Compositions comprising pharmaceutically acceptable salts and other derivatives of glucagon-like peptide-1 receptor agonists and uses thereof

Abstract

Provided herein are compounds comprising an ionic form of a GLP-1 receptor agonist, such as semaglutide, and a counterion thereof, additional esters and prodrug derivatives of semaglutide, and methods of use thereof.

Description

WSGR Docket No.: 56017-729.601 COMPOSITIONS COMPRISING PHARMACEUTICALLY ACCEPTABLE SALTS AND OTHER DERIVATIVES OF GLUCAGON-LIKE PEPTIDE-1 RECEPTOR AGONISTS AND USES THEREOF CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of U.S. Provisional Application No.63 / 558,839 filed on February 28, 2024, U.S. Provisional Application No. 63 / 658,311 filed on June 10, 2024, and U.S. Provisional Application No. 63 / 710,490 filed on October 22, 2024, the entirety of each is incorporated herein by reference. BACKGROUND

[0002] Glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide, are used for the treatment of various diseases or conditions, such as metabolic diseases, and for weight management. However, there are limitations to currently available compositions or formulations containing semaglutide and other GLP-1 receptor agonists, such as poor solubility in an aqueous environment and lower stability, which could lead to limited efficacy and high dosing. Thus, there is a need for better compositions or formulations containing GLP-1 receptor agonists, such as semaglutide. SUMMARY

[0003] In an aspect, provided herein is, inter alia, a compound comprising the structure of Formula I:Formula I, wherein: is an anion of semaglutide; andcationic component.

[0004] In another aspect, provided herein is, inter alia, a compound comprising the structure of Formula I:Formula I, wherein:WSGR Docket No.: 56017-729.601 is an anion of semaglutide; andcationic component, wherein does not have the structure of , wherein R8, R9, and R10are independently C1-C5 alkyl, and R11is C2-C5 alkyl that is unsubstituted or substituted with 1 or more hydroxyl.

[0005] In some embodiments, provided herein is a compound consisting, or consisting essentially, of the structure of Formula I.

[0006] In some embodiments, the anion of semaglutide derives from the structure of the compound in Table 2.

[0007] In some embodiments, the cationic component is selected from the group consisting of alkali metal, alkaline earth metal, a metal ion such as aluminum, sodium, lithium, potassium, magnesium, calcium, and zinc, ammonium (NH4+), a protonated or positively (+) charged ion from an aliphatic primary amine, secondary amine or tertiary amine such as 2-aminoethanol, tromethamine, dimethylamine, diethylamine, N-ethyl-glucamine, hydrabamine, trimethylamine, triethylamine, dicyclohexylamine, ethanolamine, diethanolamine, triethanolamine, dimethylethanolamine, (2,2′,2″-nitrilotris(ethanol)), 2-diethylaminoethanol, procaine or substituted procaine (e.g., chloroprocaine), meglumine, carnitine, ethylenediamine, choline, acetylcholine, aralkyl amine such as Ν,Ν-dibenzylethylenediamine, benzathine, benethamine; heterocyclic aromatic amine such as pyridine, pyrimidine, picoline, quinoline or isoquinoline, quaternary ammonium (e.g., NH4+) such as betaine, nontoxic quaternary ammonium (e.g., NMe4+, N+(C1–4alkyl)4,), tetramethylammonium, tetraethylammonium, benzyltrimethylammonium, benzyltriethylammonium, benzyltributylammonium, methyltrioctylammonium or tetrabutylammonium; 1H-imidazole, substituted-imidazole (e.g., N-alkyl imidazole, N-methyl imidazole), pyrrolidine, substituted pyrrolidine (e.g., 1-alkyl pyrrolidine, 1-methyl pyrrolidine, 1- (2-hydroxy-ethyl)-pyrrolidine), piperidine or substituted piperidine (e.g., 1-alkyl piperidine, 1- methyl piperidine), piperazine or substituted piperazine (e.g., 1-alkyl piperazine, 1-methyl piperazine, 1,4-dialkyl piperazine, 1,4-dimethyl piperazine), morpholine, substituted morpholine (e.g., N-substituted morpholine, N-methyl morpholine or 4-(2-hydroxyethyl)-morpholine), basic amino acid such as arginine, lysine, or histidine. aminoguanidine, guanidine derivatives and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, lower alkyl sulfonate and aryl sulfonate. In some embodiments, the cationic component isWSGR Docket No.: 56017-729.601 not choline. In some embodiments, the cationic component comprises the structure of:

[0008] In some embodiments, the cationic component is selected from the group consisting of alkali metal, alkaline earth metal, a metal ion, ammonium (NH4+), a protonated or positively (+) charged ion from an aliphatic primary amine, secondary amine or tertiary amine , aralkyl amine, benzathine, benethamine; heterocyclic aromatic amine, quaternary ammonium, nontoxic quaternary ammonium, 1H-imidazole, substituted-imidazole, pyrrolidine, substituted pyrrolidine, piperidine or substituted piperidine, piperazine or substituted piperazine, morpholine, substituted morpholine, basic amino acid, aminoguanidine, guanidine derivatives, and an amine cation formed using a counterion.

[0009] In some embodiments, (i) a metal ion comprises aluminum, sodium, lithium, potassium, magnesium, calcium, or zinc; (ii) the aliphatic primary amine, secondary amine, or tertiary amine comprises 2-aminoethanol, tromethamine, dimethylamine, diethylamine, N-ethyl-glucamine, hydrabamine, trimethylamine, triethylamine, dicyclohexylamine, ethanolamine, diethanolamine, triethanolamine, dimethylethanolamine, (2,2′,2″-nitrilotris(ethanol)), 2-diethylaminoethanol, procaine or substituted procaine, meglumine, carnitine, ethylenediamine, choline, or acetylcholine; (iii) aralkyl amine comprises Ν,Ν-dibenzylethylenediamine; (iv) heterocyclic aromatic amine comprises pyridine, pyrimidine, picoline, quinoline, or isoquinoline; (v) quaternary ammonium comprises NH4+or betaine; (vi) nontoxic quaternary ammonium comprises NMe4+, N+(C1–4alkyl)4,), tetramethylammonium, tetraethylammonium, benzyltrimethylammonium, benzyltriethylammonium, benzyltributylammonium, methyltrioctylammonium or tetrabutylammonium; (vii) substituted-imidazole comprises N-alkyl imidazole or N-methyl imidazole; (viii) substituted pyrrolidine comprises 1-alkyl pyrrolidine, 1-methyl pyrrolidine, or 1-(2- hydroxy-ethyl)-pyrrolidine); (ix) substituted piperidine comprises 1-alkyl piperidine or 1-methyl piperidine; (x) substituted piperazine comprises 1-alkyl piperazine, 1-methyl piperazine, 1,4-dialkyl piperazine, or 1,4-dimethyl piperazine; (xi) substituted morpholine comprises N-substituted morpholine, N-methyl morpholine ,or 4-(2- hydroxyethyl)-morpholine); (xii) basic amino acid comprises arginine, lysine, or histidine;WSGR Docket No.: 56017-729.601 (xiii) the amine cation is formed using a counterion selected from the group consisting of halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, lower alkyl sulfonate, and aryl sulfonate; or (xiv) any combination thereof.

[0010] In some embodiments, the substituted procaine comprises chloroprocaine.

[0011] In some embodiments, the cationic component is betaine.

[0012] In some embodiments, the cationic component comprise the structure of.

[0013] In some embodiments, the cationic component is selected from the group consisting of those in Table 3.

[0014] In some embodiments, any of the cationic components of Table 3 is provided in any of the molar ratios and weight ratios of Table 3 relative to one or more anions of semaglutide.

[0015] In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is selected from the group consisting of about 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, and 1:7, or any ratio between any two of these values. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:1 to about 1:7. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:2 to about 1:7. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is about 1:4. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is selected from the group consisting of about 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, and 1:7, or any ratio between any two of these values. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:1 to about 1:7. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraph, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:2 to about 1:7. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is about 1:4. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3. In someWSGR Docket No.: 56017-729.601 embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is selected from the group consisting of about 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, and 1:7, or any ratio between any two of these values. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:1 to about 1:7. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:2 to about 1:7. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is about 1:4. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a weight % (wt. %) ratio relative to the anion of semaglutide as listed in Table 3.

[0016] In some embodiments, the quaternary ammonium has the structure of wherein: R8, R9, R10, and R11are each independently a substituted or unsubstituted group selected from C1- 6 aliphatic, phenyl, cycloalkyl, 4-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0017] In some embodiments, the quaternary ammonium has the structure of wherein: R8, R9, R10, and R11are each independently a substituted or unsubstituted C1-6 aliphatic.

[0018] In some embodiments, the quaternary ammonium has the structure ofwherein: (i) R8, R9, R10, and R11are independently C1-C6alkyl; (ii) R8, R9, R10, and R11are independently C1-C4 alkyl;WSGR Docket No.: 56017-729.601 (iii) R8, R9, and R10are C2 alkyl; and R11is C1 alkyl; (iv) R8, R9, and R10are C4alkyl; and R11is C1alkyl; (v) all of R8, R9, R10, and R11are C1 alkyl; (vi) all of R8, R9, R10, and R11are C2 alkyl; (vii) all of R8, R9, R10, and R11are C3 alkyl; or (viii) all of R8, R9, R10, and R11are C4 alkyl.

[0019] In some embodiments, the cationic component is a quaternary ammonium, wherein the anion of semaglutide and quaternary ammonium are provided in a molar ratio of anion of semaglutide to quaternary ammonium that is selected from the group consisting of about 1:1, 1:2, 1:3, 1:4, 1:5, 1:6 and 1:7, or any ratio between any two of these values. In some embodiments, the cationic component is a quaternary ammonium having the structure of , wherein the anion of semaglutide and quaternary ammonium are provided in a molar ratio of anion of semaglutide to quaternary ammonium that is selected from the group consisting of about 1:1, 1:2, 1:3, 1:4, 1:5, 1:6 and 1:7, or any ratio between any two of these values.

[0020] In some embodiments, the quaternary ammonium has the structure of or.

[0021] In some embodiments, the quaternary ammonium has the structure of.

[0022] In some embodiments, the cationic component is a quaternary ammonium having the structure,, , wherein the anion of semaglutide and quaternary ammonium are provided in a molar ratio of anion of semaglutide to quaternary ammonium that is selected from the group consisting of about 1:1, 1:2, 1:3, 1:4, 1:5, 1:6 and 1:7, or any ratio between any two of these values.WSGR Docket No.: 56017-729.601

[0023] In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is selected from the group consisting of about 1 :2, 1:3, 1:4, 1:5, 1:6, and 1:7.

[0024] In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is about 1:4.

[0025] In some embodiments, a molar ratio of : is selected from the group consistingof about 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, and 1:7.

[0026] In some embodiments, a molar ratio of : is selected from the group consistingof about 1:2, 1:3, 1:4, 1:5, 1:6, and 1:7.

[0027] In some embodiments, a molar ratio of : is about 1:4.

[0028] In some embodiments, provided is a hydrate of the compound of the structure of Formula I. The term “hydrate”, as used herein, means a solid or a semi-solid form of a chemical compound containing water in a molecular complex. The water is generally in a stoichiometric amount with respect to the chemical compound. Exemplary hydrates include (compound of Formula I • ZH2O), wherein Z is from 1 to 50 equivalents of H2O.

[0029] In another aspect, provided herein is a compound comprising the structure of Formula IIa, Formula IIb, Formula IIc, or any combination thereof: Formula IIa,Formula IIb,Formula IIc,WSGR Docket No.: 56017-729.601any combination thereof is one or more cations ofsemaglutide; andanionic component.

[0030] In some embodiments, provided herein is a compound consisting, or consisting essentially, of the structure of Formula IIa, Formula IIb, Formula IIc, or any combination thereof.

[0031] In some embodiments, the one or more cations of semaglutide derive from the structure of the compound in Table 2.

[0032] In some embodiments, the anionic component is selected from the group consisting of besylate, mesylate, tosylate, sulfonate, sulfate, methylsulfate, camsylate, isethionate, edisylate, 1- hydroxy-2-naphthoate, 2,2-dichloroacetate, 2-hydroxyethanesulfonate, 2-oxoglutarate, 4- acetamidobenzoate, 4-aminosalicylate, acetate, adipate, ascorbate, aspartate, benzenesulfonate, benzoate, bromide, chloride, camphorate, camphor-10-sulfonate, caprate (decanoate), caproate (hexanoate), caprylate (octanoate), carbonate, cinnamate, citrate, cyclamate, dodecylsulfate, dodecylsulfurate, ethanesulfonate, ethane-1,2-disulfonate, ethanesulfonate, formate, fumarate, galactarate, gentisate, glucoheptonate, gluconate, glutantate, glucuronate, glutamate, glutarate, glycerophosphorate, glycine, glycolate, hippurate, hydrobromate, hydroiodide, hydrochlorate, isobutyrate, lactate, lactobionate, laurate, lysine, maleate, malate, malonate, mandelate, methanesulfonate , naphthalene-1,5-disulfonate, naphthalene-2-sulfonate, nicotinate, nitrate, oleate, orotate, oxalate, palmitate, pamoate, phosphorate, proprionate, pyroglutamate, salicylate, sebacate, stearate, succinate, sulfurate, tannate, tartarate, thiocyanate, toluenesulfonate, undecylenate, α-lipoate, 12-hydroxystearate, 2-(4-isobutylphenyl)propionate, 2-(4,4-dimethyl-2- pentanyl)-5,7,7-trimethyloctanoate, 2-aminoethanesulfonate, 2-hexyldecanoate, 2- hydroxyhippurate, 3-(4-hydroxyphenyl)propionate, 3-methylcrotonate, 3,3-diphenylpropionate, 3,4-dihydroxbenzoate, ,5-dihydroxybenzoate, 4-acetamido-benzoate, 3,7-dimethyloctanoate, 4- hydroxybenzenesulfonate, 4-hydroxybenzoate, 4-methylhexanoate, 4-methyloctanoate, valerate salts including 4-methylvalerate, 5-norbornene-2-carboxylate, 8-[(2- hydroxybenzoyl)amino]octanoate, abietate, acetylcysteine, aconitate, arachidonate, behenate, caffeate, chenodeoxycholate, citronellate, crotonate, galactonate, deoxycholate, dihydrocaffeate, 2-phenylpropionate (hydratropate), tropate, eicosanedioate, eicosapentanoate (EPA), elaidate, ellagate, erucate, ethylenediaminetetraacetate (EDTA), geranate, heptanoate, hydrocinnamate (3- phenylpropionate), isovalerate, glutathione reduced, lactate, laurate, levulinate, linoleate,WSGR Docket No.: 56017-729.601 linolenate, lithocholate, mesaconate, nonanoate, oxalate, coumarate, palmitate, perillate, pimelate, 3–phenylpropionate, pivalate, propionate, pyruvate, ricinoleate, salicylate, 2-hydroxybenzoate, sinapinate (3,5-dimethoxy-4-hydroxycinnamate), sorbate, syringate, tiglate, 2-decenoate, 2- hexenoate, 2-octenoate, 3-octenoate, 7-octenoate, ferulate, undecanoate, valerate, vanillate, perchlorate, alginate, bisulfate, borate, butyrate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, glycerophosphate, hemisulfate, hydroiodide, lauryl sulfate, 2– naphthalenesulfonate, pectinate, persulfate, phosphate, tartrate, o-(4-hydroxybenzoyl)benzoate, 1,2,-ethanedisulfonate, chlorobenzenesulfonate, 4-methylbicyclo[2.2.2]oct-2-ene-carboxylate, 4.4’-methylenebis(3-hydroxy-2- ene-1-carboxylate), trimethylacetate, tertiary butylacetate, lauryl sulfurate, hydroxynaphthoate, muconate, α-ketoglutarate, p-toluenesulfonate, p-coumarate, and p- chlorobenzenesulfonate.

[0033] In some embodiments, the anionic component is betaine. In some embodiments, the anionic component comprises the structure. In some embodiments, the anionic component has the structure of:.

[0034] In some embodiments, the one or more cations of semaglutide and anionic component are provided in a molar ratio of one or more cations of semaglutide to anionic component of about 1:1, 1:2, 1:3, or 1:4, or any ratio between any two of these values. In some embodiments, the one or more cations of semaglutide and anionic component are provided in a molar ratio of one or more cations of semaglutide to anionic component of from about 1:1 to about 1:4. In some embodiments, the one or more cations of semaglutide and anionic component are provided in a molar ratio of one or more cations of semaglutide to anionic component of from about 1:2 to about 1:4. In some embodiments, the anionic component is selected from the group of anionic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of one or more cations of semaglutide to anionic component that is about 1:1, 1:2, 1:3, or 1:4, or any ratio between any two of these values. In some embodiments, the anionic component is selected from the group of anionic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of one or more cations of semaglutide to anionic component that is from about 1:1 to about 1:4. In some embodiments, the anionic component is selected from the group of anionic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of one or more cations of semaglutide to anionic component that is from about 1:2 to about 1:4. In some embodiments, the anionic component is selected from the group of cationic components listed in Table 4. In some embodiments, theWSGR Docket No.: 56017-729.601 anionic component is selected from the group of anionic components listed in Table 4, further provided in a molar ratio of one or more cations of semaglutide to anionic component that is about 1:1, 1:2, 1:3, or 1:4, or any ratio between any two of these values. In some embodiments, the anionic component is selected from the group of anionic components listed in Table 4, further provided in a molar ratio of one or more cations of semaglutide to anionic component that is from about 1:1 to about 1:4. In some embodiments, the anionic component is selected from the group of anionic components listed in Table 4, further provided in a molar ratio of one or more cations of semaglutide to anionic component that is from about 1:2 to about 1:4. In some embodiments, the anionic component is selected from the group of anionic components listed in Table 4, further provided in a weight % (wt. %) ratio relative to the one or more cations of semaglutide as listed in Table 4.

[0035] In some embodiments, the anionic component is selected from the group consisting of those in Table 4.

[0036] In some embodiments, any of the anionic components of Table 4 is provided in any of the molar ratios and weight ratios of Table 4 relative to one or more cations of semaglutide.

[0037] In some embodiments, the anionic component and cation of semaglutide are provided in a molar ratio of cation of semaglutide to anionic component that is selected from the group consisting of about 1:1, 1:2, 1:3, and 1:4.

[0038] In some embodiments, the anionic component and cation of semaglutide are provided in a molar ratio of cation of semaglutide to anionic component that is selected from the group consisting of about 1:2, 1:3, and 1:4.

[0039] In some embodiments, the anionic component and cation of semaglutide are provided in a molar ratio of cation of semaglutide to anionic component that is about 1:3.

[0040] In some embodiments, the anionic component and cation of semaglutide are provided in a molar ratio of cation of semaglutide to anionic component that is about 1:4.

[0041] In some embodiments, a molar ratio ofanycombination thereof: is selected from the group consisting of about 1:1, 1:2, 1:3, and 1:4.

[0042] In some embodiments, a molar ratio of, , , or anyWSGR Docket No.: 56017-729.601combination thereof: is selected from the group consisting of about 1:2, 1:3, and 1:4.

[0043] In some embodiments, a molar ratio of, , , or anycombination thereof: is about 1:4.

[0044] In some embodiments, a molar ratio of, , , or anycombination thereof: is about 1:3.

[0045] In some embodiments, provided is a hydrate of the compound of the structure of Formula I. Exemplary hydrates include (compound of Formula IIa, Formula IIb, Formula IIc, or any combination thereof • ZH2O), wherein Z is from 1 to 50.

[0046] In some embodiments,(ii) a weight % (wt. %) ratio of, , , or any combination thereof is from about 0.1 wt. %: 99.9 wt. % to about 20.0 wt. %: 80.0 wt. %.

[0047] In some embodiments, (i) a molar ratio of : is from about 2:1 to about 10:1; or(ii) a molar ratio of, or any combination thereof is fromabout 2:1 to about 10:1.WSGR Docket No.: 56017-729.601

[0048] In some embodiments, (i) a molar ratio of :is from about 2:1 to about 7:1; or(ii) a molar ratioany combination thereof is fromabout 2:1 to about 7:1.

[0049] In some embodiments, (i) a molar ratio of :is from about 3:1 to about 7:1; or(ii) a molar ratio of, or any combination thereof is fromabout 3:1 to about 7:1.

[0050] In some embodiments, (i) a molar ratio of :is from about 4:1 to about 7:1; or(ii) a molar ratioany combination thereof is fromabout 4:1 to about 7:1.

[0051] In some embodiments, (i) a molar ratio of : is from about 3:1 to about 7:1; or(ii) a molar ratio of, or any combination thereof is about4:1.

[0052] In some embodiments,WSGR Docket No.: 56017-729.601 (i) a molar ratio of : is from about 3:1 to about 7:1; or (ii) a molar ratio of, , , or any combination thereof is about 4:1.

[0053] In another aspect, provided herein is a compound comprising the structure of Formula IIIa:Formula IIIa, or a pharmaceutically acceptable salt thereof, wherein:is a covalent derivative of one or more carboxyl groups of semaglutide, or a pharmaceutically acceptable salt thereof; and each R100is as defined herein.

[0054] In some embodiments, R100is methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, tert- butyl, or pentyl, fluoromethyl, difluoromethyl, trifluoromethyl, CHCH3OC(O)OCH2CH, -CH3, - CH2CH3, -CH(CH3)2, CH2CH2CH2CH3, C(CH3)3, -CH2CH2N(CH3)3+,substituted C1-6aliphatic, unsubstituted C1-6 aliphatic, substituted (C1-22)alkyl, unsubstituted (C1-22)alkyl, substituted (C1- 22)alkenyl, unsubstituted (C1-22)alkenyl, substituted phenyl, unsubstituted phenyl, substituted - C(O)R, unsubstituted -C(O)R, substituted -C(O)OR, unsubstituted -C(O)OR, substituted - C(O)N(R)2, unsubstituted -C(O)N(R)2, (C2-C12)alkanoyloxymethyl, 1-(alkanoyloxy)ethyl having from 4 to 9 carbon atoms, 1-methyl-1-(alkanoyloxy)-ethyl having from 5 to 10 carbon atoms, alkoxycarbonyloxymethyl having from 3 to 6 carbon atoms, 1-(alkoxycarbonyloxy)ethyl having from 4 to 7 carbon atoms, 1-methyl-1-(alkoxycarbonyloxy)ethyl having from 5 to 8 carbon atoms, N-(alkoxycarbonyl)aminomethyl having from 3 to 9 carbon atoms, 1-(N- (alkoxycarbonyl)amino)ethyl having from 4 to 10 carbon atoms, 3-phthalidyl, 4-crotonolactonyl, gamma-butyrolacton-4-yl, di-N,N-(C1-C2)alkylamino(C2-C3)alkyl (such as β- dimethylaminoethyl), carbamoyl-(C1-C2)alkyl, N,N-di(C1-C2)alkylcarbamoyl-(C1-C2)alkyl, piperidino-, pyrrolidino- or morpholino(C2-C3)alkyl, C1-6 aliphatic, (C1-22)alkyl, (C1-22)alkenyl, -WSGR Docket No.: 56017-729.601 C(O)R, -C(O)OR, -C(O)N(R)2, phenyl, 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, an 8-10 membered bicyclic aromatic carbocyclic ring, a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and each occurrence of R is independently hydrogen or an optionally substituted group selected from C1-6 aliphatic, a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic aromatic carbocyclic ring, a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0055] In some embodiments, the compound of Formula IIIa does not have the structure ofFormula II, wherein R8, R9, and R10are independently C1-C5 alkyl.

[0056] In another aspect, provided herein is a compound comprising the structure of Formula IIIb:Formula IIIb or a pharmaceutically acceptable salt thereof; wherein:is a covalent derivative of one or more hydroxyl groups of semaglutide, or a pharmaceutically acceptable salt thereof; and each R101is as defined herein.

[0057] In some embodiments, R101is selected from the group consisting of -CH2R, -C(O)R, - C(O)OR, -C(O)N(R)2, -OP(O)OROR, wherein each occurrence of R is independently hydrogen or an optionally substituted group selected from C1-6 aliphatic, a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic aromaticWSGR Docket No.: 56017-729.601 carbocyclic ring, a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or

[0058] R101is -CH2OCH2CH2OH, unsubstituted C(O)C1-6alkyl, substituted C(O)C1-6alkyl, substituted C(O)phenyl or unsubstituted C(O)phenyl, -(C1-C6)alkanoyloxymethyl, -1-((C1- C6)alkanoyloxy)ethyl, -1-methyl-1-((C1-C6)alkanoyloxy)ethyl, -(C1- C6)alkoxycarbonyloxymethyl, -N-(C1-C6)alkoxycarbonylaminomethyl, -succinoyl, -(C1- C6)alkanoyl, -α-amino(C1-C4)alkanoyl, -arylacyl, -α-aminoacyl, or -α-aminoacyl-α-aminoacyl, optionally, wherein each α-aminoacyl group is independently selected from the naturally occurring L-amino acids, P(O)(OH)2, -P(O)(O(C1-C6)alkyl)2 or glycosyl, and optionally, wherein the radical results from the removal of a hydroxyl group of the hemiacetal form of a carbohydrate.

[0059] In some embodiments, R101is the unsubstituted C(O)C1-6alkyl comprising COCH3, COCH2CH3, or COCH(CH3)2), or R101is the substituted C(O)C1-6alkyl comprising COCF3, COCHCF2, or -COCH2CF.

[0060] In some embodiments, R101is -C(O)R selected from the group consisting of -C(O)CH3 and -C(O)H, -C(O)OR that is -C(O)OH2), -C(O)N(R)2 selected from the group consisting of - C(O)NH2 and -C(O)N(CH3)2), or -OP(O)OROR that is -OP(O)OHOH.

[0061] In some embodiments, R101is -CHCH3OC(O)OCH2CH3.

[0062] In another aspect, provided herein is a compound comprising the structure of Formula IIIc and / or Formula IIId:Formula IIIc Formula IIId or a pharmaceutically acceptable salt of each thereof; wherein:WSGR Docket No.: 56017-729.601is each a covalent derivative of one or more amino or imidazole groups of semaglutide, or a pharmaceutically acceptable salt thereof; and each of R102and R103is as defined herein.

[0063] In some embodiments, each of R102and R103is independently selected from the group consisting of -CH2R, -C(O)R, -C(O)OR, -C(O)N(R)2, -OP(O)OROR, wherein each occurrence of R is independently hydrogen or an optionally substituted group selected from C1-6 aliphatic, a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic aromatic carbocyclic ring, a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each R102and R103is independently C(O)R, C(O)OR, C(O)R’, or C(O)NR’R”, where R’ and R” are each independently (C1-C10)alkyl, (C3-C7)cycloalkyl, benzyl, or each R102and R103is a natural α-aminoacyl or natural α-aminoacyl-natural α-aminoacyl, - C(OH)C(O)OY1, wherein Y1is H, (C1-C6)alkyl or benzyl, -C(OY2)Y3, wherein Y2is (C1-C4) alkyl and Y3is (C1-C6)alkyl, carboxy(C1-C6)alkyl, amino(C1-C4)alkyl or mono-N-or di-N,N-(C1- C6)alkylaminoalkyl, -C(Y4)Y5, wherein Y4is H or methyl and Y5is mono-N- or di-N,N-( C1- C6)alkylamino, morpholino, piperidin-1-yl or pyrrolidin-1-yl.

[0064] In some embodiments, each R102and R103is independently -CH2OCH2CH2OH or unsubstituted C(O)C1-6alkyl.

[0065] In some embodiments, R102is substituted C(O)C1-6alkyl comprising COCF3, COCHCF2, or -COCH2CF.

[0066] In some embodiments, R102is substituted C(O)phenyl or unsubstituted C(O)phenyl.

[0067] In some embodiments, R102is CHCH3OC(O)OCH2CH3.

[0068] As used herein, the term “pharmaceutically acceptable salt” refers to any of the cationic components or anionic components described herein.

[0069] In another aspect, provided herein is a pharmaceutical composition comprising theWSGR Docket No.: 56017-729.601 compound as provided herein, and a pharmaceutically acceptable excipient.

[0070] In some embodiments, the pharmaceutical composition is formulated for parenteral administration, oral administration, or implantable administration.

[0071] In some embodiments, the pharmaceutical composition is formulated for subcutaneous administration or intravenous administration.

[0072] In another aspect, provided herein is a drug delivery device comprising the compound as provided herein or the pharmaceutical composition as provided herein.

[0073] In some embodiments, the drug delivery device is a syringe, a single-dose pen with an injection needle, or an autoinjector with an injection needle.

[0074] In some embodiments, the drug delivery device is an implantable osmotic drug delivery device.

[0075] In another aspect, provided herein is a kit comprising the compound as provided herein, the pharmaceutical composition as provided herein, or the drug delivery device as provided herein.

[0076] In some embodiments, the kit as provided herein further comprises an instruction for use.

[0077] In another aspect, provided herein is a method of treating a disease or disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound as provided herein, or the pharmaceutical composition as provided herein, wherein the administering is effective to treat the disease or disorder in the subject.

[0078] In another aspect, provided herein is the compound as provided herein or the pharmaceutical composition as provided herein for use in a method of treating a disease or disorder in a subject in need thereof by administering to the subject a therapeutically effective amount of the compound as provided herein, or the pharmaceutical composition as provided herein, wherein the administering is effective to treat the disease or disorder in the subject.

[0079] In another aspect, provided herein is use of the compound as provided herein or the pharmaceutical composition as provided herein in a method of treating a disease or disorder in a subject in need thereof by administering to the subject a therapeutically effective amount of the compound as provided herein, or the pharmaceutical composition as provided herein, wherein the administering is effective to treat the disease or disorder in the subject.

[0080] In some embodiments, the compound or the pharmaceutical composition is administered to the subject using the drug delivery device as provided herein.

[0081] In some embodiments, the disease or disorder is a metabolic disease or disorder, a cardiovascular disease or disorder, chronic kidney disease, or a neurological disease or disorder.

[0082] In some embodiments, the disease or disorder is selected from the group consisting of type 1 diabetes, type 2 diabetes, obesity, overweight, metabolic dysfunction–associated fatty liverWSGR Docket No.: 56017-729.601 disease (MAFLD), metabolic dysfunction-associated steatohepatitis (MASH), and nonalcoholic steatohepatitis (NASH).

[0083] In some embodiments, the disease or disorder is selected from the group consisting of arrhythmia, coronary artery disease, heart failure, valve disease, aortic disease, congenital heart disease, heart attack, angina, cardiomyopathy, peripheral arterial disease, atherosclerosis, cardiac dysrhythmias, pericarditis, pulmonary hypertension, stroke, cerebrovascular disease, rheumatic heart disease, atrial fibrillation, Brugada syndrome, aortic stenosis, bradycardia, endocarditis, high cholesterol, and long QT syndrome.

[0084] In some embodiments, the disease or disorder is Parkinson’s disease or Alzheimer disease.

[0085] In some embodiments, the subject is human.

[0086] In some embodiments, the compound or the pharmaceutical composition is administered to the subject via parenteral administration, oral administration, or implantable administration.

[0087] In some embodiments, the compound or the pharmaceutical composition is administered to the subject via subcutaneous administration or intravenous administration.

[0088] In another aspect, provided herein is a method of reducing weight in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound as provided herein or the pharmaceutical composition as provided herein, wherein the administering is effective to reduce weight in the subject.

[0089] In another aspect, provided herein is the compound as provided herein or the pharmaceutical composition as provided herein for use in a method of reducing weight in a subject in need thereof by administering to the subject a therapeutically effective amount of the compound as provided herein or the pharmaceutical composition as provided herein, wherein the administering is effective to reduce weight in the subject.

[0090] In another aspect, provided herein is use of the compound as provided herein or the pharmaceutical composition as provided herein in a method of reducing weight in a subject in need thereof by administering to the subject a therapeutically effective amount of the compound as provided herein, or the pharmaceutical composition as provided herein, wherein the administering is effective to reduce weight in the subject.

[0091] In some embodiments, the compound or the pharmaceutical composition is administered to the subject using the drug delivery device as provided herein.

[0092] In some embodiments, the subject is human.

[0093] In some embodiments, the subject has obesity or is overweight.

