Pharmaceutical compositions comprising antibodies for treatment of c1s mediated disorders and methods of using the same

Abstract

Provided for herein are pharmaceutical compositions comprising a therapeutic antibody and uses thereof for the treatment of C1s mediated disorders.

Description

about 170 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 110 mM to about 160 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 110 mM to about 150 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 110 mM to about 140 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 110 mM to about 130 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 110 mM to about 120 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 120 mM to about 180 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 120 mM to about 170 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 120 mM to about 160 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 120 mM to about 150 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 120 mM to about 140 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 120 mM to about 130 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 130 mM to about 180 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 130 mM to about 170 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 130 mM to about 160 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 130 mM to about 150 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 130 mM to about 140 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 140 mM to about 180 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 140 mM to about 170 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 140 mM to about 160 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 140 mM to about 150 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 150 mM to about 180 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 150 mM to about 170 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 150 mM to about 160 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 160 mM to about 180 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 160 mM to about 170 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 170 mM to about 180 mM.

[0454] In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 20 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 30 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 40 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 50 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 60 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 70 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 80 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 90 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 100 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 110 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 120 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 130 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 140 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 150 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 160 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 170 mM. In some embodiments, the pharmaceutical composition comprises L-Arg-HCL that is present at a concentration of about 180 mM.

[0455] One of the major stresses that proteins (e.g., antibodies) may encounter is interfacial stress (e.g., from air / water interfaces in liquid compositions, or ice / water interfaces during freezing / thawing.) Surfactants are typically used to stabilize proteins in biopharmaceutical compositions while under stress or long-term storage to prevent or minimize aggregation and / or particle formation. Examples of a surfactant include, but are not limited to, anionic surfactants (e.g., ammonium lauryl sulfate, sodium lauryl sulfate, sodium laureth sulfate, sodium myreth sulfate, diocytl sodium sulfosuccinate, perfluorooctanesulfonate, perfluorobutanesulfonate, alkyl-aryl ether phosphates, alkyl ether phosphates, carboxylates, sodium lauroyl sarcosinate, perfluorononanoate, perfluorooctanoate); cationic surfactants (e.g., octenidine dihydrochloride, cetrimonium bromide, cetylpyridinium chloride, benzalkonium chloride, benzethonium chloride, dimethyldioctadecylammonium chloride, and dioctadecyldimethylammonium bromide); zwitterionic (amphoteric) surfactants (e.g., 3- [(3-cholamidopropyl)dimethylammonio]-l -propanesulfonate, cocamidopropyl hydroxysultaine, phosphatidyl serine, phosphatidylethanolamine, phosphatidylcholine, sphingomyelins, lauryldimethylamine oxide and myristamine oxide); non-ionic surfactants (e.g., polysorbates, poloxmaers, or Brij series); ethoxylates (e.g., fatty alcohol ethoxylate (e.g., octaethylene glycol monododecyl ether and pentaethylene glycol monododecyl ether), alkylphenolethoxylates (e.g., nonoxynols and Triton X-100); fatty acid ethoxylates, ethoxylated amines and / or fatty acid amides (e.g., poly ethoxylated tallow amine, cocamide monoethanol amine, and cocamide diethanolamine); terminally blocked ethoxylates (e.g., pol oxamers); fatty acid esters of polyhydroxy compounds; fatty acid esters of glycerol (e.g., glycerol monostearate and glycerol monolaurate); fatty acid esters of sorbitol (e.g., spans such as sorbitan monolaurate, sorbitan monostearate, and sorbitan tristearate, and polysorbates (Tweens) such as Tween 20, Tween 40, Tween 60, and Tween 80); fatty acid esters of sucrose; alkyl poly glucosides (e.g., decyl glucoside, lauryl glucoside, and octyl glucoside); or a combination thereof.

[0456] In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.001% w / v to about 0.4% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.001% w / v to about 0.2% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.001% w / v to about 0.1% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.001% w / v to about 0.01% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.01% w / v to about 0.2% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.05% w / v to about 0.15% w / v. Tn some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.1% w / v to about 0.2% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.2% w / v to about 0.4% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.001% w / v to about 0.2% w / v.

