to about 150 mM. For example, the concentration of sorbitol may be about 75 to about 125 mM. For example, the concentration of sorbitol may be about 75 to about 100 mM. For example, the concentration of sorbitol may be about 100 to about 150 mM. For example, the concentration of sorbitol may be about 100 to about 175 mM. For example, the concentration of sorbitol may be about 100 to about 200 mM. For example, the concentration of sorbitol may be about 100 to about 250 mM. For example, the concentration of sorbitol may be about 100 to about 300 mM. For example, the concentration of sorbitol may be about 150 to about 200 mM. For example, the concentration of sorbitol may be about 150 to about 250 mM. For example, the concentration of sorbitol may be about 150 to about 300 mM. For example, the concentration of sorbitol may be about 150 to about 350 mM. For example, the concentration of sorbitol may be about 150 to about 400 mM. For example, the concentration of sorbitol may be about 200 to about 400 mM. For example, the concentration of sorbitol may be about 200 to about 350 mM. For example, the concentration of sorbitol may be about 200 to about 300 mM. For example, the concentration of sorbitol may be about 200 to about 250 mM. For example, the concentration of sorbitol may be about 250 to about 400 mM. For example, the concentration of sorbitol may be about 250 to about 350 mM. For example, the concentration of sorbitol may be about 250 to about 300 mM. For example, the concentration of sorbitol may be about 300 to about 400 mM.The aforementioned concentration ranges may also be applied to mannitol in the formulations of anti-pKal antibodies, e.g., navenibart, disclosed herein.

[0129] For example, the concentration of sorbitol is about 0 mM. For example, the concentration of sorbitol is about 5 mM. For example, the concentration of sorbitol is about 10 mM. For example, the concentration of sorbitol is about 15 mM. For example, theconcentration of sorbitol is about 20 mM. For example, the concentration of sorbitol is about 25 mM. For example, the concentration of sorbitol is about 30 mM. For example, the concentration of sorbitol is about 35 mM. For example, the concentration of sorbitol is about 40 mM. For example, the concentration of sorbitol is about 45 mM. For example, the concentration of sorbitol is about 50 mM. For example, the concentration of sorbitol is about 55 mM. For example, the concentration of sorbitol is about 60 mM. For example, the concentration of sorbitol is about 65 mM. For example, the concentration of sorbitol is about 70 mM. For example, the concentration of sorbitol is about 75 mM. For example, the concentration of sorbitol is about 80 mM. For example, the concentration of sorbitol is about 85 mM. For example, the concentration of sorbitol is about 90 mM. For example, the concentration of sorbitol is about 95 mM. For example, the c ■onccntration of sorbitol is about 100 mM. For example, the concentration of sorbitol is about 105 mM. For example, the concentration of sorbitol is about 110 mM. For example, the concentration of sorbitol is about 115 mM. For example, the concentration of sorbitol is about 120 mM. For example, the concentration of sorbitol is about 125 mM. For example, the concentration of sorbitol is about 130 mM. For example, the concentration of sorbitol is about 135 mM. For example, the concentration of sorbitol is about 140 mM. For example, the concentration of sorbitol is about 145 mM. For example, the concentration of sorbitol is about 150 mM. For example, the concentration of sorbitol is about 155 mM. For example, the concentration of sorbitol is about 160 mM. For example, the concentration of sorbitol is about 165 mM. For example, the concentration of sorbitol is about 170 mM. For example, the concentration of sorbitol is about 175 mM. For example, the concentration of sorbitol is about 180 mM. For example, the concentration of sorbitol is about 185 mM. For example, the concentration of sorbitol is about 190 mM. For example, the concentration of sorbitol is about 195 mM. For example, the concentration of sorbitol is about 200 mM. For example, the concentration of sorbitol is about 205 mM. For example, the concentration of sorbitol is about 210 mM. For example, the concentration of sorbitol is about 215 mM. For example, the concentration of sorbitol is about 220 mM. For example, the concentration of sorbitol is about 225 mM. For example, the concentration of sorbitol is about 230 mM. For example, the concentration of sorbitol is about 235 mM. For example, the concentration of sorbitol is about 240 mM. For example, the concentration of sorbitol is about 245 mM. For example, the concentration of sorbitol is about 250 mM. For example, the concentration of sorbitol is about 255 mM. For example, the concentration of sorbitol is about 260 mM. For example, the concentration of sorbitol is about265 mM. For example, the concentration of sorbitol is about 270 mM. For example, the concentration of sorbitol is about 275 mM. For example, the concentration of sorbitol is about 280 mM. For example, the concentration of sorbitol is about 285 mM. For example, the concentration of sorbitol is about 290 mM. For example, the concentration of sorbitol is about 295 mM. For example, the concentration of sorbitol is about 300 mM. The aforementioned concentration ranges may also be applied to mannitol in the formulations of anti-pKal antibodies, e.g., navenibart, disclosed herein.2.5. Surfactants

[0130] The formulations of antibodies, e.g., anti-pKal antibodies, e.g., navenibart, disclosed herein may include one or more surfactants. Surfactants are used in pharmaceutical formulations of proteins, e.g., antibody formulations, for example, to protect the proteins against interaction with hydrophobic surfaces such as air / water interfaces and container surfaces. Surfactants can also protect formulated proteins against shear stress caused from agitation by lubricating the interfaces between protein molecules and container surfaces, helping to protect the protein from denaturation, degradation, and aggregation. Surfactants can also enhance solubility of proteins, e.g., antibodies, by coating hydrophobic regions of the protein, allowing the protein to solubilize in aqueous formulations.

[0131] Surfactants that may be used in pharmaceutical formulations according to this disclosure, e.g., for formulating anti-pKal antibodies, include polysorbates, poloxamers, human serum albumin, or synthetic polymers such as dextrans and polyethylene glycols (PEG). For example, one or more polysorbates may be selected for inclusion in the formulations disclosed herein such as polysorbate 20, polysorbate 40, polysorbate 60, or polysorbate 80. In certain cases, the formulation includes polysorbate 20 (also known as TWEEN®20 - polyoxyethylene (20) sorbitan monolaurate). In other cases, the formulation includes polysorbate 80 (also known as TWEEN®80 - polyoxyethylene (80) sorbitan monolaurate). For example, the formulation includes a poloxamer, such as poloxamer 188.

[0132] Accordingly, formulations of anti-pKal antibodies as disclosed herein, e.g., navenibart, may include a surfactant in an amount of 0.001% (w / v) to about 2% (w / v). For example, the formulation may include the surfactant in an amount of 0.001% (w / v) to about 1.5% (w / v). For example, the formulation may include the surfactant in an amount of 0.001% (w / v) to about 1.0% (w / v). For example, the formulation may include the surfactantin an amount of 0.001% (w / v) to about 0.5% (w / v). For example, the formulation may include the surfactant in an amount of 0.001% (w / v) to about 0.5% (w / v). For example, the formulation may include the surfactant in an amount of 0.001% (w / v) to about 0.1% (w / v). For example, the formulation may include the surfactant in an amount of 0.001% (w / v) to about 0.05% (w / v). For example, the formulation may include the surfactant in an amount of 0.01% (w / v) to about 2% (w / v). For example, the formulation may include the surfactant in an amount of 0.01% (w / v) to about 1.5% (w / v). For example, the formulation may include the surfactant in an amount of 0.01% (w / v) to about 1.0% (w / v). For example, the formulation may include the surfactant in an amount of 0.01% (w / v) to about 0.5% (w / v). For example, the formulation may include the surfactant in an amount of 0.01% (w / v) to about 0.1% (w / v). For example, the formulation may include the surfactant in an amount of 0.01% (w / v) to about 0.05% (w / v). For example, the formulation may include the surfactant in an amount of 0.02% (w / v) to about 0.07% (w / v). For example, the formulation may include the surfactant in an amount of 0.02% (w / v) to about 0.1% (w / v). For example, the formulation may include the surfactant in an amount of 0. 1% (w / v) to about 2% (w / v). For example, the formulation may include the surfactant in an amount of 0.1% (w / v) to about 1.5% (w / v). For example, the formulation may include the surfactant in an amount of 0.1% (w / v) to about 1.0% (w / v). For example, the formulation may include the surfactant in an amount of 0.1% (w / v) to about 0.5% (w / v). For example, the formulation may include the surfactant in an amount of 0.2% (w / v) to about 2% (w / v). For example, the formulation may include the surfactant in an amount of 0.2% (w / v) to about 1.0% (w / v). For example, the formulation may include the surfactant in an amount of 0.2% (w / v) to about 0.8% (w / v). For example, the formulation may include the surfactant in an amount of 0.2% (w / v) to about 0.5% (w / v). For example, the formulation may include the surfactant in an amount of 0.02% (w / v) to about 0.08% (w / v). For example, the formulation may include the surfactant in an amount of 0.03% (w / v) to about 0.06% (w / v).

[0133] In some instances, the formulations disclosed herein include polysorbate 80.Accordingly, the polysorbate 80 may be present in the formulation in an amount of 0.001% (w / v) to about 2% (w / v). For example, polysorbate 80 may be present in the formulation in an amount of 0.001% (w / v) to about 1.5% (w / v). For example, polysorbate 80 may be present in the formulation in an amount of 0.001% (w / v) to about 1.0% (w / v). For example, polysorbate 80 may be present in the formulation in an amount of 0.001% (w / v) to about0.5% (w / v). For example, polysorbate 80 may be present in the formulation in an amount of 0.001% (w / v) to about 0.5% (w / v). For example, polysorbate 80 may be present in the formulation in an amount of 0.001% (w / v) to about 0.1% (w / v). For example, polysorbate 80 may be present in the formulation in an amount of 0.001% (w / v) to about 0.05% (w / v). For example, polysorbate 80 may be present in the formulation in an amount of 0.01% (w / v) to about 2% (w / v). For example, polysorbate 80 may be present in the formulation in an amount of 0.01% (w / v) to about 1.5% (w / v). For example, polysorbate 80 may be present in the formulation in an amount of 0.01% (w / v) to about 1.0% (w / v). For example, polysorbate 80 may be present in the formulation in an amount of 0.01% (w / v) to about 0.5% (w / v). For example, polysorbate 80 may be present in the formulation in an amount of 0.01% (w / v) to about 0.1% (w / v). For example, polysorbate 80 may be present in the formulation in an amount of 0.01% (w / v) to about 0.05% (w / v). For example, the formulation may include polysorbate 80 in an amount of 0.02% (w / v) to about 0.07% (w / v). For example, the formulation may include polysorbate 80 in an amount of 0.02% (w / v) to about 0.1% (w / v). For example, polysorbate 80 may be present in the formulation in an amount of 0. 1% (w / v) to about 2% (w / v). For example, polysorbate 80 may be present in the formulation in an amount of 0.1% (w / v) to about 1.5% (w / v). For example, polysorbate 80 may be present in the formulation in an amount of 0. 1% (w / v) to about 1.0% (w / v). For example, polysorbate 80 may be present in the formulation in an amount of 0. 1% (w / v) to about 0.5% (w / v). For example, polysorbate 80 may be present in the formulation in an amount of 0.2% (w / v) to about 2% (w / v). For example, polysorbate 80 may be present in the formulation in an amount of 0.2% (w / v) to about 1.0% (w / v). For example, polysorbate 80 may be present in the formulation in an amount of 0.2% (w / v) to about 0.8% (w / v). For example, polysorbate 80 may be present in the formulation in an amount of 0.2% (w / v) to about 0.5% (w / v). For example, polysorbate 80 may be present in the formulation in an amount of 0.02% (w / v) to about 0.08% (w / v). For example, polysorbate 80 may be present in the formulation in an amount of 0.03% (w / v) to about 0.06% (w / v). For example, polysorbate 80 may be present in the formulation in an amount of about 0.05% (w / v).

[0134] In some instances, the formulations disclosed herein include polysorbate 20.Accordingly, the polysorbate 20 may be present in the formulation in an amount of 0.001% (w / v) to about 2% (w / v). For example, polysorbate 20 may be present in the formulation in an amount of 0.001% (w / v) to about 1.5% (w / v). For example, polysorbate 20 may bepresent in the formulation in an amount of 0.001% (w / v) to about 1.0% (w / v). For example, polysorbate 20 may be present in the formulation in an amount of 0.001% (w / v) to about 0.5% (w / v). For example, polysorbate 20 may be present in the formulation in an amount of 0.001% (w / v) to about 0.5% (w / v). For example, polysorbate 20 may be present in the formulation in an amount of 0.001% (w / v) to about 0.1% (w / v). For example, polysorbate 20 may be present in the formulation in an amount of 0.001% (w / v) to about 0.05% (w / v). For example, polysorbate 20 may be present in the formulation in an amount of 0.01% (w / v) to about 2% (w / v). For example, polysorbate 20 may be present in the formulation in an amount of 0.01% (w / v) to about 1.5% (w / v). For example, the formulation may include the polysorbate 20 in an amount of 0.02% (w / v) to about 0.07% (w / v). For example, the formulation may include the polysorbate 20 in an amount of 0.02% (w / v) to about 0.1% (w / v). For example, polysorbate 20 may be present in the formulation in an amount of 0.01% (w / v) to about 1.0% (w / v). For example, polysorbate 20 may be present in the formulation in an amount of 0.01% (w / v) to about 0.5% (w / v). For example, polysorbate 20 may be present in the formulation in an amount of 0.01% (w / v) to about 0. 1% (w / v). For example, polysorbate 20 may be present in the formulation in an amount of 0.01% (w / v) to about 0.05% (w / v). For example, polysorbate 20 may be present in the formulation in an amount of 0.1% (w / v) to about 2% (w / v). For example, polysorbate 20 may be present in the formulation in an amount of 0.1% (w / v) to about 1.5% (w / v). For example, polysorbate 20 may be present in the formulation in an amount of 0.1% (w / v) to about 1.0% (w / v). For example, polysorbate 20 may be present in the formulation in an amount of 0.1% (w / v) to about 0.5% (w / v). For example, polysorbate 20 may be present in the formulation in an amount of 0.2% (w / v) to about 2% (w / v). For example, polysorbate 20 may be present in the formulation in an amount of 0.2% (w / v) to about 1.0% (w / v). For example, polysorbate 20 may be present in the formulation in an amount of 0.2% (w / v) to about 0.8% (w / v). For example, polysorbate 20 may be present in the formulation in an amount of 0.2% (w / v) to about 0.5% (w / v). For example, polysorbate 20 may be present in the formulation in an amount of 0.02% (w / v) to about 0.08% (w / v). For example, polysorbate 20 may be present in the formulation in an amount of 0.03% (w / v) to about 0.06% (w / v). For example, polysorbate 20 may be present in the formulation in an amount of about 0.05% (w / v).2.6. Viscosity Reducers

[0135] When preparing antibody pharmaceutical formulations, it is important to ensure a suitable viscosity for administration. When antibody pharmaceutical formulations are administered by injection, e.g., subcutaneously or intramuscularly, ease of injection is important to ensure that a patient can successfully complete the injection. If the formulation’s viscosity is too high, the amount of force required to eject the formulation from the needle or syringe will require too much force. For some patients, the force required may be high enough such that the patient may be unable to inject the formulation from the needle or syringe, or they may experience hand fatigue when injecting the formulation. Moreover, formulations that are more viscous take longer to disperse in the subcutaneous or intramuscular tissue and can build up at the injection site, causing pain. Accordingly, formulations of the antibodies, e.g., anti-pKal antibodies disclosed herein may include one or more excipients to reduce the viscosity of the formulation to facilitate ease of administration. Excipients that impact viscosity may also have impacts on the formulation’s stability and therefore may serve a dual role in the pharmaceutical compositions disclosed herein as both a stabilizer and viscosity reducer.

[0136] For example, amino acids, e.g., free amino acids not contained within a protein or peptide, may be included in formulations of the anti-pKal antibodies, e.g., navenibart, disclosed herein, e.g., to facilitate attainment of an appropriate viscosity and / or as a stabilizer. For example, the amino acid stabilizer or viscosity reducer may be alanine, arginine, aspartic acid, cysteine, glycine, glutamic acid, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, tryptophan, or tyrosine or a combination thereof. For example, the amino acid may be arginine. For example, the amino acid may be glycine. In some instances, the amino acids may be glycine and arginine. In some instances, the amino acids may be glycine, arginine and / or proline. For example, the arginine may be e.g., L-arginine, e.g., L-arginine hydrochloride, e.g., L-arginine hydrochloride monohydrate, e.g., arginine glutamate, e.g., arginine aspartate, e.g., arginine acetate, e.g., arginine sulfate, or e.g., arginine lactobionate.

[0137] For example, sugars, such as sugar polyols, and mono- and disaccharides may be included in formulations of antibodies disclosed herein, e.g., to facilitate attainment of an appropriate viscosity and / or as a stabilizer. Sugar polyols such as mannitol, sorbitol, glycerol, erythritol, maltitol, or xylitol; monosaccharides such as glucose, fructose, galactose,mannose, or sorbose; and disaccharides such as trehalose, sucrose, maltose, and lactose, or combinations thereof may be included in the formulation in order to achieve an appropriate viscosity.

[0138] For example, the formulation may include one or more sugars, such as sorbitol, mannitol, sucrose, and / or trehalose. For example, in some instances, the formulation includes sorbitol. In other examples, the formulation includes mannitol. In yet other examples, the formulation includes sucrose. In still other examples, the formulation includes trehalose. In still other examples, the formulation includes combinations of sorbitol, mannitol, sucrose, and / or trehalose.

[0139] In some instances, the formulations of anti-pKal antibodies, e.g., navenibart, disclosed herein may include combinations of sugars and / or amino acids. For example, the amino acid may be selected from alanine, arginine, aspartic acid, cysteine, glycine, glutamic acid, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, tryptophan, or tyrosine, or combinations thereof. For example, in some instances, the formulation may include one or more amino acids, e.g., glycine, arginine, lysine, proline, and / or phenylalanine. In other examples, the formulation may include one or more sugars, e.g., sorbitol, mannitol, sucrose, and / or trehalose. For example, in some formulations, sorbitol, glycine and arginine are included. In other formulations, sorbitol and glycine are included. For example, in some instances, the formulation includes sorbitol and proline. In other instances, the formulation includes sorbitol, glycine, and proline. In yet other instances, the formulation includes sorbitol, proline, and arginine. In yet other instances, the formulation includes sorbitol and arginine, e.g., without glycine. In some instances, the formulation includes trehalose and arginine. In some instances, the formulation includes trehalose, glycine and arginine. In some instance, the formulation includes trehalose, glycine, and proline. In some instances, the formulation includes trehalose and glycine. In some instances, the formulation includes trehalose, proline, and arginine. For example, in some instances the arginine is arginine hydrochloride (HC1). For example, the arginine may be e.g., L-arginine, e.g., L-arginine hydrochloride, e.g., L-arginine hydrochloride monohydrate, e.g., arginine glutamate, e.g., arginine aspartate, e.g., arginine acetate, e.g., arginine sulfate, or e.g., arginine lactobionate.