[0094] In some embodiments, the compound or the pharmaceutical composition is administered to the subject via parenteral administration, oral administration, or implantable administration.WSGR Docket No.: 56017-729.601

[0095] In some embodiments, the compound or the pharmaceutical composition is administered to the subject via subcutaneous administration or intravenous administration. BRIEF DESCRIPTION OF THE DRAWINGS

[0096] FIG. 1 shows the chemical structure of an exemplary GLP-l receptor agonist, semaglutide. The squares depict the ionizable carboxylates, and the circles depict the ionizable basic amino groups of semaglutide.

[0097] FIG.2A shows a photograph of a representative clear solution (C) of an exemplary salt of semaglutide in water, and FIG. 2B shows a photograph of a representative solution of semaglutide free acid (i.e., base form) having visible precipitation (P) in water, both of which were obtained from Example 8.

[0098] FIG. 3A, FIG. 3B and FIG. 3C show the solubility of various exemplary salts of semaglutide at high and low temperature for extended periods, as shown by the data obtained in Example 9: solubility studies of various exemplary salts of semaglutide. FIG. 3A demonstrates that an exemplary salt of semaglutide, the choline-semaglutide salt, exhibited improved solubility in both water (right graph) and DMSO (left graph) at low and high temperatures over 40 days. FIG. 3B demonstrates that another exemplary salt of semaglutide, the sodium-semaglutide salt, was insoluble in DMSO at low temperature, e.g., at 4 ^C, and had reproducibly intermittent solubility in water at elevated temperatures, e.g., at 37 ^C. FIG. 3C demonstrates that the semaglutide free acid (i.e., base form) was too insoluble in DMSO, even at the low concentration of 1 mg / mL, to obtain data via this RP-HPLC assay due to excess precipitation.

[0099] FIG. 4 shows data from thioflavin T fluorescence aggregation studies as described in Example 10, comparing the propensity of aggregation of semaglutide free acid (i.e., base form), and exemplary salts of semaglutide, i.e., the choline-semaglutide salt and the sodium-semaglutide salt, as aqueous solutions at 1 mg / mL and 5 mg / mL.

[0100] FIG. 5 shows 1H proton nuclear magnetic resonance (NMR) spectra of choline (at baseline, fourth spectrum from top), semaglutide free acid (third spectrum from top), choline- semaglutide having a molar ratio of semaglutide:choline of 1:4 (second spectrum from top). and sodium-semaglutide having a molar ratio of semaglutide:sodium of 1:4 (top spectrum). DETAILED DESCRIPTION

[0101] Provided herein is a compound comprising an ionic form (i.e., salt form) of a therapeutic agent, particularly a GLP-1 receptor agonist, such as semaglutide, and a counterion thereof. In some embodiments, semaglutide is in a cationic form and the counterion is an anion. In some embodiments, semaglutide is in an anionic form and the counterion is a cation. In some embodiments, the compound is a salt composed of an ionic form of semaglutide and a counterionWSGR Docket No.: 56017-729.601 thereof. In some embodiments, semaglutide is a cationic component of the salt and the counterion is an anionic component of the salt. In some embodiments, semaglutide is an anionic component of the salt and the counterion is a cationic component of the salt. Semaglutide belongs to a class of medications known as glucagon-like peptide-1 (GLP-1) receptor agonists. It mimics the GLP- 1 hormone that is released in the gastrointestinal tract in response to eating. One role of GLP-1s, such as semaglutide, is to prompt the body to produce more insulin, which reduces blood glucose (sugar). Dosing of GLP-1s, such as semaglutide, particularly in higher concentrations, promotes interaction with the parts of the brain that reduce appetite and signal a feeling of satiety or fullness.

[0102] There are currently three U.S. Food and Drug Administration (FDA)-approved semaglutide products (all marketed by Novo Nordisk A / S headquartered in Copenhagen Denmark): • Ozempic^injection and Rybelsus^tablets are approved to lower blood sugar levels in adults with type 2 diabetes mellitus, in addition to diet and exercise. Ozempic^is also approved to reduce the risk of heart attack, stroke, or death in adults with type 2 diabetes mellitus and known heart disease. • Wegovy^injection is approved to help adults and children aged 12 years and older with obesity or some adults with excess weight (overweight), who also have weight-related medical problems, to lose weight and keep the weight off, in addition to diet and exercise.

[0103] Semaglutide has an amino acid sequence similar to human GLP-1, augmented by several improvements in chemical structure that render semaglutide a far superior therapeutic and more “drug-like” than endogenous GLP-1. The first six amino acids of GLP-1 are missing from the amino acid sequence of semaglutide. Substitutions are made at GLP-1 positions 8 and 34 (semaglutide positions 2 and 28) such that alanine and lysine are replaced by 2-aminoisobuteric acid and arginine, respectively. The former substitution deters breakdown by endogenous enzymes including dipeptidyl peptidase-IV, and thus enhances metabolic stability of semaglutide relative to GLP-1. Semaglutide is further modified at the lysine of position 20 by covalent attachment of a long C18 lipophilic side chain ending with a carboxylate group that increases semaglutide’s binding affinity to blood protein (albumin), which significantly prolongs the presence of this peptide in blood circulation. Consequently, semaglutide's elimination half-life (t1 / 2) from blood is about seven days (165–184 hours) vs human GLP-1’s t1 / 2 of several minutes which renders semaglutide amenable to weekly subcutaneous injection. Semaglutide comprises seven ionizable carboxylate groups, inclusive of the carboxylate group described above. Ozempic^and Wegovy^injections and the Rybelsus^tablets are all formulated as the “free acid” with respect to the ionizable carboxylate groups of semaglutide.

[0104] Applicant has discovered that semaglutide, despite being optimized for “drug-likeness”WSGR Docket No.: 56017-729.601 with respect to its amino acid sequence and chemical structure, is nonetheless unoptimized for drug-likeness with respect to potential ionic salt, ester and / or prodrug forms of this peptide. Not only is the choice of salt, ester and / or prodrug form, among numerous possibilities, critical to enhancement of certain drug like properties of semaglutide, but so too is the number of ester or prodrug moieties employed or stoichiometry of salt form employed, where either the weight / weight ratio (i.e., wt. % or % w / w) of any given salt to semaglutide peptide, generally ranging from 0.1 wt. % to 50.0 wt. % salt relative to 99.9 wt. % to 50.0 wt. % semaglutide, or molar ratio of any given salt to semaglutide peptide, generally ranging from 1:1 to 100:1, can be used to further “tune” certain desired drug like properties of this peptide relative to those of the unoptimized free acid of semaglutide.

[0105] From myriad potential permutations, Applicant conducted comparative experimentation and analyses of the resulting data to identify certain ionic salt forms, esters and prodrugs of semaglutide, in certain wt. % ratios of salt to semaglutide, generally ranging from 0.1 wt. % to 50.0 wt. % salt relative to 99.9 wt. % to 50.0 wt. % semaglutide, or in certain molar ratios from 1:1 to 100:1 of salt, ester and / or prodrug to semaglutide, that provide surprising advantages including enhanced stability and improved solubility in an aqueous environment relative to known injectable and oral administrations of the free acid of semaglutide.

[0106] Accordingly, provided are improved pharmaceutical compositions comprising disclosed salt forms of semaglutide, and in some embodiments having wt. % ratios of salt to semaglutide from 0.1 wt. % to 50.0 wt. % salt relative to 99.9 wt. % to 50.0 wt. % semaglutide, or molar ratios of salt, ester or prodrug moiety to semaglutide from 1:1 to 100:1, that have been formulated to selectively reduce the propensity for detrimental qualities, including poor solubility in an aqueous environment at any given dose relative to existing “free acid” formulation of semaglutide. As such, improved pharmaceutical compositions comprising disclosed salt forms of semaglutide of the present invention may permit lower dosing (and reduced cost of goods, i.e., COGs) as an additional means to achieve greater efficacy than existing “free acid” formulations of semaglutide. Definitions

[0107] Certain specific details of this description are set forth in order to provide a thorough understanding of various embodiments. However, one skilled in the art will understand that the present disclosure may be practiced without these details. In other instances, well-known structures have not been shown or described in detail to avoid unnecessarily obscuring descriptions of the embodiments.

[0108] Unless the context requires otherwise, throughout the specification and claims whichWSGR Docket No.: 56017-729.601 follow, the word “comprise” and variations thereof, such as, “comprises” and “comprising,” as used herein, are to be construed in an open, inclusive sense, that is, as “including, but not limited to.” Further, headings provided herein are for convenience only and do not interpret the scope or meaning of the claimed disclosure.

[0109] As used in this specification and the appended claims, the singular forms “a,” “an,” and “the,” as used herein, include plural referents unless the content clearly dictates otherwise. The use of the words “a” or “an,” as used herein, when used in conjunction with the term “comprising” herein may mean “one,” but it is also consistent with the meaning of “one or more,” “at least one,” and “one or more than one.”

[0110] It should also be noted that the term “or,” as used herein, is generally employed in its sense including “and / or” unless the content clearly dictates otherwise.

[0111] Unless otherwise defined, 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 disclosure belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present disclosure, suitable methods and materials are described below.

[0112] The term “about,” as used herein, when referring to a measurable value such as an amount, a temporal duration, and the like, is meant to encompass variations of ±20% or in some instances ±10%, or in some instances ±5%, or in some instances ±1%, or in some instances ±0.1% from the specified value, as such variations are appropriate to perform the disclosed methods. As used herein, “about” and “approximately” generally mean an acceptable degree of error for the quantity measured given the nature or precision of the measurements. Exemplary degrees of error are within 20 percent (%), typically, within 10%, and more typically, within 5% of a given range of values.

[0113] The terms “polypeptide”, “peptide” and “protein” (if single chain) are used interchangeably herein to refer to polymers of amino acids of any length. The polymer may be linear or branched, it may comprise modified amino acids, and it may be interrupted by non-amino acids. The terms also encompass an amino acid polymer that has been modified; for example, disulfide bond formation, glycosylation, lipidation, acetylation, phosphorylation, or any other manipulation, such as conjugation with a labeling component. The polypeptide can be isolated from natural sources, can be a produced by recombinant techniques from a eukaryotic or prokaryotic host, or can be a product of synthetic procedures.

[0114] The terms “nucleic acid,” “nucleic acid sequence,” “nucleotide sequence,” or “polynucleotide sequence,” and “polynucleotide” are used interchangeably. As used herein, they refer to a polymeric form of nucleotides of any length, either deoxyribonucleotides orWSGR Docket No.: 56017-729.601 ribonucleotides, or analogs thereof. The polynucleotide may be either single-stranded or double- stranded, and if single-stranded may be the coding strand or non-coding (antisense) strand. A polynucleotide may comprise modified nucleotides, such as methylated nucleotides and nucleotide analogs. The sequence of nucleotides may be interrupted by non-nucleotide components. A polynucleotide may be further modified after polymerization, such as by conjugation with a labeling component. The nucleic acid may be a recombinant polynucleotide, or a polynucleotide of genomic, cDNA, semisynthetic, or synthetic origin which either does not occur in nature or is linked to another polynucleotide in a non-natural arrangement.

[0115] The compositions and methods as provided herein encompass polypeptides and nucleic acids having the sequences specified, or sequences substantially identical or similar thereto, e.g., sequences at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%. 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, or 99.9% identical or higher to the sequence specified. In the context of an amino acid sequence, the term “substantially identical” is used herein to refer to a first amino acid that contains a sufficient or minimum number of amino acid residues that are i) identical to, or ii) conservative substitutions of aligned amino acid residues in a second amino acid sequence such that the first and second amino acid sequences can have a common structural domain and / or common functional activity. For example, amino acid sequences that contain a common structural domain having at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%.97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to a reference sequence, e.g., a sequence provided herein. In the context of nucleotide sequence, the term “substantially identical” is used herein to refer to a first nucleic acid sequence that contains a sufficient or minimum number of nucleotides that are identical to aligned nucleotides in a second nucleic acid sequence such that the first and second nucleotide sequences encode a polypeptide having common functional activity, or encode a common structural polypeptide domain or a common functional polypeptide activity. For example, nucleotide sequences having at least about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%. 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to a reference sequence, e.g., a sequence provided herein.

[0116] Calculations of homology or sequence identity between sequences (the terms are used interchangeably herein) are performed as follows. To determine the percent identity of two amino acid sequences, or of two nucleic acid sequences, the sequences are aligned for optimal comparison purposes (e.g., gaps can be introduced in one or both of a first and a second amino acid or nucleic acid sequence for optimal alignment and non-homologous sequences can beWSGR Docket No.: 56017-729.601 disregarded for comparison purposes). In a preferred embodiment, the length of a reference sequence aligned for comparison purposes is at least 30%, preferably at least 40%, more preferably at least 50%, 60%, and even more preferably at least 70%, 80%, 90%, 100% of the length of the reference sequence. The amino acid residues or nucleotides at corresponding amino acid positions or nucleotide positions are then compared. When a position in the first sequence is occupied by the same amino acid residue or nucleotide as the corresponding position in the second sequence, then the molecules are identical at that position (as used herein amino acid or nucleic acid “identity” is equivalent to amino acid or nucleic acid “homology”).

[0117] The percent identity between the two sequences is a function of the number of identical positions shared by the sequences, taking into account the number of gaps, and the length of each gap, which need to be introduced for optimal alignment of the two sequences. The comparison of sequences and determination of percent identity between two sequences can be accomplished using a mathematical algorithm. In a preferred embodiment, the percent identity between two amino acid sequences is determined using the Needleman and Wunsch ((1970) J. Mol. Biol. 48:444-453 ) algorithm which has been incorporated into the GAP program in the GCG software package (available at http: / / www.gcg.com), using either a Blossum 62 matrix or a PAM250 matrix, and a gap weight of 16, 14, 12, 10, 8, 6, or 4 and a length weight of 1, 2, 3, 4, 5, or 6. In yet another preferred embodiment, the percent identity between two nucleotide sequences is determined using the GAP program in the GCG software package (available at http: / / www.gcg.com), using a NWSgapdna.CMP matrix and a gap weight of 40, 50, 60, 70, or 80 and a length weight of 1, 2, 3, 4, 5, or 6. A particularly preferred set of parameters (and the one that should be used unless otherwise specified) are a Blossum 62 scoring matrix with a gap penalty of 12, a gap extend penalty of 4, and a frameshift gap penalty of 5.

[0118] The percent identity between two amino acid or nucleotide sequences can be determined using the algorithm of E. Meyers and W. Miller ((1989) CABIOS, 4:11-17) which has been incorporated into the ALIGN program (version 2.0), using a PAM120 weight residue table, a gap length penalty of 12 and a gap penalty of 4. The nucleic acid and protein sequences described herein can be used as a “query sequence” to perform a search against public databases to, for example, identify other family members or related sequences. Such searches can be performed using the NBLAST and XBLAST programs (version 2.0) of Altschul, et al. (1990) J. Mol. Biol. 215:403-10. BLAST nucleotide searches can be performed with the NBLAST program, score = 100, wordlength = 12 to obtain nucleotide sequences homologous to a nucleic acid molecule . BLAST protein searches can be performed with the XBLAST program, score = 50, wordlength = 3 to obtain amino acid sequences homologous to protein molecules . To obtain gapped alignments for comparison purposes, Gapped BLAST can be utilized as described in Altschul et al., (1997)WSGR Docket No.: 56017-729.601 Nucleic Acids Res. 25:3389-3402. When utilizing BLAST and Gapped BLAST programs, the default parameters of the respective programs (e.g., XBLAST and NBLAST) can be used.

[0119] The term “agonist,” as used herein, refers to a molecule or an agent that activates a receptor to produce a biological response. In contrast, the term “antagonist,” as used herein, refers to a molecule or an agent that blocks the action of the agonist, and the term “inverse agonist,” as used herein, refers to a molecule or an agent that causes an action opposite to that of the agonist. In some embodiments, the agonist may be an endogenous agonist. In some embodiments, the agonist may be an exogenous agonist. In some embodiments, the agonist may be a polypeptide. In some embodiments, the agonist may be a polynucleotide, a nucleoside, an amino acid, a sugar, a carbohydrate, a lipid, or any combination thereof. In some embodiments, the agonist may be a chemical.

[0120] The term “variant,” as used herein, refers to a polypeptide that has a substantially identical amino acid sequence to a reference amino acid sequence, or is encoded by a substantially identical nucleotide sequence. In some embodiments, the variant is a functional variant. In some embodiments, a GLP-1 receptor agonist variant can bind to GLP-1 receptor and activate the GLP- 1 receptor signaling.

[0121] The term “functional variant,” as used herein, refers to a polypeptide that has a substantially identical amino acid sequence to a reference amino acid sequence, or is encoded by a substantially identical nucleotide sequence, and is capable of having one or more activities of the reference amino acid sequence.

[0122] The term “functional fragment,” as used herein, refers to a polypeptide that has a partial amino acid sequence of a reference amino acid sequence, and is capable of having one or more activities of the reference amino acid sequence. In some embodiments, the functional fragment comprises at least about 30%, 35%, 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98% 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, or 99.9% amino acid sequence of a reference amino acid sequence. In some embodiments, the functional fragment comprises an amino acid sequence that has at most 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50 amino acid deletion from the reference amino acid sequence. In some embodiments, the functional fragment comprises an amino acid sequence that has at least 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 55, 60, 65, 70, 75, 80, 85, 90, 95, 100, 110, 120, 130, 140, 150, 160, 170, 180, 190, 200, 210, 220, 230, 240, 250, 260, 270, 280, 290, 300, 350, 400, 450, or 500 amino acids of the reference amino acid sequence.WSGR Docket No.: 56017-729.601

[0123] It is understood that the polypeptide as described herein may have additional conservative or non-essential amino acid substitutions, which do not have a substantial effect on their functions.

[0124] The term “amino acid,” as used herein, is intended to embrace all molecules, whether natural or synthetic, which include both an amino functionality and an acid functionality and capable of being included in a polymer of naturally-occurring amino acids. Exemplary amino acids include naturally-occurring amino acids; analogs, derivatives and congeners thereof; amino acid analogs having variant side chains; and all stereoisomers of any of any of the foregoing. As used herein the term “amino acid” includes both the D- or L- optical isomers and peptidomimetics.

[0125] A “conservative amino acid substitution,” as used herein, is one in which the amino acid residue is replaced with an amino acid residue having a similar side chain. Families of amino acid residues having similar side chains have been defined in the art. These families include amino acids with basic side chains (e.g., lysine, arginine, histidine), acidic side chains (e.g., aspartic acid, glutamic acid), uncharged polar side chains (e.g., glycine, asparagine, glutamine, serine, threonine, tyrosine, cysteine), nonpolar side chains (e.g., alanine, valine, leucine, isoleucine, proline, phenylalanine, methionine, tryptophan), beta-branched side chains (e.g., threonine, valine, isoleucine) and aromatic side chains (e.g., tyrosine, phenylalanine, tryptophan, histidine).

[0126] As used herein, the term “molecule” as used in, e.g., agonist molecule, polypeptide molecule, or receptor molecule, includes full-length, naturally-occurring molecules, as well as variants, e.g., functional variants (e.g., truncations, fragments, mutated (e.g., substantially similar sequences) or derivatized form thereof), so long as at least one function and / or activity of the unmodified (e.g., naturally-occurring) molecule remains.

[0127] The term “salt” and “salt form” as used interchangeably herein, refer to a compound comprising an ionic assembly of positively charged cationic components (also known as positive ions and cations) and negatively charged anionic components (also known as negative ions and anions). In some embodiments, the salt is a neutral compound with no net electric charge. In some embodiments, the cationic components and the anionic components are held together by electrostatic forces termed ionic bonds.

[0128] The term “glucagon-like peptide-1 (GLP-1),” as used herein, refers to a 30- or 31-amino- acid-long peptide hormone deriving from the tissue-specific posttranslational processing of the proglucagon peptide. As referred to herein, GLP-1 includes any of the recombinant or naturally- occurring forms of GLP-1 or variants or homologs thereof that have or maintain the GLP-1 activity (e.g., at least 40% 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity). In some aspects, the variants or homologs have at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%. 97%, 98%, 99%, 99.1%, 99.2%, 99.3%,WSGR Docket No.: 56017-729.601 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g., a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring GLP-1. In some embodiments, GLP-1 is substantially identical to the protein identified by the UniProt reference number P01275 or a variant or homolog having substantial identity thereto.

[0129] The term “glucagon-like peptide-1 (GLP-1) receptor,” as used herein, refers to a G protein-coupled receptor found on cells and involved in the control of blood sugar level via regulation of insulin secretion. In some embodiments, the GLP-1 receptor is involved in the control of blood sugar level by enhancing the insulin secretion. In some embodiments, the GLP- 1 receptor is expressed on beta cells of the pancreas. In some embodiments, the GLP-1 receptor is expressed on neurons of the brain. As referred to herein, the GLP-1 receptor includes any of the recombinant or naturally-occurring forms of the GLP-1 receptor or variants or homologs thereof that have or maintain the GLP-1 receptor activity (e.g., at least 40% 50%, 60%, 70%, 80%, 90%, 95%, 96%, 97%, 98%, 99% or 100% activity). In some aspects, the variants or homologs have at least 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%. 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% amino acid sequence identity across the whole sequence or a portion of the sequence (e.g., a 50, 100, 150 or 200 continuous amino acid portion) compared to a naturally occurring GLP-1 receptor. In some embodiments, the GLP-1 receptor is substantially identical to the protein identified by the UniProt reference number P43220 or a variant or homolog having substantial identity thereto.

[0130] The term “GLP-1 receptor agonist,” as used herein, refers to a molecule or an agent that activates the GLP-1 receptor to produce a biological response. In some embodiments, the GLP-1 receptor agonist induced regulation of the insulin secretion via activation of the GLP-1 receptor, thereby, leading to control of blood sugar level. In some embodiments, the GLP-1 receptor agonist induced enhancing the insulin secretion via activation of the GLP-1 receptor, thereby, leading to control of blood sugar level. In some embodiments, the GLP-1 receptor agonist mimics the GLP- 1 hormone, which is released in the gastrointestinal tract in response to eating. In some embodiments, the GLP-1 receptor agonist prompts the body to produce more insulin, which reduces the blood glucose. In some embodiments, the GLP-1 receptor agonist, for example, in higher concentrations, promotes interaction with the parts of the brain that reduce appetite and signal a feeling of satiety or fullness. In some embodiments, the GLP-1 receptor agonist may be an endogenous agonist. In some embodiments, the GLP-1 receptor agonist may be an exogenous agonist. In some embodiments, the GLP-1 receptor agonist may be a polypeptide. In some embodiments, the GLP-1 receptor agonist may be a polynucleotide, a nucleoside, an amino acid,WSGR Docket No.: 56017-729.601 a sugar, a carbohydrate, a lipid, or any combination thereof. In some embodiments, the GLP-1 receptor agonist may be a small molecule. Compounds and Salts

[0131] Compounds and salts of the present invention include those described generally herein. As used herein, the following definitions shall apply unless otherwise indicated. For purposes of this invention, the chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75thEd. Additionally, general principles of organic chemistry are described in “Organic Chemistry”, Thomas Sorrell, University Science Books, Sausalito: 1999, and “March’s Advanced Organic Chemistry”, 5thEd., Ed.: Smith, M.B. and March, J., John Wiley & Sons, New York: 2001, the entire contents of which are hereby incorporated by reference.

[0132] The term “aliphatic” or “aliphatic group”, as used herein, means a straight-chain (i.e., unbranched) or branched, substituted or unsubstituted hydrocarbon chain that is completely saturated or that contains one or more units of unsaturation, or a monocyclic hydrocarbon or bicyclic hydrocarbon that is completely saturated or that contains one or more units of unsaturation, but which is not aromatic (also referred to herein as "carbocycle," “cycloaliphatic” or “cycloalkyl”), that has a single point of attachment to the rest of the molecule. Unless otherwise specified, aliphatic groups contain 1-6 aliphatic carbon atoms. In some embodiments, aliphatic groups contain 1-5 aliphatic carbon atoms. In other embodiments, aliphatic groups contain 1-4 aliphatic carbon atoms. In still other embodiments, aliphatic groups contain 1-3 aliphatic carbon atoms, and in yet other embodiments, aliphatic groups contain 1-2 aliphatic carbon atoms. In some embodiments, “cycloaliphatic” (or “carbocycle” or “cycloalkyl”) refers to a monocyclic C3-C6 hydrocarbon that is completely saturated or that contains one or more units of unsaturation, but which is not aromatic, that has a single point of attachment to the rest of the molecule. Suitable aliphatic groups include, but are not limited to, linear or branched, substituted or unsubstituted alkyl, alkenyl, alkynyl groups and hybrids thereof such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl or (cycloalkyl)alkenyl.

[0133] The term “lower alkyl” refers to a C1-4 straight or branched alkyl group. Exemplary lower alkyl groups are methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and tert-butyl.

[0134] The term “lower haloalkyl” refers to a C1-4 straight or branched alkyl group that is substituted with one or more halogen atoms.

[0135] The term “heteroatom” means one or more of oxygen, sulfur, nitrogen, phosphorus, or silicon (including, any oxidized form of nitrogen, sulfur, phosphorus, or silicon; the quaternized form of any basic nitrogen or; a substitutable nitrogen of a heterocyclic ring, for example N (as inWSGR Docket No.: 56017-729.601 3,4-dihydro-2H-pyrrolyl), NH (as in pyrrolidinyl) or NR+(as in N-substituted pyrrolidinyl)).

[0136] The term "unsaturated," as used herein, means that a moiety has one or more units of unsaturation.

[0137] As used herein, the term “bivalent C1-8 (or C1-6) saturated or unsaturated, straight or branched, hydrocarbon chain”, refers to bivalent alkylene, alkenylene, and alkynylene chains that are straight or branched as defined herein.

[0138] As used herein, the term “cyclopropylenyl” refers to a bivalent cyclopropyl group of the following structure:.

[0139] The term “halogen” means F, Cl, Br, or I.

[0140] The term “aryl” used alone or as part of a larger moiety as in “aralkyl,” “aralkoxy,” or “aryloxyalkyl,” refers to monocyclic or bicyclic ring systems having a total of five to fourteen ring members, wherein at least one ring in the system is aromatic and wherein each ring in the system contains 3 to 7 ring members. The term “aryl” may be used interchangeably with the term “aryl ring.” In certain embodiments of the present invention, “aryl” refers to an aromatic ring system which includes, but not limited to, phenyl, biphenyl, naphthyl, anthracyl and the like, which may bear one or more substituents. Also included within the scope of the term “aryl,” as it is used herein, is a group in which an aromatic ring is fused to one or more non–aromatic rings, such as indanyl, phthalimidyl, naphthimidyl, phenanthridinyl, or tetrahydronaphthyl, and the like.

[0141] The terms “heteroaryl” and “heteroar–,” used alone or as part of a larger moiety, e.g., “heteroaralkyl,” or “heteroaralkoxy,” refer to groups having 5 to 10 ring atoms, preferably 5, 6, or 9 ring atoms; having 6, 10, or 14 ^ electrons shared in a cyclic array; and having, in addition to carbon atoms, from one to five heteroatoms. The term “heteroatom” refers to nitrogen, oxygen, or sulfur, and includes any oxidized form of nitrogen or sulfur, and any quaternized form of a basic nitrogen. Heteroaryl groups include, without limitation, thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolizinyl, purinyl, naphthyridinyl, and pteridinyl. The terms “heteroaryl” and “heteroar–”, as used herein, also include groups in which a heteroaromatic ring is fused to one or more aryl, cycloaliphatic, or heterocyclyl rings, where the radical or point of attachment is on the heteroaromatic ring. Nonlimiting examples include indolyl, isoindolyl, benzothienyl, benzofuranyl, dibenzofuranyl, indazolyl, benzimidazolyl, benzthiazolyl, quinolyl, isoquinolyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 4H–quinolizinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, and pyrido[2,3–b]–1,4–oxazin–3(4H)–one. A heteroaryl group may be mono– or bicyclic. The term “heteroaryl” may be used interchangeably with the terms “heteroarylWSGR Docket No.: 56017-729.601 ring,” “heteroaryl group,” or “heteroaromatic,” any of which terms include rings that are optionally substituted. The term “heteroaralkyl” refers to an alkyl group substituted by a heteroaryl, wherein the alkyl and heteroaryl portions independently are optionally substituted.

[0142] As used herein, the terms “heterocycle,” “heterocyclyl,” “heterocyclic radical,” and “heterocyclic ring” are used interchangeably and refer to a stable 5– to 7–membered monocyclic or 7–10–membered bicyclic heterocyclic moiety that is either saturated or partially unsaturated, and having, in addition to carbon atoms, one or more, preferably one to four, heteroatoms, as defined above. When used in reference to a ring atom of a heterocycle, the term "nitrogen" includes a substituted nitrogen. As an example, in a saturated or partially unsaturated ring having 0–3 heteroatoms selected from oxygen, sulfur or nitrogen, the nitrogen may be N (as in 3,4– dihydro–2H–pyrrolyl), NH (as in pyrrolidinyl), or+NR (as in N–substituted pyrrolidinyl).

[0143] A heterocyclic ring can be attached to its pendant group at any heteroatom or carbon atom that results in a stable structure and any of the ring atoms can be optionally substituted. Examples of such saturated or partially unsaturated heterocyclic radicals include, without limitation, tetrahydrofuranyl, tetrahydrothiophenyl pyrrolidinyl, piperidinyl, pyrrolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, oxazolidinyl, piperazinyl, dioxanyl, dioxolanyl, diazepinyl, oxazepinyl, thiazepinyl, morpholinyl, and quinuclidinyl. The terms “heterocycle,” “heterocyclyl,” “heterocyclyl ring,” “heterocyclic group,” “heterocyclic moiety,” and “heterocyclic radical,” are used interchangeably herein, and also include groups in which a heterocyclyl ring is fused to one or more aryl, heteroaryl, or cycloaliphatic rings, such as indolinyl, 3H–indolyl, chromanyl, phenanthridinyl, or tetrahydroquinolinyl. A heterocyclyl group may be mono– or bicyclic. The term “heterocyclylalkyl” refers to an alkyl group substituted by a heterocyclyl, wherein the alkyl and heterocyclyl portions independently are optionally substituted.

[0144] As used herein, the term “partially unsaturated” refers to a ring moiety that includes at least one double or triple bond. The term “partially unsaturated” is intended to encompass rings having multiple sites of unsaturation, but is not intended to include aryl or heteroaryl moieties, as herein defined.

[0145] As described herein, compounds of the invention may contain “optionally substituted” moieties. In general, the term “substituted,” whether preceded by the term “optionally” or not, means that one or more hydrogens of the designated moiety are replaced with a suitable substituent. Unless otherwise indicated, an “optionally substituted” group may have a suitable substituent at each substitutable position of the group, and when more than one position in any given structure may be substituted with more than one substituent selected from a specified group, the substituent may be either the same or different at every position. Combinations of substituents envisioned by this invention are preferably those that result in the formation of stable orWSGR Docket No.: 56017-729.601 chemically feasible compounds. The term “stable,” as used herein, refers to compounds that are not substantially altered when subjected to conditions to allow for their production, detection, and, in certain embodiments, their recovery, purification, and use for one or more of the purposes disclosed herein.

[0146] Suitable monovalent substituents on a substitutable carbon atom of an “optionally substituted” group are independently halogen; –(CH2)0–4R^; –(CH2)0–4OR^; -O(CH2)0-4Ro, –O– (CH2)0–4C(O)OR°; –(CH2)0–4CH(OR^)2; –(CH2)0–4SR^; –(CH2)0–4Ph, which may be substituted with R°; –(CH2)0–4O(CH2)0–1Ph which may be substituted with R°; –CH=CHPh, which may be substituted with R°; –(CH2)0–4O(CH2)0–1-pyridyl which may be substituted with R°; –NO2; –CN; –N3; -(CH2)0–4N(R^)2; –(CH2)0–4N(R^)C(O)R^; –N(R^)C(S)R^; –(CH2)0– 4N(R^)C(O)NR^2; -N(R^)C(S)NR^2; –(CH2)0–4N(R^)C(O)OR^; – N(R^)N(R^)C(O)R^; -N(R^)N(R^)C(O)NR^2; -N(R^)N(R^)C(O)OR^; –(CH2)0–4C(O)R^; – C(S)R^; –(CH2)0–4C(O)OR^; –(CH2)0–4C(O)SR^; -(CH2)0–4C(O)OSiR^3; –(CH2)0–4OC(O)R^; – OC(O)(CH2)0–4SR–, SC(S)SR°; –(CH2)0–4SC(O)R^; –(CH2)0–4C(O)NR^2; –C(S)NR^2; –C(S)SR°; –SC(S)SR°, -(CH2)0–4OC(O)NR^2; -C(O)N(OR^)R^; –C(O)C(O)R^; –C(O)CH2C(O)R^; – C(NOR^)R^; -(CH2)0–4SSR^; –(CH2)0–4S(O)2R^; –(CH2)0–4S(O)2OR^; –(CH2)0–4OS(O)2R^; – S(O)2NR^2; -(CH2)0–4S(O)R^; -N(R^)S(O)2NR^2; –N(R^)S(O)2R^; –N(OR^)R^; –C(NH)NR^2; – P(O)2R^; -P(O)R^2; -OP(O)R^2; –OP(O)(OR^)2; SiR^3; –(C1–4 straight or branched alkylene)O– N(R^)2; or –(C1–4 straight or branched alkylene)C(O)O–N(R^)2, wherein each R^ may be substituted as defined below and is independently hydrogen, C1–6 aliphatic, –CH2Ph, –O(CH2)0– 1Ph, -CH2-(5-6 membered heteroaryl ring), or a 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, notwithstanding the definition above, two independent occurrences of R^, taken together with their intervening atom(s), form a 3–12–membered saturated, partially unsaturated, or aryl mono– or bicyclic ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, which may be substituted as defined below.

[0147] Suitable monovalent substituents on R^ (or the ring formed by taking two independent occurrences of R^ together with their intervening atoms), are independently halogen, –(CH2)0–2R^, –(haloR^), –(CH2)0–2OH, –(CH2)0–2OR^, –(CH2)0–2CH(OR^)2; -O(haloR^), –CN, –N3, – (CH2)0–2C(O)R^, –(CH2)0–2C(O)OH, –(CH2)0–2C(O)OR^, –(CH2)0–2SR^, –(CH2)0–2SH, –(CH2)0– 2NH2, –(CH2)0–2NHR^, –(CH2)0–2NR^2, –NO2, –SiR^3, –OSiR^3, -C(O)SR^, –(C1–4 straight or branched alkylene)C(O)OR^, or –SSR^wherein each R^is unsubstituted or where preceded by “halo” is substituted only with one or more halogens, and is independently selected from C1–4aliphatic, –CH2Ph, –O(CH2)0–1Ph, or a 5–6–membered saturated, partially unsaturated, or aryl ringWSGR Docket No.: 56017-729.601 having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Suitable divalent substituents on a saturated carbon atom of R^ include =O and =S.

[0148] Suitable divalent substituents on a saturated carbon atom of an “optionally substituted” group include the following: =O, =S, =NNR*2, =NNHC(O)R*, =NNHC(O)OR*, =NNHS(O)2R*, =NR*, =NOR*, –O(C(R*2))2–3O–, or –S(C(R*2))2–3S–, wherein each independent occurrence of R*is selected from hydrogen, C1–6 aliphatic which may be substituted as defined below, or an unsubstituted 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Suitable divalent substituents that are bound to vicinal substitutable carbons of an “optionally substituted” group include: –O(CR*2)2– 3O–, wherein each independent occurrence of R*is selected from hydrogen, C1–6 aliphatic which may be substituted as defined below, or an unsubstituted 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0149] Suitable substituents on the aliphatic group of R*include halogen, –R^, -(haloR^), -OH, –OR^, –O(haloR^), –CN, –C(O)OH, –C(O)OR^, –NH2, –NHR^, –NR^2, or –NO2, wherein each R^is unsubstituted or where preceded by “halo” is substituted only with one or more halogens, and is independently C1–4 aliphatic, –CH2Ph, –O(CH2)0–1Ph, or a 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0150] Suitable substituents on a substitutable nitrogen of an “optionally substituted” group include – C(O)wherein each R†is independently hydrogen, C1–6 aliphatic which may be substituted as defined below, unsubstituted –OPh, or an unsubstituted 5–6–membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, notwithstanding the definition above, two independent occurrences of R†, taken together with their intervening atom(s) form an unsubstituted 3–12–membered saturated, partially unsaturated, or aryl mono– or bicyclic ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0151] Suitable substituents on the aliphatic group of R†are independently halogen, – R^, -(haloR^), –OH, –OR^, –O(haloR^), –CN, –C(O)OH, –C(O)OR^, –NH2, –NHR^, –NR^2, or -NO2, wherein each R^is unsubstituted or where preceded by “halo” is substituted only with one or more halogens, and is independently C1–4 aliphatic, –CH2Ph, –O(CH2)0–1Ph, or a 5–6– membered saturated, partially unsaturated, or aryl ring having 0–4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.WSGR Docket No.: 56017-729.601 Compounds From Semaglutide

[0152] Disclosed herein, in some embodiments, are compounds comprising certain ionic salt forms (i.e., pharmaceutically acceptable salts), esters and / or prodrugs of semaglutide, having improved qualities, including enhanced stability and improved solubility in an aqueous environment, relative to the free acid form of semaglutide that is utilized in marketed therapies Ozempic^, Wegovy^and Rybelsus^. Also disclosed are other derivatives of semaglutide.

[0153] As used herein, the terms “salt,” “salt form,” “ionic salt form” and “pharmaceutically acceptable salt,” as used herein, refers to those salts which are, within the scope of sound medical judgment, suitable for use in contact with the tissues of humans and lower animals without undue toxicity, irritation, allergic response, and the like, and are commensurate with a reasonable benefit / risk ratio. Pharmaceutically acceptable salts are well known in the art. For example, S. M. Berge et al., describe pharmaceutically acceptable salts in detail in J. Pharmaceutical Sciences, 1977, 66, 1–19, incorporated herein by reference. Pharmaceutically acceptable salts of the compounds as provided herein include those derived from suitable inorganic and organic acids and bases. Further pharmaceutically acceptable salts are discussed, for example, by P. Stahl et al., Camille G. (eds.) Handbook of Pharmaceutical Salts. Properties, Selection and Use. (2002) Zurich: Wiley-VCH; S. Berge et al., Journal of Pharmaceutical Sciences (1977) 66(1) 1-19; P. Gould, International J. of Pharmaceutics (1986) 33 201-217; Anderson et al., The Practice of Medicinal Chemistry (1996), Academic Press, New York; and in The Orange Book (Food & Drug Administration, Washington, D.C. on their website). These disclosures are incorporated herein by reference.

[0154] In certain embodiments, the compound, or pharmaceutically acceptable salt thereof, is a prodrug. As used herein, the term "prodrug" refers to compounds that are transformed in vivo to yield a disclosed compound or a pharmaceutically acceptable form of the compound. A prodrug is converted in vivo to an active compound, for example, by hydrolysis (e.g., hydrolysis in blood). In certain cases, a prodrug has improved physical and / or delivery properties over the parent compound. Prodrugs are typically designed to enhance pharmaceutically and / or pharmacokinetically based properties associated with the parent compound. The prodrug compound often offers advantages of solubility, tissue compatibility or delayed release in a mammalian organism (see, e.g., Bundgard, H., Design of Prodrugs (1985), pp. 7-9, 21-24 (Elsevier, Amsterdam). A discussion of prodrugs is provided in Higuchi, T., et al., "Pro-drugs as Novel Delivery Systems," A.C.S. Symposium Series, Vol. 14, and in Bioreversible Carriers in Drug Design, ed. Edward B. Roche, American Pharmaceutical Association and Pergamon Press, 1987. Exemplary advantages of a prodrug can include, but are not limited to, its physical properties, such as enhanced water solubility for parenteral administration at physiological pHWSGR Docket No.: 56017-729.601 compared to the parent compound, or it enhances absorption from the digestive tract, or it can enhance drug stability for long-term storage.

[0155] The term "prodrug" is also meant to include any covalently bonded carriers, which release the active compound in vivo when such prodrug is administered to a subject. Prodrugs of an active compound, as described herein, can be prepared by modifying functional groups present in the active compound in such a way that the modifications are cleaved, either in routine manipulation or in vivo, to the parent active compound. Prodrugs include compounds wherein a hydroxy, amino or mercapto group is bonded to any group that, when the prodrug of the active compound is administered to a subject, cleaves to form a free hydroxy, free amino or free mercapto group, respectively. Examples of prodrugs include, but are not limited to, acetate, formate and benzoate derivatives of an alcohol or acetamide, formamide and benzamide derivatives of an amine functional group in the active compound and the like.

[0156] In an aspect, provided herein is, inter alia, a compound comprising an ionic salt form of semaglutide having the structure of Formula I: wherein: semaglutide; and

[0157] In an aspect, provided herein is, inter alia, a compound consisting, or consisting essentially, of the structure of Formula I:Formula I, wherein:anion of semaglutide; and wherein one or more carboxyl groups of the C18 diacid, ^-Glu linker, Glu residues, and / or Asp residues of semaglutide are in the form of ; and is a catanionic component.WSGR Docket No.: 56017-729.601

[0158] As used herein, the term “C18 diacid” refers to fatty acid side chain of semaglutide having the structure –CO(CH2)16CO2. As used herein, the term “^-Glu linker” refers to the bivalent linker moiety of semaglutide having the structure –CO(CH2)2CH(CO2)NH-.

[0159] In some embodiments,does not have the structure, wherein R8, R9, and R10are independently C1-C5 alkyl, and R11is C2-C5 alkyl that is unsubstituted or substitutedwith one or more hydroxyl. In some embodiments,is not choline.

[0160] In some embodiments, provided herein is a compound consisting, or consisting essentially, of the structure of Formula I.

[0161] As used herein, “an anion of semaglutide,” having the structure, is meant to encompass from one (1) to seven (7) carboxylate anions of semaglutide corresponding to at least one carboxylate anion and up to seven carboxylate anions, the total number of carboxylic acid moieties on the semaglutide peptide. In some embodiments, the anion of semaglutide,, has from one (1) to seven (7) anions of semaglutide, as represented by Formula Ia1:Formula Ia1.

[0162] In some embodiments, the anion of semaglutide,is one anion of semaglutide, as represented by Formula Ia1-1:Formula Ia1-1,

[0163] In some embodiments, the anion of semaglutide, is two anions of semaglutide, as represented by Formula Ia1-2:Formula Ia1-2.WSGR Docket No.: 56017-729.601

[0164] In some embodiments, the anion of semaglutide, is three anions of semaglutide, as represented by Formula Ia1-3:Formula Ia1-3.

[0165] In some embodiments, the anion of semaglutide, is four anions of semaglutide, as represented by Formula Ia1-4:Formula Ia1-4.

[0166] In some embodiments, the anion of semaglutide,is five anions of semaglutide, as represented by Formula Ia1-5:Formula Ia1-5.

[0167] In some embodiments, the anion of semaglutide, is six anions of semaglutide, as represented by Formula Ia1-6:Formula Ia1-6.

[0168] In some embodiments, the anion of semaglutide,is seven anions of semaglutide, as represented by Formula Ia1-7:Formula Ia1-7.WSGR Docket No.: 56017-729.601

[0169] Accordingly, a “cationic component,” having the structure is meant to encompass from about one (1) to seven (7) cations corresponding to at least one cation and up to seven cations, provided as counterion(s) to the total potential number of carboxylate moieties on the semaglutide peptide. In some embodiments, the cationic component has from about one (1) to seven (7) cations. In some embodiments, the cationic component is one cation, corresponding to a molar ratio of semaglutide anion to cationic component of about 1:1. In some embodiments, the cationic component is two cations, corresponding to a molar ratio of semaglutide anion to cationic component of about 1:2. In some embodiments, the cationic component is three cations, corresponding to a molar ratio of semaglutide anion to cationic component of about 1:3. In some embodiments, the cationic component is four cations, corresponding to a molar ratio of semaglutide anion to cationic component of about 1:4. In some embodiments, the cationic component is five cations, corresponding to a molar ratio of semaglutide anion to cationic component of about 1:5. In some embodiments, the cationic component is six cations, corresponding to a molar ratio of semaglutide anion to cationic component of about 1:6. In some embodiments, the cationic component is seven cations, corresponding to a molar ratio of semaglutide anion to cationic component of about 1:7.

[0170] In an aspect, provided herein is a compound comprising the structure of Formula Ia2:Formula Ia2, wherein:from one to seven anions of semaglutide; andcationic component.

[0171] In some embodiments, the compound of Formula 1a2 is a compound having the structure of:Formula Ia2-1.

[0172] In some embodiments, the compound of Formula 1a2 is a compound having the structure of:WSGR Docket No.: 56017-729.601Formula Ia2-2.

[0173] In some embodiments, the compound of Formula 1a2 is a compound having the structure of:Formula Ia2-3.

[0174] In some embodiments, the compound of Formula 1a2 is a compound having the structure of:Formula Ia2-4.

[0175] In some embodiments, the compound of Formula 1a2 is a compound having the structure of:Formula Ia2-5.

[0176] In some embodiments, the compound of Formula 1a2 is a compound having the structure of:Formula Ia2-6.

[0177] In some embodiments, the compound of Formula 1a2 is a compound having the structure of:Formula Ia2-7.

[0178] In some embodiments, the cationic component of R2derives from appropriate bases and is selected from the group consisting of alkali metal, alkaline earth metal, a metal ion such as aluminum, sodium, lithium, potassium, magnesium, calcium, and zinc, ammonium (NH4+), aWSGR Docket No.: 56017-729.601 protonated or positively (+) charged ion from an aliphatic primary amine, secondary amine or tertiary amine such as 2-aminoethanol, tromethamine, dimethylamine, diethylamine, N-ethyl- glucamine, hydrabamine, trimethylamine, triethylamine, dicyclohexylamine, ethanolamine, diethanolamine, triethanolamine, dimethylethanolamine, (2,2′,2″-nitrilotris(ethanol)), 2- diethylaminoethanol, procaine or substituted procaine (e.g., chloroprocaine), meglumine, carnitine, ethylenediamine, choline, acetylcholine, aralkyl amine such as Ν,Ν- dibenzylethylenediamine, benzathine, benethamine; heterocyclic aromatic amine such as pyridine, pyrimidine, picoline, quinoline or isoquinoline, quaternary ammonium (e.g., NH4+) such as betaine, nontoxic quaternary ammonium (e.g., NMe4+, N+(C1–4alkyl)4,), tetramethylammonium, tetraethylammonium, benzyltrimethylammonium, benzyltriethylammonium, benzyltributylammonium, methyltrioctylammonium or tetrabutylammonium; 1H-imidazole, substituted-imidazole (e.g., N-alkyl imidazole, N-methyl imidazole), pyrrolidine, substituted pyrrolidine (e.g., 1-alkyl pyrrolidine, 1-methyl pyrrolidine, 1- (2-hydroxy-ethyl)-pyrrolidine), piperidine or substituted piperidine (e.g., 1-alkyl piperidine, 1- methyl piperidine), piperazine or substituted piperazine (e.g., 1-alkyl piperazine, 1-methyl piperazine, 1,4-dialkyl piperazine, 1,4-dimethyl piperazine), morpholine, substituted morpholine (e.g., N-substituted morpholine, N-methyl morpholine or 4-(2-hydroxyethyl)-morpholine), basic amino acid such as arginine, lysine, or histidine. aminoguanidine, guanidine derivatives and amine cations formed using counterions such as halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, lower alkyl sulfonate and aryl sulfonate. In some embodiments, the cationic component of R2is not choline. In some embodiments, the cationic component is betaine. In some embodiments,the cationic component comprises the structure of: . In some embodiments, the cationic component has the structure of:.

[0179] As used herein, the term “betaine” (alternatively known as “glycine betaine”) refers to a compound having a central methylene carbon (-CH2-) attached to an anionic carboxylate group - (CO2-) on one side and a positively charged cationic quaternary ammonium group -(N(CH3)3+) on the other, where the compound acts as a zwitterion having both positive and negative charges within the same molecule, as shown below.betaineWSGR Docket No.: 56017-729.601

[0180] In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is selected from the group consisting of about 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, and 1:7, or any ratio between any two of these values. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:1 to about 1:7. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:2 to about 1:7. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is about 1:4. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is selected from the group consisting of about 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, and 1:7, or any ratio between any two of these values. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:1 to about 1:7. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:2 to about 1:7. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is about 1:4. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is selected from the group consisting of about 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, and 1:7, or any ratio between any two of these values. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:1 to about 1:7. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:2 to about 1:7. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is about 1:4. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a weight % (wt. %) ratio relative to the anion of semaglutide as listed in Table 3.WSGR Docket No.: 56017-729.601

[0181] In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:3 to about 1:7. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:4 to about 1:7. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:5 to about 1:7. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:6 to about 1:7. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:3 to about 1:7. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:1 to about 1:6. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:1 to about 1:5. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:1 to about 1:4. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:1 to about 1:3. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:1 to about 1:2. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:2 to about 1:7. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:2 to about 1:6. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:2 to about 1:5. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:2 to about 1:4. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:2 to about 1:3. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:3 to about 1:7. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:3 to about 1:6. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio ofWSGR Docket No.: 56017-729.601 anion of semaglutide to cationic component that is from about 1:3 to about 1:5. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:3 to about 1:4. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:4 to about 1:7. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:4 to about 1:6. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:4 to about 1:5. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:5 to about 1:7. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:5 to about 1:6. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is about 1:1. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is about 1:2. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is about 1:3. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is about 1:4. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is about 1:5. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is about 1:6. In some embodiments, the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is about 1:7.

[0182] In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:3 to about 1:7. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:4 to about 1:7. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:5 to about 1:7. In some embodiments, the cationic component isWSGR Docket No.: 56017-729.601 selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:6 to about 1:7. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:3 to about 1:7. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:1 to about 1:6. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:1 to about 1:5. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:1 to about 1:4. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:1 to about 1:3. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:1 to about 1:2. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:2 to about 1:7. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:2 to about 1:6. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:2 to about 1:5. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:2 to about 1:4. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:2 to about 1:3. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molarWSGR Docket No.: 56017-729.601 ratio of anion of semaglutide to cationic component that is from about 1:3 to about 1:7. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:3 to about 1:6. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:3 to about 1:5. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:3 to about 1:4. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:4 to about 1:7. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:4 to about 1:6. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:4 to about 1:5. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:5 to about 1:7. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:5 to about 1:6. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is about 1:1. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is about 1:2. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is about 1:3. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is about 1:4. In some embodiments, the cationic component is selected from the group of cationic components describedWSGR Docket No.: 56017-729.601 herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is about 1:5. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is about 1:6. In some embodiments, the cationic component is selected from the group of cationic components described herein or listed in the preceding paragraphs, further provided in a molar ratio of anion of semaglutide to cationic component that is about 1:7.

[0183] In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:3 to about 1:7. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:4 to about 1:7. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:5 to about 1:7. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:6 to about 1:7. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:3 to about 1:7. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:1 to about 1:6. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:1 to about 1:5. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:1 to about 1:4. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:1 to about 1:3. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:1 to about 1:2. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:2 to about 1:7. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratioWSGR Docket No.: 56017-729.601 of anion of semaglutide to cationic component that is from about 1:2 to about 1:6. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:2 to about 1:5. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:2 to about 1:4. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:2 to about 1:3. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:3 to about 1:7. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:3 to about 1:6. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:3 to about 1:5. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:3 to about 1:4. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:4 to about 1:7. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:4 to about 1:6. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:4 to about 1:5. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:5 to about 1:7. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is from about 1:5 to about 1:6. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is about 1:1. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is about 1:2. In some embodiments, the cationic component is selected from the group of cationicWSGR Docket No.: 56017-729.601 components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is about 1:3. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is about 1:4. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is about 1:5. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is about 1:6. In some embodiments, the cationic component is selected from the group of cationic components listed in Table 3, further provided in a molar ratio of anion of semaglutide to cationic component that is about 1:7.

[0184] In some embodiments, the anion of semaglutide and betaine are provided in a molar ratio of anion of semaglutide to betaine that is from about 1:1 to about 1:7. In some embodiments, the anion of semaglutide and betaine are provided in a molar ratio of anion of semaglutide to betaine that is from about 1:2 to about 1:7. In some embodiments, the anion of semaglutide and betaine are provided in a molar ratio of anion of semaglutide to betaine that is from about 1:3 to about 1:7. In some embodiments, the anion of semaglutide and betaine are provided in a molar ratio of anion of semaglutide to betaine that is from about 1:4 to about 1:7. In some embodiments, the anion of semaglutide and betaine are provided in a molar ratio of anion of semaglutide to betaine that is from about 1:5 to about 1:7. In some embodiments, the anion of semaglutide and betaine are provided in a molar ratio of anion of semaglutide to betaine that is from about 1:6 to about 1:7. In some embodiments, the anion of semaglutide and betaine are provided in a molar ratio of anion of semaglutide to betaine that is from about 1:1 to about 1:6. In some embodiments, the anion of semaglutide and betaine are provided in a molar ratio of anion of semaglutide to betaine that is from about 1:1 to about 1:5. In some embodiments, the anion of semaglutide and betaine are provided in a molar ratio of anion of semaglutide to betaine that is from about 1:1 to about 1:4. In some embodiments, the anion of semaglutide and betaine are provided in a molar ratio of anion of semaglutide to betaine that is from about 1:1 to about 1:3. In some embodiments, the anion of semaglutide and betaine are provided in a molar ratio of anion of semaglutide to betaine that is from about 1:1 to about 1:2. In some embodiments, the anion of semaglutide and betaine are provided in a molar ratio of anion of semaglutide to betaine that is from about 1:2 to about 1:7. In some embodiments, the anion of semaglutide and betaine are provided in a molar ratio of anion of semaglutide to betaine that is from about 1:2 to about 1:6. In some embodiments, the anion of semaglutide and betaine are provided in a molar ratio of anion of semaglutide to betaine that is from about 1:2 to about 1:5. In some embodiments, the anion of semaglutide and betaineWSGR Docket No.: 56017-729.601 are provided in a molar ratio of anion of semaglutide to betaine that is from about 1:2 to about 1:4. In some embodiments, the anion of semaglutide and betaine are provided in a molar ratio of anion of semaglutide to betaine that is from about 1:2 to about 1:3. In some embodiments, the anion of semaglutide and betaine are provided in a molar ratio of anion of semaglutide to betaine that is from about 1:3 to about 1:7. In some embodiments, the anion of semaglutide and betaine are provided in a molar ratio of anion of semaglutide to betaine that is from about 1:3 to about 1:6. In some embodiments, the anion of semaglutide and betaine are provided in a molar ratio of anion of semaglutide to betaine that is from about 1:3 to about 1:5. In some embodiments, the anion of semaglutide and betaine are provided in a molar ratio of anion of semaglutide to betaine that is from about 1:3 to about 1:4. In some embodiments, the anion of semaglutide and betaine are provided in a molar ratio of anion of semaglutide to betaine that is from about 1:4 to about 1:7. In some embodiments, the anion of semaglutide and betaine are provided in a molar ratio of anion of semaglutide to betaine that is from about 1:4 to about 1:6. In some embodiments, the anion of semaglutide and betaine are provided in a molar ratio of anion of semaglutide to betaine that is from about 1:4 to about 1:5. In some embodiments, the anion of semaglutide and betaine are provided in a molar ratio of anion of semaglutide to betaine that is from about 1:5 to about 1:7. In some embodiments, the anion of semaglutide and betaine are provided in a molar ratio of anion of semaglutide to betaine that is from about 1:5 to about 1:6. In some embodiments, the anion of semaglutide and betaine are provided in a molar ratio of anion of semaglutide to betaine that is about 1:1. In some embodiments, the anion of semaglutide and betaine are provided in a molar ratio of anion of semaglutide to betaine that is about 1:2. In some embodiments, the anion of semaglutide and betaine are provided in a molar ratio of anion of semaglutide to betaine that is about 1:3. In some embodiments, the anion of semaglutide and betaine are provided in a molar ratio of anion of semaglutide to betaine that is about 1:4. In some embodiments, the anion of semaglutide and betaine are provided in a molar ratio of anion of semaglutide to betaine that is about 1:5. In some embodiments, the anion of semaglutide and betaine are provided in a molar ratio of anion of semaglutide to betaine that is about 1:6. In some embodiments, the anion of semaglutide and betaine are provided in a molar ratio of anion of semaglutide to quaternary ammonium that is about 1:7.

[0185] In some embodiments, representative alkali or alkaline earth metal salts include, but are not limited to, aluminum, sodium, lithium, potassium, calcium, magnesium, zinc and the like.

[0186] In some embodiments, N(C1–4alkyl)4+), includes tetramethyl ammonium, tetraethyl ammonium, acetylcholine, tetrapropyl ammonium and tetrabutyl ammonium.WSGR Docket No.: 56017-729.601

[0187] In some embodiments, the quaternary ammonium has the structurewherein: R8, R9, R10, and R11are each independently a substituted or unsubstituted group selected from C1-6 aliphatic, phenyl, cycloalkyl, 4-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0188] In some embodiments, the quaternary ammonium has the structurewherein: three of R8, R9, R10, and R11are each independently a substituted or unsubstituted C1-6 aliphatic, and one of R8, R9, R10, and R11is substituted or unsubstituted phenyl, cycloalkyl, 4-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0189] In some embodiments, the quaternary ammonium has the structurewherein: two of R8, R9, R10, and R11are each independently a substituted or unsubstituted C1-6 aliphatic, and two of R8, R9, R10, and R11is each independently substituted or unsubstituted phenyl, cycloalkyl, 4-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0190] In some embodiments, the quaternary ammonium has the structure of wherein: one of R8, R9, R10, and R11is a substituted or unsubstituted C1-6 aliphatic, and three of R8, R9, R10, and R11is each independently substituted or unsubstituted phenyl, cycloalkyl, 4-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 5-6 membered monocyclic heteroarylWSGR Docket No.: 56017-729.601 ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0191] In some embodiments, the quaternary ammonium has the structure of wherein: R8, R9, R10, and R11are each independently a substituted or unsubstituted C1-6 aliphatic.

[0192] In some embodiments, the quaternary ammonium has the structurewherein: (i) R8, R9, R10, and R1are independently substituted or unsubstituted C1-C6 alkyl; (ii) R8, R9, R10, and R11are independently C1-C4 alkyl (N(C1–4alkyl)4+); (iii) R8, R9, and R10are C2 alkyl; and R11is C1 alkyl; (iv) R8, R9, and R10are C4 alkyl; and R11is C1 alkyl; (v) all of R8, R9, R10, and R11are C1 alkyl (NMe4+); (vi) all of R8, R9, R10, and R11are C2 alkyl; (vii) all of R8, R9, R10, and R11are C3 alkyl; or(viii) all of R8, R9, R10, and R11 are C4 alkyl.

[0193] In some embodiments, the quaternary ammonium has the structure of, wherein R8, R9, R10, and R11are each independently substituted or unsubstituted C1-C20 alkyl or an aryl.

[0194] In some embodiments, the cationic component is a quaternary ammonium, with the proviso that the cationic component does not have the structure, wherein R8, R9, and R10are independently C1-C5 alkyl, and R11is C2-C5 alkyl that is unsubstituted or substituted with 1 or more hydroxyl. In some embodiments, the cationic component is a quaternary ammonium comprising substituted or unsubstituted C6-C20 alkyl or an aryl.

[0195] In some embodiments, the cationic component is a quaternary ammonium, wherein the anion of semaglutide and quaternary ammonium are provided in a molar ratio of anion of semaglutide to quaternary ammonium that is selected from the group consisting of about 1:1, 1:2, 1:3, 1:4, 1:5, 1:6 and 1:7, or any ratio between any two of these values. In some embodiments, theWSGR Docket No.: 56017-729.601 cationic component is a quaternary ammonium having the structure of , wherein the anion of semaglutide and quaternary ammonium having the structure of are provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structure of that is selected from the group consisting of about 1:1, 1:2, 1:3, 1:4, 1:5, 1:6 and 1:7, or any ratio between any two of these values. In some embodiments, the cationic component is a quaternary ammonium having the structure of , wherein the anion of semaglutide and the quaternary ammonium having the structure of are provided in a molar ratio of anion of semaglutide to the quaternary ammonium having the structure of that is from about 1:1 to about 1:7. In some embodiments, the cationic component is a quaternary ammonium having the structure of, wherein the anion of semaglutide and the quaternary ammonium having the structure of are provided in a molar ratio of anion of semaglutide to the quaternary ammonium having the structure of that is from about 1:2 to about 1:7. In some embodiments, the cationic component is a quaternary ammonium having the structure of, wherein the anion of semaglutide and the quaternary ammonium having the structure ofare provided in a molar ratio of anion ofWSGR Docket No.: 56017-729.601 semaglutide to the quaternary ammonium having the structure of that is from about 1:3 to about 1:7. In some embodiments, the cationic component is a quaternary ammonium having the structure of , wherein the anion of semaglutide and the quaternary ammonium having the structure of are provided in a molar ratio of anion of semaglutide to the quaternary ammonium having the structure of that is from about 1:4 to about 1:7. In some embodiments, the cationic component is a quaternary ammonium having the structure of , wherein the anion of semaglutide and the quaternary ammonium having the structure of are provided in a molar ratio of anion of semaglutide to the quaternary ammonium having the structure of that is from about 1:5 to about 1:7. In some embodiments, the cationic component is a quaternary ammonium having the structure of , wherein the anion of semaglutide and the quaternary ammonium having the structure of are provided in a molar ratio of anion of semaglutide to the quaternary ammonium having the structure of that is from about 1:6 to about 1:7. In some embodiments, the cationic component is a quaternary ammonium having the structure of , wherein the anion of semaglutide and the quaternary ammonium having theWSGR Docket No.: 56017-729.601 structure of are provided in a molar ratio of anion of semaglutide to the quaternary ammonium having the structurethat is from about 1:3 to about 1:7. In some embodiments, the cationic component is a quaternary ammonium having the structure of , wherein the anion of semaglutide and the quaternary ammonium having the structure of are provided in a molar ratio of anion of semaglutide to the quaternary ammonium having the structurethat is from about 1:1 to about 1:6. In some embodiments, the cationic component is a quaternary ammonium having the structure of , wherein the anion of semaglutide and the quaternary ammonium having the structure of are provided in a molar ratio of anion of semaglutide to the quaternary ammonium having the structure ofthat is from about 1:1 to about 1:5. In some embodiments, the cationic component is a quaternary ammonium having the structure of , wherein the anion of semaglutide and the quaternary ammonium having the structure of are provided in a molar ratio of anion of semaglutide to the quaternary ammonium having the structure of that is from about 1:1 to about 1:4. In some embodiments, the cationic component is a quaternary ammonium having the structure ofWSGR Docket No.: 56017-729.601 , wherein the anion of semaglutide and the quaternary ammonium having the structure of are provided in a molar ratio of anion of semaglutide to the quaternary ammonium having the structure of that is from about 1:1 to about 1:3. In some embodiments, the cationic component is a quaternary ammonium having the structure of , wherein the anion of semaglutide and the quaternary ammonium having the structure of are provided in a molar ratio of anion of semaglutide to the quaternary ammonium having the structure of that is from about 1:1 to about 1:2. In some embodiments, the cationic component is a quaternary ammonium having the structure of , wherein the anion of semaglutide and the quaternary ammonium having the structure of are provided in a molar ratio of anion of semaglutide to the quaternary ammonium having the structure of that is from about 1:2 to about 1:7. In some embodiments, the cationic component is a quaternary ammonium having the structure of , wherein the anion of semaglutide and the quaternary ammonium having the structure ofare provided in a molar ratio of anion of semaglutide to the quaternaryWSGR Docket No.: 56017-729.601 ammonium having the structure of that is from about 1:2 to about 1:6. In some embodiments, the cationic component is a quaternary ammonium having the structure of , wherein the anion of semaglutide and the quaternary ammonium having the structure of are provided in a molar ratio of anion of semaglutide to the quaternary ammonium having the structure of that is from about 1:2 to about 1:5. In some embodiments, the cationic component is a quaternary ammonium having the structure of , wherein the anion of semaglutide and the quaternary ammonium having the structure of are provided in a molar ratio of anion of semaglutide to the quaternary ammonium having the structure of that is from about 1:2 to about 1:4. In some embodiments, the cationic component is a quaternary ammonium having the structure of , wherein the anion of semaglutide and the quaternary ammonium having the structure of are provided in a molar ratio of anion of semaglutide to the quaternary ammonium having the structure of that is from about 1:2 to about 1:3. In some embodiments, the cationic component is a quaternary ammonium having the structure of , wherein the anion of semaglutide and the quaternary ammonium having theWSGR Docket No.: 56017-729.601 structure of are provided in a molar ratio of anion of semaglutide to the quaternary ammonium having the structurethat is from about 1:3 to about 1:7. In some embodiments, the cationic component is a quaternary ammonium having the structure of , wherein the anion of semaglutide and the quaternary ammonium having the structure of are provided in a molar ratio of anion of semaglutide to the quaternary ammonium having the structurethat is from about 1:3 to about 1:6. In some embodiments, the cationic component is a quaternary ammonium having the structure of , wherein the anion of semaglutide and the quaternary ammonium having the structure of are provided in a molar ratio of anion of semaglutide to the quaternary ammonium having the structure ofthat is from about 1:3 to about 1:5. In some embodiments, the cationic component is a quaternary ammonium having the structure of , wherein the anion of semaglutide and the quaternary ammonium having the structure of are provided in a molar ratio of anion of semaglutide to the quaternary ammonium having the structure of that is from about 1:3 to about 1:4. In some embodiments, the cationic component is a quaternary ammonium having the structure ofWSGR Docket No.: 56017-729.601 , wherein the anion of semaglutide and the quaternary ammonium having the structure of are provided in a molar ratio of anion of semaglutide to the quaternary ammonium having the structure of that is from about 1:4 to about 1:7. In some embodiments, the cationic component is a quaternary ammonium having the structure of , wherein the anion of semaglutide and the quaternary ammonium having the structure of are provided in a molar ratio of anion of semaglutide to the quaternary ammonium having the structure of that is from about 1:4 to about 1:6. In some embodiments, the cationic component is a quaternary ammonium having the structure of , wherein the anion of semaglutide and the quaternary ammonium having the structure of are provided in a molar ratio of anion of semaglutide to the quaternary ammonium having the structure of that is from about 1:4 to about 1:5. In some embodiments, the cationic component is a quaternary ammonium having the structure of , wherein the anion of semaglutide and the quaternary ammonium having the structure ofare provided in a molar ratio of anion of semaglutide to the quaternaryWSGR Docket No.: 56017-729.601 ammonium having the structure of that is from about 1:5 to about 1:7. In some embodiments, the cationic component is a quaternary ammonium having the structure of , wherein the anion of semaglutide and the quaternary ammonium having the structure of are provided in a molar ratio of anion of semaglutide to the quaternary ammonium having the structure of that is from about 1:5 to about 1:6. In some embodiments, the cationic component is a quaternary ammonium having the structure of , wherein the anion of semaglutide and the quaternary ammonium having the structure of are provided in a molar ratio of anion of semaglutide to the quaternary ammonium having the structure of that is about 1:1. In some embodiments, the cationic component is a quaternary ammonium having the structurewherein the anion of semaglutide and the quaternary ammonium having the structure of are provided in a molar ratio of anion of semaglutide to the quaternary ammonium having the structure of that is about 1:2. In some embodiments, the cationic component is a quaternary ammonium having the structure of , wherein the anion of semaglutide and theWSGR Docket No.: 56017-729.601 quaternary ammonium having the structure of are provided in a molar ratio of anion of semaglutide to the quaternary ammonium having the structure of that is about 1:3. In some embodiments, the cationic component is a quaternary ammonium having the structure of , wherein the anion of semaglutide and the quaternary ammonium having the structure of are provided in a molar ratio of anion of semaglutide to the quaternary ammonium having the structure of that is about 1:4. In some embodiments, the cationic component is a quaternary ammonium having the structure of , wherein the anion of semaglutide and the quaternary ammonium having the structure of are provided in a molar ratio of anion of semaglutide to the quaternary ammonium having the structure of that is about 1:5. In some embodiments, the cationic component is a quaternary ammonium having the structure of , wherein the anion of semaglutide and the quaternary ammonium having the structure of are provided in a molar ratio of anion of semaglutide to the quaternary ammonium having the structurethat is about 1:6. In some embodiments, the cationic component is a quaternary ammonium having the structure ofWSGR Docket No.: 56017-729.601 , wherein the anion of semaglutide and the quaternary ammonium having the structure of are provided in a molar ratio of anion of semaglutide to the quaternary ammonium having the structure of that is about 1:7.