[0140] In some embodiments, the sugar, e.g, polyol, monosaccharide or disaccharide is present in the formulations of anti-pKal antibodies, e.g., navenibart, disclosed herein in an amount greater than 0 mM to about 500 mM. For example, the concentration may be about 10 to about 500 mM. For example, the concentration may be about 10 to about 450 mM. For example, the concentration may be about 10 to about 400 mM. For example, the concentration may be about 10 to about 350 mM. For example, the concentration may be about 10 to about 300 mM. For example, the concentration may be about 10 to about 275 mM. For example, the concentration may be about 10 to about 250 mM. For example, the concentration may be about 10 to about 225 mM. For example, the concentration may be about 10 to about 200 mM. For example, the concentration may be about 10 to about 175 mM. For example, the concentration may be about 10 to about 150 mM. For example, the concentration may be about 10 to about 125 mM. For example, the concentration may be about 10 to about 100 mM. For example, the concentration may be about 10 to about 75 mM. For example, the concentration may be about 25 to about 400 mM. For example, the concentration may be about 25 to about 350 mM. For example, the concentration may be about 25 to about 300 mM. For example, the concentration may be about 25 to about 250 mM. For example, the concentration may be about 25 to about 200 mM. For example, the concentration may be about 25 to about 175 mM. For example, the concentration may be about 25 to about 150 mM. For example, the concentration may be about 25 to about 125 mM. For example, the concentration may be about 25 to about 100 mM. For example, the concentration may be about 25 to about 75 mM. For example, the concentration may be about 50 to about 400 mM. For example, the concentration may be about 50 to about 350 mM. For example, the concentration may be about 50 to about 300 mM. For example, the concentration may be about 50 to about 250 mM. For example, the concentration may be about 50 to about 200 mM. For example, the concentration may be about 50 to about 175 mM. For example, the concentration may be about 50 to about 150 mM. For example, the concentration may be about 50 to about 125 mM. For example, the concentration may be about 50 to about 100 mM. For example, the concentration may be about 75 to about 400 mM. For example, the concentration may be about 75 to about 350 mM. For example, the concentration may be about 75 to about 300 mM. For example, the concentration may be about 75 to about 250 mM. For example, the concentration may be about 75 to about 200 mM. For example, the concentration may be about 75 to about 175 mM. For example, the concentration may be about 75 to about 150 mM. For example, the concentration may beabout 75 to about 125 mM. For example, the concentration may be about 75 to about 100 mM. For example, the concentration may be about 100 to about 150 mM. For example, the concentration may be about 100 to about 175 mM. For example, the concentration may be about 100 to about 200 mM. For example, the concentration may be about 100 to about 250 mM. For example, the concentration may be about 100 to about 300 mM. For example, the concentration may be about 150 to about 200 mM. For example, the concentration may be about 150 to about 250 mM. For example, the concentration may be about 150 to about 300 mM. For example, the concentration may be about 150 to about 350 mM. For example, the concentration may be about 150 to about 400 mM. For example, the concentration may be about 200 to about 400 mM. For example, the concentration may be about 200 to about 350 mM. For example, the concentration may be about 200 to about 300 mM. For example, the concentration may be about 200 to about 250 mM. For example, the concentration may be about 250 to about 400 mM. For example, the concentration may be about 250 to about 350 mM. For example, the concentration may be about 250 to about 300 mM. For example, the concentration may be about 300 to about 400 mM. For example, the disaccharide may be trehalose, sucrose, maltose, or lactose. For example, the polyol may be sorbitol or mannitol. For example, the polyol may be sorbitol.

[0141] In some embodiments, the amino acid, e.g., free amino acid not connected to a protein or peptide, is present in the formulations of anti-pKal antibodies, e.g., navenibart, disclosed herein in an amount greater than 0 mM to about 500 mM. For example, the concentration may be about 10 to about 500 mM. For example, the concentration may be about 10 to about 450 mM. For example, the concentration may be about 10 to about 400 mM. For example, the concentration may be about 10 to about 350 mM. For example, the concentration may be about 10 to about 300 mM. For example, the concentration may be about 10 to about 275 mM. For example, the concentration may be about 10 to about 250 mM. For example, the concentration may be about 10 to about 225 mM. For example, the concentration may be about 10 to about 200 mM. For example, the concentration may be about 10 to about 175 mM. For example, the concentration may be about 10 to about 150 mM. For example, the concentration may be about 10 to about 125 mM. For example, the concentration may be about 10 to about 100 mM. For example, the concentration may be about 10 to about 75 mM. For example, the concentration may be about 25 to about 400 mM. For example, the concentration may be about 25 to about 350 mM. For example, theconcentration may be about 25 to about 300 mM. For example, the concentration may be about 25 to about 250 mM. For example, the concentration may be about 25 to about 200 mM. For example, the concentration may be about 25 to about 175 mM. For example, the concentration may be about 25 to about 150 mM. For example, the concentration may be about 25 to about 125 mM. For example, the concentration may be about 25 to about 100 mM. For example, the concentration may be about 25 to about 75 mM. For example, the concentration may be about 50 to about 400 mM. For example, the concentration may be about 50 to about 350 mM. For example, the concentration may be about 50 to about 300 mM. For example, the concentration may be about 50 to about 250 mM. For example, the concentration may be about 50 to about 200 mM. For example, the concentration may be about 50 to about 175 mM. For example, the concentration may be about 50 to about 150 mM. For example, the concentration may be about 50 to about 125 mM. For example, the concentration may be about 50 to about 100 mM. For example, the concentration may be about 75 to about 400 mM. For example, the concentration may be about 75 to about 350 mM. For example, the concentration may be about 75 to about 300 mM. For example, the concentration may be about 75 to about 250 mM. For example, the concentration may be about 75 to about 200 mM. For example, the concentration may be about 75 to about 175 mM. For example, the concentration may be about 75 to about 150 mM. For example, the concentration may be about 75 to about 125 mM. For example, the concentration may be about 75 to about 100 mM. For example, the concentration may be about 100 to about 150 mM. For example, the concentration may be about 100 to about 175 mM. For example, the concentration may be about 100 to about 200 mM. For example, the concentration may be about 100 to about 250 mM. For example, the concentration may be about 100 to about 300 mM. For example, the concentration may be about 150 to about 200 mM. For example, the concentration may be about 150 to about 250 mM. For example, the concentration may be about 150 to about 300 mM. For example, the concentration may be about 150 to about 350 mM. For example, the concentration may be about 150 to about 400 mM. For example, the concentration may be about 200 to about 400 mM. For example, the concentration may be about 200 to about 350 mM. For example, the concentration may be about 200 to about 300 mM. For example, the concentration may be about 200 to about 250 mM. For example, the concentration may be about 250 to about 400 mM. For example, the concentration may be about 250 to about 350 mM. For example, the concentration may be about 250 to about 300 mM. For example, the concentration may be about 300 to about 400 mM. For example, theamino acid may be glycine, arginine, lysine, proline, or phenylalanine. For example, the amino acid is glycine. For example, the amino acid is arginine, e.g., arginine HC1.

[0142] In some formulations of anti-pKal antibodies disclosed herein, glycine is included, e.g., free glycine, e.g., L-glycine. In such cases, the concentration of glycine may be about 10 to about 500 mM. For example, the concentration of glycine may be about 10 to about 450 mM. For example, the concentration of glycine may be about 10 to about 400 mM. For example, the concentration of glycine may be about 10 to about 350 mM. For example, the concentration of glycine may be about 10 to about 300 mM. For example, the concentration of glycine may be about 10 to about 275 mM. For example, the concentration of glycine may be about 10 to about 250 mM. For example, the concentration of glycine may be about 10 to about 225 mM. For example, the concentration of glycine may be about 10 to about 200 mM. For example, the concentration of glycine may be about 10 to about 175 mM. For example, the concentration of glycine may be about 10 to about 150 mM. For example, the concentration of glycine may be about 10 to about 125 mM. For example, the concentration of glycine may be about 10 to about 100 mM. For example, the concentration of glycine may be about 10 to about 75 mM. For example, the concentration of glycine may be about 25 to about 400 mM. For example, the concentration of glycine may be about 25 to about 350 mM. For example, the concentration of glycine may be about 25 to about 300 mM. For example, the concentration of glycine may be about 25 to about 250 mM. For example, the concentration of glycine may be about 25 to about 200 mM. For example, the concentration of glycine may be about 25 to about 175 mM. For example, the concentration of glycine may be about 25 to about 150 mM. For example, the concentration of glycine may be about 25 to about 125 mM. For example, the concentration of glycine may be about 25 to about 100 mM. For example, the concentration of glycine may be about 25 to about 75 mM. For example, the concentration of glycine may be about 50 to about 400 mM. For example, the concentration of glycine may be about 50 to about 350 mM. For example, the concentration of glycine may be about 50 to about 300 mM. For example, the concentration of glycine may be about 50 to about 250 mM. For example, the concentration of glycine may be about 50 to about 200 mM. For example, the concentration of glycine may be about 50 to about 175 mM. For example, the concentration of glycine may be about 50 to about 150 mM. For example, the concentration of glycine may be about 50 to about 125 mM. For example, the concentration of glycine may be about 50 to about 100 mM. For example, the concentrationof glycine may be about 60 to about 90 mM. For example, the concentration of glycine may be about 60 to about 100 mM. For example, the concentration of glycine may be about 60 to about 150 mM. For example, the concentration of glycine may be about 60 to about 200 mM. For example, the concentration of glycine may be about 60 to about 250 mM. For example, the concentration of glycine may be about 75 to about 400 mM. For example, the concentration of glycine may be about 75 to about 350 mM. For example, the concentration of glycine may be about 75 to about 300 mM. For example, the concentration of glycine may be about 75 to about 250 mM. For example, the concentration of glycine may be about 75 to about 200 mM. For example, the concentration of glycine may be about 75 to about 175 mM. For example, the concentration of glycine may be about 75 to about 150 mM. For example, the concentration of glycine may be about 75 to about 125 mM. For example, the concentration of glycine may be about 75 to about 100 mM. For example, the concentration of glycine may be about 100 to about 150 mM. For example, the concentration of glycine may be about 100 to about 175 mM. For example, the concentration of glycine may be about 100 to about 200 mM. For example, the concentration of glycine may be about 100 to about 250 mM. For example, the concentration of glycine may be about 100 to about 300 mM. For example, the concentration of glycine may be about 150 to about 200 mM. For example, the concentration of glycine may be about 150 to about 250 mM. For example, the concentration of glycine may be about 150 to about 300 mM. For example, the concentration of glycine may be about 150 to about 350 mM. For example, the concentration of glycine may be about 150 to about 400 mM. For example, the concentration of glycine may be about 200 to about 400 mM. For example, the concentration of glycine may be about 200 to about 350 mM. For example, the concentration of glycine may be about 200 to about 300 mM. For example, the concentration of glycine may be about 200 to about 250 mM. For example, the concentration of glycine may be about 250 to about 400 mM. For example, the concentration of glycine may be about 250 to about 350 mM. For example, the concentration of glycine may be about 250 to about 300 mM. For example, the concentration of glycine may be about 300 to about 400 mM. The glycine may be combined with arginine. The glycine may be combined with proline. The glycine may be combined with arginine and proline.

[0143] For example, the concentration of glycine is about 0 mM. For example, the concentration of glycine is about 5 mM. For example, the concentration of glycine is about 10 mM. For example, the concentration of glycine is about 15 mM. For example, theconcentration of glycine is about 20 mM. For example, the concentration of glycine is about 25 mM. For example, the concentration of glycine is about 30 mM. For example, the concentration of glycine is about 35 mM. For example, the concentration of glycine is about 40 mM. For example, the concentration of glycine is about 45 mM. For example, the concentration of glycine is about 50 mM. For example, the concentration of glycine is about 55 mM. For example, the concentration of glycine is about 60 mM. For example, the concentration of glycine is about 65 mM. For example, the concentration of glycine is about 70 mM. For example, the concentration of glycine is about 75 mM. For example, the concentration of glycine is about 80 mM. For example, the concentration of glycine is about 85 mM. For example, the concentration of glycine is about 90 mM. For example, the concentration of glycine is about 95 mM. For example, the c onccntration of glycine is about 100 mM. For example, the concentration of glycine is about 105 mM. For example, the concentration of glycine is about 110 mM. For example, the concentration of glycine is about 115 mM. For example, the concentration of glycine is about 120 mM. For example, the concentration of glycine is about 125 mM. For example, the concentration of glycine is about 130 mM. For example, the concentration of glycine is about 135 mM. For example, the concentration of glycine is about 140 mM. For example, the concentration of glycine is about 145 mM. For example, the concentration of glycine is about 150 mM. For example, the concentration of glycine is about 155 mM. For example, the concentration of glycine is about 160 mM. For example, the concentration of glycine is about 165 mM. For example, the concentration of glycine is about 170 mM. For example, the concentration of glycine is about 175 mM. For example, the concentration of glycine is about 180 mM. For example, the concentration of glycine is about 185 mM. For example, the concentration of glycine is about 190 mM. For example, the concentration of glycine is about 195 mM. For example, the concentration of glycine is about 200 mM. For example, the concentration of glycine is about 205 mM. For example, the concentration of glycine is about 210 mM. For example, the concentration of glycine is about 215 mM. For example, the concentration of glycine is about 220 mM. For example, the concentration of glycine is about 225 mM. For example, the concentration of glycine is about 230 mM. For example, the concentration of glycine is about 235 mM. For example, the concentration of glycine is about 240 mM. For example, the concentration of glycine is about 245 mM. For example, the concentration of glycine is about 250 mM. For example, the concentration of glycine is about 255 mM. For example, the concentration of glycine is about 260 mM. For example, the concentration of glycine is about265 mM. For example, the concentration of glycine is about 270 mM. For example, the concentration of glycine is about 275 mM. For example, the concentration of glycine is about 280 mM. For example, the concentration of glycine is about 285 mM. For example, the concentration of glycine is about 290 mM. For example, the concentration of glycine is about 295 mM. For example, the concentration of glycine is about 300 mM. The glycine may be used in addition to another viscosity reducer. For example, glycine may be combined with arginine. For example, the glycine may be combined with proline. For example, the glycine may be combined with arginine and proline.

[0144] In some embodiments, two or more amino acids, e.g., free amino acids not connected to a protein or peptide, are present in the formulations of anti-pKal antibodies, e.g., navenibart, disclosed herein, each in an amount greater than 0 mM to about 500 mM. For example, the concentration of each ammo acid may be about 10 to about 500 mM. For example, the concentration may be about 10 to about 450 mM. For example, the concentration of each amino acid may be about 10 to about 400 mM. For example, the concentration of each amino acid may be about 10 to about 350 mM. For example, the concentration of each amino acid may be about 10 to about 300 mM. For example, the concentration of each amino acid may be about 10 to about 275 mM. For example, the concentration of each amino acid may be about 10 to about 250 mM. For example, the concentration of each amino acid may be about 10 to about 225 mM. For example, the concentration of each amino acid may be about 10 to about 200 mM. For example, the concentration of each amino acid may be about 10 to about 175 mM. For example, the concentration of each amino acid may be about 10 to about 150 mM. For example, the concentration of each amino acid may be about 10 to about 125 mM. For example, the concentration of each amino acid may be about 10 to about 100 mM. For example, the concentration of each amino acid may be about 10 to about 75 mM. For example, the concentration of each amino acid may be about 25 to about 400 mM. For example, the concentration of each amino acid may be about 25 to about 350 mM. For example, the concentration of each amino acid may be about 25 to about 300 mM. For example, the concentration of each amino acid may be about 25 to about 250 mM. For example, the concentration of each amino acid may be about 25 to about 200 mM. For example, the concentration of each amino acid may be about 25 to about 175 mM. For example, the concentration of each amino acid may be about 25 to about 150 mM. For example, theconcentration of each amino acid may be about 25 to about 125 mM. For example, the concentration of each amino acid may be about 25 to about 100 mM. For example, the concentration may be about 25 to about 75 mM. For example, the concentration may be about 50 to about 400 mM. For example, the concentration may be about 50 to about 350 mM. For example, the concentration may be about 50 to about 300 mM. For example, the concentration may be about 50 to about 250 mM. For example, the concentration may be about 50 to about 200 mM. For example, the concentration may be about 50 to about 175 mM. For example, the concentration may be about 50 to about 150 mM. For example, the concentration may be about 50 to about 125 mM. For example, the concentration may be about 50 to about 100 mM. For example, the concentration may be about 75 to about 400 mM. For example, the concentration may be about 75 to about 350 mM. For example, the concentration may be about 75 to about 300 mM. For example, the concentration may be about 75 to about 250 mM. For example, the concentration may be about 75 to about 200 mM. For example, the concentration may be about 75 to about 175 mM. For example, the concentration may be about 75 to about 150 mM. For example, the concentration may be about 75 to about 125 mM. For example, the concentration may be about 75 to about 100 mM. For example, the concentration may be about 100 to about 150 mM. For example, the concentration may be about 100 to about 175 mM. For example, the concentration may be about 100 to about 200 mM. For example, the concentration may be about 100 to about 250 mM. For example, the concentration may be about 100 to about 300 mM. For example, the concentration may be about 150 to about 200 mM. For example, the concentration may be about 150 to about 250 mM. For example, the concentration may be about 150 to about 300 mM. For example, the concentration may be about 150 to about 350 mM. For example, the concentration may be about 150 to about 400 mM. For example, the concentration may be about 200 to about 400 mM. For example, the concentration may be about 200 to about 350 mM. For example, the concentration may be about 200 to about 300 mM. For example, the concentration may be about 200 to about 250 mM. For example, the concentration may be about 250 to about 400 mM. For example, the concentration may be about 250 to about 350 mM. For example, the concentration may be about 250 to about 300 mM. For example, the concentration may be about 300 to about 400 mM. For example, the amino acid may be glycine, arginine, lysine, proline, or phenylalanine. For example, the amino acids are arginine e.g., arginine HC1 and glycine. For example, the amino acids are arginine, glycine and / orproline. These amino acids may be in addition to any amino acid serving in the formulation as an anti-oxidant or buffer, for example.