[0196] In some embodiments, the quaternary ammonium has the structure of, wherein R15, R16, R17are each independently a substituted or unsubstituted group selected from C1-6 aliphatic, phenyl, cycloalkyl, 4-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur; R18, R19, R20, and R21are each independently hydrogen, halogen, substituted or unsubstituted C1-6 aliphatic; and R22is hydrogen, or substituted or unsubstituted group selected from -C(O)-C1-6 aliphatic, C1-6 aliphatic, phenyl, cycloalkyl, 4-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0197] In some embodiments, R22is selected from the group consisting of -C(O)CH3, -C(O)CF3, -C(O)CH2F, -C(O)CHF2, -CH3, -CF3, -CH2F, -CHF2, -CH2CH3, and -CH2CH2CH3, and CH(CH3)2

[0198] In some embodiments, the quaternary ammonium has the structure of, wherein R15, R16, R17are each independently a substituted or unsubstituted group selected from C1-6aliphatic, phenyl, cycloalkyl, 4-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected fromWSGR Docket No.: 56017-729.601 nitrogen, oxygen, or sulfur; R18, R19, R20, and R21are each independently hydrogen, halogen, substituted or unsubstituted C1-6 aliphatic; and R23is hydrogen, or substituted or unsubstituted group selected from C1-6 aliphatic, phenyl, cycloalkyl, 4-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0199] In some embodiments, R23is selected from the group consisting of -CH3, -CF3, -CH2F, and -CHF2.

[0200] In some embodiments, the cationic component is a quaternary ammonium having the structurewherein the anion of semaglutide and quaternary ammonium having the structure oforare provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is selected from the group consisting of about 1:1, 1:2, 1:3, 1:4, 1:5, 1:6 and 1:7 or any ratio between any two of these values.

[0201] In some embodiments, the anion of semaglutide and quaternary ammonium having the structureare provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structureWSGR Docket No.: 56017-729.601ammonium having the structurethat is from about 1:2 to about 1:7. In some embodiments, the anion of semaglutide and quaternary ammonium having the structureare provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structure ofthat is from about 1:3 to about 1:7. In some embodiments, the anion of semaglutide and quaternary ammonium having the structure ofare provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structure ofthat is from about 1:4 to about 1:7. In some embodiments, the anion ofWSGR Docket No.: 56017-729.601 semaglutide and quaternary ammonium having the structureare provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is from about 1:5 to about 1:7. In some embodiments, the anion of semaglutide and quaternary ammonium having the structureare provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structure ofthat is from about 1:6 to about 1:7. In some embodiments, the anion of semaglutide and quaternary ammonium having the structure ofare provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is from about 1:1 to about 1:6. In some embodiments, the anion of semaglutide and quaternary ammonium having the structureWSGR Docket No.: 56017-729.601are provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is from about 1:1 to about 1:5. In some embodiments, the anion of semaglutide and quaternary ammonium having the structureare provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structure ofthat is from about 1:1 to about 1:4. In some embodiments, the anion of semaglutide and quaternary ammonium having the structure ofare provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structureWSGR Docket No.: 56017-729.601 ammonium having the structurethat is from about 1:1 to about 1:2. In some embodiments, the anion of semaglutide and quaternary ammonium having the structureare provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structure ofthat is from about 1:2 to about 1:7. In some embodiments, the anion of semaglutide and quaternary ammonium having the structure ofare provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structure ofammonium having the structurethat is from about 1:2 to about 1:5. In some embodiments, the anion of semaglutide and quaternary ammoniumWSGR Docket No.: 56017-729.601 having the structureare provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structure ofthat is from about 1:2 to about 1:4. In some embodiments, the anion of semaglutide and quaternary ammonium having the structure ofare provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structureammonium having the structurethat is from about 1:3 to about 1:7. In some embodiments, the anion of semaglutide and quaternary ammonium having the structureare provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structure ofWSGR Docket No.: 56017-729.601that is from about 1:3 to about 1:6. In some embodiments, the anion of semaglutide and quaternary ammonium having the structure ofare provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structureammonium having the structurethat is from about 1:3 to about 1:4. In some embodiments, the anion of semaglutide and quaternary ammonium having the structureare provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structure ofthat is from about 1:4 to about 1:7. In some embodiments, the anion of semaglutide and quaternary ammonium having the structure ofWSGR Docket No.: 56017-729.601are provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structureammonium having the structurethat is from about 1:4 to about 1:5. In some embodiments, the anion of semaglutide and quaternary ammonium having the structureare provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structure ofthat is from about 1:5 to about 1:7. In some embodiments, the anion of semaglutide and quaternary ammonium having the structure ofare provided in a molar ratio of anion ofWSGR Docket No.: 56017-729.601 semaglutide to quaternary ammonium having the structureammonium having the structurethat is about 1:1. In some embodiments, the anion of semaglutide and quaternary ammonium having the structureare provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is about 1:2. In some embodiments, the anion of semaglutide and quaternary ammonium having the structureare provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is about 1:3. In some embodiments, theWSGR Docket No.: 56017-729.601 anion of semaglutide and quaternary ammonium having the structureare provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is about 1:4. In some embodiments, the anion of semaglutide and quaternary ammonium having the structureare provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is about 1:5. In some embodiments, the anion of semaglutide and quaternary ammonium having the structureare provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is about 1:6. In some embodiments, the anion of semaglutide and quaternary ammonium having the structureare provided in a molar ratio of anion of semaglutide to quaternaryWSGR Docket No.: 56017-729.601 ammonium having the structurethat is about 1:7.

[0202] In some embodiments, the quaternary ammonium has the structure selected from the ,

[0203] In some embodiments, the quaternary ammonium has the structure of.

[0204] In some embodiments, the cationic component is a quaternary ammonium having the structure,wherein the anion of semaglutide and quaternary ammonium having the structure,are provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is selected from the group consisting of about 1:1, 1:2, 1:3, 1:4, 1:5, 1:6 and 1:7 or any ratio between any two of these values.

[0205] In some embodiments, the anion of semaglutide and quaternary ammonium having theWSGR Docket No.: 56017-729.601 structure of,are provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structure oforthat is from about 1:1 to about 1:7. In some embodiments, the anion of semaglutide and quaternary ammonium having the structure of,are provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is from about 1:2 to about 1:7. In some embodiments, the anion of semaglutide and quaternary ammonium having the structure of,are provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is from about 1:3 to about 1:7. In some embodiments, the anionWSGR Docket No.: 56017-729.601 of semaglutide and quaternary ammonium having the structure of,are provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is from about 1:4 to about 1:7. In some embodiments, the anion of semaglutide and quaternary ammonium having the structure of,are provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is from about 1:5 to about 1:7. In some embodiments, the anion of semaglutide and quaternary ammonium having the structureare provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is from about 1:6 to about 1:7. In some embodiments, the anionWSGR Docket No.: 56017-729.601 of semaglutide and quaternary ammonium having the structure of,are provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is from about 1:1 to about 1:6. In some embodiments, the anion of semaglutide and quaternary ammonium having the structure of,are provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is from about 1:1 to about 1:5. In some embodiments, the anion of semaglutide and quaternary ammonium having the structureare provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is from about 1:1 to about 1:4. In some embodiments, the anionWSGR Docket No.: 56017-729.601 of semaglutide and quaternary ammonium having the structure of,are provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is from about 1:1 to about 1:3. In some embodiments, the anion of semaglutide and quaternary ammonium having the structure of,are provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is from about 1:1 to about 1:2. In some embodiments, the anion of semaglutide and quaternary ammonium having the structureare provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is from about 1:2 to about 1:7. In some embodiments, the anionWSGR Docket No.: 56017-729.601 of semaglutide and quaternary ammonium having the structure of,are provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is from about 1:2 to about 1:6. In some embodiments, the anion of semaglutide and quaternary ammonium having the structure of,are provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is from about 1:2 to about 1:5. In some embodiments, the anion of semaglutide and quaternary ammonium having the structureare provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is from about 1:2 to about 1:4. In some embodiments, the anionWSGR Docket No.: 56017-729.601 of semaglutide and quaternary ammonium having the structure of,are provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is from about 1:2 to about 1:3. In some embodiments, the anion of semaglutide and quaternary ammonium having the structure of,are provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is from about 1:3 to about 1:7. In some embodiments, the anion of semaglutide and quaternary ammonium having the structureare provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is from about 1:3 to about 1:6. In some embodiments, the anionWSGR Docket No.: 56017-729.601 of semaglutide and quaternary ammonium having the structure of,are provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is from about 1:3 to about 1:5. In some embodiments, the anion of semaglutide and quaternary ammonium having the structure of,are provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is from about 1:3 to about 1:4. In some embodiments, the anion of semaglutide and quaternary ammonium having the structureare provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is from about 1:4 to about 1:7. In some embodiments, the anionWSGR Docket No.: 56017-729.601 of semaglutide and quaternary ammonium having the structure of,are provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is from about 1:4 to about 1:6. In some embodiments, the anion of semaglutide and quaternary ammonium having the structure of,are provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is from about 1:4 to about 1:5. In some embodiments, the anion of semaglutide and quaternary ammonium having the structureare provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is from about 1:5 to about 1:7. In some embodiments, the anionWSGR Docket No.: 56017-729.601 of semaglutide and quaternary ammonium having the structureprovided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is from about 1:5 to about 1:6. In some embodiments, the anion of semaglutide and quaternary ammonium having the structureprovided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is about 1:1. In some embodiments, the anion of semaglutide and quaternary ammonium having the structure of,provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is about 1:2. In some embodiments, the anion of semaglutideWSGR Docket No.: 56017-729.601 and quaternary ammonium having the structure of,are provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is about 1:3. In some embodiments, the anion of semaglutide and quaternary ammonium having the structure,are provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is about 1:4. In some embodiments, the anion of semaglutide and quaternary ammonium having the structure,provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is about 1:5. In some embodiments, the anion of semaglutideWSGR Docket No.: 56017-729.601 and quaternary ammonium having the structure,are provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structurethat is about 1:6. In some embodiments, the anion of semaglutide and quaternary ammonium having the structure of,provided in a molar ratio of anion of semaglutide to quaternary ammonium having the structure

[0206] In some embodiments, the cationic component is choline. In some embodiments, the cationic component is acetylcholine. In some embodiments, the cationic component is choline wherein the anion of semaglutide and choline are provided in a molar ratio of anion of semaglutide to choline that is selected from the group consisting of about 1:1, 1:2, 1:3, 1:4, 1:5, 1:6 and 1:7 or any ratio between any two of these values. In some embodiments, the cationic component is choline, wherein the anion of semaglutide and choline are provided in a molar ratio of anion of semaglutide to choline that is from about 1:1 to about 1:7. In some embodiments, the cationic component is choline, wherein the anion of semaglutide and choline are provided in a molar ratio of anion of semaglutide to choline that is from about 1:2 to about 1:7. In some embodiments, the cationic component is choline, wherein the anion of semaglutide and choline are provided in a molar ratio of anion of semaglutide to choline that is from about 1:3 to about 1:7. In some embodiments, the cationic component is choline, wherein the anion of semaglutide and cholineWSGR Docket No.: 56017-729.601 are provided in a molar ratio of anion of semaglutide to choline that is from about 1:4 to about 1:7. In some embodiments, the cationic component is choline, wherein the anion of semaglutide and choline are provided in a molar ratio of anion of semaglutide to choline that is from about 1:5 to about 1:7. In some embodiments, the cationic component is choline, wherein the anion of semaglutide and choline are provided in a molar ratio of anion of semaglutide to choline that is from about 1:6 to about 1:7. In some embodiments, the cationic component is choline, wherein the anion of semaglutide and choline are provided in a molar ratio of anion of semaglutide to choline that is from about 1:1 to about 1:6. In some embodiments, the cationic component is choline, wherein the anion of semaglutide and choline are provided in a molar ratio of anion of semaglutide to choline that is from about 1:1 to about 1:5. In some embodiments, the cationic component is choline, wherein the anion of semaglutide and choline are provided in a molar ratio of anion of semaglutide to choline that is from about 1:1 to about 1:4. In some embodiments, the cationic component is choline, wherein the anion of semaglutide and choline are provided in a molar ratio of anion of semaglutide to choline that is from about 1:1 to about 1:3. In some embodiments, the cationic component is choline, wherein the anion of semaglutide and choline are provided in a molar ratio of anion of semaglutide to choline that is from about 1:1 to about 1:2. In some embodiments, the cationic component is choline, wherein the anion of semaglutide and choline are provided in a molar ratio of anion of semaglutide to choline that is from about 1:2 to about 1:7. In some embodiments, the cationic component is choline, wherein the anion of semaglutide and choline are provided in a molar ratio of anion of semaglutide to choline that is from about 1:2 to about 1:6. In some embodiments, the cationic component is choline, wherein the anion of semaglutide and choline are provided in a molar ratio of anion of semaglutide to choline that is from about 1:2 to about 1:5. In some embodiments, the cationic component is choline, wherein the anion of semaglutide and choline are provided in a molar ratio of anion of semaglutide to choline that is from about 1:2 to about 1:4. In some embodiments, the cationic component is choline, wherein the anion of semaglutide and choline are provided in a molar ratio of anion of semaglutide to choline that is from about 1:2 to about 1:3. In some embodiments, the cationic component is choline, wherein the anion of semaglutide and choline are provided in a molar ratio of anion of semaglutide to choline that is from about 1:3 to about 1:7. In some embodiments, the cationic component is choline, wherein the anion of semaglutide and choline are provided in a molar ratio of anion of semaglutide to choline that is from about 1:3 to about 1:6. In some embodiments, the cationic component is choline, wherein the anion of semaglutide and choline are provided in a molar ratio of anion of semaglutide to choline that is from about 1:3 to about 1:5. In some embodiments, the cationic component is choline, wherein the anion of semaglutide and choline are provided in a molar ratio of anion of semaglutide to choline that isWSGR Docket No.: 56017-729.601 from about 1:3 to about 1:4. In some embodiments, the cationic component is choline, wherein the anion of semaglutide and choline are provided in a molar ratio of anion of semaglutide to choline that is from about 1:4 to about 1:7. In some embodiments, the cationic component is choline, wherein the anion of semaglutide and choline are provided in a molar ratio of anion of semaglutide to choline that is from about 1:4 to about 1:6. In some embodiments, the cationic component is choline, wherein the anion of semaglutide and choline are provided in a molar ratio of anion of semaglutide to choline that is from about 1:4 to about 1:5. In some embodiments, the cationic component is choline, wherein the anion of semaglutide and choline are provided in a molar ratio of anion of semaglutide to choline that is from about 1:5 to about 1:7. In some embodiments, the cationic component is choline, wherein the anion of semaglutide and choline are provided in a molar ratio of anion of semaglutide to choline that is from about 1:5 to about 1:6. In some embodiments, the cationic component is choline, wherein the anion of semaglutide and choline are provided in a molar ratio of anion of semaglutide to choline that is about 1:1. In some embodiments, the cationic component is choline, wherein the anion of semaglutide and choline are provided in a molar ratio of anion of semaglutide to choline that is about 1:2. In some embodiments, the cationic component is choline, wherein the anion of semaglutide and choline are provided in a molar ratio of anion of semaglutide to choline that is about 1:3. In some embodiments, the cationic component is choline, wherein the anion of semaglutide and choline are provided in a molar ratio of anion of semaglutide to choline that is about 1:4. In some embodiments, the cationic component is choline, wherein the anion of semaglutide and choline are provided in a molar ratio of anion of semaglutide to choline that is about 1:5. In some embodiments, the cationic component is choline, wherein the anion of semaglutide and choline are provided in a molar ratio of anion of semaglutide to choline that is about 1:6. In some embodiments, the cationic component is choline, wherein the anion of semaglutide and choline are provided in a molar ratio of anion of semaglutide to choline that is about 1:7.

[0207] In some embodiments, the cationic component is acetylcholine wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide to acetylcholine that is selected from the group consisting of about 1:1, 1:2, 1:3, 1:4, 1:5, 1:6 and 1:7 or any ratio between any two of these values. In some embodiments, the cationic component is acetylcholine, wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide to acetylcholine that is from about 1:1 to about 1:7. In some embodiments, the cationic component is acetylcholine, wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide to acetylcholine that is from about 1:2 to about 1:7. In some embodiments, the cationic component is acetylcholine, wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide toWSGR Docket No.: 56017-729.601 acetylcholine that is from about 1:3 to about 1:7. In some embodiments, the cationic component is acetylcholine, wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide to acetylcholine that is from about 1:4 to about 1:7. In some embodiments, the cationic component is acetylcholine, wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide to acetylcholine that is from about 1:5 to about 1:7. In some embodiments, the cationic component is acetylcholine, wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide to acetylcholine that is from about 1:6 to about 1:7. In some embodiments, the cationic component is acetylcholine, wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide to acetylcholine that is from about 1:1 to about 1:6. In some embodiments, the cationic component is acetylcholine, wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide to acetylcholine that is from about 1:1 to about 1:5. In some embodiments, the cationic component is acetylcholine, wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide to acetylcholine that is from about 1:1 to about 1:4. In some embodiments, the cationic component is acetylcholine, wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide to acetylcholine that is from about 1:1 to about 1:3. In some embodiments, the cationic component is acetylcholine, wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide to acetylcholine that is from about 1:1 to about 1:2. In some embodiments, the cationic component is acetylcholine, wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide to acetylcholine that is from about 1:2 to about 1:7. In some embodiments, the cationic component is acetylcholine, wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide to acetylcholine that is from about 1:2 to about 1:6. In some embodiments, the cationic component is acetylcholine, wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide to acetylcholine that is from about 1:2 to about 1:5. In some embodiments, the cationic component is acetylcholine, wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide to acetylcholine that is from about 1:2 to about 1:4. In some embodiments, the cationic component is acetylcholine, wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide to acetylcholine that is from about 1:2 to about 1:3. In some embodiments, the cationic component is acetylcholine, wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide to acetylcholine that is from about 1:3 to about 1:7. In some embodiments, the cationic component is acetylcholine, wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide toWSGR Docket No.: 56017-729.601 acetylcholine that is from about 1:3 to about 1:6. In some embodiments, the cationic component is acetylcholine, wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide to acetylcholine that is from about 1:3 to about 1:5. In some embodiments, the cationic component is acetylcholine, wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide to acetylcholine that is from about 1:3 to about 1:4. In some embodiments, the cationic component is acetylcholine, wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide to acetylcholine that is from about 1:4 to about 1:7. In some embodiments, the cationic component is acetylcholine, wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide to acetylcholine that is from about 1:4 to about 1:6. In some embodiments, the cationic component is acetylcholine, wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide to acetylcholine that is from about 1:4 to about 1:5. In some embodiments, the cationic component is acetylcholine, wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide to acetylcholine that is from about 1:5 to about 1:7. In some embodiments, the cationic component is acetylcholine, wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide to acetylcholine that is from about 1:5 to about 1:6. In some embodiments, the cationic component is acetylcholine, wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide to acetylcholine that is about 1:1. In some embodiments, the cationic component is acetylcholine, wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide to acetylcholine that is about 1:2. In some embodiments, the cationic component is acetylcholine, wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide to acetylcholine that is about 1:3. In some embodiments, the cationic component is acetylcholine, wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide to acetylcholine that is about 1:4. In some embodiments, the cationic component is acetylcholine, wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide to acetylcholine that is about 1:5. In some embodiments, the cationic component is acetylcholine, wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide to acetylcholine that is about 1:6. In some embodiments, the cationic component is acetylcholine, wherein the anion of semaglutide and acetylcholine are provided in a molar ratio of anion of semaglutide to acetylcholine that is about 1:7.

[0208] In some embodiments, the cationic component excludes choline. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio of anion of cagrilintide to the cationic component that excludes choline selected from theWSGR Docket No.: 56017-729.601 group consisting of about 1:1, 1:2, 1:3, 1:4, 1:5, 1:6 and 1:7 or any ratio between any two of these values. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio of anion of cagrilintide to the cationic component that excludes choline that is from about 1:1 to about 1:7. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio of anion of cagrilintide to the cationic component that excludes choline that is from about 1:2 to about 1:7. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio of anion of cagrilintide to the cationic component that excludes choline that is from about 1:3 to about 1:7. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio of anion of cagrilintide to the cationic component that excludes choline that is from about 1:4 to about 1:7. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio of anion of cagrilintide to the cationic component that excludes choline that is from about 1:5 to about 1:7. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio of anion of cagrilintide to the cationic component that excludes choline that is from about 1:6 to about 1:7. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio of anion of cagrilintide to the cationic component that excludes choline that is from about 1:1 to about 1:6. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio of anion of cagrilintide to the cationic component that excludes choline that is from about 1:1 to about 1:5. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio of anion of cagrilintide to the cationic component that excludes choline that is from about 1:1 to about 1:4. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio of anion of cagrilintide to the cationic component that excludes choline that is from about 1:1 to about 1:3. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio of anion of cagrilintide to the cationic component that excludes choline that is from about 1:1 to about 1:2. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio of anion of cagrilintide to the cationic component that excludes choline that is from about 1:2 to about 1:7. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio of anion of cagrilintide to the cationic component that excludes choline that is from about 1:2 to about 1:6. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio ofWSGR Docket No.: 56017-729.601 anion of cagrilintide to the cationic component that excludes choline that is from about 1:2 to about 1:5. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio of anion of cagrilintide to the cationic component that excludes choline that is from about 1:2 to about 1:4. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio of anion of cagrilintide to the cationic component that excludes choline that is from about 1:2 to about 1:3. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio of anion of cagrilintide to the cationic component that excludes choline that is from about 1:3 to about 1:7. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio of anion of cagrilintide to the cationic component that excludes choline that is from about 1:3 to about 1:6. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio of anion of cagrilintide to the cationic component that excludes choline that is from about 1:3 to about 1:5. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio of anion of cagrilintide to the cationic component that excludes choline that is from about 1:3 to about 1:4. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio of anion of cagrilintide to the cationic component that excludes choline that is from about 1:4 to about 1:7. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio of anion of cagrilintide to the cationic component that excludes choline that is from about 1:4 to about 1:6. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio of anion of cagrilintide to the cationic component that excludes choline that is from about 1:4 to about 1:5. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio of anion of cagrilintide to the cationic component that excludes choline that is from about 1:5 to about 1:7. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio of anion of cagrilintide to the cationic component that excludes choline that is from about 1:5 to about 1:6. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio of anion of cagrilintide to the cationic component that excludes choline that is about 1:1. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio of anion of cagrilintide to the cationic component that excludes choline that is about 1:2. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio of anion of cagrilintide to the cationic componentWSGR Docket No.: 56017-729.601 that excludes choline that is about 1:3. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio of anion of cagrilintide to the cationic component that excludes choline that is about 1:4. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio of anion of cagrilintide to the cationic component that excludes choline that is about 1:5. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio of anion of cagrilintide to the cationic component that excludes choline that is about 1:6. In some embodiments, the anion of semaglutide and the cationic component that excludes choline are provided in a molar ratio of anion of cagrilintide to the cationic component that excludes choline that is about 1:7.

[0209] In some embodiments, provided is a hydrate of the compound of Formula I. The term “hydrate”, as used herein, means a solid or a semi-solid form of a chemical compound containing water in a molecular complex. The water is generally in a stoichiometric amount with respect to the chemical compound. Exemplary hydrates include (compound of Formula I • ZH2O), wherein Z is from 1 to 50 equivalents of H2O. In some embodiments, Z is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38,, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50. In some embodiments, Z is between any two of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38,, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 and 50.

[0210] In some embodiments, the cationic component is a quaternary ammonium having the structure of , wherein R8, R9, and R10are independently C1-C5 alkyl, and R11is C2- C5 alkyl that is unsubstituted or substituted with 1 or more hydroxyl.

[0211] In another aspect, provided herein is a compound comprising an ionic salt form of semaglutide having the structure of Formula IIa, Formula IIb, Formula IIc, or any combination thereof: Formula IIa,WSGR Docket No.: 56017-729.601 Formula IIb,Formula IIc, wherein, , , or any combination thereof is one or more cations of semaglutide; andanionic component.

[0212] In some embodiments, provided herein is a compound consisting, or consisting essentially, of the structure of Formula IIa, Formula IIb, Formula IIc, or any combination thereof.

[0213] As used herein, “one or more cations of semaglutide,” having the structure ,, , or any combination thereof, is meant to encompass from one (1) to four (4) cations of semaglutide corresponding to at least one protonated amino moiety and up to five protonated amino moieties of semaglutide, the total number of basic amino moieties on the semaglutide peptide. In some embodiments, the one or more cations of semaglutide, having thestructureany combination thereof, has from one (1) to four(4) cations of semaglutide. In some embodiments, the one or more cations of semaglutide is one cation of semaglutide. In some embodiments, the one or more cations of semaglutide is two cations of semaglutide. In some embodiments, the one or more cations of semaglutide is three cations of semaglutide. In some embodiments, the one or more cations of semaglutide is four cations of semaglutide.WSGR Docket No.: 56017-729.601

[0214] Accordingly, the “anionic component,” having the structure , is meant to encompass from about one (1) to four (4) anions corresponding to at least one anion and up to five anions, provided as counterion(s) to the total potential number of protonated basic amino moieties on the semaglutide peptide. In some embodiments, the anionic component of semaglutide has from about one (1) to four (4) anions of semaglutide. In some embodiments, the anionic component is one anion, corresponding to a molar ratio of one or more cations of semaglutide to anionic component of about 1:1. In some embodiments, the anionic component is two anions, corresponding to a molar ratio of one or more cations of semaglutide to anionic component of about 1:2. In some embodiments, the anionic component is three anions, corresponding to a molar ratio of one or more cations of semaglutide to anionic component of about 1:3. In some embodiments, the anionic component is four anions, corresponding to a molar ratio of one or more cations of semaglutide to anionic component of about 1:4.

[0215] In some embodiments, the one or more cations of semaglutide derive from the structure of the compound in Table 2.

[0216] In some embodiments, the anionic component of R7include, but are not limited to, inorganic acids such as hydrochloric acid, hydrobromic acid, phosphoric acid, sulfuric acid and perchloric acid or with organic acids such as acetic acid, oxalic acid, maleic acid, tartaric acid, citric acid, succinic acid, or malonic acid or by using other methods used in the art such as ion exchange.

[0217] In some embodiments, the anionic component of R7is selected from the group consisting of besylate, mesylate, tosylate, sulfonate, sulfate, methylsulfate, camsylate, isethionate, edisylate, 1-hydroxy-2-naphthoate, 2,2-dichloroacetate, 2-hydroxyethanesulfonate, 2-oxoglutarate, 4- acetamidobenzoate, 4-aminosalicylate, acetate, adipate, ascorbate, aspartate, benzenesulfonate, benzoate, bromide, chloride, camphorate, camphor-10-sulfonate, caprate (decanoate), caproate (hexanoate), caprylate (octanoate), carbonate, cinnamate, citrate, cyclamate, dodecylsulfate, dodecylsulfurate, ethanesulfonate, ethane-1,2-disulfonate, ethanesulfonate, formate, fumarate, galactarate, gentisate, glucoheptonate, gluconate, glutantate, glucuronate, glutamate, glutarate, glycerophosphorate, glycine, glycolate, hippurate, hydrobromate, hydroiodide, hydrochlorate, isobutyrate, lactate, lactobionate, laurate, lysine, maleate, malate, malonate, mandelate, methanesulfonate , naphthalene-1,5-disulfonate, naphthalene-2-sulfonate, nicotinate, nitrate, oleate, orotate, oxalate, palmitate, pamoate, phosphorate, proprionate, pyroglutamate, salicylate, sebacate, stearate, succinate, sulfurate, tannate, tartarate, thiocyanate, toluenesulfonate, undecylenate, α-lipoate, 12-hydroxystearate, 2-(4-isobutylphenyl)propionate, 2-(4,4-dimethyl-2- pentanyl)-5,7,7-trimethyloctanoate, 2-aminoethanesulfonate, 2-hexyldecanoate, 2-WSGR Docket No.: 56017-729.601 hydroxyhippurate, 3-(4-hydroxyphenyl)propionate, 3-methylcrotonate, 3,3-diphenylpropionate, 3,4-dihydroxbenzoate, ,5-dihydroxybenzoate, 4-acetamido-benzoate, 3,7-dimethyloctanoate, 4- hydroxybenzenesulfonate, 4-hydroxybenzoate, 4-methylhexanoate, 4-methyloctanoate, valerate salts including 4-methylvalerate, 5-norbornene-2-carboxylate, 8-[(2- hydroxybenzoyl)amino]octanoate, abietate, acetylcysteine, aconitate, arachidonate, behenate, caffeate, chenodeoxycholate, citronellate, crotonate, galactonate, deoxycholate, dihydrocaffeate, 2-phenylpropionate (hydratropate), tropate, eicosanedioate, eicosapentanoate (EPA), elaidate, ellagate, erucate, ethylenediaminetetraacetate (EDTA), geranate, heptanoate, hydrocinnamate (3- phenylpropionate), isovalerate, glutathione reduced, lactate, laurate, levulinate, linoleate, linolenate, lithocholate, mesaconate, nonanoate, oxalate, coumarate, palmitate, perillate, pimelate, 3–phenylpropionate, pivalate, propionate, pyruvate, ricinoleate, salicylate, 2-hydroxybenzoate, sinapinate (3,5-dimethoxy-4-hydroxycinnamate), sorbate, syringate, tiglate, 2-decenoate, 2- hexenoate, 2-octenoate, 3-octenoate, 7-octenoate, ferulate, undecanoate, valerate, vanillate, perchlorate, alginate, bisulfate, borate, butyrate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, glycerophosphate, hemisulfate, hydroiodide, lauryl sulfate, 2– naphthalenesulfonate, pectinate, persulfate, phosphate, tartrate, o-(4-hydroxybenzoyl)benzoate, 1,2,-ethanedisulfonate, chlorobenzenesulfonate, 4-methylbicyclo[2.2.2]oct-2-ene-carboxylate, 4.4’-methylenebis(3-hydroxy-2- ene-1-carboxylate), trimethylacetate, tertiary butylacetate, lauryl sulfurate, hydroxynaphthoate, muconate, α-ketoglutarate, p-toluenesulfonate, p-coumarate, and p-chlorobenzenesulfonate. In some embodiments, the anionic component () is betaine. In someembodiments, the anionic component ( ) comprises the structure of:In someembodiments, the anionic component ( ) has the structure of:

[0218] In some embodiments, the one or more cations of semaglutide and anionic component are provided in a molar ratio of one or more cations of semaglutide to anionic component of about 1:1, 1:2, 1:3, or 1:4, or any ratio between any two of these values. In some embodiments, the one or more cations of semaglutide and anionic component are provided in a molar ratio of one or more cations of semaglutide to anionic component of from about 1:1 to about 1:4. In some embodiments, the one or more cations of semaglutide and anionic component are provided in a molar ratio of one or more cations of semaglutide to anionic component of from about 1:2 to about 1:4. In some embodiments, the anionic component is selected from the group of anionic components described herein, further provided in a molar ratio of one or more cations ofWSGR Docket No.: 56017-729.601 semaglutide to anionic component that is about 1:1, 1:2, 1:3, or 1:4, or any ratio between any two of these values. In some embodiments, the anionic component is selected from the group of anionic components described herein, further provided in a molar ratio of one or more cations of semaglutide to anionic component that is from about 1:1 to about 1:4. In some embodiments, the anionic component is selected from the group of anionic components described herein, further provided in a molar ratio of one or more cations of semaglutide to anionic component that is from about 1:2 to about 1:4. In some embodiments, the anionic component is selected from the group of cationic components listed in Table 4. In some embodiments, the anionic component is selected from the group of anionic components listed in Table 4, further provided in a molar ratio of one or more cations of semaglutide to anionic component that is about 1:1, 1:2, 1:3, or 1:4, or any ratio between any two of these values. In some embodiments, the anionic component is selected from the group of anionic components listed in Table 4, further provided in a molar ratio of one or more cations of semaglutide to anionic component that is from 1:1 to about 1:4. In some embodiments, the anionic component is selected from the group of anionic components listed in Table 4, further provided in a molar ratio of one or more cations of semaglutide to anionic component that is from 1:2 to about 1:4. In some embodiments, the anionic component is selected from the group of anionic components listed in Table 4, further provided in a weight % (wt. %) ratio relative to the one or more cations of semaglutide as listed in Table 4.

[0219] In some embodiments, the one or more cations of semaglutide and anionic component are provided in a molar ratio of one or more cations of semaglutide to anionic component of from about 1:1 to about 1:4. In some embodiments, the one or more cations of semaglutide and anioniccomponent are provided in a molar ratio of one or more cations of semaglutide to anioniccomponent of from about 1:2 to about 1:4. In some embodiments, the one or more cations of semaglutide and anionic component are provided in a molar ratio of one or more cations of semaglutide to anionic component of from about 1:3 to about 1:4. In some embodiments, the one or more cations of semaglutide and anionic component are provided in a molar ratio of one or more cations of semaglutide to anionic component of from about 1:1 to about 1:3. In some embodiments, the one or more cations of semaglutide and anionic component are provided in a molar ratio of one or more cations of semaglutide to anionic component of from about 1:1 to about 1:2. In some embodiments, the one or more cations of semaglutide and anionic component are provided in a molar ratio of one or more cations of semaglutide to anionic component of from about 1:2 to about 1:4. In some embodiments, the one or more cations of semaglutide and anionic component are provided in a molar ratio of one or more cations of semaglutide to anionic component of from about 1:2 to about 1:3.In some embodiments, the one or more cations of semaglutide and anionic component are provided in a molar ratio of one or more cations ofWSGR Docket No.: 56017-729.601 semaglutide to anionic component of from about 1:3 to about 1:4. In some embodiments, the one or more cations of semaglutide and anionic component are provided in a molar ratio of one or more cations of semaglutide to anionic component of about 1:1. In some embodiments, the one or more cations of semaglutide and anionic component are provided in a molar ratio of one or more cations of semaglutide to anionic component of about 1:2. In some embodiments, the one or more cations of semaglutide and anionic component are provided in a molar ratio of one or more cations of semaglutide to anionic component of about 1:3. In some embodiments, the one or more cations of semaglutide and anionic component are provided in a molar ratio of one or more cations of semaglutide to anionic component of about 1:4.

[0220] In some embodiments, the anionic component is selected from the group of anionic components described herein, further provided in a molar ratio of one or more cations of semaglutide to anionic component of from about 1:1 to about 1:4. In some embodiments, the anionic component is selected from the group of anionic components described herein, further provided in a molar ratio of one or more cations of semaglutide to anionic component of from about 1:2 to about 1:4. In some embodiments, the anionic component is selected from the group of anionic components described herein, further provided in a molar ratio of one or more cations of semaglutide to anionic component of from about 1:3 to about 1:4. In some embodiments, the anionic component is selected from the group of anionic components described herein, further provided in a molar ratio of one or more cations of semaglutide to anionic component of from about 1:1 to about 1:3. In some embodiments, the anionic component is selected from the group of anionic components described herein, further provided in a molar ratio of one or more cations of semaglutide to anionic component of from about 1:1 to about 1:2. In some embodiments, the anionic component is selected from the group of anionic components described herein, further provided in a molar ratio of one or more cations of semaglutide to anionic component of from about 1:2 to about 1:4. In some embodiments, the anionic component is selected from the group of anionic components described herein, further provided in a molar ratio of one or more cations of semaglutide to anionic component of from about 1:2 to about 1:3.In some embodiments, the anionic component is selected from the group of anionic components described herein, further provided in a molar ratio of one or more cations of semaglutide to anionic component of from about 1:3 to about 1:4. In some embodiments, the anionic component is selected from the group of anionic components described herein, further provided in a molar ratio of one or more cations of semaglutide to anionic component of about 1:1. In some embodiments, the anionic component is selected from the group of anionic components described herein, further provided in a molar ratio of one or more cations of semaglutide to anionic component of about 1:2. In some embodiments, the anionic component is selected from the group of anionic components describedWSGR Docket No.: 56017-729.601 herein, further provided in a molar ratio of one or more cations of semaglutide to anionic component of about 1:3. In some embodiments, the anionic component is selected from the group of anionic components described herein, further provided in a molar ratio of one or more cations of semaglutide to anionic component of about 1:4.

[0221] In some embodiments, the anionic component is selected from the group of anionic components listed in Table 4, further provided in a molar ratio of one or more cations of semaglutide to anionic component of from about 1:1 to about 1:4. In some embodiments, the anionic component is selected from the group of anionic components listed in Table 4, further provided in a molar ratio of one or more cations of semaglutide to anionic component of from about 1:2 to about 1:4. In some embodiments, the anionic component is selected from the group of anionic components listed in Table 4, further provided in a molar ratio of one or more cations of semaglutide to anionic component of from about 1:3 to about 1:4. In some embodiments, the anionic component is selected from the group of anionic components listed in Table 4, further provided in a molar ratio of one or more cations of semaglutide to anionic component of from about 1:1 to about 1:3. In some embodiments, the anionic component is selected from the group of anionic components listed in Table 4, further provided in a molar ratio of one or more cations of semaglutide to anionic component of from about 1:1 to about 1:2. In some embodiments, the anionic component is selected from the group of anionic components listed in Table 4, further provided in a molar ratio of one or more cations of semaglutide to anionic component of from about 1:2 to about 1:4. In some embodiments, the anionic component is selected from the group of anionic components listed in Table 4, further provided in a molar ratio of one or more cations of semaglutide to anionic component of from about 1:2 to about 1:3.In some embodiments, the anionic component is selected from the group of anionic components listed in Table 4, further provided in a molar ratio of one or more cations of semaglutide to anionic component of from about 1:3 to about 1:4. In some embodiments, the anionic component is selected from the group of anionic components listed in Table 4, further provided in a molar ratio of one or more cations of semaglutide to anionic component of about 1:1. In some embodiments, the anionic component is selected from the group of anionic components listed in Table 4, further provided in a molar ratio of one or more cations of semaglutide to anionic component of about 1:2. In some embodiments, the anionic component is selected from the group of anionic components listed in Table 4, further provided in a molar ratio of one or more cations of semaglutide to anionic component of about 1:3. In some embodiments, the anionic component is selected from the group of anionic components listed in Table 4, further provided in a molar ratio of one or more cations of semaglutide to anionic component of about 1:4.

[0222] In some embodiments, the one or more cations of semaglutide and betaine are providedWSGR Docket No.: 56017-729.601 in a molar ratio of one or more cations of semaglutide to betaine of from about 1:1 to about 1:4. In some embodiments, the one or more cations of semaglutide and betaine are provided in a molar ratio of one or more cations of semaglutide to betaine of from about 1:2 to about 1:4. In some embodiments, the one or more cations of semaglutide and betaine are provided in a molar ratio of one or more cations of semaglutide to betaine of from about 1:3 to about 1:4. In some embodiments, the one or more cations of semaglutide and betaine are provided in a molar ratio of one or more cations of semaglutide to betaine of from about 1:1 to about 1:3. In some embodiments, the one or more cations of semaglutide and betaine are provided in a molar ratio of one or more cations of semaglutide to betaine of from about 1:1 to about 1:2. In some embodiments, the one or more cations of semaglutide and betaine are provided in a molar ratio of one or more cations of semaglutide to betaine of from about 1:2 to about 1:4. In some embodiments, the one or more cations of semaglutide and betaine are provided in a molar ratio of one or more cations of semaglutide to betaine of from about 1:2 to about 1:3.In some embodiments, the one or more cations of semaglutide and betaine are provided in a molar ratio of one or more cations of semaglutide to betaine of from about 1:3 to about 1:4. In some embodiments, the one or more cations of semaglutide and betaine are provided in a molar ratio of one or more cations of semaglutide to betaine of about 1:1. In some embodiments, the one or more cations of semaglutide and betaine are provided in a molar ratio of one or more cations of semaglutide to betaine of about 1:2. In some embodiments, the one or more cations of semaglutide and betaine are provided in a molar ratio of one or more cations of semaglutide to betaine of about 1:3. In some embodiments, the one or more cations of semaglutide and betaine are provided in a molar ratio of one or more cations of semaglutide to betaine of about 1:4.

[0223] In some embodiments, provided is a hydrate of the compound of Formula IIa, Formula IIb, Formula IIc, or any combination thereof. Exemplary hydrates include (compound of Formula IIa, Formula IIb, Formula IIc, or any combination thereof • ZH2O), wherein Z is from 1 to 50. In some embodiments, Z is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38,, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50. In some embodiments, Z is between any two of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38,, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 and 50.

[0224] In an aspect, provided herein is, inter alia, a compound comprising the structure of Formula IIIa:WSGR Docket No.: 56017-729.601 Formula IIIa or a pharmaceutically acceptable salt thereof; wherein: is a covalent derivative of one or more carboxyl groups of semaglutide, or a pharmaceutically acceptable salt thereof, wherein the covalent derivative of one or more carboxyl groups are of the C18 diacid, ^-Glu linker, Glu residues, and / or Asp residues of semaglutide; and each R100is independently selected from an optionally substituted group consisting of C1-6 aliphatic, (C1-22)alkyl, (C1-22)alkenyl, -C(O)R, -C(O)OR, -C(O)N(R)2, phenyl, 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, an 8-10 membered bicyclic aromatic carbocyclic ring, a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and each occurrence of R is independently hydrogen or an optionally substituted group selected from C1-6aliphatic, a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic aromatic carbocyclic ring, a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0225] In some embodiments, the compound of Formula IIIa does not have the structure ofFormula II, wherein R8, R9, and R10are independently C1-C5 alkyl.

[0226] In some embodiments, R100is substituted C1-6 aliphatic, unsubstituted C1-6 aliphatic, substituted (C1-22)alkyl, unsubstituted (C1-22)alkyl, substituted (C1-22)alkenyl, unsubstituted (C1- 22)alkenyl, substituted phenyl, unsubstituted phenyl, substituted -C(O)R, unsubstituted -C(O)R, substituted -C(O)OR, unsubstituted -C(O)OR, substituted -C(O)N(R)2, or unsubstituted -WSGR Docket No.: 56017-729.601 C(O)N(R)2.

[0227] In some embodiments, R100is methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, tert- butyl, or pentyl. In some embodiments, R100is fluoromethyl, difluoromethyl, or trifluoromethyl. In some embodiments, R100is CHCH3OC(O)OCH2CH3.

[0228] In some embodiments, R100is -CH3, -CH2CH3, -CH(CH3)2, CH2CH2CH2CH3, C(CH3)3, -CH2CH2N(CH3)3+

[0229] In some embodiments, R100is (C2-C12)alkanoyloxymethyl, 1-(alkanoyloxy)ethyl having from 4 to 9 carbon atoms, 1-methyl-1-(alkanoyloxy)-ethyl having from 5 to 10 carbon atoms, alkoxycarbonyloxymethyl having from 3 to 6 carbon atoms, 1-(alkoxycarbonyloxy)ethyl having from 4 to 7 carbon atoms, 1-methyl-1-(alkoxycarbonyloxy)ethyl having from 5 to 8 carbon atoms, N-(alkoxycarbonyl)aminomethyl having from 3 to 9 carbon atoms, 1-(N- (alkoxycarbonyl)amino)ethyl having from 4 to 10 carbon atoms, 3-phthalidyl, 4-crotonolactonyl, gamma-butyrolacton-4-yl, di-N,N-(C1-C2)alkylamino(C2-C3)alkyl (such as β- dimethylaminoethyl), carbamoyl-(C1-C2)alkyl, N,N-di(C1-C2)alkylcarbamoyl-(C1-C2)alkyl and piperidino-, pyrrolidino- or morpholino(C2-C3)alkyl.

[0230] In some embodiments, the compound of Formula IIIa is formed from the carboxyl of the –CO(CH2)16CO2 diacid moiety of semaglutide.

[0231] In some embodiments, the compound of Formula IIIa is formed from the carboxyl of the (^Glu) linker of semaglutide.

[0232] In some embodiments, the compound of Formula IIIa is formed from the side chain carboxyl of one or more aspartic acid or glutamic acid residues of semaglutide.

[0233] In some embodiments, provided herein is a compound comprising the structure of Formula IIIa1:Formula IIIa1. or a pharmaceutically acceptable salt thereof.

[0234] In some embodiments, provided herein is a compound comprising the structure of Formula IIIa1-1:WSGR Docket No.: 56017-729.601 Formula IIIa1-1 or a pharmaceutically acceptable salt thereof.

[0235] In some embodiments, provided herein is a compound comprising the structure of Formula IIIa1-1:Formula IIIa1-1 or a pharmaceutically acceptable salt thereof; wherein R100is -CH3, -CH2CH3, -CH(CH3)2, CH2CH2CH2CH3, C(CH3)3, -CH2CH2N(CH3)3+.

[0236] In some embodiments, provided herein is a compound comprising the structure of Formula IIIa1-1:Formula IIIa1-1 or a pharmaceutically acceptable salt thereof; wherein R100is -CH3, -CH2CH3, -CH(CH3)2, CH2CH2CH2CH3, C(CH3)3, or -CH2CH2N(CH3)3+, and the compound of Formula IIIa1-1 is formed from the terminal carboxyl moiety of the –CO(CH2)16CO2 diacid moiety of semaglutide.

[0237] In some embodiments, provided herein is a compound comprising the structure of Formula IIIa1-2:Formula IIIa1-2 or a pharmaceutically acceptable salt thereof.

[0238] In some embodiments, provided herein is a compound comprising the structure of Formula IIIa1-3:WSGR Docket No.: 56017-729.601 Formula IIIa1-3 or a pharmaceutically acceptable salt thereof.

[0239] In some embodiments, provided herein is a compound comprising the structure of Formula IIIa1-4:Formula IIIa1-4 or a pharmaceutically acceptable salt thereof.

[0240] In some embodiments, provided herein is a compound comprising the structure of Formula IIIa1-5:Formula IIIa1-5 or a pharmaceutically acceptable salt thereof.

[0241] In some embodiments, provided herein is a compound comprising the structure of Formula IIIa1-6:Formula IIIa1-6 or a pharmaceutically acceptable salt thereof.

[0242] In some embodiments, provided herein is a compound comprising the structure of Formula IIIa1-7:Formula IIIa1-7 or a pharmaceutically acceptable salt thereof.

[0243] In some embodiments, provided is a hydrate of the compound of Formula IIIa. Exemplary hydrates include (compound of Formula IIIa • ZH2O), wherein Z is from 1 to 50. InWSGR Docket No.: 56017-729.601 some embodiments, Z is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38,, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50. In some embodiments, Z is between any two of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38,, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 and 50.

[0244] In an aspect, provided herein is, inter alia, a compound comprising the structure of Formula IIIb: ; Formula IIIb or a pharmaceutically acceptable salt thereof wherein: is a covalent derivative of one or more hydroxyl groups of semaglutide, or a pharmaceutically acceptable salt thereof; wherein one or more hydroxyl groups of the Ser residues, Thr residues, and / or Tyr residues of semaglutide are in the form of ; and each R101is independently selected from an optionally substituted group consisting of -CH2R, - C(O)R (such as -C(O)CH3 or -C(O)H), -C(O)OR (such as -C(O)OH2), -C(O)N(R)2 (such as - C(O)NH2 or -C(O)N(CH3)2), -OP(O)OROR (such as -OP(O)OHOH); and each occurrence of R is independently hydrogen or an optionally substituted group selected from C1-6 aliphatic, a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic aromatic carbocyclic ring, a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0245] In some embodiments, R101is -CH2OCH2CH2OH, unsubstituted C(O)C1-6alkyl such as COCH3, COCH2CH3, or COCH(CH3)2). In some embodiments, R101is substituted C(O)C1-6alkyl such as COCF3, COCHCF2, or -COCH2CF. In some embodiments, R101is substituted C(O)phenyl or unsubstituted C(O)phenyl. In some embodiments, R101is -(C1-C6)alkanoyloxymethyl, -1-((C1- C6)alkanoyloxy)ethyl, -1-methyl-1-((C1-C6)alkanoyloxy)ethyl, -(C1- C6)alkoxycarbonyloxymethyl, -N-(C1-C6)alkoxycarbonylaminomethyl, -succinoyl, -(C1-WSGR Docket No.: 56017-729.601 C6)alkanoyl, -α-amino(C1-C4)alkanoyl, -arylacyl and -α-aminoacyl, or -α-aminoacyl-α- aminoacyl, where each α-aminoacyl group is independently selected from the naturally occurring L-amino acids, P(O)(OH)2, -P(O)(O(C1-C6)alkyl)2 or glycosyl (the radical resulting from the removal of a hydroxyl group of the hemiacetal form of a carbohydrate). In some embodiments, R101is CHCH3OC(O)OCH2CH3.

[0246] In some embodiments, the compound of Formula IIIb is formed from the side chain hydroxyl moiety of one or more serine, threonine or tyrosine residues of semaglutide.

[0247] In some embodiments, provided herein is a compound comprising the structure of Formula IIIb1:Formula IIIb1 or a pharmaceutically acceptable salt thereof.

[0248] In some embodiments, provided herein is a compound comprising the structure of Formula IIIb1-1:Formula IIIb1-1 or a pharmaceutically acceptable salt thereof.

[0249] In some embodiments, provided herein is a compound comprising the structure of Formula IIIb1-2:Formula IIIb1-2 or a pharmaceutically acceptable salt thereof.

[0250] In some embodiments, provided herein is a compound comprising the structure of Formula IIIb1-3:Formula IIIb1-3. or a pharmaceutically acceptable salt thereof.WSGR Docket No.: 56017-729.601

[0251] In some embodiments, provided herein is a compound comprising the structure of Formula IIIb1-4:Formula IIIb1-4 or a pharmaceutically acceptable salt thereof.

[0252] In some embodiments, provided herein is a compound comprising the structure of Formula IIIb1-5:Formula IIIb1-5 or a pharmaceutically acceptable salt thereof.

[0253] In some embodiments, provided herein is a compound comprising the structure of Formula IIIb1-6:Formula IIIb1-6 or a pharmaceutically acceptable salt thereof.

[0254] In some embodiments, provided is a hydrate of the compound of the structure of Formula IIIb. Exemplary hydrates include (compound of Formula IIIb • ZH2O), wherein Z is from 1 to 50. In some embodiments, Z is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38,, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50. In some embodiments, Z is between any two of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38,, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 and 50.

[0255] In an aspect, provided herein is, inter alia, a compound comprising the structure of Formula IIIc and / or Formula IIId:WSGR Docket No.: 56017-729.601Formula IIIc Formula IIId or a pharmaceutically acceptable salt or each thereof; wherein: is a covalent derivative of one or more amino groups of semaglutide, or a pharmaceutically acceptable salt thereof; wherein the one or more amino groups of the Arg residues and / or terminal amino group of semaglutide are in the form of ;is a covalent derivative of the imidazole group of semaglutide, or a pharmaceutically acceptable salt thereof; wherein the imidazole group of the His residue of semaglutide is in the form of, and each R102and R103is independently selected from an optionally substituted group consisting of - CH2R, -C(O)R (such as -C(O)CH3 -C(O) CH2CH3 or -C(O)H), -C(O)OR (such as -C(O)OH2), - C(O)N(R)2 (such as -C(O)NH2 or -C(O)NHR), -OP(O)OROR (such as -OP(O)OHOH); and eachWSGR Docket No.: 56017-729.601 occurrence of R is independently hydrogen or an optionally substituted group selected from C1-6aliphatic, a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic aromatic carbocyclic ring, a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

[0256] In some embodiments, each R102and R103is independently -CH2OCH2CH2OH, unsubstituted C(O)C1-6alkyl such as COCH3, COCH2CH3, or COCH(CH3)2). In some embodiments, R102is substituted C(O)C1-6alkyl such as COCF3, COCHCF2, or -COCH2CF. In some embodiments, R102is substituted C(O)phenyl or unsubstituted C(O)phenyl. In some embodiments, R102is CHCH3OC(O)OCH2CH3.

[0257] In some embodiments, each R102and R103is independently C(O)R, C(O)OR, C(O)NR’R”, where R’ and R” are each independently (C1-C10)alkyl, (C3-C7)cycloalkyl, benzyl, or C(O)R’ is a natural α-aminoacyl or natural α-aminoacyl-natural α-aminoacyl, - C(OH)C(O)OY1wherein Y1is H, (C1-C6)alkyl or benzyl, -C(OY2)Y3wherein Y2is (C1-C4) alkyl and Y3is (C1-C6)alkyl, carboxy(C1-C6)alkyl, amino(C1-C4)alkyl or mono-N-or di-N,N-(C1- C6)alkylaminoalkyl, -C(Y4)Y5wherein Y4is H or methyl and Y5is mono-N- or di-N,N-( C1- C6)alkylamino, morpholino, piperidin-1-yl or pyrrolidin-1-yl.

[0258] In some embodiments, provided herein is a compound comprising the structure of Formula IIIc1Formula IIIc1 or a pharmaceutically acceptable salt thereof.

[0259] In some embodiments, provided herein is a compound comprising the structure of Formula IIIc1-1:Formula IIIc1-1 or a pharmaceutically acceptable salt thereof.WSGR Docket No.: 56017-729.601

[0260] In some embodiments, provided herein is a compound comprising the structure of Formula IIIc1-2:Formula IIIc1-2 or a pharmaceutically acceptable salt thereof.

[0261] In some embodiments, provided herein is a compound comprising the structure of Formula IIIc1-3:Formula IIIc1-3 or a pharmaceutically acceptable salt thereof.

[0262] In some embodiments, provided herein is a compound comprising the structure of Formula IIId:Formula IIId or a pharmaceutically acceptable salt thereof.

[0263] In some embodiments, provided is a hydrate of the compound of Formula IIIc or Formula IIId. Exemplary hydrates include (compound of Formula IIIc or Formula IIId • ZH2O), wherein Z is from 1 to 50. In some embodiments, Z is 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38,, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, or 50. In some embodiments, Z is between any two of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38,, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49 and 50. Ratios of Counterion(s) to Ionic Salt Form of Semaglutide

[0264] In some embodiments,WSGR Docket No.: 56017-729.601 (i) a weight % (wt. %) ratio of : is from about 0.1 wt. %: 99.9 wt. % to about 20.0 wt. %: 80.0 wt. %; or (ii) a weight % (wt. %) ratio ofany combination thereof is from about 0.1 wt. %: 99.9 wt. % to about 20.0 wt. %: 80.0 wt. %.

[0265] In some embodiments,(i) a molar ratio of : is from about 2:1 to about 10:1; or (ii) a molar ratio ofany combination thereof is from about 2:1 to about 10:1.

[0266] In some embodiments, (i) a molar ratio of : is from about 2:1 to about 7:1; or(ii) a molar ratioany combination thereof is fromabout 2:1 to about 7:1.

[0267] In some embodiments, (i) a molar ratio of : is from about 3:1 to about 7:1; or(ii) a molar ratioany combination thereof is fromabout 3:1 to about 7:1.

[0268] In some embodiments,WSGR Docket No.: 56017-729.601 (i) a molar ratio of : is from about 4:1 to about 7:1; or (ii) a molar ratio ofany combination thereof is from about 4:1 to about 7:1.

[0269] In some embodiments, (i) a molar ratio of : is from about 3:1 to about 7:1; or (ii) a molar ratio ofany combination thereof is about 4:1. Ratios of Counterion(s) to Ionic Salt Form of Semaglutide

[0270] In some embodiments, a weight % (wt. %) ratio of : is from about 0.1 wt. %: 99.9 wt. % to about 20.0 wt. %: 80.0 wt. %.

[0271] In some embodiments, a weight % (wt. %) ratio of : is from about 0.2 wt. %: 99.8 wt. %, from about 0.3 wt. %: 99.7 wt. %, from about 0.4 wt. %: 99.6 wt. %, from about 0.5 wt. %: 99.5 wt. %, from about 0.6 wt. %: 99.4 wt. %, from about 0.7 wt. %: 99.3 wt. %, from about 0.8 wt. %: 99.2 wt. %, from about 0.9 wt. %: 99.1 wt. %, from about 1.0 wt. %: 99.0 wt. %, from about 1.1 wt. %: 98.9 wt. %, from about 1.2 wt. %: 98.8 wt. %, from about 1.3 wt. %: 98.7 wt. %, from about 1.4 wt. %: 98.6 wt. %, from about 1.5 wt. %: 98.5 wt. %, from about 1.6 wt. %: 98.4 wt. %, from about 1.7 wt. %: 98.3 wt. %, from about 1.8 wt. %: 98.2 wt. %, from about 1.9 wt. %: 98.1 wt. %, from about 2.0 wt. %: 98.0 wt. %, from about 3.0 wt. %: 97.0 wt. %, from about 4.0 wt. %: 96.0 wt. %, from about 5.0 wt. %: 95.0 wt. %, from about 6.0 wt. %: 94.0 wt. %, from about 7.0 wt. %: 93.0 wt. %, from about 8.0 wt. %: 92.0 wt. %, from about 9.0 wt. %: 91.0 wt. %, from about 10 wt. %: 90 wt. %, from about 11 wt. %: 89 wt. %, from about 12 wt. %: 88 wt. %, from about 13 wt. %: 87 wt. %, from about 14 wt. %: 86 wt. %, from about 15 wt. %: 85 wt. %, from about 16 wt. %: 84 wt. %, from about 17 wt. %: 83 wt. %, from about 18 wt. %: 82WSGR Docket No.: 56017-729.601 wt. %, from about 19 wt. %: 81 wt. %, from about 20 wt. %: 80 wt. %, from about 21 wt. %: 79 wt. %, from about 22 wt. %: 78 wt. %, from about 23 wt. %: 77 wt. %, from about 24 wt. %: 76 wt. %, from about 25 wt. %: 75 wt. %, from about 26 wt. %: 74 wt. %, from about 27 wt. %: 73 wt. %, from about 28 wt. %: 72 wt. %, from about 29 wt. %: 71 wt. %, from about 30 wt. %: 70 wt. %, from about 35 wt. %: 65 wt. %, from about 40 wt. %: 60 wt. %, from about 45 wt. %: 55 wt. %, from about 50 wt. %: 50 wt. %, from about 55 wt. %: 45 wt. %, from about 60 wt. %: 40 wt. %, from about 65 wt. %: 35 wt. %, from about 70 wt. %: 30 wt. %, from about 75 wt. %: 25 wt. %, from about 80 wt. %: 20 wt. %, from about 85 wt. %: 15 wt. %, from about 90 wt. %: 10 wt. %, or from about 95 wt. %: 5 wt. %.

[0272] In some embodiments, a weight % (wt. %) ratio of : is to about 20.0 wt. %: 80.0 wt. %. In some embodiments, a weight % (wt. %) ratio of : is to about 0.2 wt. %: 99.8 wt. %, to about 0.3 wt. %: 99.7 wt. %, to about 0.4 wt. %: 99.6 wt. %, to about 0.5 wt. %: 99.5 wt. %, to about 0.6 wt. %: 99.4 wt. %, to about 0.7 wt. %: 99.3 wt. %, to about 0.8 wt. %: 99.2 wt. %, to about 0.9 wt. %: 99.1 wt. %, to about 1.0 wt. %: 99.0 wt. %, to about 1.1 wt. %: 98.9 wt. %, to about 1.2 wt. %: 98.8 wt. %, to about 1.3 wt. %: 98.7 wt. %, to about 1.4 wt. %: 98.6 wt. %, to about 1.5 wt. %: 98.5 wt. %, to about 1.6 wt. %: 98.4 wt. %, to about 1.7 wt. %: 98.3 wt. %, to about 1.8 wt. %: 98.2 wt. %, to about 1.9 wt. %: 98.1 wt. %, to about 2.0 wt. %: 98.0 wt. %, to about 3.0 wt. %: 97.0 wt. %, to about 4.0 wt. %: 96.0 wt. %, to about 5.0 wt. %: 95.0 wt. %, to about 6.0 wt. %: 94.0 wt. %, to about 7.0 wt. %: 93.0 wt. %, to about 8.0 wt. %: 92.0 wt. %, to about 9.0 wt. %: 91.0 wt. %, to about 10 wt. %: 90 wt. %, to about 11 wt. %: 89 wt. %, to about 12 wt. %: 88 wt. %, to about 13 wt. %: 87 wt. %, to about 14 wt. %: 86 wt. %, to about 15 wt. %: 85 wt. %, to about 16 wt. %: 84 wt. %, to about 17 wt. %: 83 wt. %, to about 18 wt. %: 82 wt. %, to about 19 wt. %: 81 wt. %, to about 20 wt. %: 80 wt. %, to about 21 wt. %: 79 wt. %, to about 22 wt. %: 78 wt. %, to about 23 wt. %: 77 wt. %, to about 24 wt. %: 76 wt. %, to about 25 wt. %: 75 wt. %, to about 26 wt. %: 74 wt. %, to about 27 wt. %: 73 wt. %, to about 28 wt. %: 72 wt. %, to about 29 wt. %: 71 wt. %, to about 30 wt. %: 70 wt. %, to about 35 wt. %: 65 wt. %, to about 40 wt. %: 60 wt. %, to about 45 wt. %: 55 wt. %, to about 50 wt. %: 50 wt. %, to about 55 wt. %: 45 wt. %, to about 60 wt. %: 40 wt. %, to about 65 wt. %: 35 wt. %, to about 70 wt. %: 30 wt. %, to about 75 wt. %: 25 wt. %, to about 80 wt. %: 20 wt. %, to about 85 wt. %: 15 wt. %, to about 90 wt. %: 10 wt. %, or to about 95 wt. %: 5 wt. %.