[0145] In some formulations of anti-pKal antibodies, e.g., navenibart, disclosed herein, arginine is included. The arginine may be included in addition to another viscosity reducer. For example, the arginine may be combined with glycine and / or proline. For example, the arginine may be combined with glycine. The arginine may be arginine HC1. The arginine may be e.g., L-arginine, e.g., L-arginine hydrochloride, e.g., L-arginine hydrochloride monohydrate, e.g., arginine glutamate, e.g., arginine aspartate, e.g., arginine acetate, e.g., arginine sulfate, or e.g., arginine lactobionate. In such cases, the concentration of arginine may be about 10 to about 500 mM. For example, the concentration of arginine may be about 10 to about 450 mM. For example, the concentration of arginine may be about 10 to about 400 mM. For example, the concentration of arginine may be about 10 to about 350 mM. For example, the concentration of arginine may be about 10 to about 300 mM. For example, the concentration of arginine may be about 10 to about 275 mM. For example, the concentration of arginine may be about 10 to about 250 mM. For example, the concentration of arginine may be about 10 to about 225 mM. For example, the concentration of arginine may be about 10 to about 200 mM. For example, the concentration of arginine may be about 10 to about 175 mM. For example, the concentration of arginine may be about 10 to about 150 mM. For example, the concentration of arginine may be about 10 to about 125 mM. For example, the concentration of arginine may be about 10 to about 100 mM. For example, the concentration of arginine may be about 10 to about 75 mM. For example, the concentration of arginine may be about 25 to about 400 mM. For example, the concentration of arginine may be about 25 to about 350 mM. For example, the concentration of arginine may be about 25 to about 300 mM. For example, the concentration of arginine may be about 25 to about 250 mM. For example, the concentration of arginine may be about 25 to about 200 mM. For example, the concentration of arginine may be about 25 to about 175 mM. For example, the concentration of arginine may be about 25 to about 150 mM. For example, the concentration of arginine may be about 25 to about 125 mM. For example, the concentration of arginine may be about 25 to about 100 mM. For example, the concentration of arginine may be about 25 to about 75 mM. For example, the concentration of arginine may be about 50 to about 400 mM. For example, the concentration of arginine may be about 50 to about 350 mM. For example, the concentration of arginine may be about 50 to about 300 mM. For example, the concentrationof arginine may be about 50 to about 250 mM. For example, the concentration of arginine may be about 50 to about 200 mM. For example, the concentration of arginine may be about 50 to about 175 mM. For example, the concentration of arginine may be about 50 to about 150 mM. For example, the concentration of arginine may be about 50 to about 125 mM. For example, the concentration of arginine may be about 50 to about 100 mM. For example, the concentration of arginine may be about 50 to about 90 mM. For example, the concentration of arginine may be about 60 to about 90 mM. For example, the concentration of arginine may be about 60 to about 100 mM. For example, the concentration of arginine may be about 60 to about 150 mM. For example, the concentration of arginine may be about 60 to about 200 mM. For example, the concentration of arginine may be about 75 to about 400 mM. For example, the concentration of arginine may be about 75 to about 350 mM. For example, the concentration of arginine may be about 75 to about 300 mM. For example, the concentration of arginine may be about 75 to about 250 mM. For example, the concentration of arginine may be about 75 to about 200 mM. For example, the concentration of arginine may be about 75 to about 175 mM. For example, the concentration of arginine may be about 75 to about 150 mM. For example, the concentration of arginine may be about 75 to about 125 mM. For example, the concentration of arginine may be about 75 to about 100 mM. For example, the concentration of arginine may be about 100 to about 150 mM. For example, the concentration of arginine may be about 100 to about 175 mM. For example, the concentration of arginine may be about 100 to about 200 mM. For example, the concentration of arginine may be about 100 to about 250 mM. For example, the concentration of arginine may be about 100 to about 300 mM. For example, the concentration of arginine may be about 150 to about 200 mM. For example, the concentration of arginine may be about 150 to about 250 mM. For example, the concentration of arginine may be about 150 to about 300 mM. For example, the concentration of arginine may be about 150 to about 350 mM. For example, the concentration of arginine may be about 150 to about 400 mM. For example, the concentration of arginine may be about 200 to about 400 mM. For example, the concentration of arginine may be about 200 to about 350 mM. For example, the concentration of arginine may be about 200 to about 300 mM. For example, the concentration of arginine may be about 200 to about 250 mM. For example, the concentration of arginine may be about 250 to about 400 mM. For example, the concentration of arginine may be about 250 to about 350 mM. For example, theconcentration of arginine may be about 250 to about 300 mM. For example, the concentration of arginine may be about 300 to about 325 mM. For example, the concentration of arginine may be about 325 to about 350 mM. For example, the concentration of arginine may be about 350 to about 375 mM. For example, the concentration of arginine may be about 375 to about 400 mM. For example, the concentration of arginine may be about 300 to about 400 mM. For example, the concentration of arginine may be about 300 to about 500 mM. For example, the concentration of arginine may be about 400 to about 500 mM. For example, the concentration of arginine may be about 400 to about 425 mM. For example, the concentration of arginine may be about 425 to about 450 mM. For example, the concentration of arginine may be about 450 to about 475 mM. For example, the concentration of arginine may be about 475 to about 500 mM. The arginine may be combined with glycine. The arginine may be combined with proline. The arginine may be combined with glycine and proline. If arginine is combined with glycine and / or proline, the concentration of glycine and / or proline may be the same as or different than the concentration of arginine. Any of the concentration ranges disclosed above for arginine may also be the concentration range of glycine or proline in a formulation of an anti-pKal antibody, such as navenibart, disclosed herein.

[0146] For example, the concentration of arginine is about 0 mM. For example, the concentration of arginine is about 5 mM. For example, the concentration of arginine is about 10 mM. For example, the concentration of arginine is about 15 mM. For example, the concentration of arginine is about 20 mM. For example, the concentration of arginine is about 25 mM. For example, the concentration of arginine is about 30 mM. For example, the concentration of arginine is about 35 mM. For example, the concentration of arginine is about 40 mM. For example, the concentration of arginine is about 45 mM. For example, the concentration of arginine is about 50 mM. For example, the concentration of arginine is about 55 mM. For example, the concentration of arginine is about 60 mM. For example, the concentration of arginine is about 65 mM. For example, the concentration of arginine is about 70 mM. For example, the concentration of arginine is about 75 mM. For example, the concentration of arginine is about 80 mM. For example, the concentration of arginine is about 85 mM. For example, the concentration of arginine is about 90 mM. For example, the concentration of arginine is about 95 mM. For example, the concentration of arginine is about100 mM. For example, the concentration of arginine is about 105 mM. For example, the concentration of arginine is about 110 mM. For example, the concentration of arginine is about 115 mM. For example, the concentration of arginine is about 120 mM. For example, the concentration of arginine is about 125 mM. For example, the concentration of arginine is about 130 mM. For example, the concentration of arginine is about 135 mM. For example, the concentration of arginine is about 140 mM. For example, the concentration of arginine is about 145 mM. For example, the concentration of arginine is about 150 mM. For example, the concentration of arginine is about 155 mM. For example, the concentration of arginine is about 160 mM. For example, the concentration of arginine is about 165 mM. For example, the concentration of arginine is about 170 mM. For example, the concentration of arginine is about 175 mM. For example, the concentration of arginine is about 180 mM. For example, the concentration of arginine is about 185 mM. For example, the concentration of arginine is about 190 mM. For example, the concentration of arginine is about 195 mM. For example, the concentration of arginine is about 200 mM. For example, the concentration of arginine is about 205 mM. For example, the concentration of arginine is about 210 mM. For example, the concentration of arginine is about 215 mM. For example, the concentration of arginine is about 220 mM. For example, the concentration of arginine is about 225 mM. For example, the concentration of arginine is about 230 mM. For example, the concentration of arginine is about 235 mM. For example, the concentration of arginine is about 240 mM. For example, the concentration of arginine is about 245 mM. For example, the concentration of arginine is about 250 mM. For example, the concentration of arginine is about 255 mM. For example, the concentration of arginine is about 260 mM. For example, the concentration of arginine is about 265 mM. For example, the concentration of arginine is about 270 mM. For example, the concentration of arginine is about 275 mM. For example, the concentration of arginine is about 280 mM. For example, the concentration of arginine is about 285 mM. For example, the concentration of arginine is about 290 mM. For example, the concentration of arginine is about 295 mM. For example, the concentration of arginine is about 300 mM. The arginine may be combined with glycine at the same or a different concentration. The arginine may be combined with proline at the same or a different concentration. The arginine may be combined with glycine and proline at the same or a different concentration.

[0147] For example, the concentration of each of arginine and glycine is about 0 mM. For example, the concentration of each of arginine and glycine is about 5 mM. For example, theconcentration of each of arginine and glycine is about 10 mM. For example, the concentration of each of arginine and glycine is about 15 mM. For example, the concentration of each of arginine and glycine is about 20 mM. For example, the concentration of each of arginine and glycine is about 25 mM. For example, the concentration of each of arginine and glycine is about 30 mM. For example, the concentration of each of arginine and glycine is about 35 mM. For example, the concentration of each of arginine and glycine is about 40 mM. For example, the concentration of each of arginine and glycine is about 45 mM. For example, the concentration of each of arginine and glycine is about 50 mM. For example, the concentration of each of arginine and glycine is about 55 mM. For example, the concentration of each of arginine and glycine is about 60 mM. For example, the concentration of each of arginine and glycine is about 65 mM. For example, the concentration of each of arginine and glycine is about 70 mM. For example, the concentration of each of arginine and glycine is about 75 mM. For example, the concentration of each of arginine and glycine is about 80 mM. For example, the concentration of each of arginine and glycine is about 85 mM. For example, the concentration of each of arginine and glycine is about 90 mM. For example, the concentration of each of arginine and glycine is about 95 mM. For example, the concentration of each of arginine and glycine is about 100 mM. For example, the concentration of each of arginine and glycine is about 105 mM. For example, the concentration of each of arginine and glycine is about 110 mM. For example, the concentration of each of arginine and glycine is about 115 mM. For example, the concentration of each of arginine and glycine is about 120 mM. For example, the concentration of each of arginine and glycine is about 125 mM. For example, the concentration of each of arginine and glycine is about 130 mM. For example, the concentration of each of arginine and glycine is about 135 mM. For example, the concentration of each of arginine and glycine is about 140 mM. For example, the concentration of each of arginine and glycine is about 145 mM. For example, the concentration of each of arginine and glycine is about 150 mM. For example, the concentration of each of arginine and glycine is about 155 mM. For example, the concentration of each of arginine and glycine is about 160 mM. For example, the concentration of each of arginine and glycine is about 165 mM. For example, the concentration of each of arginine and glycine is about 170 mM. For example, the concentration of each of arginine and glycine is about 175 mM. For example, the concentration of each of arginine and glycine is about 180 mM. For example, the concentration of each of arginine and glycine is about 185 mM. For example, theconcentration of each of arginine and glycine is about 195 mM. For example, the concentration of arginine is about 200 mM. For example, the concentration of each of arginine and glycine is about 205 mM. For example, the concentration of each of arginine and glycine is about 215 mM. For example, the concentration of each of arginine and glycine is about 220 mM. For example, the concentration of each of arginine and glycine is about 225 mM. For example, the concentration of each of arginine and glycine is about 230 mM. For example, the concentration of each of arginine and glycine is about 235 mM. For example, the concentration of each of arginine and glycine is about 240 mM. For example, the concentration of each of arginine and glycine is about 245 mM. For example, the concentration of each of arginine and glycine is about 250 mM. For example, the concentration of arginine is about 255 mM. For example, the concentration of each of arginine and glycine is about 260 mM. For example, the concentration of each of arginine and glycine is about 265 mM. For example, the concentration of each of arginine and glycine is about 270 mM. For example, the concentration of each of arginine and glycine is about 15 mM. For example, the concentration of each of arginine and glycine is about 280 mM. For example, the concentration of each of arginine and glycine is about 285 mM. For example, the concentration of each of arginine and glycine is about 290 mM. For example, the concentration of each of arginine and glycine is about 295 mM. For example, the concentration of each of arginine and glycine is about 300 mM.

[0148] In some instances, the formulations of anti-pKal antibodies, e.g., navenibart, disclosed herein include both arginine and glycine, e.g., as viscosity reducers. In such embodiments, the free amino acids glycine and arginine are each present in the formulations of anti-pKal antibodies, e.g., navenibart, disclosed herein in an amount greater than 0 mM to about 500 mM. For example, the concentration of each of arginine and glycine may be about 10 to about 500 mM. For example, the concentration of each of arginine and glycine may be about 10 to about 450 mM. For example, the concentration of each of arginine and glycine may be about 10 to about 400 mM. For example, the concentration of each of arginine and glycine may be about 10 to about 350 mM. For example, the concentration of each of arginine and glycine may be about 10 to about 300 mM. For example, the concentration of each of arginine and glycine may be about 10 to about 275 mM. For example, the concentration of each of arginine and glycine may be about 10 to about 250 mM. For example, the concentration of each of arginine and glycine may be about 10 to about 225mM. For example, the concentration of each of arginine and glycine may be about 10 to about 200 mM. For example, the concentration of each of arginine and glycine may be about 10 to about 175 mM. For example, the concentration of each of arginine and glycine may be about 10 to about 150 mM. For example, the concentration of each of arginine and glycine may be about 10 to about 125 mM. For example, the concentration of each of arginine and glycine may be about 10 to about 100 mM. For example, the concentration of each of arginine and glycine may be about 10 to about 75 mM. For example, the concentration of each of arginine and glycine may be about 25 to about 400 mM. For example, the concentration of each of arginine and glycine may be about 25 to about 350 mM. For example, the concentration of each of arginine and glycine may be about 25 to about 300 mM. For example, the concentration of each of arginine and glycine may be about 25 to about 250 mM. For example, the concentration of each of arginine and glycine may be about 25 to about 200 mM. For example, the concentration of each of arginine and glycine may be about 25 to about 175 mM. For example, the concentration of each of arginine and glycine may be about 25 to about 150 mM. For example, the concentration of each of arginine and glycine may be about 25 to about 125 mM. For example, the concentration of each of arginine and glycine may be about 25 to about 100 mM. For example, the concentration of each of arginine and glycine may be about 25 to about 75 mM. For example, the concentration of each of arginine and glycine may be about 50 to about 400 mM. For example, the concentration of each of arginine and glycine may be about 50 to about 350 mM. For example, the concentration of each of arginine and glycine may be about 50 to about 300 mM. For example, the concentration of each of arginine and glycine may be about 50 to about 250 mM. For example, the concentration of each of arginine and glycine may be about 50 to about 200 mM. For example, the concentration of each of arginine and glycine may be about 50 to about 175 mM. For example, the concentration of each of arginine and glycine may be about 50 to about 150 mM. For example, the concentration of each of arginine and glycine may be about 50 to about 125 mM. For example, the concentration of each of arginine and glycine may be about 50 to about 100 mM. For example, the concentration of each of arginine and glycine may be about 60 to about 90 mM. For example, the concentration of each of arginine and glycine may be about 60 to about 100 mM. For example, the concentration of each of arginine and glycine may be about 60 to about 150 mM. For example, the concentration of each of arginine and glycine may be about 60 to about 200 mM. For example, the concentration of each of arginine and glycine may beabout 75 to about 400 mM. For example, the concentration of each of arginine and glycine may be about 75 to about 350 mM. For example, the concentration of each of arginine and glycine may be about 75 to about 300 mM. For example, the concentration of each of arginine and glycine may be about 75 to about 250 mM. For example, the concentration of each of arginine and glycine may be about 75 to about 200 mM. For example, the concentration of each of arginine and glycine may be about 75 to about 175 mM. For example, the concentration of each of arginine and glycine may be about 75 to about 150 mM. For example, the concentration of each of arginine and glycine may be about 75 to about 125 mM. For example, the concentration of each of arginine and glycine may be about 75 to about 100 mM. For example, the concentration of each of arginine and glycine may be about 100 to about 150 mM. For example, the concentration of each of arginine and glycine may be about 100 to about 175 mM. For example, the concentration of each of arginine and glycine may be about 100 to about 200 mM. For example, the concentration of each of arginine and glycine may be about 100 to about 250 mM. For example, the concentration of each of arginine and glycine may be about 100 to about 300 mM. For example, the concentration of each of arginine and glycine may be about 150 to about 200 mM. For example, the concentration of each of arginine and glycine may be about 150 to about 250 mM. For example, the concentration of each of arginine and glycine may be about 150 to about 300 mM. For example, the concentration of each of arginine and glycine may be about 150 to about 350 mM. For example, the concentration of each of arginine and glycine may be about 150 to about 400 mM. For example, the concentration of each of arginine and glycine may be about 200 to about 400 mM. For example, the concentration of each of arginine and glycine may be about 200 to about 350 mM. For example, the concentration of each of arginine and glycine may be about 200 to about 300 mM. For example, the concentration of each of arginine and glycine may be about 200 to about 250 mM. For example, the concentration of each of arginine and glycine may be about 250 to about 400 mM. For example, the concentration of each of arginine and glycine may be about 250 to about 350 mM. For example, the concentration of each of arginine and glycine may be about 250 to about 300 mM. For example, the concentration of each of arginine and glycine may be about 300 to about 400 mM. For example, the amino acid may be glycine, arginine, lysine, proline, or phenylalanine.2. 7. pH

[0149] The pH of formulations of antibodies is critical to ensuring the stability and solubility of the protein and to ensure that other excipients, such as any buffer operate at their optimal capacity.