[0273] In some embodiments, a weight % (wt. %) ratio of : is from about 0.2 wt. %:WSGR Docket No.: 56017-729.601 99.8 wt. % to about 95 wt. %: 5 wt. % , from about 0.3 wt. %: 99.7 wt. % to about 95 wt. %: 5 wt. %, from about 0.4 wt. %: 99.6 wt. % to about 95 wt. %: 5 wt. %, from about 0.5 wt. %: 99.5 wt. % to about 95 wt. %: 5 wt. %, from about 0.6 wt. %: 99.4 wt. % to about 95 wt. %: 5 wt. %, from about 0.7 wt. %: 99.3 wt. % to about 95 wt. %: 5 wt. %, from about 0.8 wt. %: 99.2 wt. % to about 95 wt. %: 5 wt. %, from about 0.9 wt. %: 99.1 wt. % to about 95 wt. %: 5 wt. %, from about 1.0 wt. %: 99.0 wt. % to about 95 wt. %: 5 wt. %, from about 1.1 wt. %: 98.9 wt. % to about 95 wt. %: 5 wt. %, from about 1.2 wt. %: 98.8 wt. % to about 95 wt. %: 5 wt. %, from about 1.3 wt. %: 98.7 wt. % to about 95 wt. %: 5 wt. %, from about 1.4 wt. %: 98.6 wt. % to about 95 wt. %: 5 wt. %, from about 1.5 wt. %: 98.5 wt. % to about 95 wt. %: 5 wt. %, from about 1.6 wt. %: 98.4 wt. % to about 95 wt. %: 5 wt. %, from about 1.7 wt. %: 98.3 wt. % to about 95 wt. %: 5 wt. %, from about 1.8 wt. %: 98.2 wt. % to about 95 wt. %: 5 wt. %, from about 1.9 wt. %: 98.1 wt. % to about 95 wt. %: 5 wt. %, from about 2.0 wt. %: 98.0 wt. % to about 95 wt. %: 5 wt. %, from about 3.0 wt. %: 97.0 wt. % to about 95 wt. %: 5 wt. %, from about 4.0 wt. %: 96.0 wt. % to about 95 wt. %: 5 wt. %, from about 5.0 wt. %: 95.0 wt. % to about 95 wt. %: 5 wt. %, from about 6.0 wt. %: 94.0 wt. % to about 95 wt. %: 5 wt. %, from about 7.0 wt. %: 93.0 wt. % to about 95 wt. %: 5 wt. %, from about 8.0 wt. %: 92.0 wt. % to about 95 wt. %: 5 wt. %, from about 9.0 wt. %: 91.0 wt. % to about 95 wt. %: 5 wt. %, from about 10 wt. %: 90 wt. % to about 95 wt. %: 5 wt. %, from about 11 wt. %: 89 wt. % to about 95 wt. %: 5 wt. %, from about 12 wt. %: 88 wt. % to about 95 wt. %: 5 wt. %, from about 13 wt. %: 87 wt. % to about 95 wt. %: 5 wt. %, from about 14 wt. %: 86 wt. % to about 95 wt. %: 5 wt. %, from about 15 wt. %: 85 wt. % to about 95 wt. %: 5 wt. %, from about 16 wt. %: 84 wt. % to about 95 wt. %: 5 wt. %, from about 17 wt. %: 83 wt. % to about 95 wt. %: 5 wt. %, from about 18 wt. %: 82 wt. % to about 95 wt. %: 5 wt. %, from about 19 wt. %: 81 wt. % to about 95 wt. %: 5 wt. %, from about 20 wt. %: 80 wt. % to about 95 wt. %: 5 wt. %, from about 21 wt. %: 79 wt. % to about 95 wt. %: 5 wt. %, from about 22 wt. %: 78 wt. % to about 95 wt. %: 5 wt. %, from about 23 wt. %: 77 wt. % to about 95 wt. %: 5 wt. %, from about 24 wt. %: 76 wt. % to about 95 wt. %: 5 wt. %, from about 25 wt. %: 75 wt. % to about 95 wt. %: 5 wt. %, from about 26 wt. %: 74 wt. % to about 95 wt. %: 5 wt. %, from about 27 wt. %: 73 wt. % to about 95 wt. %: 5 wt. %, from about 28 wt. %: 72 wt. % to about 95 wt. %: 5 wt. %, from about 29 wt. %: 71 wt. % to about 95 wt. %: 5 wt. %, from about 30 wt. %: 70 wt. % to about 95 wt. %: 5 wt. %, from about 35 wt. %: 65 wt. % to about 95 wt. %: 5 wt. %, from about 40 wt. %: 60 wt. % to about 95 wt. %: 5 wt. %, from about 45 wt. %: 55 wt. % to about 95 wt. %: 5 wt. %, from about 50 wt. %: 50 wt. % to about 95 wt. %: 5 wt. %, from about 55 wt. %: 45 wt. % to about 95 wt. %: 5 wt. %, from about 60 wt. %: 40 wt. % to about 95 wt. %: 5 wt. %, from about 65 wt. %: 35 wt. % to about 95 wt. %: 5 wt. %, from about 70 wt. %: 30 wt. % to about 95 wt. %: 5 wt. %, from about 75 wt. %: 25 wt. % to about 95 wt. %: 5 wt. %, from about 80 wt. %:WSGR Docket No.: 56017-729.601 20 wt. % to about 95 wt. %: 5 wt. %, from about 85 wt. %: 15 wt. % to about 95 wt. %: 5 wt. %, or from about 90 wt. %: 10 wt. % to about 95 wt. %: 5 wt. %.

[0274] In some embodiments, a weight % (wt. %) ratio of : is from about 0.1 wt. %: 99.9 wt. % to about 0.2 wt. %: 99.8 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 0.3 wt. %: 99.7 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 0.4 wt. %: 99.6 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 0.5 wt. %: 99.5 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 0.6 wt. %: 99.4 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 0.7 wt. %: 99.3 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 0.8 wt. %: 99.2 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 0.9 wt. %: 99.1 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 1.0 wt. %: 99.0 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 1.1 wt. %: 98.9 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 1.2 wt. %: 98.8 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 1.3 wt. %: 98.7 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 1.4 wt. %: 98.6 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 1.5 wt. %: 98.5 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 1.6 wt. %: 98.4 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 1.7 wt. %: 98.3 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 1.8 wt. %: 98.2 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 1.9 wt. %: 98.1 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 2.0 wt. %: 98.0 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 3.0 wt. %: 97.0 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 4.0 wt. %: 96.0 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 5.0 wt. %: 95.0 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 6.0 wt. %: 94.0 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 7.0 wt. %: 93.0 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 8.0 wt. %: 92.0 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 9.0 wt. %: 91.0 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 10 wt. %: 90 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 11 wt. %: 89 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 12 wt. %: 88 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 13 wt. %: 87 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 14 wt. %: 86 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 15 wt. %: 85 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 16 wt. %: 84 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 17 wt. %: 83 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 18 wt. %: 82 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 19 wt. %: 81 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 20 wt. %: 80 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 21 wt. %: 79 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 22 wt. %: 78 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 23 wt. %: 77 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 24 wt. %: 76 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 25 wt. %: 75 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 26 wt. %: 74 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 27 wt. %: 73 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 28 wt. %: 72 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 29 wt. %: 71 wt. %, from about 0.1 wt. %: 99.9 wt. % toWSGR Docket No.: 56017-729.601 about 30 wt. %: 70 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 35 wt. %: 65 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 40 wt. %: 60 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 45 wt. %: 55 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 50 wt. %: 50 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 55 wt. %: 45 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 60 wt. %: 40 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 65 wt. %: 35 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 70 wt. %: 30 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 75 wt. %: 25 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 80 wt. %: 20 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 85 wt. %: 15 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 90 wt. %: 10 wt. %, or from about 0.1 wt. %: 99.9 wt. % to about 95 wt. %: 5 wt. %.

[0275] In some embodiments, a weight % (wt. %) ratio of : is from about 0.1 wt. %: 99.9 wt. % to about 95 wt. %: 5 wt. %, from about 0.2 wt. %: 99.8 wt. % to about 90 wt. %: 10 wt. %, from about 0.3 wt. %: 99.7 wt. % to about 85 wt. %: 15 wt. %, from about 0.4 wt. %: 99.6 wt. % to about 80 wt. %: 20 wt. %, from about 0.5 wt. %: 99.5 wt. % to about 75 wt. %: 25 wt. %, from about 0.6 wt. %: 99.4 wt. % to about 70 wt. %: 30 wt. %, from about 0.7 wt. %: 99.3 wt. % to about 65 wt. %: 35 wt. %, from about 0.8 wt. %: 99.2 wt. % to about 60 wt. %: 40 wt. %, from about 0.9 wt. %: 99.1 wt. % to about 55 wt. %: 45 wt. %, from about 1.0 wt. %: 99.0 wt. % to about 50 wt. %: 50 wt. %, from about 1.1 wt. %: 98.9 wt. % to about 45 wt. %: 55 wt. %, from about 1.2 wt. %: 98.8 wt. % to about 40 wt. %: 60 wt. %, from about 1.3 wt. %: 98.7 wt. % to about 35 wt. %: 65 wt. %, from about 1.4 wt. %: 98.6 wt. % to about 30 wt. %: 70 wt. %, from about 1.5 wt. %: 98.5 wt. % to about 29 wt. %: 71 wt. %, from about 1.6 wt. %: 98.4 wt. % to about 28 wt. %: 72 wt. %, from about 1.7 wt. %: 98.3 wt. % to about 27 wt. %: 73 wt. %, from about 1.8 wt. %: 98.2 wt. % to about 26 wt. %: 74 wt. %, from about 1.9 wt. %: 98.1 wt. % to about 25 wt. %: 75 wt. %, from about 2.0 wt. %: 98.0 wt. % to about 24 wt. %: 76 wt. %, from about 3.0 wt. %: 97.0 wt. % to about 23 wt. %: 77 wt. %, from about 4.0 wt. %: 96.0 wt. % to about 22 wt. %: 78 wt. %, from about 5.0 wt. %: 95.0 wt. % to about 21 wt. %: 79 wt. %, from about 6.0 wt. %: 94.0 wt. % to about 20 wt. %: 80 wt. %, from about 7.0 wt. %: 93.0 wt. % to about 19 wt. %: 81 wt. %, from about 8.0 wt. %: 92.0 wt. % to about 18 wt. %: 82 wt. %, from about 9.0 wt. %: 91.0 wt. % to about 17 wt. %: 83 wt. %, from about 10 wt. %: 90 wt. % to about 16 wt. %: 84 wt. %, from about 11 wt. %: 89 wt. % to about 15 wt. %: 85 wt. %, or from about 12 wt. %: 88 wt. % to about 14 wt. %: 86 wt. %.

[0276] In some embodiments, a weight % (wt. %) ratio of : is about 0.1 wt. %: 99.9 wt. %, about 0.2 wt. %: 99.8 wt. %, about 0.3 wt. %: 99.7 wt. %, about 0.4 wt. %: 99.6 wt. %, about 0.5 wt. %: 99.5 wt. %, about 0.6 wt. %: 99.4 wt. %, about 0.7 wt. %: 99.3 wt. %, about 0.8WSGR Docket No.: 56017-729.601 wt. %: 99.2 wt. %, about 0.9 wt. %: 99.1 wt. %, about 1.0 wt. %: 99.0 wt. %, about 1.1 wt. %: 98.9 wt. %, about 1.2 wt. %: 98.8 wt. %, about 1.3 wt. %: 98.7 wt. %, about 1.4 wt. %: 98.6 wt. %, about 1.5 wt. %: 98.5 wt. %, about 1.6 wt. %: 98.4 wt. %, about 1.7 wt. %: 98.3 wt. %, about 1.8 wt. %: 98.2 wt. %, about 1.9 wt. %: 98.1 wt. %, about 2.0 wt. %: 98.0 wt. %, about 3.0 wt. %: 97.0 wt. %, about 4.0 wt. %: 96.0 wt. %, about 5.0 wt. %: 95.0 wt. %, about 6.0 wt. %: 94.0 wt. %, about 7.0 wt. %: 93.0 wt. %, about 8.0 wt. %: 92.0 wt. %, about 9.0 wt. %: 91.0 wt. %, about 10 wt. %: 90 wt. %, about 11 wt. %: 89 wt. %, about 12 wt. %: 88 wt. %, about 13 wt. %: 87 wt. %, about 14 wt. %: 86 wt. %, about 15 wt. %: 85 wt. %, about 16 wt. %: 84 wt. %, about 17 wt. %: 83 wt. %, about 18 wt. %: 82 wt. %, about 19 wt. %: 81 wt. %, about 20 wt. %: 80 wt. %, about 21 wt. %: 79 wt. %, about 22 wt. %: 78 wt. %, about 23 wt. %: 77 wt. %, about 24 wt. %: 76 wt. %, about 25 wt. %: 75 wt. %, about 26 wt. %: 74 wt. %, about 27 wt. %: 73 wt. %, about 28 wt. %: 72 wt. %, about 29 wt. %: 71 wt. %, about 30 wt. %: 70 wt. %, about 35 wt. %: 65 wt. %, about 40 wt. %: 60 wt. %, about 45 wt. %: 55 wt. %, about 50 wt. %: 50 wt. %, about 55 wt. %: 45 wt. %, about 60 wt. %: 40 wt. %, about 65 wt. %: 35 wt. %, about 70 wt. %: 30 wt. %, about 75 wt. %: 25 wt. %, about 80 wt. %: 20 wt. %, about 85 wt. %: 15 wt. %, about 90 wt. %: 10 wt. %, or about 95 wt. %: 5 wt. %.

[0277] In some embodiments, a weight % (wt. %) ratio of :,, or any combination thereof is from about 0.1 wt. %: 99.9 wt. % to about 20.0 wt. %: 80.0 wt. %.

[0278] In some embodiments, a weight % (wt. %) ratio of : ,,, or any combination thereof is from about 0.2 wt. %: 99.8 wt. %, from about 0.3 wt. %: 99.7 wt. %, from about 0.4 wt. %: 99.6 wt. %, from about 0.5 wt. %: 99.5 wt. %, from about 0.6 wt. %: 99.4 wt. %, from about 0.7 wt. %: 99.3 wt. %, from about 0.8 wt. %: 99.2 wt. %, fromWSGR Docket No.: 56017-729.601 about 0.9 wt. %: 99.1 wt. %, from about 1.0 wt. %: 99.0 wt. %, from about 1.1 wt. %: 98.9 wt. %, from about 1.2 wt. %: 98.8 wt. %, from about 1.3 wt. %: 98.7 wt. %, from about 1.4 wt. %: 98.6 wt. %, from about 1.5 wt. %: 98.5 wt. %, from about 1.6 wt. %: 98.4 wt. %, from about 1.7 wt. %: 98.3 wt. %, from about 1.8 wt. %: 98.2 wt. %, from about 1.9 wt. %: 98.1 wt. %, from about 2.0 wt. %: 98.0 wt. %, from about 3.0 wt. %: 97.0 wt. %, from about 4.0 wt. %: 96.0 wt. %, from about 5.0 wt. %: 95.0 wt. %, from about 6.0 wt. %: 94.0 wt. %, from about 7.0 wt. %: 93.0 wt. %, from about 8.0 wt. %: 92.0 wt. %, from about 9.0 wt. %: 91.0 wt. %, from about 10 wt. %: 90 wt. %, from about 11 wt. %: 89 wt. %, from about 12 wt. %: 88 wt. %, from about 13 wt. %: 87 wt. %, from about 14 wt. %: 86 wt. %, from about 15 wt. %: 85 wt. %, from about 16 wt. %: 84 wt. %, from about 17 wt. %: 83 wt. %, from about 18 wt. %: 82 wt. %, from about 19 wt. %: 81 wt. %, from about 20 wt. %: 80 wt. %, from about 21 wt. %: 79 wt. %, from about 22 wt. %: 78 wt. %, from about 23 wt. %: 77 wt. %, from about 24 wt. %: 76 wt. %, from about 25 wt. %: 75 wt. %, from about 26 wt. %: 74 wt. %, from about 27 wt. %: 73 wt. %, from about 28 wt. %: 72 wt. %, from about 29 wt. %: 71 wt. %, from about 30 wt. %: 70 wt. %, from about 35 wt. %: 65 wt. %, from about 40 wt. %: 60 wt. %, from about 45 wt. %: 55 wt. %, from about 50 wt. %: 50 wt. %, from about 55 wt. %: 45 wt. %, from about 60 wt. %: 40 wt. %, from about 65 wt. %: 35 wt. %, from about 70 wt. %: 30 wt. %, from about 75 wt. %: 25 wt. %, from about 80 wt. %: 20 wt. %, from about 85 wt. %: 15 wt. %, from about 90 wt. %: 10 wt. %, or from about 95 wt. %: 5 wt.

[0279] In some embodiments, a weight % (wt. %) ratio of : ,,to about 0.2 wt. %: 99.8 wt. %, to about 0.3 wt. %: 99.7 wt. %, to about 0.4 wt. %: 99.6 wt. %, to about 0.5 wt. %: 99.5 wt. %, to about 0.6 wt. %: 99.4 wt. %, to about 0.7 wt. %: 99.3 wt. %, to about 0.8 wt. %: 99.2 wt. %, to about 0.9 wt. %: 99.1 wt. %, to about 1.0 wt. %: 99.0 wt. %, to about 1.1 wt. %: 98.9 wt. %, to about 1.2 wt. %: 98.8 wt. %, to about 1.3 wt. %: 98.7 wt. %, toWSGR Docket No.: 56017-729.601 about 1.4 wt. %: 98.6 wt. %, to about 1.5 wt. %: 98.5 wt. %, to about 1.6 wt. %: 98.4 wt. %, to about 1.7 wt. %: 98.3 wt. %, to about 1.8 wt. %: 98.2 wt. %, to about 1.9 wt. %: 98.1 wt. %, to about 2.0 wt. %: 98.0 wt. %, to about 3.0 wt. %: 97.0 wt. %, to about 4.0 wt. %: 96.0 wt. %, to about 5.0 wt. %: 95.0 wt. %, to about 6.0 wt. %: 94.0 wt. %, to about 7.0 wt. %: 93.0 wt. %, to about 8.0 wt. %: 92.0 wt. %, to about 9.0 wt. %: 91.0 wt. %, to about 10 wt. %: 90 wt. %, to about 11 wt. %: 89 wt. %, to about 12 wt. %: 88 wt. %, to about 13 wt. %: 87 wt. %, to about 14 wt. %: 86 wt. %, to about 15 wt. %: 85 wt. %, to about 16 wt. %: 84 wt. %, to about 17 wt. %: 83 wt. %, to about 18 wt. %: 82 wt. %, to about 19 wt. %: 81 wt. %, to about 20 wt. %: 80 wt. %, to about 21 wt. %: 79 wt. %, to about 22 wt. %: 78 wt. %, to about 23 wt. %: 77 wt. %, to about 24 wt. %: 76 wt. %, to about 25 wt. %: 75 wt. %, to about 26 wt. %: 74 wt. %, to about 27 wt. %: 73 wt. %, to about 28 wt. %: 72 wt. %, to about 29 wt. %: 71 wt. %, to about 30 wt. %: 70 wt. %, to about 35 wt. %: 65 wt. %, to about 40 wt. %: 60 wt. %, to about 45 wt. %: 55 wt. %, to about 50 wt. %: 50 wt. %, to about 55 wt. %: 45 wt. %, to about 60 wt. %: 40 wt. %, to about 65 wt. %: 35 wt. %, to about 70 wt. %: 30 wt. %, to about 75 wt. %: 25 wt. %, to about 80 wt. %: 20 wt. %, to about 85 wt. %: 15 wt. %, to about 90 wt. %: 10 wt. %, or to about 95 wt. %: 5 wt. %.

[0280] In some embodiments, a weight % (wt. %) ratio of :,, or any combination thereof is from about 0.2 wt. %: 99.8 wt. % to about 95 wt. %: 5 wt. % , from about 0.3 wt. %: 99.7 wt. % to about 95 wt. %: 5 wt. %, from about 0.4 wt. %: 99.6 wt. % to about 95 wt. %: 5 wt. %, from about 0.5 wt. %: 99.5 wt. % to about 95 wt. %: 5 wt. %, from about 0.6 wt. %: 99.4 wt. % to about 95 wt. %: 5 wt. %, from about 0.7 wt. %: 99.3 wt. % to about 95 wt. %: 5 wt. %, from about 0.8 wt. %: 99.2 wt. % to about 95 wt. %: 5 wt. %, from about 0.9 wt. %: 99.1 wt. % to about 95 wt. %: 5 wt. %, from about 1.0 wt. %: 99.0 wt. % to about 95 wt. %: 5 wt. %, from about 1.1 wt. %: 98.9 wt. % to about 95 wt. %: 5 wt. %, from about 1.2 wt. %: 98.8 wt. % to about 95 wt. %: 5 wt. %, from about 1.3 wt. %: 98.7 wt. % to about 95 wt. %: 5 wt. %, from about 1.4 wt. %: 98.6 wt. % to about 95 wt. %: 5 wt. %, from about 1.5 wt. %: 98.5 wt. % to about 95 wt. %: 5 wt. %, from about 1.6 wt. %: 98.4 wt. % to about 95 wt. %: 5 wt. %, from about 1.7 wt. %: 98.3 wt. % to about 95 wt. %: 5 wt. %, from about 1.8 wt. %: 98.2 wt. % to about 95 wt. %: 5 wt. %, from about 1.9 wt. %: 98.1 wt. % to about 95 wt. %: 5 wt. %, from about 2.0 wt. %: 98.0 wt. % to about 95 wt. %: 5 wt. %, from about 3.0 wt. %: 97.0 wt. % to aboutWSGR Docket No.: 56017-729.601 95 wt. %: 5 wt. %, from about 4.0 wt. %: 96.0 wt. % to about 95 wt. %: 5 wt. %, from about 5.0 wt. %: 95.0 wt. % to about 95 wt. %: 5 wt. %, from about 6.0 wt. %: 94.0 wt. % to about 95 wt. %: 5 wt. %, from about 7.0 wt. %: 93.0 wt. % to about 95 wt. %: 5 wt. %, from about 8.0 wt. %: 92.0 wt. % to about 95 wt. %: 5 wt. %, from about 9.0 wt. %: 91.0 wt. % to about 95 wt. %: 5 wt. %, from about 10 wt. %: 90 wt. % to about 95 wt. %: 5 wt. %, from about 11 wt. %: 89 wt. % to about 95 wt. %: 5 wt. %, from about 12 wt. %: 88 wt. % to about 95 wt. %: 5 wt. %, from about 13 wt. %: 87 wt. % to about 95 wt. %: 5 wt. %, from about 14 wt. %: 86 wt. % to about 95 wt. %: 5 wt. %, from about 15 wt. %: 85 wt. % to about 95 wt. %: 5 wt. %, from about 16 wt. %: 84 wt. % to about 95 wt. %: 5 wt. %, from about 17 wt. %: 83 wt. % to about 95 wt. %: 5 wt. %, from about 18 wt. %: 82 wt. % to about 95 wt. %: 5 wt. %, from about 19 wt. %: 81 wt. % to about 95 wt. %: 5 wt. %, from about 20 wt. %: 80 wt. % to about 95 wt. %: 5 wt. %, from about 21 wt. %: 79 wt. % to about 95 wt. %: 5 wt. %, from about 22 wt. %: 78 wt. % to about 95 wt. %: 5 wt. %, from about 23 wt. %: 77 wt. % to about 95 wt. %: 5 wt. %, from about 24 wt. %: 76 wt. % to about 95 wt. %: 5 wt. %, from about 25 wt. %: 75 wt. % to about 95 wt. %: 5 wt. %, from about 26 wt. %: 74 wt. % to about 95 wt. %: 5 wt. %, from about 27 wt. %: 73 wt. % to about 95 wt. %: 5 wt. %, from about 28 wt. %: 72 wt. % to about 95 wt. %: 5 wt. %, from about 29 wt. %: 71 wt. % to about 95 wt. %: 5 wt. %, from about 30 wt. %: 70 wt. % to about 95 wt. %: 5 wt. %, from about 35 wt. %: 65 wt. % to about 95 wt. %: 5 wt. %, from about 40 wt. %: 60 wt. % to about 95 wt. %: 5 wt. %, from about 45 wt. %: 55 wt. % to about 95 wt. %: 5 wt. %, from about 50 wt. %: 50 wt. % to about 95 wt. %: 5 wt. %, from about 55 wt. %: 45 wt. % to about 95 wt. %: 5 wt. %, from about 60 wt. %: 40 wt. % to about 95 wt. %: 5 wt. %, from about 65 wt. %: 35 wt. % to about 95 wt. %: 5 wt. %, from about 70 wt. %: 30 wt. % to about 95 wt. %: 5 wt. %, from about 75 wt. %: 25 wt. % to about 95 wt. %: 5 wt. %, from about 80 wt. %: 20 wt. % to about 95 wt. %: 5 wt. %, from about 85 wt. %: 15 wt. % to about 95 wt. %: 5 wt. %, or from about 90 wt. %: 10 wt. % to about 95 wt. %: 5 wt. %.

[0281] In some embodiments, a weight % (wt. %) ratio of :,, or any combination thereof is from about 0.1 wt. %: 99.9 wt. % to about 0.2 wt. %: 99.8 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 0.3 wt. %: 99.7 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 0.4 wt. %: 99.6 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 0.5 wt.WSGR Docket No.: 56017-729.601 %: 99.5 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 0.6 wt. %: 99.4 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 0.7 wt. %: 99.3 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 0.8 wt. %: 99.2 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 0.9 wt. %: 99.1 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 1.0 wt. %: 99.0 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 1.1 wt. %: 98.9 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 1.2 wt. %: 98.8 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 1.3 wt. %: 98.7 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 1.4 wt. %: 98.6 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 1.5 wt. %: 98.5 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 1.6 wt. %: 98.4 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 1.7 wt. %: 98.3 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 1.8 wt. %: 98.2 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 1.9 wt. %: 98.1 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 2.0 wt. %: 98.0 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 3.0 wt. %: 97.0 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 4.0 wt. %: 96.0 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 5.0 wt. %: 95.0 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 6.0 wt. %: 94.0 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 7.0 wt. %: 93.0 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 8.0 wt. %: 92.0 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 9.0 wt. %: 91.0 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 10 wt. %: 90 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 11 wt. %: 89 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 12 wt. %: 88 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 13 wt. %: 87 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 14 wt. %: 86 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 15 wt. %: 85 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 16 wt. %: 84 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 17 wt. %: 83 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 18 wt. %: 82 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 19 wt. %: 81 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 20 wt. %: 80 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 21 wt. %: 79 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 22 wt. %: 78 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 23 wt. %: 77 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 24 wt. %: 76 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 25 wt. %: 75 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 26 wt. %: 74 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 27 wt. %: 73 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 28 wt. %: 72 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 29 wt. %: 71 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 30 wt. %: 70 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 35 wt. %: 65 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 40 wt. %: 60 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 45 wt. %: 55 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 50 wt. %: 50 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 55 wt. %: 45 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 60 wt. %: 40 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 65 wt. %: 35 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 70 wt. %: 30 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 75 wt. %: 25 wt. %, fromWSGR Docket No.: 56017-729.601 about 0.1 wt. %: 99.9 wt. % to about 80 wt. %: 20 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 85 wt. %: 15 wt. %, from about 0.1 wt. %: 99.9 wt. % to about 90 wt. %: 10 wt. %, or from about 0.1 wt. %: 99.9 wt. % to about 95 wt. %: 5 wt. %.

[0282] In some embodiments, a weight % (wt. %) ratio of,, or any combination thereof is from about 0.1 wt. %: 99.9 wt. % to about 95 wt. %: 5 wt. %, from about 0.2 wt. %: 99.8 wt. % to about 90 wt. %: 10 wt. %, from about 0.3 wt. %: 99.7 wt. % to about 85 wt. %: 15 wt. %, from about 0.4 wt. %: 99.6 wt. % to about 80 wt. %: 20 wt. %, from about 0.5 wt. %: 99.5 wt. % to about 75 wt. %: 25 wt. %, from about 0.6 wt. %: 99.4 wt. % to about 70 wt. %: 30 wt. %, from about 0.7 wt. %: 99.3 wt. % to about 65 wt. %: 35 wt. %, from about 0.8 wt. %: 99.2 wt. % to about 60 wt. %: 40 wt. %, from about 0.9 wt. %: 99.1 wt. % to about 55 wt. %: 45 wt. %, from about 1.0 wt. %: 99.0 wt. % to about 50 wt. %: 50 wt. %, from about 1.1 wt. %: 98.9 wt. % to about 45 wt. %: 55 wt. %, from about 1.2 wt. %: 98.8 wt. % to about 40 wt. %: 60 wt. %, from about 1.3 wt. %: 98.7 wt. % to about 35 wt. %: 65 wt. %, from about 1.4 wt. %: 98.6 wt. % to about 30 wt. %: 70 wt. %, from about 1.5 wt. %: 98.5 wt. % to about 29 wt. %: 71 wt. %, from about 1.6 wt. %: 98.4 wt. % to about 28 wt. %: 72 wt. %, from about 1.7 wt. %: 98.3 wt. % to about 27 wt. %: 73 wt. %, from about 1.8 wt. %: 98.2 wt. % to about 26 wt. %: 74 wt. %, from about 1.9 wt. %: 98.1 wt. % to about 25 wt. %: 75 wt. %, from about 2.0 wt. %: 98.0 wt. % to about 24 wt. %: 76 wt. %, from about 3.0 wt. %: 97.0 wt. % to about 23 wt. %: 77 wt. %, from about 4.0 wt. %: 96.0 wt. % to about 22 wt. %: 78 wt. %, from about 5.0 wt. %: 95.0 wt. % to about 21 wt. %: 79 wt. %, from about 6.0 wt. %: 94.0 wt. % to about 20 wt. %: 80 wt. %, from about 7.0 wt. %: 93.0 wt. % to about 19 wt. %: 81 wt. %, from about 8.0 wt. %: 92.0 wt. % to about 18 wt. %: 82 wt. %, from about 9.0 wt. %: 91.0 wt. % to about 17 wt. %: 83 wt. %, from about 10 wt. %: 90 wt. % to about 16 wt. %: 84 wt. %, from about 11 wt. %: 89 wt. % to about 15 wt. %: 85 wt. %, or from about 12 wt. %: 88 wt. % to about 14 wt. %: 86 wt. %.

[0283] In some embodiments, a weight % (wt. %) ratio of :,WSGR Docket No.: 56017-729.601, or any combination thereof is about 0.1 wt. %: 99.9 wt. %, about 0.2 wt. %: 99.8 wt. %, about 0.3 wt. %: 99.7 wt. %, about 0.4 wt. %: 99.6 wt. %, about 0.5 wt. %: 99.5 wt. %, about 0.6 wt. %: 99.4 wt. %, about 0.7 wt. %: 99.3 wt. %, about 0.8 wt. %: 99.2 wt. %, about 0.9 wt. %: 99.1 wt. %, about 1.0 wt. %: 99.0 wt. %, about 1.1 wt. %: 98.9 wt. %, about 1.2 wt. %: 98.8 wt. %, about 1.3 wt. %: 98.7 wt. %, about 1.4 wt. %: 98.6 wt. %, about 1.5 wt. %: 98.5 wt. %, about 1.6 wt. %: 98.4 wt. %, about 1.7 wt. %: 98.3 wt. %, about 1.8 wt. %: 98.2 wt. %, about 1.9 wt. %: 98.1 wt. %, about 2.0 wt. %: 98.0 wt. %, about 3.0 wt. %: 97.0 wt. %, about 4.0 wt. %: 96.0 wt. %, about 5.0 wt. %: 95.0 wt. %, about 6.0 wt. %: 94.0 wt. %, about 7.0 wt. %: 93.0 wt. %, about 8.0 wt. %: 92.0 wt. %, about 9.0 wt. %: 91.0 wt. %, about 10 wt. %: 90 wt. %, about 11 wt. %: 89 wt. %, about 12 wt. %: 88 wt. %, about 13 wt. %: 87 wt. %, about 14 wt. %: 86 wt. %, about 15 wt. %: 85 wt. %, about 16 wt. %: 84 wt. %, about 17 wt. %: 83 wt. %, about 18 wt. %: 82 wt. %, about 19 wt. %: 81 wt. %, about 20 wt. %: 80 wt. %, about 21 wt. %: 79 wt. %, about 22 wt. %: 78 wt. %, about 23 wt. %: 77 wt. %, about 24 wt. %: 76 wt. %, about 25 wt. %: 75 wt. %, about 26 wt. %: 74 wt. %, about 27 wt. %: 73 wt. %, about 28 wt. %: 72 wt. %, about 29 wt. %: 71 wt. %, about 30 wt. %: 70 wt. %, about 35 wt. %: 65 wt. %, about 40 wt. %: 60 wt. %, about 45 wt. %: 55 wt. %, about 50 wt. %: 50 wt. %, about 55 wt. %: 45 wt. %, about 60 wt. %: 40 wt. %, about 65 wt. %: 35 wt. %, about 70 wt. %: 30 wt. %, about 75 wt. %: 25 wt. %, about 80 wt. %: 20 wt. %, about 85 wt. %: 15 wt. %, about 90 wt. %: 10 wt. %, or about 95 wt. %: 5 wt. %

[0284] In some embodiments, a molar ratio of :is from about 2:1 to about 10:1, or any ratio between any two of these values. In some embodiments, a molar ratio of : is from about 2:1 to about 7:1, or any ratio between any two of these values. In some embodiments, a molar ratio of : is from about 3:1 to about 7:1, or any ratio between any two of these values. In some embodiments, a molar ratio of : is from about 3:1 to about 7:1, or any ratio between any two of these values.

[0285] In some embodiments, a molar ratio of :is from about 1:1, from about 1:2, from about 1:3, from about 1:4, from about 1:5, from about 1:6, from about 1:7, from about 1:8, from about 1:9, from about 1:10, from about 1:11, from about 1:12, from about 1:13, from aboutWSGR Docket No.: 56017-729.601 1:14, from about 1:15, from about 1:16, from about 1:17, from about 1:18, from about 1:19, from about 1:20, from about 1:21, from about 1:22, from about 1:23, from about 1:24, from about 1:25, from about 1:26, from about 1:27, from about 1:28, from about 1:29, or from about 1:30, or any ratio between any two of these values.

[0286] In some embodiments, a molar ratio of :is from about 1:1, from about 2:1, from about 3:1, from about 4:1, from about 5:1, from about 6:1, from about 7:1, from about 8:1, from about 9:1, from about 10:1, from about 11:1, from about 12:1, from about 13:1, from about 14:1, from about 15:1, from about 16:1, from about 17:1, from about 18:1, from about 19:1, from about 20:1, from about 21:1, from about 22:1, from about 23:1, from about 24:1, from about 25:1, from about 26:1, from about 27:1, from about 28:1, from about 29:1, or from about 30:1, or any ratio between any two of these values.

[0287] In some embodiments, a molar ratio of : is to about 1:2, to about 1:3, to about 1:4, to about 1:5, to about 1:6, to about 1:7, to about 1:8, to about 1:9, to about 1:10, to about 1:11, to about 1:12, to about 1:13, to about 1:14, to about 1:15, to about 1:16, to about 1:17, to about 1:18, to about 1:19, to about 1:20, to about 1:21, to about 1:22, to about 1:23, to about 1:24, to about 1:25, to about 1:26, to about 1:27, to about 1:28, to about 1:29, or to about 1:30, or any ratio between any two of these values.

[0288] In some embodiments, a molar ratio of : is to about 1:1, to about 2:1, to about 3:1, to about 4:1, to about 5:1, to about 6:1, to about 7:1, to about 8:1, to about 9:1, to about 10:1, to about 11:1, to about 12:1, to about 13:1, to about 14:1, to about 15:1, to about 16:1, to about 17:1, to about 18:1, to about 19:1, to about 20:1, to about 21:1, to about 22:1, to about 23:1, to about 24:1, to about 25:1, to about 26:1, to about 27:1, to about 28:1, to about 29:1, or to about 30:1, or any ratio between any two of these values.

[0289] In some embodiments, a molar ratio of : is from about 1:1 to about 1:2, from about 1:1 to about 1:3, from about 1:1 to about 1:4, from about 1:1 to about 1:5, from about 1:1 to about 1:6, from about 1:1 to about 1:7, from about 1:1 to about 1:8, from about 1:1 to about 1:9, from about 1:1 to about 1:10, from about 1:1 to about 1:11, from about 1:1 to about 1:12, from about 1:1 to about 1:13, from about 1:1 to about 1:14, from about 1:1 to about 1:15, from about 1:1 to about 1:16, from about 1:1 to about 1:17, from about 1:1 to about 1:18, from about 1:1 to about 1:19, from about 1:1 to about 1:20, from about 1:1 to about 1:21, from about 1:1 toWSGR Docket No.: 56017-729.601 about 1:22, from about 1:1 to about 1:23, from about 1:1 to about 1:24, from about 1:1 to about 1:25, from about 1:1 to about 1:26, from about 1:1 to about 1:27, from about 1:1 to about 1:28, from about 1:1 to about 1:29, or from about 1:1 to about 1:30, or any ratio between any two of these values.

[0290] In some embodiments, a molar ratio of :is from about 1:1 to about 1:30, from about 1:2 to about 1:30, from about 1:3 to about 1:30, from about 1:4 to about 1:30, from about 1:5 to about 1:30, from about 1:6 to about 1:30, from about 1:7 to about 1:30, from about 1:8 to about 1:30, from about 1:9 to about 1:30, from about 1:10 to about 1:30, from about 1:11 to about 1:30, from about 1:12 to about 1:30, from about 1:13 to about 1:30, from about 1:14 to about 1:30, from about 1:15 to about 1:30, from about 1:16 to about 1:30, from about 1:17 to about 1:30, from about 1:18 to about 1:30, from about 1:19 to about 1:30, from about 1:20 to about 1:30, from about 1:21 to about 1:30, from about 1:22 to about 1:30, from about 1:23 to about 1:30, from about 1:24 to about 1:30, from about 1:25 to about 1:30, from about 1:26 to about 1:30, from about 1:27 to about 1:30, from about 1:28 to about 1:30, or from about 1:29 to about 1:30, or any ratio between any two of these values.

[0291] In some embodiments, a molar ratio of : is from about 1:1 to about 2:1, from about 1:1 to about 3:1, from about 1:1 to about 4:1, from about 1:1 to about 5:1, from about 1:1 to about 6:1, from about 1:1 to about 7:1, from about 1:1 to about 8:1, from about 1:1 to about 9:1, from about 1:1 to about 10:1, from about 1:1 to about 11:1, from about 1:1 to about 12:1, from about 1:1 to about 13:1, from about 1:1 to about 14:1, from about 1:1 to about 15:1, from about 1:1 to about 16:1, from about 1:1 to about 17:1, from about 1:1 to about 18:1, from about 1:1 to about 19:1, from about 1:1 to about 20:1, from about 1:1 to about 21:1, from about 1:1 to about 22:1, from about 1:1 to about 23:1, from about 1:1 to about 24:1, from about 1:1 to about 25:1, from about 1:1 to about 26:1, from about 1:1 to about 27:1, from about 1:1 to about 28:1, from about 1:1 to about 29:1, or from about 1:1 to about 30:1, or any ratio between any two of these values.

[0292] In some embodiments, a molar ratio of : is from about 1:1 to about 30:1, from about 2:1 to about 30:1, from about 3:1 to about 30:1, from about 4:1 to about 30:1, from about 5:1 to about 30:1, from about 6:1 to about 30:1, from about 7:1 to about 30:1, from about 8:1 to about 30:1, from about 9:1 to about 30:1, from about 10:1 to about 30:1, from about 11:1 to about 30:1, from about 12:1 to about 30:1, from about 13:1 to about 30:1, from about 14:1 to about 30:1,WSGR Docket No.: 56017-729.601 from about 15:1 to about 30:1, from about 16:1 to about 30:1, from about 17:1 to about 30:1, from about 18:1 to about 30:1, from about 19:1 to about 30:1, from about 20:1 to about 30:1, from about 21:1 to about 30:1, from about 22:1 to about 30:1, from about 23:1 to about 30:1, from about 24:1 to about 30:1, from about 25:1 to about 30:1, from about 26:1 to about 30:1, from about 27:1 to about 30:1, from about 28:1 to about 30:1, or from about 29:1 to about 30:1, or any ratio between any two of these values.

[0293] In some embodiments, a molar ratio of :is from about 1:1 to about 10:1, from about 2:1 to about 10:1, from about 3:1 to about 10:1, from about 4:1 to about 10:1, from about 5:1 to about 10:1, from about 6:1 to about 10:1, from about 7:1 to about 10:1, from about 8:1 to about 10:1, or from about 9:1 to about 10:1, or any ratio between any two of these values. In some embodiments, a molar ratio of : is from about 1:1 to about 10:1, from about 1:1 to about 9:1, from about 1:1 to about 8:1, from about 1:1 to about 7:1, from about 1:1 to about 6:1, from about 1:1 to about 5:1, from about 1:1 to about 4:1, from about 1:1 to about 3:1, or from about 1:1 to about 2:1, or any ratio between any two of these values.

[0294] In some embodiments, a molar ratio of : is from about 1:1 to about 7:1, from about 2:1 to about 7:1, from about 3:1 to about 7:1, from about 4:1 to about 7:1, from about 5:1 to about 7:1, or from about 6:1 to about 7:1, or any ratio between any two of these values. In some embodiments, a molar ratio of : is from about 1:1 to about 7:1, from about 1:1 to about 6:1, from about 1:1 to about 5:1, from about 1:1 to about 4:1, from about 1:1 to about 3:1, or from about 1:1 to about 2:1, or any ratio between any two of these values.

[0295] In some embodiments, a molar ratio of :is about 1:1 , about 1:2, about 1:3, about 1:4, about 1:5, about 1:6, about 1:7, about 1:8, about 1:9, about 1:10, about 1:11, about 1:12, about 1:13, about 1:14, about 1:15, about 1:16, about 1:17, about 1:18, about 1:19, about 1:20, about 1:21, about 1:22, about 1:23, about 1:24, about 1:25, about 1:26, about 1:27, about 1:28, about 1:29, or about 1:30, or any ratio between any two of these values.

[0296] In some embodiments, a molar ratio of :is about 1:1, about 2:1, about 3:1, about 4:1, about 5:1, about 6:1, about 7:1, about 8:1, about 9:1, about 10:1, about 11:1, about 12:1, about 13:1, about 14:1, about 15:1, about 16:1, about 17:1, about 18:1, about 19:1, about 20:1,WSGR Docket No.: 56017-729.601 about 21:1, about 22:1, about 23:1, about 24:1, about 25:1, about 26:1, about 27:1, about 28:1, about 29:1, or about 30:1, or any ratio between any two of these values.

[0297] In some embodiments, a molar ratio of : is from about 1:1 to about 1:7. In some embodiments, a molar ratio of : is from about 1:2 to about 1:7. In some embodiments, a molar ratio of : is from about 1:3 to about 1:7. In some embodiments, a molar ratio of : is from about 1:4 to about 1:7. In some embodiments, a molar ratio of : is from about 1:5 to about 1:7. In some embodiments, a molar ratio ofis from about 1:6 to about 1:7. In some embodiments, a molar ratio: is from about 1:1 to about 1:6. In some embodiments, a molar ratio of : is from about 1:1 to about1:5. In some embodiments, a molar ratio of : is from about 1:1 to about 1:4. In some embodiments, a molar ratio of : is from about 1:1 to about 1:3. In some embodiments, a molar ratio of : is from about 1:1 to about 1:2. In some embodiments, a molar ratio: is from about 1:2 to about 1:7. In some embodiments, a molar ratio ofis from about 1:2 to about 1:6. In some embodiments, a molar ratio: is from about 1:2 to about 1:5. In some embodiments, a molar ratio: is from about 1:2 to about 1:4. In some embodiments, a molar ratio of : is from about 1:2 to about 1:3. In some embodiments, a molar ratio of : is from about 1:3 to about 1:7. In some embodiments,WSGR Docket No.: 56017-729.601 a molar ratio of : is from about 1:3 to about 1:6. In some embodiments, a molar ratioof : some a : is from about 1:3 to about 1:4. In some embodiments, a molar ratio of : is from about 1:4 to about 1:7. In some embodiments, a molar ratio of : is from about 1:4 to about 1:6. In some embodiments, a molar ratio of : is from about 1:4 to about 1:5. In some embodiments, a molar ratio of : is from about 1:5 to about 1:7. In some embodiments, a molar ratio of : is from about 1:5 to about 1:6. In some embodiments, a molar ratio ofis about 1:2. Insome embodiments, a molar ratio of : is about 1:3. In some embodiments, a molar ratiosome embodiments, a molar ratio of : is about 1:6. In some embodiments, a molar ratioabout 1:7.

[0298] In some embodiments, a molar ratio ofanycombination thereof is from about 2:1 to about 10:1. In some embodiments, a molar ratio of :WSGR Docket No.: 56017-729.601, , , or any combination thereof is from about 2:1 to about 7:1. Insome embodiments, a molar ratioany combinationthereof is from about 3:1 to about 7:1. In some embodiments, a molar ratio of : ,, , or any combination thereof is from about 4:1 to about 7:1. In someembodiments, a molar ratioany combination thereofis about 4:1.

[0299] In some embodiments, a molar ratio of, or anycombination thereof is from about 1:1, from about 1:2, from about 1:3, from about 1:4, from about 1:5, from about 1:6, from about 1:7, from about 1:8, from about 1:9, from about 1:10, from about 1:11, from about 1:12, from about 1:13, from about 1:14, from about 1:15, from about 1:16, from about 1:17, from about 1:18, from about 1:19, from about 1:20, from about 1:21, from about 1:22, from about 1:23, from about 1:24, from about 1:25, from about 1:26, from about 1:27, from about 1:28, from about 1:29, or from about 1:30, or any ratio between any two of these values.WSGR Docket No.: 56017-729.601

[0300] In some embodiments, a molar ratioanycombination thereof is from about 1:1, from about 2:1, from about 3:1, from about 4:1, from about 5:1, from about 6:1, from about 7:1, from about 8:1, from about 9:1, from about 10:1, from about 11:1, from about 12:1, from about 13:1, from about 14:1, from about 15:1, from about 16:1, from about 17:1, from about 18:1, from about 19:1, from about 20:1, from about 21:1, from about 22:1, from about 23:1, from about 24:1, from about 25:1, from about 26:1, from about 27:1, from about 28:1, or from about 29:1, from about 30:1, or any ratio between any two of these values.

[0301] In some embodiments, a molar ratio of, or anycombination thereof is to about 1:2, to about 1:3, to about 1:4, to about 1:5, to about 1:6, to about 1:7, to about 1:8, to about 1:9, to about 1:10, to about 1:11, to about 1:12, to about 1:13, to about 1:14, to about 1:15, to about 1:16, to about 1:17, to about 1:18, to about 1:19, to about 1:20, to about 1:21, to about 1:22, to about 1:23, to about 1:24, to about 1:25, to about 1:26, to about 1:27, to about 1:28, to about 1:29, or to about 1:30, or any ratio between any two of these values.

[0302] In some embodiments, a molar ratio of, or anycombination thereof is to about 1:1, to about 2:1, to about 3:1, to about 4:1, to about 5:1, to about 6:1, to about 7:1, to about 8:1, to about 9:1, to about 10:1, to about 11:1, to about 12:1, to about 13:1, to about 14:1, to about 15:1, to about 16:1, to about 17:1, to about 18:1, to about 19:1, to about 20:1, to about 21:1, to about 22:1, to about 23:1, to about 24:1, to about 25:1, to about 26:1, to about 27:1, to about 28:1, to about 29:1, or to about 30:1, or any ratio between any two of these values.

[0303] In some embodiments, a molar ratio of, or anycombination thereof is from about 1:1 to about 1:2, from about 1:1 to about 1:3, from about 1:1 toWSGR Docket No.: 56017-729.601 about 1:4, from about 1:1 to about 1:5, from about 1:1 to about 1:6, from about 1:1 to about 1:7, from about 1:1 to about 1:8, from about 1:1 to about 1:9, from about 1:1 to about 1:10, from about 1:1 to about 1:11, from about 1:1 to about 1:12, from about 1:1 to about 1:13, from about 1:1 to about 1:14, from about 1:1 to about 1:15, from about 1:1 to about 1:16, from about 1:1 to about 1:17, from about 1:1 to about 1:18, from about 1:1 to about 1:19, from about 1:1 to about 1:20, from about 1:1 to about 1:21, from about 1:1 to about 1:22, from about 1:1 to about 1:23, from about 1:1 to about 1:24, from about 1:1 to about 1:25, from about 1:1 to about 1:26, from about 1:1 to about 1:27, from about 1:1 to about 1:28, from about 1:1 to about 1:29, or from about 1:1 to about 1:30.

[0304] In some embodiments, a molar ratio of, or anycombination thereof is from about 1:1 to about 1:30, from about 1:2 to about 1:30, from about 1:3 to about 1:30, from about 1:4 to about 1:30, from about 1:5 to about 1:30, from about 1:6 to about 1:30, from about 1:7 to about 1:30, from about 1:8 to about 1:30, from about 1:9 to about 1:30, from about 1:10 to about 1:30, from about 1:11 to about 1:30, from about 1:12 to about 1:30, from about 1:13 to about 1:30, from about 1:14 to about 1:30, from about 1:15 to about 1:30, from about 1:16 to about 1:30, from about 1:17 to about 1:30, from about 1:18 to about 1:30, from about 1:19 to about 1:30, from about 1:20 to about 1:30, from about 1:21 to about 1:30, from about 1:22 to about 1:30, from about 1:23 to about 1:30, from about 1:24 to about 1:30, from about 1:25 to about 1:30, from about 1:26 to about 1:30, from about 1:27 to about 1:30, from about 1:28 to about 1:30, or from about 1:29 to about 1:30.

[0305] In some embodiments, a molar ratioanycombination thereof is from about 1:1 to about 2:1, from about 1:1 to about 3:1, from about 1:1 to about 4:1, from about 1:1 to about 5:1, from about 1:1 to about 6:1, from about 1:1 to about 7:1, from about 1:1 to about 8:1, from about 1:1 to about 9:1, from about 1:1 to about 10:1, from about 1:1 to about 11:1, from about 1:1 to about 12:1, from about 1:1 to about 13:1, from about 1:1 to about 14:1, from about 1:1 to about 15:1, from about 1:1 to about 16:1, from about 1:1 to about 17:1, from about 1:1 to about 18:1, from about 1:1 to about 19:1, from about 1:1 to about 20:1, from about 1:1 to about 21:1, from about 1:1 to about 22:1, from about 1:1 to about 23:1, fromWSGR Docket No.: 56017-729.601 about 1:1 to about 24:1, from about 1:1 to about 25:1, from about 1:1 to about 26:1, from about 1:1 to about 27:1, from about 1:1 to about 28:1, from about 1:1 to about 29:1, or from about 1:1 to about 30:1.

[0306] In some embodiments, a molar ratioanycombination thereof is from about 1:1 to about 30:1, from about 2:1 to about 30:1, from about 3:1 to about 30:1, from about 4:1 to about 30:1, from about 5:1 to about 30:1, from about 6:1 to about 30:1, from about 7:1 to about 30:1, from about 8:1 to about 30:1, from about 9:1 to about 30:1, from about 10:1 to about 30:1, from about 11:1 to about 30:1, from about 12:1 to about 30:1, from about 13:1 to about 30:1, from about 14:1 to about 30:1, from about 15:1 to about 30:1, from about 16:1 to about 30:1, from about 17:1 to about 30:1, from about 18:1 to about 30:1, from about 19:1 to about 30:1, from about 20:1 to about 30:1, from about 21:1 to about 30:1, from about 22:1 to about 30:1, from about 23:1 to about 30:1, from about 24:1 to about 30:1, from about 25:1 to about 30:1, from about 26:1 to about 30:1, from about 27:1 to about 30:1, from about 28:1 to about 30:1, or from about 29:1 to about 30:1.

[0307] In some embodiments, a molar ratiocombination thereof is from about 1:1 to about 10:1, from about 2:1 to about 10:1, from about 3:1 to about 10:1, from about 4:1 to about 10:1, from about 5:1 to about 10:1, from about 6:1 to about 10:1, from about 7:1 to about 10:1, from about 8:1 to about 10:1, or from about 9:1 to about 10:1.In some embodiments, a molar ratio of, or anycombination thereof is from about 1:1 to about 10:1, from about 1:1 to about 9:1, from about 1:1 to about 8:1, from about 1:1 to about 7:1, from about 1:1 to about 6:1, from about 1:1 to about 5:1, from about 1:1 to about 4:1, from about 1:1 to about 3:1, or from about 1:1 to about 2:1.WSGR Docket No.: 56017-729.601

[0308] In some embodiments, a molar ratioanycombination thereof is from about 1:1 to about 7:1, from about 2:1 to about 7:1, from about 3:1 to about 7:1, from about 4:1 to about 7:1, from about 5:1 to about 7:1, or from about 6:1 to about7:1. In some embodiments, a molar ratio of :, or anycombination thereof is from about 1:1 to about 7:1, from about 1:1 to about 6:1, from about 1:1 to about 5:1, from about 1:1 to about 4:1, from about 1:1 to about 3:1, or from about 1:1 to about 2:1.

[0309] In some embodiments, a molar ratio of, or anycombination thereof is about 1:1 , about 1:2, about 1:3, about 1:4, about 1:5, about 1:6, about 1:7, about 1:8, about 1:9, about 1:10, about 1:11, about 1:12, about 1:13, about 1:14, about 1:15, about 1:16, about 1:17, about 1:18, about 1:19, about 1:20, about 1:21, about 1:22, about 1:23, about 1:24, about 1:25, about 1:26, about 1:27, about 1:28, about 1:29, or about 1:30, or any ratio between any two of these values.

[0310] In some embodiments, a molar ratio of, or anycombination thereof is about 1:1, about 2:1, about 3:1, about 4:1, about 5:1, about 6:1, about 7:1, about 8:1, about 9:1, about 10:1, about 11:1, about 12:1, about 13:1, about 14:1, about 15:1, about 16:1, about 17:1, about 18:1, about 19:1, about 20:1, about 21:1, about 22:1, about 23:1, about 24:1, about 25:1, about 26:1, about 27:1, about 28:1, about 29:1, or about 30:1, or any ratio between any two of these values.WSGR Docket No.: 56017-729.601

[0311] In some embodiments, a molar ratio of, , , or anycombination thereof: is about 1:1 to about 1:4. In some embodiments, a molar ratio of ,, or any combination thereof: is from about 1:2 to about 1:4. Insome embodiments, a molar ratio of, , , or any combinationthereof: is from about 1:3 to about 1:4. In some embodiments, a molar ratio of ,, , ,thereof: is from about 1:1 to about 1:2. In some embodiments, a molar ratio of,is from about 1:2 to about 1:4. InWSGR Docket No.: 56017-729.601 some embodiments, a molar ratio of, , , or any combinationthereof: is from about 1:2 to about 1:3.In some embodiments, a molar ratio of ,is from about 1:3 to about 1:4. Insome embodiments, a molar ratio of, , , or any combinationthereof: is about 1:1. In some embodiments, a molar ratio of,embodiments, a molar ratioany combination thereof:is about 1:4.WSGR Docket No.: 56017-729.601 GLP-1 receptor agonists

[0312] In some embodiments, the therapeutic agent is a GLP-l receptor agonist or a functional variant thereof. In some embodiments, the GLP-1 receptor agonist is a polypeptide having an amino acid sequence similar to the GLP-1 hormone. In some embodiments, the GLP-1 receptor agonist comprises one or more chemical modifications that are different from endogenous GLP- 1. In some embodiments, the one or more chemical modifications render the GLP-1 receptor agonist superior therapeutic effects compared with endogenous GLP-1. In some embodiments, the GLP-1 receptor agonist comprise a sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%. 97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the endogenous GLP- 1 sequence (e.g., SEQ ID NO: 1 or SEQ ID NO: 2)). In some embodiments, the GLP-1 receptor agonist comprise the endogenous GLP-1 sequence (e.g., SEQ ID NO: 1 or SEQ ID NO: 2).

[0313] In some embodiments, the GLP-1 receptor agonist comprising the substitution of an alanine at position 8 of the endogenous GLP-1 sequence (SEQ ID NO: 1 or SEQ ID NO: 2) replaced with 2-aminoisobuteric acid exhibits an enhanced metabolic stability compared with endogenous GLP-1. In some embodiments, the GLP-1 receptor agonist comprising the substitution of an alanine at position 8 of the endogenous GLP-1 sequence (SEQ ID NO: 1 or SEQ ID NO: 2) replaced with 2-aminoisobuteric acid exhibits resistance to the breakdown by endogenous enzymes, such as dipeptidyl peptidase-IV.

[0314] In some embodiments, the GLP-1 receptor agonist comprises a sequence having at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%.97%, 98%, 99%, 99.1%, 99.2%, 99.3%, 99.4%, 99.5%, 99.6%, 99.7%, 99.8%, 99.9%, or 100% sequence identity to the sequence of SEQ ID NO: 5. In some embodiments, the GLP-1 receptor agonist comprises the sequence of SEQ ID NO: 5. In some embodiments, semaglutide comprises the sequence of SEQ ID NO: 5. “Weight % Ratios of Semaglutide: Counterion

[0315] In some embodiments, the compounds as provided herein, e.g., the salt forms of a GLP- l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of a counterion to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 0.1 wt. % to 50.0 wt. % counterion relative to 99.9 wt. % to 50.0 wt. % a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof. In some embodiments, the compounds as provided herein, e.g., the salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of a counterion to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 0.1 wt. % to 0.5 wt. % salt. In someWSGR Docket No.: 56017-729.601 embodiments, the compounds as provided herein, e.g., the salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of a counterion to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 0.5 wt. % to 1.0 wt. % salt. In some embodiments, the compounds as provided herein, e.g., the salt forms of a GLP- l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of a counterion to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 1.0 wt. % to 1.5 wt. % salt. In some embodiments, the compounds as provided herein, e.g., the salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of a counterion to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 1.5 wt. % to 2.0 wt. % salt. In some embodiments, the compounds as provided herein, e.g., the salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of a counterion to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 2.0 wt. % to 2.5 wt. % salt. In some embodiments, the compounds as provided herein, e.g., the salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of a counterion to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 2.5 wt. % to 3.0 wt. % salt. In some embodiments, the compounds as provided herein, e.g., the salt forms of a GLP- l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of a counterion to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 3.0 wt. % to 3.5 wt. % salt. In some embodiments, the compounds as provided herein, e.g., the salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of a counterion to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 3.5 wt. % to 4.0 wt. % salt. In some embodiments, the compounds as provided herein, e.g., the salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of a counterion to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 4.0 wt. % to 4.5 wt. % salt. In some embodiments, the compounds as provided herein, e.g., the salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of a counterion to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 4.5 wt. % to 5.0 wt. % salt. In some embodiments, the compounds as provided herein, e.g., the salt forms of a GLP- l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of a counterion to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 5.0 wt. % to 5.5 wt. % salt. In some embodiments, the compounds as provided herein, e.g., the salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of a counterion to a GLP-l receptor agonist (e.g., semaglutide) or aWSGR Docket No.: 56017-729.601 functional variant thereof from 5.5 wt. % to 6.0 wt. % salt. In some embodiments, the compounds as provided herein, e.g., the salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of a counterion to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 6.0 wt. % to 7.5 wt. % salt. In some embodiments, the compounds as provided herein, e.g., the salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of a counterion to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 6.5 wt. % to 7.0 wt. % salt. In some embodiments, the compounds as provided herein, e.g., the salt forms of a GLP- l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of a counterion to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 7.0 wt. % to 7.5 wt. % salt. In some embodiments, the compounds as provided herein, e.g., the salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of a counterion to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 7.5 wt. % to 8.0 wt. % salt. In some embodiments, the compounds as provided herein, e.g., the salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of a counterion to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 8.0 wt. % to 8.5 wt. % salt. In some embodiments, the compounds as provided herein, e.g., the salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of a counterion to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 8.5 wt. % to 9.0 wt. % salt. In some embodiments, the compounds as provided herein, e.g., the salt forms of a GLP- l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of a counterion to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 9.0 wt. % to 9.5 wt. % salt. In some embodiments, the compounds as provided herein, e.g., the salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of a counterion to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 9.5 wt. % to 10.0 wt. % salt. In some embodiments, the compounds as provided herein, e.g., the salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of a counterion to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 10.0 wt. % to 15.0 wt. % salt. In some embodiments, the compounds as provided herein, e.g., the salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of a counterion to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 15.0 wt. % to 20.0 wt. % salt. In some embodiments, the compounds as provided herein, e.g., the salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt.WSGR Docket No.: 56017-729.601 % ratios of a counterion to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 20.0 wt. % to 30.0 wt. % salt. In some embodiments, the compounds as provided herein, e.g., the salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of a counterion to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 30.0 wt. % to 40.0 wt. % salt. In some embodiments, the compounds as provided herein, e.g., the salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of a counterion to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 40.0 wt. % to 50.0 wt. % salt. Exemplary Pharmaceutically Acceptable Salt Forms of Semaglutide

[0316] In some embodiments, the compound as provided herein, e.g., the salt form of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof, comprises an aluminum salt of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof. In some embodiments, the compound as provided herein, e.g., the salt form of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof, comprises a sodium salt of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof. In some embodiments, the compound as provided herein, e.g., the salt form of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof, comprises a lithium salt of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof. In some embodiments, the compound as provided herein, e.g., the salt form of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof, comprises a potassium salt of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof. In some embodiments, the compound as provided herein, e.g., the salt form of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof, comprises a calcium salt of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof. In some embodiments, the compound as provided herein, e.g., the salt form of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof, comprises a magnesium salt of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof. In some embodiments, the compound as provided herein, e.g., the salt form of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof, comprises a zinc salt of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof. In some embodiments, the compound as provided herein, e.g., the salt form of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof, comprises an ammonium (i.e., NH4+) salt of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof. In some embodiments, the compound as provided herein, e.g., the salt form of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof, comprises an NMe4+salt of a GLP-l receptorWSGR Docket No.: 56017-729.601 agonist (e.g., semaglutide) or a functional variant thereof. In some embodiments, the compound as provided herein, e.g., the salt form of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof, comprises an N(C1–4alkyl)4+salt of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof. In some embodiments, the compound as provided herein, e.g., the salt form of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof, comprises an amine cation salt of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof.