[0150] Formulations of antibodies, e.g., anti-pKal antibodies, e.g., navenibart, disclosed herein may have a pH in the range of, for example, 4.0 to 8.0. For example, in some cases the pH of the formulation is in the range of about 4.5 to about 5.0. For example, in some cases the pH of the formulation is in the range of about 4.5 to about 5.5. For example, in some cases the pH of the formulation is in the range of about 4.5 to about 6.0. For example, in some cases the pH of the formulation is in the range of about 4.5 to about 6.5. For example, in some cases the pH of the formulation is in the range of about 4.5 to about 7.0. For example, in some cases the pH of the formulation is in the range of about 4.5 to about 7.5. For example, in some cases the pH of the formulation is in the range of about 5.0 to about 5.5. For example, in some cases the pH of the formulation is in the range of about 5.0 to about 6.0. For example, in some cases the pH of the formulation is in the range of about 5.0 to about 6.5. For example, in some cases the pH of the formulation is in the range of about 5.0 to about 7.0. For example, in some cases the pH of the formulation is in the range of about 5.0 to about 7.5. For example, in some cases the pH of the formulation is in the range of about 5.5 to about 8.0. For example, in some cases the pH of the formulation is in the range of about 5.5 to about 6.0. For example, in some cases the pH of the formulation is in the range of about 5.5 to about 6.3. For example, in some cases the pH of the formulation is in the range of about 5.5 to about 6.5. For example, in some cases the pH of the formulation is in the range of about 5.5 to about 7.0. For example, in some cases the pH of the formulation is in the range of about 5.5 to about 7.5. For example, in some cases the pH of the formulation is in the range of about 5.5 to about 8.0. For example, in some cases the pH of the formulation is in the range of about 6.0 to about 6.5. For example, in some cases the pH of the formulation is in the range of about 6.0 to about 7.0. For example, in some cases the pH of the formulation is in the range of about 6.0 to about 7.5. For example, in some cases the pH of the formulation is in the range of about 6.0 to about 8.0. For example, in some cases the pH of the formulation is in the range of about 6.5 to about 7.0. For example, in some cases the pH of the formulation is in the range of about 6.5 to about 7.5. For example, in some cases the pH of the formulation is in the range of about 6.5 to about8.0. For example, in some cases the pH of the formulation is in the range of about 7.0 to about 7.5. For example, in some cases the pH of the formulation is in the range of about 7.5 to about 8.0.

[0151] Formulations of antibodies, e.g., anti-pKal antibodies, e.g., navenibart, disclosed herein may have a pH in the range of, for example, 4.0 to 8.0. For example, in some cases the pH of the formulation is about 4.0. For example, in some cases the pH of the formulation is about 4.1. For example, in some cases the pH of the formulation is about 4.2. For example, in some cases the pH of the formulation is about 4.3. For example, in some cases the pH of the formulation is about 4.4. For example, in some cases the pH of the formulation is about 4.5. For example, in some cases the pH of the formulation is about 4.6. For example, in some cases the pH of the formulation is about 4.7. For example, in some cases the pH of the formulation is about 4.8. For example, in some cases the pH of the formulation is about 4.9. For example, in some cases the pH of the formulation is about 5.0. For example, in some cases the pH of the formulation is about 5.1. For example, in some cases the pH of the formulation is about 5.2. For example, in some cases the pH of the formulation is about 5.3. For example, in some cases the pH of the formulation is about 5.4. For example, in some cases the pH of the formulation is about 5.5. For example, in some cases the pH of the formulation is about 5.6. For example, in some cases the pH of the formulation is about 5.7. For example, in some cases the pH of the formulation is about 5.8. For example, in some cases the pH of the formulation is about 5.9. For example, in some cases the pH of the formulation is about 6.0. For example, in some cases the pH of the formulation is about 6.1. For example, in some cases the pH of the formulation is about 6.2. For example, in some cases the pH of the formulation is about 6.3. For example, in some cases the pH of the formulation is about 6.4. For example, in some cases the pH of the formulation is about 6.5. For example, in some cases the pH of the formulation is about 6.6. For example, in some cases the pH of the formulation is about 6.7. For example, in some cases the pH of the formulation is about 6.8. For example, in some cases the pH of the formulation is about 6.9. For example, in some cases the pH of the formulation is about 7.0. For example, in some cases the pH of the formulation is about 7.1. For example, in some cases the pH of the formulation is about 7.2. For example, in some cases the pH of the formulation is about 7.3. For example, in some cases the pH of the formulation is about 7.4. For example, in some cases the pH of the formulation is about 7.5. For example, in some cases the pH of theformulation is about 7.6. For example, in some cases the pH of the formulation is about 7.7. For example, in some cases the pH of the formulation is about 7.8. For example, in some cases the pH of the formulation is about 7.9. For example, in some cases the pH of the formulation is about 8.0.2.8. Osmolality

[0152] Osmolality refers to the concentration of osmotically active particles in a solution, typically measured in osmoles (or milliosmoles) of solute per kilogram of solvent (Osm / kg or mOsm / kg).

[0153] In some instances, formulations of antibodies disclosed herein, e.g., anti-pKal antibodies, e.g., navenibart, are formulated as an isotonic solution, e.g., with an osmolality similar to that of blood, e.g., serum or plasma, e.g., about 275 to 295 mOsm / kg. Formulations that are isotonic with blood can prevent adverse reactions, such as swelling which may occur with hypotonic solutions or irritation and discomfort at the injections site. In certain instances, the osmolality of the formulation does not exceed 600 mOsm / kg. In other instances, the osmolality of the formulation does not exceed 500 mOsm / kg. In yet other instances, the osmolality of the formulation does not exceed 400 mOsm / kg. In other instances, the osmolality of the formulation does not exceed 300 mOsm / kg. In some formulations, the osmolality is in a range of about 200 mOsm / kg to about 300 mOsm / kg. In some formulations, the osmolality is in a range of about 200 mOsm / kg to about 350 mOsm / kg. In some formulations, the osmolality is in a range of about 200 mOsm / kg to about 400 mOsm / kg. In some formulations, the osmolality is in a range of about 200 mOsm / kg to about 450 mOsm / kg. In some formulations, the osmolality is in a range of about 200 mOsm / kg to about 500 mOsm / kg. In some formulations, the osmolality is in a range of about 200 mOsm / kg to about 550 mOsm / kg. In some formulations, the osmolality is in a range of about 200 mOsm / kg to about 600 mOsm / kg.2.9. Storage Conditions

[0154] The pharmaceutical formulations disclosed herein can be prepared and stored as a liquid formulation, e.g., an aqueous formulation. In certain instances, the pharmaceutical formulation is a liquid formulation, e.g., an aqueous formulation, that is frozen for storage (-20°C to -70°C) after formulation. In other instances, the pharmaceutical formulation is a liquid formulation, e.g., an aqueous formulation, that is held under refrigerated conditions(typically 2°C to -8°C, e.g., about 5°C) after formulation. In other instances, the pharmaceutical formulation is a liquid formulation, e.g., an aqueous formulation, that is held at room temperature (typically 20-25°C, e.g., about 20°C, e.g., about 25°C) before preparation for administration. In certain instances, the pharmaceutical formulation is stored at a suitable temperature and protected from light. In some instances, the pharmaceutical formulation is lyophilized and reconstituted prior to administration.2.10. Other Considerations

[0155] The pharmaceutical formulations disclosed herein can be sterile. Sterilization can be accomplished, for example, by filtration through sterile filtration membranes. If formulations are lyophilized, filter sterilization can be conducted prior to or following lyophilization.3. Exemplary Formulations

[0156] The excipients disclosed herein may be combined in a variety of ways to formulate the anti-pKal antibodies, e.g., navenibart, disclosed herein. The following are some exemplary and non-limiting formulations contemplated by the disclosure.

[0157] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody, e.g., navenibart, a buffer, an anti-oxidant, a sugar (e.g., a polyol, monosaccharide, or disaccharide), and optionally, a surfactant (e.g., a polysorbate or poloxamer). In some embodiments, the formulation includes a surfactant, e.g., a polysorbate or poloxamer, e.g, PS80 or PS20.

[0158] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody, e.g., navenibart, a buffer, an anti-oxidant, an amino acid (e.g, alanine, arginine, aspartic acid, cysteine, glycine, glutamic acid, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, tryptophan, or tyrosine) (that is not the buffer or the antioxidant), and optionally, a surfactant (e.g., a polysorbate or poloxamer). In some embodiments, the formulation further includes a surfactant, e.g., a polysorbate or poloxamer, e.g., PS80 or PS20.

[0159] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody, e.g., navenibart, an amino acid buffer (e.g. histidine, arginine, alanine, phenylalanine, glycine, cysteine, serine, glutamic acid, or aspartic acid), an anti-oxidant, asugar (e.g., a polyol, monosaccharide, or disaccharide), and optionally, a surfactant (e.g., a polysorbate or poloxamer). In some embodiments, the formulation further includes a surfactant, e.g. , a polysorbate or poloxamer, e.g. , PS80 or PS20.

[0160] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody, e.g., navenibart, an amino acid buffer (e.g. histidine, arginine, alanine, phenylalanine, glycine, cysteine, serine, glutamic acid, or aspartic acid), an anti-oxidant, an amino acid (e.g., alanine, arginine, aspartic acid, cysteine, glycine, glutamic acid, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, tryptophan, or tyrosine) (that is not the buffer or the antioxidant), and optionally, a surfactant (e.g. , a polysorbate or poloxamer). In some embodiments, the formulation further includes a surfactant, e.g. , a polysorbate or poloxamer, e.g. , PS80 or PS20.

[0161] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody, e.g., navenibart, a buffer (e.g, a citrate buffer, a succinate buffer, an acetate buffer, a carbonate buffer, or a phosphate buffer), an anti-oxidant, a sugar (e.g., a polyol, monosaccharide, or disaccharide), and optionally, a surfactant (e.g., a polysorbate or poloxamer). In some embodiments, the formulation further includes a surfactant, e.g., a polysorbate or poloxamer, e.g., PS80 or PS20.

[0162] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody, e.g., navenibart, a buffer (e.g., a citrate buffer, a succinate buffer, an acetate buffer, a carbonate buffer, or a phosphate buffer), an anti-oxidant, an amino acid (e.g., alanine, arginine, aspartic acid, cysteine, glycine, glutamic acid, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, tryptophan, or tyrosine) (that is not the buffer or the antioxidant), and optionally, a surfactant (e.g., a polysorbate or poloxamer). In some embodiments, the formulation further includes a surfactant, e.g., a polysorbate or poloxamer, e.g., PS80 or PS20.

[0163] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody, e.g., navenibart, histidine buffer, an anti-oxidant, a sugar (e.g., a polyol, monosaccharide, or disaccharide), and optionally, a surfactant (e.g., a polysorbate or poloxamer). In some embodiments, the formulation further includes a surfactant, e.g., a polysorbate or poloxamer, e.g., PS80 or PS20.

[0164] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody, e.g., navenibart, a histidine buffer, an anti-oxidant, an amino acid (e.g., alanine, arginine, aspartic acid, cysteine, glycine, glutamic acid, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, tryptophan, or tyrosine) (that is not the buffer or the antioxidant), and optionally, a surfactant (e.g., a polysorbate or poloxamer). In some embodiments, the formulation further includes a surfactant, e.g., a polysorbate or poloxamer, e.g., PS80 or PS20.

[0165] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody, e.g., navenibart; a succinate, acetate, or a phosphate buffer; an antioxidant (e.g., methionine, cysteine, or EDTA); a sugar (e.g., a polyol, monosaccharide, or disaccharide), and optionally, a surfactant (e.g. , a polysorbate or poloxamer). In some embodiments, the formulation further includes a surfactant, e.g., a polysorbate or poloxamer, e.g., PS80 or PS20.

[0166] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody, e.g., navenibart; a succinate, acetate, or a phosphate buffer; an antioxidant (e.g., methionine, cysteine, or EDTA); an amino acid (e.g., alanine, arginine, aspartic acid, cysteine, glycine, glutamic acid, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, serine, tryptophan, or tyrosine) (that is not the antioxidant), and optionally, a surfactant (e.g. , a polysorbate or poloxamer). In some embodiments, the formulation further includes a surfactant, e.g. , a polysorbate or poloxamer, e.g. , PS80 or PS20.

[0167] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody, e.g. , navenibart, a histidine buffer, methionine, a sugar (e.g. , a polyol, monosaccharide, or disaccharide), and optionally, a surfactant (e.g., a polysorbate or poloxamer). In some embodiments, the formulation further includes a surfactant, e.g., a polysorbate or poloxamer, e.g., PS80 or PS20.

[0168] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody, e.g., navenibart, histidine buffer, methionine, an amino acid (e.g., alanine, arginine, aspartic acid, cysteine, glycine, glutamic acid, isoleucine, leucine, lysine, phenylalanine, proline, serine, tryptophan, or tyrosine) (that is not the antioxidant or the buffer), and optionally, a surfactant (e.g., a polysorbate or poloxamer). In someembodiments, the formulation further includes a surfactant, e.g., a polysorbate or poloxamer, e.g. , PS80 or PS20. In some embodiments, the amino acid that is not the antioxidant or buffer is glycine.

[0169] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody, e.g., navenibart, an acetate, phosphate, or succinate buffer, an antioxidant (e.g., methionine or EDTA), a sugar (e.g., a polyol, monosaccharide, or disaccharide), and optionally, a surfactant (e.g., a polysorbate or poloxamer). In some embodiments, the formulation further includes a surfactant, e.g. , a polysorbate or poloxamer, e.g. , PS80 or PS20. In some embodiments, the sugar is mannitol or sorbitol. In some embodiments, the anti-oxidant is methionine.

[0170] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody, e.g., navenibart, an acetate, phosphate or succinate buffer, an anti-oxidant (e.g., methionine or EDTA), an amino acid (e.g., alanine, arginine, aspartic acid, cysteine, glycine, glutamic acid, isoleucine, leucine, lysine, phenylalanine, proline, serine, tryptophan, or tyrosine) (that is not the antioxidant or the buffer), and optionally, a surfactant (e.g. , a polysorbate or poloxamer). In some embodiments, the formulation further includes a surfactant, e.g. , a polysorbate or poloxamer, e.g. , PS80 or PS20. In some embodiments, the amino acid is arginine and / or glycine.

[0171] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody, e.g., navenibart, a histidine buffer, methionine, an amino acid (e.g., alanine, arginine, aspartic acid, cysteine, glycine, glutamic acid, isoleucine, leucine, lysine, phenylalanine, proline, serine, tryptophan, or tyrosine) (in addition to the histidine buffer and methionine), a sugar (e.g, a polyol, monosaccharide, or disaccharide), and optionally, a surfactant (e.g., a polysorbate or poloxamer). In some embodiments, the formulation further includes a surfactant, e.g., a polysorbate or poloxamer, e.g., PS80 or PS20. For example, the sugar may be mannitol or sorbitol.

[0172] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody, e.g., navenibart, a histidine buffer, an anti-oxidant (e.g, methionine or EDTA), one or more amino acids (e.g, alanine, arginine, lysine, glycine, proline, or serine) (in addition to the histidine buffer and antioxidant), and optionally, a surfactant (e.g., a polysorbate or poloxamer). In some embodiments, the formulation further includes asurfactant, e.g. , a polysorbate or poloxamer, e.g. , PS80 or PS20. For example, the one or more amino acids may be arginine, proline, and / or glycine. For example, the anti-oxidant may be methionine.

[0173] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody, e.g., navenibart, a histidine buffer, an anti-oxidant (e.g., methionine or EDTA), one or more sugars (e.g., a polyol, monosaccharide, or disaccharide), and optionally, a surfactant (e.g., a polysorbate or poloxamer). In some embodiments, the formulation further includes a surfactant, e.g. , a polysorbate or poloxamer, e.g. , PS80 or PS20. For example, the sugar may be mannitol or sorbitol. For example, the anti-oxidant may be methionine.

[0174] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody, e.g., navenibart, a histidine buffer, an anti-oxidant (e.g., methionine or EDTA), one or more amino acids (e.g., alanine, arginine, lysine, glycine, proline, or serine) (in addition to the histidine buffer and antioxidant), a sugar (e.g., a polyol, monosaccharide, or disaccharide), and optionally, a surfactant (e.g., a polysorbate or poloxamer). In some embodiments, the formulation further includes a surfactant, e.g., a polysorbate or poloxamer, e.g. , PS80 or PS20. For example, the sugar may be mannitol or sorbitol. For example, the one or more amino acids may be arginine, proline, and / or glycine. For example, the antioxidant may be methionine.

[0175] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody, e.g., navenibart, a histidine buffer, an anti-oxidant (e.g., methionine or EDTA), one or more amino acids (e.g., alanine, arginine, lysine, glycine, proline, or serine) (in addition to the histidine buffer and antioxidant), one or more sugars (e.g., a polyol, monosaccharide, or disaccharide), and optionally, a surfactant (e.g. , a polysorbate or poloxamer). In some embodiments, the formulation further includes a surfactant, e.g., a polysorbate or poloxamer, e.g. , PS80 or PS20. For example, the sugar may be mannitol or sorbitol. For example, the one or more amino acids may be arginine, proline, and / or glycine. For example, the anti-oxidant may be methionine.

[0176] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody, e.g., navenibart, a histidine buffer, an anti-oxidant (e.g., methionine or EDTA), one or more amino acids (e.g., alanine, arginine, lysine, glycine, proline, or serine)(in addition to the histidine buffer and antioxidant), one or more of mannitol, sorbitol, trehalose, or sucrose, and optionally, a surfactant (e.g. , a polysorbate or poloxamer). In some embodiments, the formulation further includes a surfactant, e.g., a polysorbate or poloxamer, e.g., PS80 or PS20.

[0177] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody, e.g., navenibart, a histidine buffer, an anti-oxidant (e.g, methionine or EDTA), one or more of alanine, arginine, lysine, glycine, proline, mannitol, sorbitol, trehalose, or sucrose, and optionally, a surfactant (e.g. , a polysorbate or poloxamer). In some embodiments, the formulation further includes a surfactant, e.g., a polysorbate or poloxamer, e.g., PS80 or PS20.

[0178] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody, e.g., navenibart, a histidine buffer, methionine, one or more of alanine, arginine, lysine, glycine, proline, mannitol, sorbitol, trehalose, or sucrose, and optionally, a surfactant (e.g., a polysorbate or poloxamer). In some embodiments, the formulation further includes a surfactant, e.g., a polysorbate or poloxamer, e.g., PS80 or PS20.

[0179] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody, e.g., navenibart, a histidine buffer, methionine, one or more of arginine, glycine, or sorbitol, and optionally, a surfactant (e.g. , a polysorbate or poloxamer). In some instances, mannitol is substituted for the sorbitol. In some embodiments, the formulation further includes a surfactant, e.g. , a polysorbate or poloxamer, e.g. , PS80 or PS20.

[0180] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody, e.g., navenibart, a histidine buffer, methionine, arginine, glycine, and sorbitol, and optionally, a surfactant (e.g, a polysorbate or poloxamer). In some instances, mannitol is substituted for the sorbitol. In some embodiments, the formulation further includes a surfactant, e.g., a polysorbate or poloxamer, e.g., PS80 or PS20.

[0181] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody, e.g., navenibart, a histidine buffer, methionine, glycine, and sorbitol, and optionally, a surfactant (e.g. , a polysorbate or poloxamer). In some instances, mannitol is substituted for the sorbitol. In some embodiments, the formulation further includes a surfactant, e.g., a polysorbate or poloxamer, e.g., PS80 or PS20.

[0182] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody, e.g., navenibart, a histidine buffer, methionine, proline, and sorbitol, and optionally, a surfactant (e.g. , a polysorbate or poloxamer). In some instances, mannitol is substituted for the sorbitol. In some embodiments, the formulation further includes a surfactant, e.g. , a polysorbate or poloxamer, e.g. , PS80 or PS20.

[0183] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody, e.g., navenibart, a histidine buffer, methionine, proline, and sorbitol, and optionally, a surfactant (e.g. , a polysorbate or poloxamer). In some instances, mannitol is substituted for the sorbitol. In some embodiments, the formulation further includes a surfactant, e.g., a polysorbate or poloxamer, e.g., PS80 or PS20.

[0184] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody, e.g., navenibart, a histidine buffer, methionine, glycine, proline, and sorbitol, and optionally, a surfactant (e.g., a polysorbate or poloxamer). In some instances, mannitol is substituted for the sorbitol. In some embodiments, the formulation further includes a surfactant, e.g., a polysorbate or poloxamer, e.g., PS80 or PS20.

[0185] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody, e.g., navenibart, a histidine buffer, methionine, arginine, proline, and sorbitol, and optionally, a surfactant (e.g., a polysorbate or poloxamer). In some instances, mannitol is substituted for the sorbitol. In some embodiments, the formulation further includes a surfactant, e.g., a polysorbate or poloxamer, e.g., PS80 or PS20.

[0186] In the aforementioned exemplary formulations, the anti-pKal antibody e.g, navenibart, may be present in a concentration as set forth in Section III (1) herein. The anti- pKal antibody e.g. , navenibart, may be present in a concentration of about 50 mg / mL to about 500 mg / mL, e.g., 70-200 mg / mL, e.g, 125-175 mg / mL, e.g., 135-165 mg / mL, e.g., 150 mg / mL. The anti-pKal antibody may be, for example, an anti-pKal antibody having a heavy chain having the amino acid sequence of SEQ ID NO: 9, and a light chain having the amino acid sequence of SEQ ID NO: 10, e.g., the antibody is STAR-0215, also known as navenibart. The anti-pKal antibody may be an antibody comprising the Complementarity Determining Region Sequences (CDRs) of a heavy chain variable region having the amino acid sequence of SEQ ID NO: 7, and CDRs of a light chain variable region having the amino acid sequence of SEQ ID NO: 8. The anti-pKal antibody may be an antibody comprising animmunoglobulin heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7, and an immunoglobulin light chain variable region comprising the amino acid sequence of SEQ ID NO: 8. The anti-pKal antibody may further comprise a constant region comprising an M252Y, an S254T, and a T256E mutation as numbered according to the EU numbering index.

[0187] In the aforementioned exemplary formulations, the buffer may be present in a concentration as set forth in Section III (2.2) herein; the anti-oxidant may be present in a concentration as set forth in Section III (2.3) herein; any polyol, disaccharide, or amino acid (that is not the buffer or antioxidant) may be present in a concentration as set forth in Section III (2.4) herein and / or Section III (2.6) herein; any surfactant may be present in a concentration as set forth in Section III (2.5) herein; and the pH may be in a range suitable for the selected buffer, for example, as set forth in Section III (2.7) herein.

[0188] In the aforementioned exemplary formulations, the buffer may be present in a concentration of about 0.01 mM to about 200 mM, the antioxidant may be present in a concentration of about 0.01 mM to about 100 mM, any polyol, disaccharide, or amino acid (that is not the buffer or antioxidant) may be present in the formulations in a concentration of about 0.01 mM to about 500 mM; any surfactant may be present in a concentration of 0.01% (w / v) to 1% (w / v). The pH may be in a range suitable for the selected buffer. The buffer may be histidine, acetate, succinate, or phosphate. The buffer may be histidine.

[0189] In the aforementioned exemplary formulations, the buffer may be present in a concentration of about 5 mM to about 50 mM, the antioxidant may be present in a concentration of about 5 mM to about 50 mM, any polyol, disaccharide, or amino acid (that is not the buffer or antioxidant) may be present in the formulations in a concentration of about 50 mM to about 200 mM; any surfactant may be present in a concentration of 0.01% (w / v) to 1% (w / v). The pH may be in a range suitable for the selected buffer. The buffer may be histidine, acetate, succinate, or phosphate. The buffer may be histidine. The buffer may be acetate, succinate, or phosphate.

[0190] In the aforementioned exemplary formulations, the buffer may be present in a concentration of about 5 mM to about 15 mM, the antioxidant may be present in a concentration of about 5 mM to about 15 mM, any polyol, disaccharide, or amino acid (that is not the buffer or antioxidant) may be present in the formulations in a concentration of about50 mM to about 150 mM; any surfactant may be present in a concentration of 0.01% (w / v) to 1% (w / v). The pH may be in a range suitable for the selected buffer.

[0191] In the aforementioned exemplary formulations, the buffer may be present in a concentration of about 5 mM to about 15 mM, e.g., about 10 mM; the antioxidant may be present in a concentration of about 8 mM to about 12 mM; any polyol, disaccharide, or amino acid (that is not the buffer or antioxidant) may be present in the formulations in a concentration of about 60 mM to about 90 mM, e.g., about 75 mM; any surfactant may be present in a concentration of 0.01% (w / v) to 1% (w / v), e.g., 0.02% (w / v) to 0.07% (w / v), e.g., 0.05% (w / v). The pH may be in a range suitable for the selected buffer, e.g., 5.5-6.3.

[0192] In a further exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody having a heavy chain having the amino acid sequence of SEQ ID NO:9, and a light chain having the amino acid sequence of SEQ ID NO: 10, e.g. , navenibart, present in a concentration of about 50 to about 500 mg / mL, e.g., about 70 mg / mL to about 250 mg / mL; a histidine buffer present in a concentration of about 0.01 mM to about 100 mM, e.g., about 5 to about 50 mM; methionine present in concentration of about 0.01 mM to about 100 mM, e.g. , about 5 to about 50 mM; one or more of alanine, arginine, lysine, glycine, proline, mannitol, sorbitol, trehalose, or sucrose each present in a concentration of about 0.01 mM to about 500 mM, e.g. about 10 to about 300 mM; and a surfactant that is polysorbate 20 or polysorbate 80 present in an amount of about 0.01% (w / v) to about 1% (w / v). The pH is in a range of about 5.0 to about 6.5.

[0193] In a further exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody having a heavy chain having the amino acid sequence of SEQ ID NON, and a light chain having the amino acid sequence of SEQ ID NO: 10, e.g. , navenibart, present in a concentration of about 50 to about 500 mg / mL, e.g., about 70 mg / mL to about 250 mg / mL; a histidine buffer present in a concentration of about 0.01 mM to about 100 mM, e.g., about 5 to about 50 mM; methionine present in concentration of about 0.01 mM to about 100 mM, e.g., about 5 to about 50 mM; arginine present in a concentration of about 0.01 mM to about 500 mM, e.g., about 10 to about 300 mM; one of sorbitol or mannitol present in a concentration of about 0.01 mM to about 500 mM, e.g., about 10 to about 300 mM; and a surfactant that is polysorbate 20 or polysorbate 80 present in an amount of about 0.01% (w / v) to about 1% (w / v). The pH is in a range of about 5.0 to about 6.5.

[0194] In a further exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody having a heavy chain having the amino acid sequence of SEQ ID NO:9, and a light chain having the amino acid sequence of SEQ ID NO: 10, e.g. , navenibart, present in a concentration of about 50 to about 500 mg / mL, e.g., about 70 mg / mL to about 250 mg / mL; a histidine buffer present in a concentration of about 0.01 mM to about 100 mM, e.g., about 5 to about 50 mM; methionine present in concentration of about 0.01 mM to about 100 mM, e.g., about 5 to about 50 mM; arginine present in a concentration of about 0.01 mM to about 500 mM, e.g., about 10 to about 300 mM; glycine present in a concentration of about 0.01 mM to about 500 mM, e.g., about 10 to about 300 mM; and a surfactant that is polysorbate 20 or polysorbate 80 present in an amount of about 0.01% (w / v) to about 1% (w / v). The pH is in a range of about 5.0 to about 6.5.

[0195] In a further exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody having a heavy chain having the amino acid sequence of SEQ ID NO:9, and a light chain having the amino acid sequence of SEQ ID NO: 10, e.g. , navenibart, present in a concentration of about 50 to about 500 mg / mL, e.g., about 70 mg / mL to about 250 mg / mL; a histidine buffer present in a concentration of about 0.01 mM to about 100 mM, e.g., about 5 to about 50 mM; methionine present in concentration of about 0.01 mM to about 100 mM, e.g., about 5 to about 50 mM; one or more of arginine, glycine, proline, mannitol, or sorbitol each present in a concentration of about 0.01 mM to about 500 mM, e.g. , about 10 to about 300 mM; and a surfactant that is polysorbate 20 or polysorbate 80 present in an amount of about 0.01% (w / v) to about 1% (w / v). The pH is in a range of about 5.0 to about 6.5.

[0196] In a further exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody having a heavy chain having the amino acid sequence of SEQ ID NO:9, and a light chain having the amino acid sequence of SEQ ID NO: 10, e.g. , navenibart, present in a concentration of about 70 mg / mL to about 250 mg / mL, e.g., about 135 to about 165 mg / mL, a histidine buffer present in a concentration of about 5 to about 50 mM, e.g., about 5-15 mM; methionine present in concentration of about 5 to about 50 mM, e.g., about 5-15 mM; sorbitol or mannitol present at a concentration of about 50 to about 300 mM, e.g., about 75 to about 150 mM; one or more of arginine, glycine, or proline each present in a concentration of about 50 to about 300 mM, e.g., about 75 to about 150 mM; anda surfactant that is polysorbate 20 or polysorbate 80 present in an amount of about 0.01% (w / v) to about 1% (w / v). The pH is in a range of about 5.0 to about 6.5.

[0197] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody having a heavy chain having the amino acid sequence of SEQ ID NO:9, and a light chain having the amino acid sequence of SEQ ID NO: 10, e.g. , navenibart, present in a concentration of about 50 to about 500 mg / mL, e.g., about 70 mg / mL to about 250 mg / mL; a histidine buffer present in a concentration of about 0.01 mM to about 100 mM, e.g., about 5 to about 50 mM; methionine present in concentration of about 0.01 mM to about 100 mM, e.g., about 5 to about 50 mM; arginine present in a concentration of about 5 to about 500 mM e.g., about 10 to about 300 mM; glycine present in a concentration of about 10 mM to about 300 mM, and sorbitol present in a concentration of about 10 to about 200 mM, and a surfactant that is polysorbate 20 or polysorbate 80 present in an amount of about 0.01% (w / v) to about 1% (w / v). The pH is in a range of about 5.0 to about 6.5. In some instances, mannitol is substituted for the sorbitol or the glycine at up to 500 mM.

[0198] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody having a heavy chain having the amino acid sequence of SEQ ID NO:9, and a light chain having the amino acid sequence of SEQ ID NO: 10, e.g. , navenibart, present in a concentration of about 50 to about 500 mg / mL, e.g., about 70 mg / mL to about 250 mg / mL; a histidine buffer present in a concentration of about 0.01 mM to about 100 mM, e.g., about 5 to about 50 mM; methionine present in concentration of about 0.01 mM to about 100 mM, e.g., about 5 to about 50 mM; glycine present in a concentration of about 10 mM to about 300 mM, and sorbitol present in a concentration of about 10 to about 200 mM, and a surfactant that is polysorbate 20 or polysorbate 80 present in an amount of about 0.01% (w / v) to about 1% (w / v). The pH is in a range of about 5.0 to about 6.5. In some instances, mannitol is substituted for the sorbitol or the glycine at up to 500 mM.

[0199] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody having a heavy chain having the amino acid sequence of SEQ ID NO:9, and a light chain having the amino acid sequence of SEQ ID NO: 10, e.g. , navenibart, present in a concentration of about 50 to about 500 mg / mL, e.g., about 70 mg / mL to about 250 mg / mL; a histidine buffer present in a concentration of about 0.01 mM to about 100 mM, e.g., about 5 to about 50 mM; methionine present in concentration of about 0.01 mM to about100 mM, e.g., about 5 to about 50 mM; proline present in a concentration of about 10 mM to about 300 mM, and sorbitol present in a concentration of about 10 to about 200 mM, and a surfactant that is polysorbate 20 or polysorbate 80 present in an amount of about 0.01% (w / v) to about 1% (w / v). The pH is in a range of about 5.0 to about 6.5. In some instances, mannitol is substituted for sorbitol at up to 500 mM.

[0200] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody having a heavy chain having the amino acid sequence of SEQ ID NO:9, and a light chain having the amino acid sequence of SEQ ID NO: 10, e.g. , navenibart, present in a concentration of about 50 to about 500 mg / mL, e.g., about 70 mg / mL to about 250 mg / mL; a histidine buffer present in a concentration of about 0.01 mM to about 100 mM, e.g., about 5 to about 50 mM; methionine present in concentration of about 0.01 mM to about 100 mM, e.g., about 5 to about 50 mM; proline present in a concentration of about 5 to about 500 mM, e.g., about 10 to about 300 mM; glycine present in a concentration of about 10 mM to about 300 mM; sorbitol present in a concentration of about 10 to about 200 mM; and a surfactant that is polysorbate 20 or polysorbate 80 present in an amount of about 0.01% (w / v) to about 1% (w / v). The pH is in a range of about 5.0 to about 6.5. In some instances, mannitol is substituted for one of glycine, or sorbitol at up to 500 mM.

[0201] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody having a heavy chain having the amino acid sequence of SEQ ID NO:9, and a light chain having the amino acid sequence of SEQ ID NO: 10, e.g. , navenibart, present in a concentration of about 50 to about 500 mg / mL, e.g., about 70 mg / mL to about 250 mg / mL; a histidine buffer present in a concentration of about 0.01 mM to about 100 mM, e.g., about 5 to about 50 mM; methionine present in concentration of about 0.01 mM to about 100 mM, e.g., about 5 to about 50 mM; proline present in a concentration of about 5 to about 500 mM, e.g., about 10 to about 200 mM; arginine present in a concentration of about 10 mM to about 500 mM, e.g., about 10 to about 200 mM; sorbitol present in a concentration of about 10 to about 200 mM, and a surfactant that is polysorbate 20 or polysorbate 80 present in an amount of about 0.01% (w / v) to about 1% (w / v). The pH is in a range of about 5.0 to about 6.5. In some instances, mannitol is substituted for one of proline, arginine or sorbitol at up to 500 mM.

[0202] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody having a heavy chain having the amino acid sequence of SEQ ID NO:9, and a light chain having the amino acid sequence of SEQ ID NO: 10, e.g. , navenibart, present in a concentration of about 50 to about 500 mg / mL, e.g., about 70 mg / mL to about 250 mg / mL; a histidine buffer present in a concentration of about 5 mM to about 50 mM; methionine present in concentration about 5 to about 50 mM; sorbitol present in a concentration of about 100 to about 300 mM; glycine present in a concentration of about 50 mM to about 300 mM; and a surfactant that is polysorbate 20 or 80 present in an amount of about 0.01% (w / v) to about 1% (w / v). The pH is in a range of about 5.0 to about 6.5. For example, the pH is about 5.5 to about 6.0. In some instances, mannitol is substituted for one of sorbitol or glycine at up to 500 mM.

[0203] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody having a heavy chain having the amino acid sequence of SEQ ID NO:9, and a light chain having the amino acid sequence of SEQ ID NO: 10, e.g. , navenibart, present in a concentration of about 70 mg / mL to about 250 mg / mL, e.g. , about 150 mg / mL; a histidine buffer, e.g., histidine hydrochloride, present in a concentration of about 5-15 mM, e.g., about 10 mM; methionine, e.g., free methionine, present in concentration of about 5-15 mM, e.g., about 10 mM; sorbitol present in a concentration of about 100 to about 300 mM, e.g., about 150 mM; glycine, e.g., free glycine, present in a concentration of about 50 mM to about 150 mM, e.g., about 75 mM; polysorbate 20 or polysorbate 80, e.g., polysorbate 80, present in an amount of about 0.01% (w / v) to about 1% (w / v), e.g. about 0.05% (w / v). The pH is in a range of about 5.5 to about 6.0, e.g., about 5.8. In some instances, mannitol is substituted for one of sorbitol or glycine at up to 500 mM.

[0204] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody having a heavy chain having the amino acid sequence of SEQ ID NO:9, and a light chain having the amino acid sequence of SEQ ID NO: 10, e.g. , navenibart, present in a concentration of about 70 mg / mL to about 250 mg / mL, e.g. , about 150 mg / mL; a histidine buffer, e.g., histidine hydrochloride, present in a concentration of about 5-15 mM, e.g., about 10 mM; methionine, e.g., free methionine, e.g., L-methionine, present in concentration of about 5-15 mM, e.g., about 10 mM; sorbitol present in a concentration of about 50 to about 300 mM, e.g., about 75 mM; glycine, e.g., free glycine, e.g., L-glycine, present in a concentration of about 50 mM to about 300 mM, e.g., about 75 mM; arginine,e.g., arginine hydrochloride, present in a concentration of about 50 mM to about 300 mM, e.g., about 75 mM; polysorbate 20 or polysorbate 80, e.g, polysorbate 80, present in an amount of about 0.01% (w / v) to about 1% (w / v), e.g. about 0.05% (w / v). The pH is in a range of about 5.5 to about 6.0, e.g., about 5.8. In some instances, mannitol is substituted for one of sorbitol or glycine at up to 500 mM.