[0317] In some embodiments, the compound as provided herein, e.g., the salt form of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof comprises an aluminum salt of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof formulated in a wt. % ratio of from 0.1 wt. % to 50.0 wt. % aluminum cation relative to 99.9 wt. % to 50.0 wt. % a GLP- l receptor agonist (e.g., semaglutide) or a functional variant thereof. In some embodiments, certain aluminum salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of aluminum salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 0.1 wt. % to 0.5 wt. % aluminum salt. In some embodiments, certain aluminum salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of aluminum salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 0.5 wt. % to 1.0 wt. % aluminum salt. In some embodiments, certain aluminum salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of aluminum salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 1.0 wt. % to 1.5 wt. % aluminum salt. In some embodiments, certain aluminum salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of aluminum salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 1.5 wt. % to 2.0 wt. % aluminum salt. In some embodiments, certain aluminum salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of aluminum salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 2.0 wt. % to 2.5 wt. % aluminum salt. In some embodiments, certain aluminum salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of aluminum salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 2.5 wt. % to 3.0 wt. % aluminum salt. In some embodiments, certain aluminum salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of aluminum salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 3.0 wt. % to 3.5 wt. % aluminum salt. In some embodiments, certain aluminum salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereofWSGR Docket No.: 56017-729.601 are formulated in wt. % ratios of aluminum salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 3.5 wt. % to 4.0 wt. % aluminum salt. In some embodiments, certain aluminum salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of aluminum salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 4.0 wt. % to 4.5 wt. % aluminum salt. In some embodiments, certain aluminum salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of aluminum salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 4.5 wt. % to 5.0 wt. % aluminum salt. In some embodiments, certain aluminum salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of aluminum salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 5.0 wt. % to 5.5 wt. % aluminum salt. In some embodiments, certain aluminum salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of aluminum salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 5.5 wt. % to 6.0 wt. % aluminum salt. In some embodiments, certain aluminum salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of aluminum salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 6.0 wt. % to 7.5 wt. % aluminum salt. In some embodiments, certain aluminum salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of aluminum salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 6.5 wt. % to 7.0 wt. % aluminum salt. In some embodiments, certain aluminum salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of aluminum salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 7.0 wt. % to 7.5 wt. % aluminum salt. In some embodiments, certain aluminum salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of aluminum salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 7.5 wt. % to 8.0 wt. % aluminum salt. In some embodiments, certain aluminum salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of aluminum salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 8.0 wt. % to 8.5 wt. % aluminum salt. In some embodiments, certain aluminum salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of aluminum salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 8.5 wt. % to 9.0 wt. % aluminum salt. In some embodiments, certain aluminum salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios ofWSGR Docket No.: 56017-729.601 aluminum salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 9.0 wt. % to 9.5 wt. % aluminum salt. In some embodiments, certain aluminum salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of aluminum salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 9.5 wt. % to 10.0 wt. % aluminum salt. In some embodiments, certain aluminum salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of aluminum salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 10.0 wt. % to 15.0 wt. % aluminum salt. In some embodiments, certain aluminum salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of aluminum salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 15.0 wt. % to 20.0 wt. % aluminum salt. In some embodiments, certain aluminum salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of aluminum salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 20.0 wt. % to 30.0 wt. % aluminum salt. In some embodiments, certain aluminum salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of aluminum salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 30.0 wt. % to 40.0 wt. % aluminum salt. In some embodiments, certain aluminum salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of aluminum salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 40.0 wt. % to 50.0 wt. % aluminum salt.

[0318] In some embodiments, the compound as provided herein, e.g., the salt form of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof comprises a sodium salt of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof formulated in a wt. % ratio of from 0.1 wt. % to 50.0 wt. % sodium cation relative to 99.9 wt. % to 50.0 wt. % a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof. In some embodiments, certain sodium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of sodium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 0.1 wt. % to 0.5 wt. % sodium salt. In some embodiments, certain sodium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of sodium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 0.5 wt. % to 1.0 wt. % sodium salt. In some embodiments, certain sodium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of sodium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 1.0 wt. % to 1.5 wt. % sodium salt. In some embodiments, certainWSGR Docket No.: 56017-729.601 sodium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of sodium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 1.5 wt. % to 2.0 wt. % sodium salt. In some embodiments, certain sodium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of sodium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 2.0 wt. % to 2.5 wt. % sodium salt. In some embodiments, certain sodium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of sodium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 2.5 wt. % to 3.0 wt. % sodium salt. In some embodiments, certain sodium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of sodium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 3.0 wt. % to 3.5 wt. % sodium salt. In some embodiments, certain sodium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of sodium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 3.5 wt. % to 4.0 wt. % sodium salt. In some embodiments, certain sodium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of sodium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 4.0 wt. % to 4.5 wt. % sodium salt. In some embodiments, certain sodium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of sodium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 4.5 wt. % to 5.0 wt. % sodium salt. In some embodiments, certain sodium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of sodium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 5.0 wt. % to 5.5 wt. % sodium salt. In some embodiments, certain sodium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of sodium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 5.5 wt. % to 6.0 wt. % sodium salt. In some embodiments, certain sodium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of sodium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 6.0 wt. % to 7.5 wt. % sodium salt. In some embodiments, certain sodium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of sodium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 6.5 wt. % to 7.0 wt. % sodium salt. In some embodiments, certain sodium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of sodium salt to a GLP-l receptor agonist (e.g., semaglutide) or aWSGR Docket No.: 56017-729.601 functional variant thereof from 7.0 wt. % to 7.5 wt. % sodium salt. In some embodiments, certain sodium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of sodium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 7.5 wt. % to 8.0 wt. % sodium salt. In some embodiments, certain sodium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of sodium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 8.0 wt. % to 8.5 wt. % sodium salt. In some embodiments, certain sodium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of sodium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 8.5 wt. % to 9.0 wt. % sodium salt. In some embodiments, certain sodium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of sodium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 9.0 wt. % to 9.5 wt. % sodium salt. In some embodiments, certain sodium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of sodium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 9.5 wt. % to 10.0 wt. % sodium salt. In some embodiments, certain sodium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of sodium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 10.0 wt. % to 15.0 wt. % sodium salt. In some embodiments, certain sodium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of sodium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 15.0 wt. % to 20.0 wt. % sodium salt. In some embodiments, certain sodium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of sodium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 20.0 wt. % to 30.0 wt. % sodium salt. In some embodiments, certain sodium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of sodium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 30.0 wt. % to 40.0 wt. % sodium salt. In some embodiments, certain sodium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of sodium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 40.0 wt. % to 50.0 wt. % sodium salt.

[0319] In some embodiments, the compound as provided herein, e.g., the salt form of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof comprises a lithium salt of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof formulated in a wt. % ratio of from 0.1 wt. % to 50.0 wt. % lithium cation relative to 99.9 wt. % to 50.0 wt. % a GLP-lWSGR Docket No.: 56017-729.601 receptor agonist (e.g., semaglutide) or a functional variant thereof. In some embodiments, certain lithium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of lithium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 0.1 wt. % to 0.5 wt. % lithium salt. In some embodiments, certain lithium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of lithium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 0.5 wt. % to 1.0 wt. % lithium salt. In some embodiments, certain lithium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of lithium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 1.0 wt. % to 1.5 wt. % lithium salt. In some embodiments, certain lithium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of lithium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 1.5 wt. % to 2.0 wt. % lithium salt. In some embodiments, certain lithium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of lithium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 2.0 wt. % to 2.5 wt. % lithium salt. In some embodiments, certain lithium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of lithium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 2.5 wt. % to 3.0 wt. % lithium salt. In some embodiments, certain lithium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of lithium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 3.0 wt. % to 3.5 wt. % lithium salt. In some embodiments, certain lithium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of lithium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 3.5 wt. % to 4.0 wt. % lithium salt. In some embodiments, certain lithium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of lithium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 4.0 wt. % to 4.5 wt. % lithium salt. In some embodiments, certain lithium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of lithium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 4.5 wt. % to 5.0 wt. % lithium salt. In some embodiments, certain lithium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of lithium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 5.0 wt. % to 5.5 wt. % lithium salt. In some embodiments, certain lithium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereofWSGR Docket No.: 56017-729.601 are formulated in wt. % ratios of lithium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 5.5 wt. % to 6.0 wt. % lithium salt. In some embodiments, certain lithium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of lithium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 6.0 wt. % to 7.5 wt. % lithium salt. In some embodiments, certain lithium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of lithium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 6.5 wt. % to 7.0 wt. % lithium salt. In some embodiments, certain lithium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of lithium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 7.0 wt. % to 7.5 wt. % lithium salt. In some embodiments, certain lithium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of lithium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 7.5 wt. % to 8.0 wt. % lithium salt. In some embodiments, certain lithium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of lithium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 8.0 wt. % to 8.5 wt. % lithium salt. In some embodiments, certain lithium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of lithium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 8.5 wt. % to 9.0 wt. % lithium salt. In some embodiments, certain lithium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of lithium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 9.0 wt. % to 9.5 wt. % lithium salt. In some embodiments, certain lithium salt forms of a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof are formulated in wt. % ratios of lithium salt to a GLP-l receptor agonist (e.g., semaglutide) or a functional variant thereof from 9.5 wt. % to 10.0 wt. % lithium...

Claims

WSGR Docket No.: 56017-729.601 CLAIMS What is claimed is:

1. A compound comprising the structure of Formula I:Formula I, wherein: semaglutide; andwherein does not have the structure, wherein R8, R9, and R10are independently C1-C5 alkyl, and R11is C2-C5 alkyl that is unsubstituted or substituted with 1 or more hydroxyl.

2. The compound of claim 1, wherein the anion of semaglutide derives from the structure of the compound in Table 2.

3. The compound of claim 1 or 2, wherein the cationic component is selected from the group consisting of alkali metal, alkaline earth metal, a metal ion, ammonium (NH4+), a protonated or positively (+) charged ion from an aliphatic primary amine, secondary amine or tertiary amine, aralkyl amine, benzathine, benethamine, heterocyclic aromatic amine, quaternary ammonium, nontoxic quaternary ammonium, 1H-imidazole, substituted- imidazole, pyrrolidine, substituted pyrrolidine, piperidine or substituted piperidine, piperazine or substituted piperazine, morpholine, substituted morpholine, basic amino acid, aminoguanidine, guanidine derivatives, and an amine cation formed using a counterion.

4. The compound of claim 3, wherein: (i) a metal ion comprises aluminum, sodium, lithium, potassium, magnesium, calcium, or zinc; (ii) the aliphatic primary amine, secondary amine, or tertiary amine comprises 2- aminoethanol, tromethamine, dimethylamine, diethylamine, N-ethyl-glucamine, hydrabamine, trimethylamine, triethylamine, dicyclohexylamine, ethanolamine, diethanolamine, triethanolamine, dimethylethanolamine, (2,2′,2″-nitrilotris(ethanol)), 2-WSGR Docket No.: 56017-729.601 diethylaminoethanol, procaine or substituted procaine, meglumine, carnitine, ethylenediamine, choline, or acetylcholine; (iii) aralkyl amine comprises Ν,Ν-dibenzylethylenediamine; (iv) heterocyclic aromatic amine comprises pyridine, pyrimidine, picoline, quinoline, or isoquinoline; (v) quaternary ammonium comprises NH4+or betaine; (vi) nontoxic quaternary ammonium comprises NMe4+, N+(C1–4alkyl)4,), tetramethylammonium, tetraethylammonium, benzyltrimethylammonium, benzyltriethylammonium, benzyltributylammonium, methyltrioctylammonium or tetrabutylammonium; (vii) substituted-imidazole comprises N-alkyl imidazole or N-methyl imidazole; (viii) substituted pyrrolidine comprises 1-alkyl pyrrolidine, 1-methyl pyrrolidine, or 1-(2- hydroxy-ethyl)-pyrrolidine); (ix) substituted piperidine comprises 1-alkyl piperidine or 1-methyl piperidine; (x) substituted piperazine comprises 1-alkyl piperazine, 1-methyl piperazine, 1,4-dialkyl piperazine, or 1,4-dimethyl piperazine; (xi) substituted morpholine comprises N-substituted morpholine, N-methyl morpholine ,or 4-(2-hydroxyethyl)-morpholine); (xii) basic amino acid comprises arginine, lysine, or histidine; (xiii) the amine cation is formed using a counterion selected from the group consisting of halide, hydroxide, carboxylate, sulfate, phosphate, nitrate, lower alkyl sulfonate, and aryl sulfonate; or (xiv) any combination thereof.

5. The compound of claim 4, wherein the substituted procaine comprises chloroprocaine.

6. The compound of claim 3, wherein the cationic component is betaine.

7. The compound of any one of claims 1, 2 and 3, wherein the cationic component comprise the structure8. The compound of claim 1 or 2, wherein the cationic component is selected from the group consisting of those in Table 3.

9. The compound of claim 8, wherein any of the cationic components of Table 3 is provided in any of the molar ratios and weight ratios of Table 3 relative to one or more anions of semaglutide.

10. The compound of claim 3, wherein the quaternary ammonium has the structure ofWSGR Docket No.: 56017-729.601wherein: R8, R9, R10, and R11are each independently a substituted or unsubstituted group selected from C1-6 aliphatic, phenyl, cycloalkyl, 4-7 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or 5-6 membered monocyclic heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

11. The compound of claim 3, wherein the quaternary ammonium has the structure ofwherein: R8, R9, R10, and R11are each independently a substituted or unsubstituted C1-6 aliphatic.

12. The compound of claim 3, wherein the quaternary ammonium has the structure of wherein: (i) R8, R9, R10, and R11are independently C1-C6 alkyl; (ii) R8, R9, R10, and R11are independently C1-C4 alkyl; (iii) R8, R9, and R10are C2 alkyl and R11is C1 alkyl; (iv) R8, R9, and R10are C4 alkyl and R11is C1 alkyl; (v) all of R8, R9, R10, and R11are C1 alkyl; (vi) all of R8, R9, R10, and R11are C2 alkyl; (vii) all of R8, R9, R10, and R11are C3 alkyl; or (viii) all of R8, R9, R10, and R11are C4 alkyl.

13. The compound of claim 3, wherein the quaternary ammonium has the structure of14. The compound of claim 3, wherein the quaternary ammonium has the structure ofWSGR Docket No.: 56017-729.

601.

15. The compound of any one of claims 1-14, wherein the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is selected from the group consisting of about 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, and 1:

7.

16. The compound of any one of claims 1-14, wherein the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is selected from the group consisting of about 1:2, 1:3, 1:4, 1:5, 1:6, and 1:

7.

17. The compound of any one of claims 1-14, wherein the cationic component and anion of semaglutide are provided in a molar ratio of anion of semaglutide to cationic component that is about 1:4.

18. The compound of any one of claims 1-14, wherein a molar ratio of : isselected from the group consisting of about 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, and 1:7.

19. The compound of any one of claims 1-14, wherein a molar ratio of : isselected from the group consisting of about 1:2, 1:3, 1:4, 1:5, 1:6, and 1:7.

20. The compound of any one of claims 1-14, wherein a molar ratio of : is about1:

4.

21. A compound comprising the structure of Formula IIa, Formula IIb, Formula IIc, or any combination thereof: Formula IIa,Formula IIb,WSGR Docket No.: 56017-729.601 Formula IIc, whereinany combination thereof is one or morecations of semaglutide; andanionic component.

22. The compound of claim 21, wherein the one or more cations of semaglutide derive from the structure of the compound in Table 2.

23. The compound of claim 21 or 22, wherein the anionic component is selected from the group consisting of besylate, mesylate, tosylate, sulfonate, sulfate, methylsulfate, camsylate, isethionate, edisylate, 1-hydroxy-2-naphthoate, 2,2-dichloroacetate, 2- hydroxyethanesulfonate, 2-oxoglutarate, 4-acetamidobenzoate, 4-aminosalicylate, acetate, adipate, ascorbate, aspartate, benzenesulfonate, benzoate, bromide, chloride, camphorate, camphor-10-sulfonate, caprate (decanoate), caproate (hexanoate), caprylate (octanoate), carbonate, cinnamate, citrate, cyclamate, dodecylsulfate, dodecylsulfurate, ethanesulfonate, ethane-1,2-disulfonate, ethanesulfonate, formate, fumarate, galactarate, gentisate, glucoheptonate, gluconate, glutantate, glucuronate, glutamate, glutarate, glycerophosphorate, glycine, glycolate, hippurate, hydrobromate, hydroiodide, hydrochlorate, isobutyrate, lactate, lactobionate, laurate, lysine, maleate, malate, malonate, mandelate, methanesulfonate , naphthalene-1,5-disulfonate, naphthalene-2-sulfonate, nicotinate, nitrate, oleate, orotate, oxalate, palmitate, pamoate, phosphorate, proprionate, pyroglutamate, salicylate, sebacate, stearate, succinate, sulfurate, tannate, tartarate, thiocyanate, toluenesulfonate, undecylenate, α-lipoate, 12-hydroxystearate, 2-(4- isobutylphenyl)propionate, 2-(4,4-dimethyl-2-pentanyl)-5,7,7-trimethyloctanoate, 2- aminoethanesulfonate, 2-hexyldecanoate, 2-hydroxyhippurate, 3-(4- hydroxyphenyl)propionate, 3-methylcrotonate, 3,3-diphenylpropionate, 3,4- dihydroxbenzoate, ,5-dihydroxybenzoate, 4-acetamido-benzoate, 3,7-dimethyloctanoate, 4-hydroxybenzenesulfonate, 4-hydroxybenzoate, 4-methylhexanoate, 4-methyloctanoate, valerate salts including 4-methylvalerate, 5-norbornene-2-carboxylate, 8-[(2- hydroxybenzoyl)amino]octanoate, abietate, acetylcysteine, aconitate, arachidonate, behenate, caffeate, chenodeoxycholate, citronellate, crotonate, galactonate, deoxycholate, dihydrocaffeate, 2-phenylpropionate (hydratropate), tropate, eicosanedioate, eicosapentanoate (EPA), elaidate, ellagate, erucate, ethylenediaminetetraacetate (EDTA),WSGR Docket No.: 56017-729.601 geranate, heptanoate, hydrocinnamate (3-phenylpropionate), isovalerate, glutathione reduced, lactate, laurate, levulinate, linoleate, linolenate, lithocholate, mesaconate, nonanoate, oxalate, coumarate, palmitate, perillate, pimelate, 3–phenylpropionate, pivalate, propionate, pyruvate, ricinoleate, salicylate, 2-hydroxybenzoate, sinapinate (3,5- dimethoxy-4-hydroxycinnamate), sorbate, syringate, tiglate, 2-decenoate, 2-hexenoate, 2- octenoate, 3-octenoate, 7-octenoate, ferulate, undecanoate, valerate, vanillate, perchlorate, alginate, bisulfate, borate, butyrate, camphorsulfonate, cyclopentanepropionate, digluconate, dodecylsulfate, glycerophosphate, hemisulfate, hydroiodide, lauryl sulfate, 2–naphthalenesulfonate, pectinate, persulfate, phosphate, tartrate, o-(4- hydroxybenzoyl)benzoate, 1,2,-ethanedisulfonate, chlorobenzenesulfonate, 4- methylbicyclo[2.2.2]oct-2-ene-carboxylate, 4.4’-methylenebis(3-hydroxy-2- ene-1- carboxylate), trimethylacetate, tertiary butylacetate, lauryl sulfurate, hydroxynaphthoate, muconate, α-ketoglutarate, p-toluenesulfonate, p-coumarate, and p- chlorobenzenesulfonate.

24. The compound of claim 21 or 22, wherein the anionic component is selected from the group consisting of those in Table 4.

25. The compound of claim 24, wherein any of the anionic components of Table 4 is provided in any of the molar ratios and weight ratios of Table 4 relative to one or more cations of semaglutide.

26. The compound of any one of claims 21-25, wherein the anionic component and cation of semaglutide are provided in a molar ratio of cation of semaglutide to anionic component that is selected from the group consisting of about 1:1, 1:2, 1:3, and 1:

4.

27. The compound of any one of claims 21-25, wherein the anionic component and cation of semaglutide are provided in a molar ratio of cation of semaglutide to anionic component that is selected from the group consisting of about 1:2, 1:3, and 1:

4.

28. The compound of any one of claims 21-25, wherein the anionic component and cation of semaglutide are provided in a molar ratio of cation of semaglutide to anionic component that is about 1:

3.

29. The compound of any one of claims 21-25, wherein the anionic component and cation of semaglutide are provided in a molar ratio of cation of semaglutide to anionic component that is about 1:

4.

30. The compound of any one of claims 21-25, wherein a molar ratioWSGR Docket No.: 56017-729.601 ,, or any combination thereof: is selected from the group consisting ofabout 1:1, 1:2, 1:3, and 1:

4.

31. The compound of any one of claims 21-25, wherein a molar ratio of, ,or any combination thereof: is selected from the group consisting ofand 1:

4. of any one of claims 21-25, wherein a molar ratio of,, , or any combination thereof: is about 1:4.of any one of claims 21-25, wherein a molar ratio of,,or any combination thereof: is about 1:3.of any one of claims 1-33, wherein: (i) a weight % (wt. %) ratio of :is from about 0.1 wt. %: 99.9 wt. % to about 20.0 wt. %: 80.0 wt. %; orWSGR Docket No.: 56017-729.601 (ii) a weight % (wt. %) ratioany combination thereof is from about 0.1 wt. %: 99.9 wt. % to about 20.0 wt. %: 80.0 wt. %.

35. The compound of any one of claims 1-34, wherein: (i) a molar ratio of : is from about 2:1 to about 10:1; or (ii) a molar ratio of, , , or any combination thereof is from about 2:1 to about 10:

1.

36. The compound of any one of claims 1-35, wherein:(i) a molar ratio of : is from about 2:1 to about 7:1; or (ii) a molar ratio of, , , or any combination thereof is from about 2:1 to about 7:

1. . The compound of any one of claims 1-36, wherein: (i) a molar ratio of : is from about 3:1 to about 7:1; or (ii) a molar ratio of :, , , or any combination thereof is from about 3:1 to about 7:

1.

38. The compound of any one of claims 1-37, wherein: (i) a molar ratioabout 7:1; orWSGR Docket No.: 56017-729.601 (ii) a molar ratioany combination thereof is from about 4:1 to about 7:

1.

39. The compound of any one of claims 1-37, wherein: (i) a molar ratio of : is from about 3:1 to about 7:1; or (ii) a molar ratio of, , , or any combination thereof is about 4:

1.

40. A compound comprising the structure of Formula IIIa:Formula IIIa, or a pharmaceutically acceptable salt thereof, wherein: is a covalent derivative of one or more carboxyl groups of semaglutide, or a pharmaceutically acceptable salt thereof; and R100is methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, tert-butyl, or pentyl, fluoromethyl, difluoromethyl, trifluoromethyl, CHCH3OC(O)OCH2CH, -CH3, -CH2CH3, -CH(CH3)2, CH2CH2CH2CH3, C(CH3)3, -CH2CH2N(CH3)3+,substituted C1-6 aliphatic, unsubstituted C1-6 aliphatic, substituted (C1-22)alkyl, unsubstituted (C1-22)alkyl, substituted (C1-22)alkenyl, unsubstituted (C1-22)alkenyl, substituted phenyl, unsubstituted phenyl, substituted -C(O)R, unsubstituted -C(O)R, substituted -C(O)OR, unsubstituted -C(O)OR, substituted -C(O)N(R)2, unsubstituted -C(O)N(R)2, (C2-C12)alkanoyloxymethyl, 1-(alkanoyloxy)ethyl having from 4 to 9 carbon atoms, 1-methyl-1-(alkanoyloxy)-ethyl having from 5 to 10 carbon atoms, alkoxycarbonyloxymethyl having from 3 to 6 carbon atoms, 1-(alkoxycarbonyloxy)ethyl having from 4 to 7 carbon atoms, 1-methyl-1-(alkoxycarbonyloxy)ethyl having from 5 to 8 carbon atoms, N-(alkoxycarbonyl)aminomethyl having from 3 to 9 carbon atoms, 1-(N-WSGR Docket No.: 56017-729.601 (alkoxycarbonyl)amino)ethyl having from 4 to 10 carbon atoms, 3-phthalidyl, 4-crotonolactonyl, gamma-butyrolacton-4-yl, di-N,N-(C1-C2)alkylamino(C2-C3)alkyl (such as β- dimethylaminoethyl), carbamoyl-(C1-C2)alkyl, N,N-di(C1-C2)alkylcarbamoyl-(C1-C2)alkyl, piperidino-, pyrrolidino- or morpholino(C2-C3)alkyl, C1-6 aliphatic, (C1-22)alkyl, (C1-22)alkenyl, - C(O)R, -C(O)OR, -C(O)N(R)2, phenyl, 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, an 8-10 membered bicyclic aromatic carbocyclic ring, a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; and each occurrence of R is independently hydrogen or an optionally substituted group selected from C1-6 aliphatic, a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic aromatic carbocyclic ring, a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, or an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur.

41. The compound of claim 40, wherein the compound of Formula IIIa does not have the structureFormula II, wherein R8, R9, and R10are independently C1-C5 alkyl.

42. A compound comprising the structure of Formula IIIb:Formula IIIb or a pharmaceutically acceptable salt thereof; wherein:is a covalent derivative of one or more hydroxyl groups of semaglutide, or a pharmaceutically acceptable salt thereof; and wherein: R101is selected from the group consisting of -CH2R, -C(O)R, -C(O)OR, -C(O)N(R)2, - OP(O)OROR, wherein each occurrence of R is independently hydrogen or an optionallyWSGR Docket No.: 56017-729.601 substituted group selected from C1-6 aliphatic, a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic aromatic carbocyclic ring, a 4- 8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; or R101is -CH2OCH2CH2OH, unsubstituted C(O)C1-6alkyl, substituted C(O)C1-6alkyl, substituted C(O)phenyl or unsubstituted C(O)phenyl, -(C1-C6)alkanoyloxymethyl, -1-((C1- C6)alkanoyloxy)ethyl, -1-methyl-1-((C1-C6)alkanoyloxy)ethyl, -(C1- C6)alkoxycarbonyloxymethyl, -N-(C1-C6)alkoxycarbonylaminomethyl, -succinoyl, -(C1- C6)alkanoyl, -α-amino(C1-C4)alkanoyl, -arylacyl, -α-aminoacyl, or -α-aminoacyl-α-aminoacyl, optionally, wherein each α-aminoacyl group is independently selected from the naturally occurring L-amino acids, P(O)(OH)2, -P(O)(O(C1-C6)alkyl)2 or glycosyl, and optionally, wherein the radical results from the removal of a hydroxyl group of the hemiacetal form of a carbohydrate.

43. The compound of claim 42, wherein R101is the unsubstituted C(O)C1-6alkyl comprising COCH3, COCH2CH3, or COCH(CH3)2), or R101is the substituted C(O)C1-6alkyl comprising COCF3, COCHCF2, or -COCH2CF.

44. The compound of claim 42, wherein R101is -C(O)R selected from the group consisting of -C(O)CH3 and -C(O)H, -C(O)OR that is -C(O)OH2), -C(O)N(R)2 selected from the group consisting of -C(O)NH2 and -C(O)N(CH3)2), or -OP(O)OROR that is - OP(O)OHOH.

45. The compound of claim 42, wherein R101is -CHCH3OC(O)OCH2CH3.

46. A compound comprising the structure of Formula IIIc and / or Formula IIId:and / or Formula IIIc Formula IIId or a pharmaceutically acceptable salt of each thereof; wherein:WSGR Docket No.: 56017-729.601is each a covalent derivative of one or more amino or imidazole groups of semaglutide, or a pharmaceutically acceptable salt thereof; and wherein: each of R102and R103is independently selected from the group consisting of -CH2R, -C(O)R, -C(O)OR, -C(O)N(R)2, -OP(O)OROR, wherein each occurrence of R is independently hydrogen or an optionally substituted group selected from C1-6 aliphatic, a 3-8 membered saturated or partially unsaturated monocyclic carbocyclic ring, phenyl, an 8-10 membered bicyclic aromatic carbocyclic ring, a 4-8 membered saturated or partially unsaturated monocyclic heterocyclic ring having 1-2 heteroatoms independently selected from nitrogen, oxygen, and sulfur, a 5-6 membered monocyclic heteroaromatic ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, and sulfur, and an 8-10 membered bicyclic heteroaromatic ring having 1-5 heteroatoms independently selected from nitrogen, oxygen, and sulfur; each R102and R103is independently C(O)R, C(O)OR, C(O)R’, or C(O)NR’R”, where R’ and R” are each independently (C1-C10)alkyl, (C3-C7)cycloalkyl, benzyl, or each R102and R103is a natural α-aminoacyl or natural α-aminoacyl-natural α-aminoacyl, - C(OH)C(O)OY1, wherein Y1is H, (C1-C6)alkyl or benzyl, -C(OY2)Y3, wherein Y2is (C1-C4) alkyl and Y3is (C1-C6)alkyl, carboxy(C1-C6)alkyl, amino(C1-C4)alkyl or mono-N-or di-N,N- (C1-C6)alkylaminoalkyl, -C(Y4)Y5, wherein Y4is H or methyl and Y5is mono-N- or di-N,N- ( C1-C6)alkylamino, morpholino, piperidin-1-yl or pyrrolidin-1-yl.

47. The compound of claim 46, wherein each R102and R103is independently - CH2OCH2CH2OH or unsubstituted C(O)C1-6alkyl.

48. The compound of claim 46, wherein R102is substituted C(O)C1-6alkyl comprising COCF3, COCHCF2, or -COCH2CF.

49. The compound of claim 46, wherein R102is substituted C(O)phenyl or unsubstituted C(O)phenyl.

50. The compound of claim 46, wherein R102is CHCH3OC(O)OCH2CH3.

51. A pharmaceutical composition comprising the compound of any one of claims 1-50, and a pharmaceutically acceptable excipient.WSGR Docket No.: 56017-729.601 52. The pharmaceutical composition of claim 51, wherein the pharmaceutical composition is formulated for parenteral administration, oral administration, or implantable administration.

53. The pharmaceutical composition of claim 51 or 52, wherein the pharmaceutical composition is formulated for subcutaneous administration or intravenous administration.

54. A drug delivery device comprising the compound of any one of claims 1-50, or the pharmaceutical composition of any one of claims 51-53.

55. The drug delivery device of claim 54, wherein the drug delivery device is a syringe, a single-dose pen with an injection needle, or an autoinjector with an injection needle.

56. The drug delivery device of claim 54, wherein the drug delivery device is an implantable osmotic drug delivery device.

57. A kit comprising the compound of any one of claims 1-50, the pharmaceutical composition of any one of claims 51-53, or the drug delivery device of any one of claims 54-56.

58. The kit of claim 57, further comprising an instruction for use.

59. A method of treating a disease or disorder in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of any one of claims 1-50, or the pharmaceutical composition of any one of claims 51-53, wherein the administering is effective to treat the disease or disorder in the subject.

60. The method of claim 59, wherein the compound or the pharmaceutical composition is administered to the subject using the drug delivery device of any one of claims 54-56.

61. The method of claim 59 or 60, wherein the disease or disorder is a metabolic disease or disorder, a cardiovascular disease or disorder, chronic kidney disease, or a neurological disease or disorder.

62. The method of any one of claims 59-61, wherein the disease or disorder is selected from the group consisting of type 1 diabetes, type 2 diabetes, obesity, overweight, metabolic dysfunction–associated fatty liver disease (MAFLD), metabolic dysfunction-associated steatohepatitis (MASH), and nonalcoholic steatohepatitis (NASH).

63. The method of any one of claims 59-61, wherein the disease or disorder is selected from the group consisting of arrhythmia, coronary artery disease, heart failure, valve disease, aortic disease, congenital heart disease, heart attack, angina, cardiomyopathy, peripheral arterial disease, atherosclerosis, cardiac dysrhythmias, pericarditis, pulmonary hypertension, stroke, cerebrovascular disease, rheumatic heart disease, atrial fibrillation,WSGR Docket No.: 56017-729.601 Brugada syndrome, aortic stenosis, bradycardia, endocarditis, high cholesterol, and long QT syndrome.

64. The method of any one of claims 59-61, wherein the disease or disorder is Parkinson’s disease or Alzheimer disease.

65. The method of any one of claims 59-64, wherein the subject is human.

66. The method of any one of claims 59-65, wherein the compound or the pharmaceutical composition is administered to the subject via parenteral administration, oral administration, or implantable administration.

67. The method of any one of claims 59-66, wherein the compound or the pharmaceutical composition is administered to the subject via subcutaneous administration or intravenous administration.

68. A method of reducing weight in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the compound of any one of claims 1-50 or the pharmaceutical composition of any one of claims 51-53, wherein the administering is effective to reduce weight in the subject.

69. The method of claim 68, wherein the compound or the pharmaceutical composition is administered to the subject using the drug delivery device of any one of claims 54-56.

70. The method of claim 68 or 69, wherein the subject is human.

71. The method of any one of claims 68-70, wherein the subject has obesity or is overweight.

72. The method of any one of claims 68-71, wherein the compound or the pharmaceutical composition is administered to the subject via parenteral administration, oral administration, or implantable administration.

73. The method of any one of claims 68-72, wherein the compound or the pharmaceutical composition is administered to the subject via subcutaneous administration or intravenous administration.

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