[0205] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody having a heavy chain having the amino acid sequence of SEQ ID NO:9, and a light chain having the amino acid sequence of SEQ ID NO: 10, e.g. , navenibart, present in a concentration of about 70 mg / mL to about 250 mg / mL, e.g. , about 150 mg / mL; a histidine buffer, e.g., histidine hydrochloride, present in a concentration of about 5-15 mM, e.g., about 10 mM; methionine, e.g., free methionine, e.g., L-methionine, present in concentration of about 5-15 mM, e.g., about 10 mM; sorbitol present in a concentration of about 50 to about 300 mM, e.g., about 75 mM; glycine, e.g., free glycine, e.g., L-glycine, present in a concentration of about 50 mM to about 300 mM, e.g., about 75 mM; arginine, e.g., arginine hydrochloride, present in a concentration of about 50 mM to about 300 mM, e.g., about 75 mM; polysorbate 20 or polysorbate 80, e.g., polysorbate 80 present in an amount of about 0.01% (w / v) to about 1% (w / v), e.g. about 0.05% (w / v). The pH is in a range of about 5.5 to about 6.5, e.g., about 5.8. In some instances, mannitol is substituted for one of sorbitol or glycine at up to 500 mM.

[0206] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody having a heavy chain having the amino acid sequence of SEQ ID NO:9, and a light chain having the amino acid sequence of SEQ ID NO: 10, e.g. , navenibart, present in a concentration of about 135 mg / mL to about 165 mg / mL, e.g., about 150 mg / mL; a histidine buffer, e.g., histidine hydrochloride, present in a concentration of about 5-15 mM, e.g., about 10 mM; methionine, e.g., free methionine, e.g., L-methionine, present in concentration of about 8-12 mM, e.g., about 10 mM; sorbitol present in a concentration of about 60 to about 90 mM, e.g., about 75 mM; glycine, e.g., free glycine, e.g., L-glycine, present in a concentration of about 60 mM to about 90 mM, e.g., about 75 mM; arginine, e.g., arginine hydrochloride, present in a concentration of about 60 mM to about 90 mM, e.g., about 75 mM; polysorbate 20 or polysorbate 80, e.g., polysorbate 80 present in an amount of about 0.02% (w / v) to about 0.07% (w / v), e.g. about 0.05% (w / v). The pH is in a range ofabout 5.5 to about 6.3, e.g., about 5.8. In some instances, mannitol is substituted for one of sorbitol or glycine.

[0207] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody having a heavy chain having the amino acid sequence of SEQ ID NO:9, and a light chain having the amino acid sequence of SEQ ID NO: 10, e.g. , navenibart, present in a concentration of about 135 mg / mL to about 165 mg / mL, e.g., about 150 mg / mL; a histidine buffer, e.g., histidine hydrochloride, present in a concentration of about 5-15 mM, e.g., about 10 mM; methionine, e.g., free methionine, e.g., L-methionine, present in concentration of about 5-150 mM, e.g., about 8-12 mM, e.g., about 10 mM; sorbitol present in a concentration of about 50 to about 150 mM, e.g., about 75 mM; glycine, e.g., free glycine, e.g., L-glycine, present in a concentration of about 50 mM to about 150 mM, e.g., about 75 mM; arginine, e.g., arginine hydrochloride, present in a concentration of about 50 mM to about 150 mM, e.g., about 75 mM; polysorbate 20 or polysorbate 80, e.g., polysorbate 80 present in an amount of about 0.02% (w / v) to about 0.1% (w / v), e.g. about 0.05% (w / v). The pH is in a range of about 5.5 to about 7.0, e.g., about 5.8. In some instances, mannitol is substituted for one of sorbitol or glycine.

[0208] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody having a heavy chain having the amino acid sequence of SEQ ID NO:9, and a light chain having the amino acid sequence of SEQ ID NO: 10, e.g. , navenibart, present in a concentration of about 150 mg / mL; a histidine buffer, e.g. , histidine hydrochloride, present in a concentration of about 10 mM; methionine, e.g., free methionine, e.g., L- methionine, present in concentration of about 10 mM; sorbitol present in a concentration of about 150 mM; glycine, e.g., free glycine, e.g., L-glycine, present in a concentration of about 75 mM; polysorbate 80 present in an amount of 0.05% (w / v). The pH is about 5.8.

[0209] In one exemplary formulation, a liquid pharmaceutical composition comprises an anti-pKal antibody having a heavy chain having the amino acid sequence of SEQ ID NO:9, and a light chain having the amino acid sequence of SEQ ID NO: 10, e.g. , navenibart, present in a concentration of about 150 mg / mL; a histidine buffer, e.g. , histidine hydrochloride, present in a concentration of about 10 mM; methionine, e.g., free methionine, e.g., L- methionine, present in concentration of about 10 mM; sorbitol present in a concentration of about 75 mM; glycine, e.g., free glycine, e.g., L-glycine, present in a concentration of about75 mM; arginine, e.g.. arginine hydrochloride, present in a concentration of about 75 mM; polysorbate 80 present in an amount of about 0.05% (w / v). The pH is about 5.8.

[0210] The disclosure also contemplates that each of the aforementioned exemplary formulations may be modified such that the concentration of the buffer is 0 mM. In other words, the formulations are contemplated that do not include a buffer. For example, such formulations may rely on the inherent buffering capacity of the anti-pKal antibody, e.g., navenibart, and therefore do not require inclusion of an excipient with buffering capacity, e.g., buffering capacity within the pH range of the formulation.

[0211] The liquid pharmaceutical composition may comprise one of the formulations listed in the Table 5. For example, the liquid pharmaceutical composition comprises formulation 1 of Table 5. For example, the liquid pharmaceutical composition comprises formulation 2 of Table 5. For example, the liquid pharmaceutical composition comprises formulation 3 of Table 5. For example, the liquid pharmaceutical composition comprises formulation 4 of Table 5. For example, the liquid pharmaceutical composition comprises formulation 5 of Table 5. For example, the liquid pharmaceutical composition comprises formulation 6 of Table 5. For example, the liquid pharmaceutical composition comprises formulation 7 of Table 5. For example, the liquid pharmaceutical composition comprises formulation 8 of Table 5. For example, the liquid pharmaceutical composition comprises formulation 9 of Table 5. For example, the liquid pharmaceutical composition comprises formulation 10 of Table 5. For example, the liquid pharmaceutical composition comprises formulation 11 of Table 5. For example, the liquid pharmaceutical composition comprises formulation 12 of Table 5. For example, the liquid pharmaceutical composition comprises formulation 13 of Table 5. For example, the liquid pharmaceutical composition comprises formulation 14 of Table 5. For example, the liquid pharmaceutical composition comprises formulation 15 of Table 5. For example, the liquid pharmaceutical composition comprises formulation 16 of Table 5. For example, the liquid pharmaceutical composition comprises formulation 17 of Table 5. For example, the liquid pharmaceutical composition comprises formulation 18 of Table 5. For example, the liquid pharmaceutical composition comprises formulation 19 of Table 5. For example, the liquid pharmaceutical composition comprises formulation 20 of Table 5. For example, the liquid pharmaceutical composition comprises formulation 21 of Table 5. For example, the liquid pharmaceutical composition comprises formulation 22 of Table 5. For example, the liquid pharmaceutical composition comprisesformulation 23 of Table 5. For example, the liquid pharmaceutical composition comprises formulation 24 of Table 5. For example, the liquid pharmaceutical composition comprises formulation 25 of Table 5. For example, the liquid pharmaceutical composition comprises formulation 26 of Table 5. For example, the liquid pharmaceutical composition comprises formulation 27 of Table 5. For example, the liquid pharmaceutical composition comprises formulation 28 of Table 5. For example, the liquid pharmaceutical composition comprises formulation 29 of Table 5. For example, the liquid pharmaceutical composition comprises formulation 30 of Table 5. For example, the liquid pharmaceutical composition comprises formulation 31 of Table 5. Table 5. Exemplary Navenibart Formulations

[0212] The liquid pharmaceutical composition may comprise one of the formulations listed in the Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 1 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 2 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 3 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 4 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 5 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 6 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 7 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 8 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 9 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 10 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 11 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 12 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 13 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 14 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 15 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 16 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 17 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 18 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 19 of Table 5.1. For example, the liquid pharmaceutical composition comprisesformulation 20 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 21 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 22 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 23 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 24 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 25 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 26 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 27 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 28 of Table 5. 1. For example, the liquid pharmaceutical composition comprises formulation 29 of Table 5. 1. For example, the liquid pharmaceutical composition comprises formulation 30 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 31 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 32 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 33 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 34 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 35 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 36 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 37 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 38 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 39 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 40 of Table 5.1. For example, the liquid pharmaceutical composition comprises formulation 41 of Table 5.1.Table 5.1. Exemplary Navenibart Formulations

[0213] In one embodiment, the liquid pharmaceutical compos tion comprises about 70 to about 200 mg / mL navenibart; about 5 to about 25 mM histidine; about 5 to about 25 mM methionine; about 50 to about 200 mM sorbitol or mannitol; about 50 to about 200 mM each of one or more of glycine, arginine, and / or proline; and about 0.01 to about 0.1% polysorbate 20 or polysorbate 80 wherein the composition has a pH of about 5.5 to about 6.5.

[0214] In one embodiment, the liquid pharmaceutical composition comprises about 70 to about 200 mg / mL navenibart; about 5 to about 25 mM histidine; about 5 to about 25 mM methionine; about 50 to about 200 mM sorbitol; about 50 to about 200 mM each of one or more of glycine, arginine, and / or proline; and about 0.01 to about 0.1% polysorbate 20 or polysorbate 80 wherein the composition has a pH of about 5.5 to about 6.5.

[0215] In one embodiment, the liquid pharmaceutical composition comprises about 70 to about 200 mg / mL navenibart; about 5 to about 25 mM histidine; about 5 to about 25 mM methionine; about 50 to about 200 mM mannitol; about 50 to about 200 mM each of one or more of glycine, arginine, and / or proline; and about 0.01 to about 0.1% polysorbate 20 or polysorbate 80 wherein the composition has a pH of about 5.5 to about 6.5.

[0216] In one embodiment, the liquid pharmaceutical composition comprises about 70 to about 200 mg / mL navenibart, e.g., about 150 mg / mL; about 5 to about 25 mM histidine, e.g., about 20 mM; and about 50 to about 500 mM glycine or mannitol and the composition has a pH of about 5.0 to about 6.5, e.g., about 5.5. The composition may further include about 25 to about 75 mg / L EDTA or about 25 to about 75 mM methionine. For example, in some embodiments, the composition includes about 100-200 mM glycine, e.g., about 150 mM. For example, in some embodiments, the composition includes about 200 mM to about 400 mM mannitol, e.g., about 300 mM.

[0217] In one embodiment, the liquid pharmaceutical composition comprises about 70 to about 200 mg / mL navenibart, e.g., about 150 mg / mL; about 5 to about 25 mM histidine, e.g., about 20 mM; and the composition has a pH of about 5.0 to about 6.5, e.g., about 5.5. The composition may further include about 25 to about 75 mg / L EDTA or about 25 to about 75 mM methionine and / or 100 mM to about 300 mM arginine, glycine or proline and / or about 200 mM to about 400 mM mannitol or sorbitol. For example, in some embodiments, the composition includes about 100-200 mM glycine, e.g., about 150 mM. For example, in some embodiments, the composition includes about 200 mM to about 400 mM mannitol, e.g., about 300 mM.

[0218] In one embodiment, the liquid pharmaceutical composition comprises about 70 to about 200 mg / mL navenibart, e.g., about 150 mg / mL; about 5 to about 25 mM, e.g., about 10 mM, of a buffer selected from histidine, succinate, acetate, or phosphate; and about 50 to about 400 mM of one of glycine, mannitol, or sorbitol. The composition may further includepolysorbate 20 or polysorbate 80 at about 0.01 to about 0.1% (w / v), e.g., about 0.05%. (w / v), or e.g., about 0.02% (w / v). The composition may further include an antioxidant such as methionine in an amount of about 5 to about 25 mM, e.g., about 10 mM. In some examples, the composition includes glycine, mannitol, or sorbitol in an amount of about 50 to about 400 mM, e.g., about 300 mM, or e.g., about 150 mM. In some examples, the composition includes glycine, mannitol, or sorbitol in an amount of about 50 to about 150 mM, e.g., about 75 mM. In some embodiments, the buffer is histidine and the pH of the composition may range from about 5.5 to about 6.5. In some embodiments, the buffer is acetate and the pH of the composition may range from about 4.5 to about 5.5. In some embodiments, the buffer is succinate and the pH of the composition may range from about 4.5 to about 5.5. In some embodiments, the buffer is phosphate and the pH of the composition may range from about 6.5 to about 7.5.

[0219] In one embodiment, the liquid pharmaceutical composition comprises about 70 to about 200 mg / mL navenibart, e.g., about 150 mg / mL; about 5 to about 25 mM, e.g, about 10 mM, of a buffer selected from succinate, acetate, or phosphate; and about 50 to about 400 mM of one of glycine, mannitol, or sorbitol. The composition may further include polysorbate 20 or polysorbate 80 at about 0.01 to about 0.1% (w / v), e.g., about 0.05%. (w / v), or e.g., about 0.02% (w / v). The composition may further include an antioxidant such as methionine in an amount of about 5 to about 25 mM, e.g., about 10 mM. In some examples, the composition includes glycine, mannitol, or sorbitol in an amount of about 50 to about 400 mM, e.g, about 300 mM, or e.g., about 150 mM. In some examples, the composition includes glycine, mannitol, or sorbitol in an amount of about 50 to about 150 mM, e.g., about 75 mM. In some embodiments, the buffer is acetate and the pH of the composition may range from about 4.5 to about 5.5. In some embodiments, the buffer is succinate and the pH of the composition may range from about 4.5 to about 5.5. In some embodiments, the buffer is phosphate and the pH of the composition may range from about 6.5 to about 7.5.

[0220] In one embodiment, the liquid pharmaceutical composition comprises about 70 to about 200 mg / mL navenibart, e.g., about 150 mg / mL; about 5 to about 25 mM, e.g, about 10 mM, of a buffer selected from histidine, succinate, acetate, or phosphate; and about 50 to about 400 mM of one of arginine, glycine, mannitol, or sorbitol. The composition may further include polysorbate 20 or polysorbate 80 at about 0.01 to about 0. 1% (w / v), e.g., about 0.05%. (w / v), or e.g., about 0.02% (w / v). The composition may further include anantioxidant such as methionine in an amount of about 5 to about 25 mM, e.g., about 10 mM. In some examples, the composition includes arginine, glycine, mannitol, or sorbitol in an amount of about 50 to about 400 mM, e.g., about 300 mM, or e.g, about 150 mM. In some embodiments, the buffer is histidine and the pH of the composition may range from about 5.5 to about 6.5. In some embodiments, the buffer is acetate and the pH of the composition may range from about 4.5 to about 5.5. In some embodiments, the buffer is succinate and the pH of the composition may range from about 4.5 to about 5.5. In some embodiments, the buffer is phosphate and the pH of the composition may range from about 6.5 to about 7.5.

[0221] In one embodiment, the liquid pharmaceutical composition comprises about 70 to about 200 mg / mL navenibart, e.g., about 150 mg / mL; about 5 to about 25 mM, e.g, about 10 mM, of a buffer selected from succinate, acetate, or phosphate; and about 50 to about 400 mM of one of arginine, glycine, mannitol, or sorbitol. The composition may further include polysorbate 20 or polysorbate 80 at about 0.01 to about 0.1% (w / v), e.g., about 0.05%. (w / v), or e.g., about 0.02% (w / v). The composition may further include an antioxidant such as methionine in an amount of about 5 to about 25 mM, e.g., about 10 mM. In some examples, the composition includes arginine, glycine, mannitol, or sorbitol in an amount of about 50 to about 400 mM, e.g, about 300 mM, or e.g., about 150 mM. In some embodiments, the buffer is acetate and the pH of the composition may range from about 4.5 to about 5.5. In some embodiments, the buffer is succinate and the pH of the composition may range from about 4.5 to about 5.5. In some embodiments, the buffer is phosphate and the pH of the composition may range from about 6.5 to about 7.5.

[0222] In one embodiment, the liquid pharmaceutical composition comprises about 70 to about 200 mg / mL navenibart, e.g., about 150 mg / mL; about 5 to about 25 mM, e.g, about 10 mM, of a buffer selected from succinate, acetate, or phosphate; and about 50 to about 400 mM of one of arginine, glycine, mannitol, or sorbitol. The composition may further include polysorbate 20 or polysorbate 80 at about 0.01 to about 0.1% (w / v), e.g., about 0.05%. (w / v), or e.g., about 0.02% (w / v). The composition may further include an antioxidant such as methionine in an amount of about 5 to about 25 mM, e.g., about 10 mM. In some examples, the composition includes arginine, glycine, mannitol, or sorbitol in an amount of about 50 to about 400 mM, e.g, about 300 mM, or e.g., about 150 mM. In some embodiments, the buffer is acetate and the pH of the composition may range from about 4.5 to about 5.5. In some embodiments, the buffer is succinate and the pH of the composition may range fromabout 4.5 to about 5.5. In some embodiments, the buffer is phosphate and the pH of the composition may range from about 6.5 to about 7.5.

[0223] In one embodiment, the liquid pharmaceutical composition comprises 10 mM histidine-HCl, 10 mM L-methionine, 150 mM sorbitol, 75 mM glycine, 0.02% PS20, and 150 mg / mL navenibart, where the composition has a pH of about 5.8.

[0224] In one embodiment, the liquid pharmaceutical composition comprises 10 mM histidine-HCl, 10 mM L-methionine, 300 mM sorbitol, 75 mM glycine, 0.02% PS20, and 150 mg / mL navenibart, where the composition has a pH of about 5.8.

[0225] In one embodiment, the liquid pharmaceutical composition comprises 10 mM histidine-HCl, 10 mM L-methionine, 75 mM sorbitol, 75 mM glycine, 75 mM arginine HC1, 0.05% PS80, and 150 mg / mL navenibart, where the composition has a pH of about 5.8.IV. Administration of anti-pKal Antibody Formulations1. Modes of Administration

[0226] The anti-pKal antibody formulations disclosed herein are designed, for example, for administration by injection, e.g., subcutaneous or intramuscular injection. However, these formulations may also be suitable for other routes of administration including intravenous administration (IV). In certain examples, the pharmaceutical formulations disclosed herein are designed for subcutaneous (SC) administration. In other examples, the pharmaceutical formulations disclosed herein are designed for intramuscular (IM) administration.

[0227] The antibodies disclosed herein may also be administered intravenously, for example, by intravenous infusion, such as drip infusion or pump infusion. Alternatively, the antibodies disclosed herein may be administered via intravenous push or bolus injection via a port or catheter. Infusion may be effected through a port or catheter placed in a vein of the patient. The port or catheter may be a PICC line, tunneled catheter, or implanted port, for example. In some embodiments, the intravenous administration is performed by a medical professional, whereas in some embodiments, the administration is performed by the subject, z.e., the antibody is self-administered. A fixed dose of the antibody may be provided into the port or catheter, or may be provided into a delivery solution for drip administration.2. Injection Devices

[0228] The glide force and break loose force of an injection device impact the ease with which the formulation can be ejected from the injection device, as well as the comfort of the person administering the injection and the subject receiving the injection. The break loose force is the initial resistance encountered when starting to move the plunger from a static position and represents the force required to overcome the static friction between the plunger and the syringe barrel, whereas the glide force is the resistance felt when the plunger of the syringe is moved to administer the drug after the initial break loose force has been overcome, and represents the smoothness of plunger movement against the barrel of the syringe. The back pressure caused by the viscosity of the liquid and pressure created by reducing the area through which the liquid is expelled as it moves into the needle impacts the glide force. Optimal break loose and glide forces give the user more control over the injection process, thereby preventing prevent discomfort (to both administrator and subject) and tissue damage that can occur when the formulation is not delivered with a consistent force and flow rate over the duration of the injection.

[0229] Accordingly, for administration by injection, for example, subcutaneously or intramuscularly, an appropriate injection device can be selected that together, with the formulation, provides an appropriate glide force (GF) and break loose (BL) force to facilitate injecting the formulation subcutaneously (or intramuscularly) into a subject.

[0230] An injection device may be selected so that when it is used in combination with the formulations disclosed herein, the break loose and glide forces resulting from the combination of the formulation and the injection device are optimized. For example, for high concentration antibody formulations, including formulations disclosed herein, where viscosity In certain cases, the BL force when a device is used in combination with a formulation disclosed herein should not exceed about 25 N. In other cases, the BL force when a device is used in combination with a formulation disclosed herein should not exceed about 20 N. In some cases, the BL force when the device is used in combination with a formulation disclosed herein is about 10 N to about 20 N. In some cases, the glide force when a device is used in combination with a formulation disclosed herein does not exceed 15 N. In other cases, the glide force when the device is used in combination with a formulation disclosed herein is about 10 N to about 15 N. In yet other cases, the glide force when the device is used in combination with a formulation disclosed herein does not exceed 10 N. Inother cases, the glide force when the device is used in combination with a formulation disclosed herein is about 5 N to about 10 N. In other cases, the glide force when the device is used in combination with a formulation disclosed herein is about 5 N to about 15 N.

[0231] Accordingly, in some instances, the formulations of the invention may be provided in a prefdled syringe (PFS). The syringe may include a barrel (which contains the pharmaceutical formulation), a plunger (for pushing the drug out of the syringe), and a needle through which the formulation is transported from the syringe into the subject, e.g., into the subject’s tissue such as the thigh, abdomen or buttock. In some instances, to minimize pain and increase tolerability of the injection in the subject a needle of gauge 30 or less is used. In some instances, the needle is of gauge 25 or less. In some instances, the needle is, for example, a 23-27 gauge needle. For example, the needle is a 27 gauge needle. For subcutaneous administration, a needle should be selected of appropriate length to access subcutaneous tissue. A needle in the range of 1 / 2 inch (12 mm) to 5 / 8 inch (16 mm) in length may be suitable for subcutaneous administration in most adults, but if the subject has minimal subcutaneous tissue, a needle from 5 / 16 inch (8 mm) to 1 / 2 inch (12 mm) may be selected.

[0232] A syringe having a volume of about 2-3 mb, e.g., about 2.25 mb, is suitable for administering the high concentration anti-pKal antibody formulations disclosed herein. A syringe having a volume of up to about 5 mb is also suitable for administering the high concentration anti-pKal antibody formulations disclosed herein. The syringe chosen, the volume of the dose in the syringe, and the viscosity of the formulation can collectively impact the time it takes to complete the injection, e.g., subcutaneously or intramuscularly into the subject. Injections that take longer than 20-30 seconds are generally uncomfortable for the patient and difficult to administer. A volume of about 2-3 mb can be administered in a 20-30 second time period. Therefore, selecting a syringe that holds a volume that can be administered in a reasonable time frame is important as ensuring that the full amount of pharmaceutical composition inside the syringe can be administered in about 20 seconds or less. This ensures a tolerable time of dosing for the patient. Therefore, in certain instances, the pharmaceutical formulation when used in combination with a delivery (injection) device disclosed herein permits the volume of pharmaceutical composition in the syringe to be injected into the subject within about 20 seconds. In some instances, the delivery time is about 15 seconds or less. In even other instances, the delivery time can be less than about 10 seconds.

[0233] The barrel of the syringe may be made of suitable materials such as polypropylene, polycarbonate, cyclic olefin polymer (COP) or cyclic olefin copolymer (COC), polyethylene, or even glass. Glass may be selected, for example, because it is essentially chemically inert. Accordingly, when selecting a syringe for pre-filling, e.g., where the formulation will be stored in the syringe after formulation and finish, a glass syringe may be selected to minimize potential negative impacts of the container on the formulation during storage. The barrel of the syringe may be coated with a lubricant to reduce the break loose or glide force of the device. For example, the syringe barrel may be coated with silicone. The silicone, in some cases, may be applied through, e.g. , heat treatment to coat the syringe barrel. In other cases, the silicone may be cross-linked to the surface molecules of the syringe barrel.

[0234] The plunger component of the syringe may be selected to ensure optimal BL and G forces. The plunger is typically fitted with a stopper material at the interface with the formulation. This material may be made from synthetic rubbers such as chlorobutyl rubber or bromobutyl rubber, or silicone.

[0235] Exemplary syringes that may be used include the NiPro D2F™ prefillable glass syringe, the SCHOTT syriQ™ prefillable glass syringe, BD Neopak™ prefilled glass syringe, or BD Hypak™ prefilled glass syringe. A syringe of suitable volume should be selected to maximize the dose that can be administered from one syringe.

[0236] The formulations of anti-plasma kallikrein antibodies disclosed herein may be administered subcutaneously via a syringe, e.g. , fitted with a needle. The syringe may be a prefilled syringe. The syringe may be injected into the subject manually. In some instances, however, the prefilled syringe may be loaded into an auto-injector device, where the device performs the injection once the subject has positioned the device appropriately on the body for subcutaneous administration. Alternatively, the antibodies may be administered subcutaneously via a prefilled autoinjector pen, or via a prefilled cartridge inserted into an autoinjector pen. The autoinjector may be an electronic autoinjector or mechanical autoinjector. In the case of an autoinjector, the formulation may be carried in a high volume cartridge, e.g., up to 10 m , that is placed in the autoinjector device. The antibody formulation may be contained within a vial where the dose is removed from the vial via a needle and injected subcutaneously with a needle, for example a 23-27 gauge 5 / 8 inch needle.Alternatively, the antibodies can be administered subcutaneously via a wearable or “on-body” device loaded with the dose. Subcutaneous injection may be to the subject’s thigh, buttock, or abdomen, for example. In some embodiments, the subcutaneous injection is performed by the subject, z.e., the antibody is self-administered.

[0237] It should be understood that elements and / or features of a composition or a method described herein can be combined in a variety of ways without departing from the spirit and scope of the present invention, whether explicit or implicit herein. For example, where reference is made to a particular compound, that compound can be used in various embodiments of compositions of the present invention and / or in methods of the present invention, unless otherwise understood from the context. In other words, within this application, embodiments have been described and depicted in a way that enables a clear and concise application to be written and drawn, but it is intended and will be appreciated that embodiments may be variously combined or separated without parting from the present teachings and invention(s). For example, it will be appreciated that all features described and depicted herein can be applicable to all aspects of the invention(s) described and depicted herein.

[0238] The subject matter is now described with reference to the following examples. These examples are provided for the purpose of illustration only and the claims should in no way be construed as being limited to these examples, but rather should be construed to encompass any and all variations which become evident as a result of the teaching provided herein. Those of skill in the art will readily recognize a variety of non-critical parameters that could be changed or modified to yield essentially similar results.EXAMPLESEXAMPLE 1. Formulation of STAR-0215 Anti-plasma Kallikr ein antibody.

[0239] Studies were undertaken to develop a STAR-0215 formulation suitable for a high concentration of the antibody, but also having properties suitable for manufacturing, storage, and dosing, and promoting the physical and chemical stability of STAR-0215.

[0240] Formulation development studies were designed to evaluate high throughput conformational and colloidal stability of STAR-0215. Conformational stability refers to the ability of the molecule to maintain its native structure and fold properly, while colloidalstability refers to the ability of the native protein in solution to avoid aggregation, precipitation, or phase separations.1. STAR-015 Stock Solution Preparation

[0241] Approximately 0.5 g of STAR-0215 in 20 mM histidine-HCl buffer, 150 mM NaCl, pH 6.0) was dialyzed into 2L of purified water for a total of 6 hours at 2-8°C using a 30 mb capacity dialysis cassette (Thermo Fisher Slide-A-Lyzer; 20,000 MWCO; 12-30mL). After dialysis, the protein solution from the cassette was then concentrated by centrifugal filtration to a final concentration of 50 mg / mL. Material was used within 3 days of buffer exchange and was stored below -60°C until the next step.

[0242] The quality of the STAR-0215 raw material was determined by SEC-HPLC and peptide mapping. The initial monomer purity of 96.5% was determined to be sufficient for formulation development studies.

[0243] Peptide mapping was performed to assess the presence of major host cell proteins that could impact the protein stability or quantity of formulation excipients. Of the proteins identified, putative phospholipase B-like 2 was the only documented HCP that could introduce polysorbate degradation, although this was considered to be a low risk.

[0244] The STAR-0215 raw material was also assessed for post-translational modifications. Two CDR oxidation “hotspots” were oxidized over 0.5% without forced oxidation stress. Nonetheless, the quality of this material was considered adequate for formulation development studies.2. Stability-Prediction Screening

[0245] A stability predicting screening was conducted with a 96-well screening study format. The stock STAR-0215 solution was a protein solution in WFI at approximately 50 mg / mL. The target concentration for buffer systems (acetate, succinate, histidine, phosphate) was 10 mM, the target excipient concentration was 300 mM (arginine, glycine, mannitol, NaCl, sorbitol, sucrose, trehalose), and the target protein concentration was 10 mg / mL. Samples were prepared in a ninety-six (96) well master deep plate where each formulation sample was prepared by using liquid handling robotic system (TECAN). Appropriate amounts of 10X buffer stock solution, 5X (3X for Mannitol) excipient stock solution andSTAR-0215 protein stock solution into respective wells. The solution contents were mixed before WFI was added to QS to the final volume of 1.5 mL.

[0246] Conformational Stability Screening: The protein melting temperature (Tm) by pDSF and unfolding temperature (Th) by SYPRO dye binding are summarized in Table 6 and Table 7, respectively. As a stability indicating assay, the higher Tm or Th values are generally associated with better conformational stability. A good agreement was found between the Tm and Th values for the STAR-0215 molecule. Conformational stability appeared to be poor at low pH ranges and improved as pH increased. For formulations in acetate, succinate, and histidine buffer systems, the Tm value increased as buffer pH increased. As the comparison of acetate and succinate conditions at the same pH, as well the comparison of histidine and phosphate buffer conditions at the same pH endpoints showed, ionic strength did not appear to exert a strong influence on the conformation stability of STAR-0215. The conformational stability in Arginine and NaCl formulations was less desirable in all pH endpoints, which may suggest that salt bridges could be heavily involved in the conformation stability of the Fab region.Table 6. Tm (°C) results by pDSF for the 96 formu ationsTable 7. Th (°C) results by SYPRO dye binding for 96 formulations.

[0247] Colloidal stability (kD) Hydrodynamic radius (Rh), determined by Dynamic Light Scattering (DLS), was converted to translational diffusion coefficient (Dt), and the diffusion interaction parameter (kD) was then calculated based on the Dt values at different protein concentrations. In general, a positive kD value represents repulsive interactions between protein molecules, and hence, greater colloidal stability; a negative kD value represents attractive interactions between protein molecules, and hence, less colloidal stability. Table 8 shows the kD results of the 96 formulations. Positive kD values (shown in italics) were found at lower pH ranges and in low ionic strength solutions. Negative kD values were observed in majority of samples formulated with succinate and phosphate buffers as well as with excipients like arginine and sodium chloride. Overall, these observations suggest that STAR-0215 may engage in weak repulsive interaction that could be interrupted by high ionic strength solutions. Nevertheless, glycine, mannitol, sorbitol, and sucrose all demonstrated the ability to provide colloidal stability with the acetate, succinate and histidine buffers as demonstrated by positive kD values. Sorbitol was shown to provide better conformational and colloidal stability compared to NaCl.Table 8. kD (mL / g) results from Colloidal stability assay for each formulation.3. In-silico Modeling

[0248] In silico modelling of STAR-0215 was performed. Positively charged, negatively charged and hydrophobic patches on the surface of STAR-0215 were modelled with Molecular Operating Environment. Several solvent-accessible methionine residues were identified in the surface patches.4. CDR Oxidation Impact Study

[0249] Untreated (control) MAbs solutions were buffer-exchanged into 20 mM sodium phosphate buffer at pH 7.5 using Zeba Spin Desalting Columns, aliquoted (~1.0 m ) and frozen at -80°C until evaluation.

[0250] Tm / Th determinations were carried out using plates containing 10 mg / mL protein. kD measurements were carried out using six plates containing 1 mg / mL, 2 mg / mL, 3 mg / mL, 4 mg / mL, 5 mg / mL, and 10 mg / mL protein. Hydrodynamic radius of the mAb clusters at different concentration is used to calculate the kD which is used as an indicator of protein’s colloidal stability in each formulation.

[0251] The samples to evaluate selective Met oxidation were prepared by adding H2O2 (3%, w / w) to stock mAb solutions at a protein-toTLCh molar ratio of 1 : 100. IgG concentration is at 10 mg / mL and the sample solutions were mixed gently and incubated at 25°C for 24 hours followed by addition of 3- fold molar excess of a L-Met solution (200 mM) to quench the oxidation reaction. The mAb solutions were then buffer-exchanged into20 mM sodium phosphate buffer at pH 7.5 using Zeba Spin Desalting Columns, aliquoted (~1.0 mL) and frozen at -80°C until analyses.

[0252] The sample to evaluate selective Trp oxidation were prepared by adding 2,2’- Azobis (2 -methylpropionamidine) dihydrochloride (AAPH; 2 mg / mL) to stock mAb solutions at a protein-to-AAPH molar ratio of 1: 100. Free L-Met (10 mg / mL) was also added to the solution to protect the Met residue from oxidation. The solutions were mixed gently and incubated at 37°C for 1 day followed by a buffer-exchange into 20 mM sodium phosphate buffer at pH 7.5 using Zeba Spin Desalting Columns, aliquoted (~1.0 mL) and frozen at -80°C until analyses.

[0253] The analyses of the treated samples included protein concentration determination, conformational stability assay by pDSF.

[0254] Given the two experimentally verified hotspots in the CDR region, a small-scale impact study was performed to study the effect of CDR oxidation on potency and conformational stability. Three top clones were selected for this study to determine whether the oxidation impact could be different among STAR-0215 generated by different clones. However, across the three clones, no clone differences were observed.5. Microscale High Concentration Feasibility Study

[0255] A list of candidates was assembled for a microscale high concentration feasibility study based on the results from the stability-prediction screenings study and the preliminary CDR sequence analyses. To account for any potential self-buffering potential at high concentration, buffer strength was set at 20 mM. Due to the presence of CDR oxidation hotspots, it was anticipated that an antioxidant would be included in the final formulation; thus, EDTA and / or methionine were included in this concentration feasibility study to assess their impact on solution viscosity at high protein concentration. The STAR-0215 in original buffer (20 mM histidine-HCl buffer, 150 mM NaCl, pH 6.0) was concentrated and subject to buffer exchange using Unchained Labs Big Tuna automated buffer dialysis instrument (Pleasanton, CA). By concentrating STAR-0215 in several formulation up to 200 mg / mL it was intended to show whether the viscosity level could be reduced to below 20 cP for ease of filling and administration.

[0256] Based on the results from the stability-prediction screening studies, the combination of histidine buffer with glycine and mannitol was selected to be evaluated in the microscale high concentration feasibility study. pH was selected at pH 5.5 to maximize the colloidal stability. Disodium EDTA and L-methionine were included as antioxidants to control metal-catalyzed oxidation or radical-induced oxidation, respectively. The concentration of the antibody was 150 mg / mL and viscosity measurements at 150 mg / mL are presented in Table 9.Table 9. Microscale high concentration feasibility study results.

[0257] Formulations with mannitol generally had a lower viscosity than the formulation with glycine alone; however, formulations with glycine and EDTA or methionine had similar viscosities to the mannitol containing formulations.6. Plate-based Pre-formulation Stress Study

[0258] A plate-based pre-formulation screening study was conducted. Excipients tested were glycine, mannitol, and sorbitol, alone and in combination with L-methionine as an antioxidant. The buffers were 10 mM acetate, succinate, histidine, and phosphate. Sodium chloride, L-arginine, sucrose, and trehalose were eliminated due results from colloidal stability testing. Samples were prepared by using liquid handling robotic system (TECAN)

[0259] A ninety-six (96) well master deep plate where 1.5 mb of each formulation sample were prepared. STAR-015 (Lot#: Dl-QS-05-01-01) was formulated into the 96 formulations to the final concentration of 10 mg / mL. Three (3) identical microplates, used for TO, a freeze / thaw study, and a thermal stress study were prepared from the master deep plate. The freeze / thaw study was conducted by freezing at -80 °C for twenty-four (24) hours and thawing at room temperature for six (6) hours inside a laminar flow hood, covered inaluminum pouch to avoid light exposure. Samples were analyzed after five (5) freeze / thaw cycles. The thermal stress study was conducted by staging the microplate, which was covered by an adhesive lid and sealed in a shield bag by using an impulse vacuum sealer at 40°C for two weeks. Analytical testing included visual appearance / color, R-CGE, NR-CGE, CZE, SEC-HPLC, and UV A280 / A350 at the outset and then at the study’s conclusion.7. Preliminary forced degradation study and surfactant screening study

[0260] The design of the preliminary forced degradation and surfactant screening included 8 chemical forced degradation conditions and three surfactant types in a matrix of 96 formulations as shown in Table 10. The forced degradation study plate was formulated with STAR-0215 that was buffer exchanged into purified water. Concentrated buffer stocks were added to the plate and mixed by shaking on ThermoMixer. Final protein concentration for the forced degradation plate was 10 mg / mL. The forced degradation / surfactant screening study was carried out in high throughput plate format that included a thermal stress at 25°C for 72 hours and an agitation stress at 900 RPM for 72 hours. All samples were analyzed by visual inspection, SEC-HPLC and UV A350. The forced degraded samples were also analyzed by iCE, R / NR-CGE, and peptide mapping to elucidate the degradation pathways.Table 10. Preliminary Forced Degradation and Surfactant Screening ExperimentalPlate Design

[0261] A forced degradation plate was formulated to combine chemical degradation with surfactant screening. The results for the surfactant screening study are presented in Table 11. Aggregation levels remined low at low pH endpoints due to optimal colloidal stability. As pH increased and approached the molecule’s isoelectric point of approximately 8.2, the colloidal stability decreased resulting in high levels of aggregation. STAR-0215 concentration was 10 mg / mL for this study.

[0262] The %HMW levels were comparable in PS80 and PS20 containing compositions at low pH conditions. At pH 5.5, the %HMW levels were lower or comparable in PS 20 containing compositions compared to PS 80 containing compositions. At high pH conditions (pH 8.5 and 9.5), compositions with polysorbate 80 had lower %HMW levels than in PS 20 containing compositions. Compositions with poloxamer 188 contained the least amount of high molecular weight species at high pH conditions. PS20, PS80, poloxamer 188 showed similar protection to the product against interfacial stress. Table 11. Surfactant Screening Plate Results by SEC-HPLC (%HMW).

[0263] The forced degradation samples were analyzed by icIEF, R-CGE and NR-CGE.The results are presented in Table 12.Table 12. Forced degradation study results by SEC-HPLC, icIEF, R-CGE, and NR- CGE.

[0264] At pH 2.5, STAR-0215 underwent extensive fragmentation, shown in both R and NR CGE data, as the main degradation pathway. The majority of the fragmentation at pH 2.5 may come from peptide fragmentation as the fragmentation levels were comparable between NR-CGE and R-CGE. A significant decrease in %main variant and increases in both acidic and basic species were observed in icIEF results. At pH 2.5, the protein molecule carries large number of positive charges and is not prone to aggregation, even though the conformational stability is significantly compromised.

[0265] At pH 3.5, the STAR-0215 underwent fragmentation. The rate of reaction appeared slower than at pH 2.5. These fragmentations appeared to come from disulfide- related cleavage (about 11% difference in NR and R-CGE fragmentation) and peptide cleavage (11.3% in R-CGE fragmentation). A decrease in %main and an increase in %acidic variants were observed; however, the rates of changes in charge variants were slower than those observed at pH 2.5, especially for the % basic variant that remained almost unchanged compared to the control sample.

[0266] At pH 5.5, with metal oxidizers (MCO), STAR-0215 underwent both fragmentation and aggregation compared to control. Compared to the control, a comparablelow molecular weight (LMW) level was observed in the R-CGE results (2.4% vs 2.9%) and a higher LMW level was observed in NR-CGE results (12.3% vs 7.5%) indicating most of the fragmentation was likely due to disulfide-related fragments. The SEC and R-CGE results showed that aggregation levels were elevated compared to the control. The icIEF results showed that the charge variant profile in the MCO challenged samples remained similar to the control.

[0267] At pH 5.5 with peroxide, aggregation level was elevated (5.1% in SEC result) and appeared to be largely from covalent linkage indicated by a noticeably elevated high molecular weight (HMW) level of 3.4% in R-CGE results. icIEF results showed a significant increase in %acidic variant, decrease in % main, and a slight increase in % basic variant. NR- CGE results showed a slight increase in fragmentation.

[0268] At pH 8.5, STAR-0215 underwent deamidation and aggregation. Increased acidic species could be assigned to ASN deamidation to ASP and increase in aggregation could largely come from covalent linkage (3.5 % HMW in R-CGE vs 1.2 % HMW in NR-CGE). Fragmentation was slightly increased (0.2% in SEC results). At pH 8.5 with glucose, SEC results showed an increased aggregate level compared to the control (3.7% vs 0.6%). icIEF results showed a very significant increase in % acidic variants (83%) and a very significant decrease in % main (15.3%) signaling the presence of major glycation hotspot(s).

[0269] At pH 9.5, aggregation, acidic species and fragmentation all increased compared to control. The increase in acidic species could be attributed to deamidation due to the high pH condition. Aggregation moderately increased and could be largely attributed to covalent linkage (3.4% HMW in R-CGE and 1.6% in NR-CGE).8. High concentration formulation development study

[0270] Approximately 10 grams of STAR-0215 (20 mM histidine-HCl buffer, 150 mM NaCl, pH 6.0) was buffer exchanged into two final candidate formulations and concentrated to 150 mg / mL by UFDF.9. Viscosity as a Function of Protein Concentration

[0271] A concentration versus viscosity curve was generated by buffer exchanging and concentrating STAR-0215 in the targe...

Claims

CLAIMS1. A liquid pharmaceutical composition comprising: a) an anti -plasma kallikrein antibody comprising: i) Complementarity Determining Region Sequences (CDRs) of a heavy chain variable region having the amino acid sequence of SEQ ID NO: 7, and CDRs of a light chain variable region having the amino acid sequence of SEQ ID NO: 8, wherein the antibody further comprises a constant region comprising an M252Y, an S254T, and a T256E mutation as numbered according to the EU numbering index; ii) an immunoglobulin heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7, and an immunoglobulin light chain variable region comprising the amino acid sequence of SEQ ID NO: 8, wherein the antibody further comprises a constant region comprising an M252Y, an S254T, and a T256E mutation as numbered according to the EU numbering index; or iii) an immunoglobulin heavy chain comprising the amino acid sequence of SEQ ID NO:9 and a light chain comprising the amino acid sequence of SEQ ID NO:

10. b) a buffer selected from histidine, acetate, succinate, or phosphate; and c) an anti-oxidant.

2. The composition of claim 1, wherein the buffer is histidine.

3. The composition of claim 2, wherein the histidine is histidine hydrochloride.

4. The composition of any one of claims 1-3, further comprising a sugar selected from a polyol, monosaccharide or disaccharide.

5. The composition of claim 4, wherein the sugar is sorbitol.

6. The composition of claim 4, wherein the sugar is mannitol, sucrose or trehalose.

7. The composition of any one of claims 1-6, further comprising one or more amino acids selected from alanine, arginine, aspartic acid, glycine, glutamic acid, isoleucine, leucine, lysine, proline.

8. The composition of any one of claims 1-6, further comprising one or more amino acids selected from arginine, glycine, or proline.

9. The composition of any one of claims 1-8, further comprising glycine.

10. The composition of any one of claims 1-9, further comprising arginine.

11. The composition of any one of claims 1-10, further comprising glycine and arginine.

12. The composition of any one of claims 7-11, wherein the glycine is free glycine, e.g.,L-glycine.

13. The composition of any one of claims 7-12, wherein the arginine is arginine hydrochloride.

14. The composition of any one of claims 1-13, further comprising proline.

15. The composition of any one of claims 1-14, further comprising a surfactant.

16. The composition of claim 15, wherein the surfactant is a polysorbate or a poloxamer.

17. The composition of claim 15 or 16, wherein the surfactant is polysorbate 20 or polysorbate 80.

18. The composition of any one of claims 15-17, wherein the surfactant is polysorbate 80.

19. The composition of any one of claims 15-17, wherein the surfactant is polysorbate 20.

20. The composition of any one of claims 1-19, wherein the buffer is a phosphate buffer, e.g. a phosphate salt.

21. The composition of any one of claims 1 or 4-19, wherein the buffer is a succinate buffer, e.g., a succinate salt.

22. The composition of any one of claims 1 or 4-19, wherein the buffer is an acetate buffer, e.g., an acetate salt.

23. The composition of any one of claims 1-22, wherein the antioxidant is methionine, cysteine, DTPA, DFOA, or EDTA.

24. The composition of any one of claims 1-23, wherein the antioxidant is methionine.

25. The composition of claim 23 or 24, wherein the methionine is free methionine, e.g., L-methionine.

26. The composition of any one of claims 1-25, wherein the pH of the composition is in the range of about 5.0 to about 7.5.

27. The composition of claim 26, wherein the pH is about 5.0 to about 6.5.

28. The composition of claim 26, wherein the pH is about 5.5 to about 6.0.

29. The composition of claim 26, wherein the pH is about 5.8.

30. The composition of any one of claims 1-29, further comprising water for injection.

31. The composition of any one of claims 1-30, wherein the anti-pKal antibody is present at a concentration between 50-500 mg / mL.

32. The composition of any one of claims 1-31, wherein the anti-pKal antibody is present at a concentration between 70-250 mg / mL.

33. The composition of any one of claims 1-32, wherein the anti-pKal antibody is present at a concentration between 100-200 mg / mL.

34. The composition of any one of claims 1-33, wherein the anti-pKal antibody is present at a concentration between 150-200 mg / mL.

35. The composition of any one of claims 1-33, wherein the anti-pKal antibody is present at a concentration between 135-165 mg / mL.

36. The composition of any one of claims 1-35, wherein the anti-pKal antibody is present at a concentration of about 150 mg / mL.

37. The composition of any one of claims 1-34, wherein the anti-pKal antibody is present at a concentration of about 175 mg / mL.

38. The composition of any one of claims 15-37, wherein the surfactant is present in the composition in a range of about 0.01 to about 1% w / v of the composition.

39. The composition of any one of claims 15-37, wherein the surfactant is present in the composition in a range of about 0.02 to about 0.07% w / v of the composition.

40. The composition of any one of claims 15-37, wherein the surfactant is present in the composition in a range of about 0.02 to about 0.1% w / v of the composition.

41. The composition of any one of claims 15-37, wherein the surfactant is present in the composition in a range of about 0.03 to about 0.06% w / v of the composition.’42. The composition of any one of claims 15-41, wherein the surfactant is present in the composition in an amount of about 0.05% w / v of the composition.

43. The composition of any one of claims 1-42, wherein the buffer is present in the composition at a concentration of about 0.01 to about 500 mM.

44. The composition of any one of claims 1-43, wherein the buffer is present in the composition at a concentration of about 0.01 to about 200 mM.

45. The composition of any one of claims 1-44, wherein the buffer is present in the composition at a concentration of about 5 to about 50 mM.

46. The composition of any one of claims 1-45, wherein the buffer is present in the composition at a concentration of about 5 to about 15 mM.

47. The composition of any one of claims 1-46, wherein the buffer is present in the composition at a concentration of about 8 to about 12 mM.

48. The composition of any one of claims 1-47, wherein the buffer is present in the composition at a concentration of about 10 M.

49. The composition of any one of claims 4-48, wherein the sugar is present in the composition at concentration of about 0.01 to about 500 mM.

50. The composition of any one of claims 4-49, wherein the sugar is present in the composition at a concentration of about 250 to 500 mM.

51. The composition of any one of claims 4-50, wherein the sugar is present in the composition at a concentration of about 50 to about 300 mM.

52. The composition of any one of claims 4-51, wherein the sugar is present in the composition at a concentration of about 100 to about 200 mM.

53. The composition of any one of claims 4-52, wherein the sugar is present in the composition at a concentration of about 50 to about 150 mM.

54. The composition of any one of claims 4-53, wherein the sugar is present in the composition at a concentration of about 60 to about 90 mM.

55. The composition of any one of claims 5-48, wherein the sorbitol is present in a concentration of about 50 to about 300 mM.

56. The composition of any one of claims 5-48, wherein the sorbitol is present in a concentration of about 50 to about 150 mM.

57. The composition of any one of claims 5-48, wherein the sorbitol is present in a concentration of about 150 mM.

58. The composition of any one of claims 5-48, wherein the sorbitol is present in a concentration of about 75 mM.

59. The composition of any one of claims 7-58, wherein the one or more amino acids is each present in the composition at a concentration of about 0.01 to about 500 mM.

60. The composition of any one of claims 7-59, wherein the one or more amino acids is each present in the composition at a concentration of about 50 to about 300 mM.

61. The composition of any one of claims 7-60, wherein the one or more amino acids is each present in the composition at a concentration of about 50 to about 150 mM.

62. The composition of any one of claims 7-61, wherein the one or more amino acids is each present in the composition at a concentration of about 60 to about 90 mM.

63. The composition of any one of claims 7-62, wherein the one or more amino acids is each present in an amount of about 150 mM.

64. The composition of any one of claims 7-62, wherein the one or more amino acids is each present in the composition at a concentration of about 50 to about 100 mM.

65. The composition of any one of claims 7-62 or 64, wherein the one or more amino acids is each present in an amount of about 75 mM.

66. The composition of any one of claims 7-65, wherein glycine is present in an amount of about 50 to 500 mM.

67. The composition of any one of claims 7-66, wherein glycine is present in an amount of about 100 to 300 mM.

68. The composition of any one of claims 7-67 wherein glycine is present in an amount of about 75 to about 150 mM.

69. The composition of any one of claims 7-66, wherein the glycine is present in an amount of about 60-90 mM.

70. The composition of any one of claims 7-68, wherein glycine is present in an amount of about 75 mM.

71. The composition of any one of claims 7-68, wherein glycine is present in an amount of about 150 mM.

72. The composition of any one of claims 7-71, wherein arginine is present in an amount of about 50 to 500 mM.

73. The composition of any one of claims 7-72, wherein arginine is present in an amount of about 100 to 300 mM.

74. The composition of any one of claims 7-73, wherein arginine is present in an amount of about 75 to about 150 mM.

75. The composition of any one of claims 7-72, wherein arginine is present in an amount of about 60 to about 90 mM.

76. The composition of any one of claims 7-73, wherein arginine is present in an amount of about 75 mM.

77. The composition of any one of claims 7-73, wherein arginine is present in an amount of about 150 mM.

78. The composition of any one of claims 1-77, wherein the antioxidant is present in an amount of about 0.01 to about 500 mM.

79. The composition of any one of claims 1-78, wherein the antioxidant is present in an amount of about 0.01 to about 200 mM.

80. The composition of any one of claims 1-79, wherein the antioxidant is present in an amount of about 5 to about 50 mM.

81. The composition of any one of claims 1-80, wherein the antioxidant is present in an amount of about 5 to about 15 mM.

82. The composition of any one of claims 1-81, wherein the antioxidant is present in an amount of about 8 to about 12 mM.

83. The composition of any one of claims 1-82, wherein the antioxidant is present in an amount of about 10 mM.

84. The composition of any one of claims 1-83, wherein the osmolality of the composition is less than about 400 mOsm / kg.

85. The composition of any one of claims 1-84, wherein the osmolality of the composition is less than about 350 mOsm / kg.

86. The composition of any one of claims 1-85, wherein anti-pKal antibody comprises an immunoglobulin heavy chain comprising the amino acid sequence of SEQ ID NO:9 and a light chain comprising the amino acid sequence of SEQ ID NO: 10.

87. The composition of any one of claims 1-86, wherein anti-pKal antibody comprises Complementarity Determining Region Sequences (CDRs) of a heavy chain variable region having the amino acid sequence of SEQ ID NO: 7, and CDRs of a light chain variable region having the amino acid sequence of SEQ ID NO: 8, wherein theantibody further comprises a constant region comprising an M252Y, an S254T, and a T256E mutation as numbered according to the EU numbering index.

88. The composition of any one of claims 1-87, wherein anti-pKal antibody comprises an immunoglobulin heavy chain variable region comprising the amino acid sequence of SEQ ID NO: 7, and an immunoglobulin light chain variable region comprising the amino acid sequence of SEQ ID NO: 8, wherein the antibody further comprises a constant region comprising an M252Y, an S254T, and a T256E mutation as numbered according to the EU numbering index.

89. The composition of any one of claims 1-88, wherein the antibody is navenibart.

90. The composition of any one of claims 1-89, wherein the viscosity of the pharmaceutical composition is less than about 15 cP at about 25°C.

91. The composition of any one of claims 1-90, wherein the viscosity of the pharmaceutical composition is less than about 10 cP at about 25°C.

92. A drug delivery device comprising the liquid pharmaceutical composition of any one of claims 1-91, and a syringe comprising a plunger and a barrel, wherein the pharmaceutical composition is contained within the barrel and a surface of the barrel in contact with the pharmaceutical composition comprises a siliconized surface.

93. The drug delivery device of claim 92, wherein the barrel comprises glass.

94. The drug delivery device of claim 92 or 93, wherein the plunger comprises a stopper that in combination with the siliconized silicone surface of the barrel and the composition produces a glide force sufficient to eject the pharmaceutical formulation from the syringe into a subject subcutaneously in 20 seconds or less.

95. The drug delivery device of any one of claims 92-94, wherein the siliconized surface is cross-linked silicone.

96. The drug delivery device of any one of claims 92-95, wherein the device in combination with the pharmaceutical composition produces a break loose force that does not exceed 25 N.

97. The drug delivery device of any one of claims 92-96, wherein the device in combination with the pharmaceutical composition produces a break loose force of from about 10 to about 20 N.

98. The drug delivery device of any one of claims 92-97, wherein the device in combination with the pharmaceutical composition produces a glide force that does not exceed 15 N.

99. The drug delivery device of any one of claims 92-98, wherein the device in combination with the pharmaceutical composition produces a glide force of about 5 N to about 15 N.

100. The drug delivery device of any one of claims 92-99, wherein, at the time of use, the pharmaceutical composition has a temperature of about 20°C to about 25°C.

101. The drug delivery device of any one of claims 92-100, wherein the syringe barrel is dimensioned to contain about 2 mL of the pharmaceutical composition.

102. The drug delivery device of any one of claims 92-101, wherein the syringe is disposed within an auto injection device.

103. The drug delivery device of any one of claims 92-102, wherein the syringe further comprises a needle.

104. The drug delivery device of claim 103, wherein the needle is a 23-27 gauge needle.

105. The drug delivery device of claim 103 or 104, wherein the needle is a 27 gauge needle.

106. A method of treating a plasma kallikrein dependent disorder in a subject comprising administering to the subject the pharmaceutical composition of any one of claims 1- 91, thereby to treat the plasma kallikrein dependent disorder.

107. The method of claim 106, wherein the plasma kallikrein dependent disorder is hereditary angioedema (HAE).

108. The method of claim 106 or 107, wherein the subject is a human.

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