[0457] In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.001% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.002% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.003% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.004% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.005% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.006% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.007% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.008% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.009% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.01% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.02% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.03% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.04% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.05% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.06% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.07% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.08% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.09% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.10% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.11% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.12% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.13% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.14% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.15% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.16% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.17% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.18% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.19% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.20% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.25% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.3% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.35% w / v. In some embodiments, the pharmaceutical composition comprises a surfactant present at a concentration of about 0.4% w / v.

[0458] In some embodiments, the pharmaceutical composition comprises a surfactant selected from polysorbate (PS)80, polysorbate (PS)20, polyethylene glycol (PG)3350, poloxamer (P)188, or any combination thereof. In some embodiments, the pharmaceutical composition comprises PS80. In some embodiments, the pharmaceutical composition comprises PS20. In some embodiments, the pharmaceutical composition comprises PG3350. In some embodiments, the pharmaceutical composition comprises Pl88.

[0459] In some embodiments, the surfactant is a poloxamer. Poloxamers are nonionic triblock copolymers composed of a central hydrophobic chain of polyoxypropylene (polypropylene oxide)) flanked by two hydrophilic chains of polyoxyethylene (poly(ethylene oxide)). Examples of a poloxamer include, but are not limited to, poloxamer 188, poloxamer 407, poloxamer 184, poloxamer 124, or a combination thereof.

[0460] In some embodiments, the pharmaceutical composition comprises Pl88 present at a concentration of about 0.001% w / v to about 0.1% w / v. In some embodiments, the pharmaceutical composition comprises P188 present at a concentration of about 0.001% w / v to about 0.01% w / v. In some embodiments, the pharmaceutical composition comprises Pl 88 present at a concentration of about 0.01% w / v to about 0.2% w / v. In some embodiments, the pharmaceutical composition comprises Pl88 present at concentration of about 0.2% w / v to about 0.4% w / v. In some embodiments, the pharmaceutical composition comprises P188 present at a concentration of about 0.001% w / v to about 0.2% w / v. In some embodiments, the pharmaceutical composition comprises P188 present at a concentration of about 0.001% w / v to about 0.4% w / v.

[0461] In some embodiments, the pharmaceutical composition comprises Pl88 present at a concentration of about 0.001% w / v. In some embodiments, the pharmaceutical composition comprises Pl 88 present at a concentration of about 0.002% w / v. In some embodiments, the pharmaceutical composition comprises Pl88 present at a concentration of about 0.003% w / v. In some embodiments, the pharmaceutical composition comprises P188 present at a concentration of about 0.004% w / v. In some embodiments, the pharmaceutical composition comprises Pl88 present at a concentration of about 0.005% w / v. In some embodiments, the pharmaceutical composition comprises Pl 88 present at a concentration of about 0.006% w / v. In some embodiments, the pharmaceutical composition comprises Pl88 present at a concentration of about 0.007% w / v. In some embodiments, the pharmaceutical composition comprises Pl88 present at a concentration of about 0.008% w / v. In some embodiments, the pharmaceutical composition comprises Pl88 present at a concentration of about 0.009% w / v. In some embodiments, the pharmaceutical composition comprises P188 present at a concentration of about 0.01% w / v. In some embodiments, the pharmaceutical composition comprises Pl88 present at a concentration of about 0.02% w / v. In some embodiments, the pharmaceutical composition comprises Pl 88 present at a concentration of about 0.03% w / v. In some embodiments, the pharmaceutical composition comprises Pl 88 present at a concentration of about 0.04% w / v. In some embodiments, the pharmaceutical composition comprises Pl88 present at a concentration of about 0.05% w / v. In some embodiments, the pharmaceutical composition comprises Pl88 present at a concentration of about 0.06% w / v. In some embodiments, the pharmaceutical composition comprises P188 present at a concentration of about 0.07% w / v. In some embodiments, the pharmaceutical composition comprises Pl 88 present at a concentration of about 0.08% w / v. In some embodiments, the pharmaceutical composition comprises P188 present at a concentration of about 0.09% w / v. In some embodiments, the pharmaceutical composition comprises Pl88 present at a concentration of about 0.10% w / v. In some embodiments, the pharmaceutical composition comprises P188 present at a concentration of about 0.11% w / v. In some embodiments, the pharmaceutical composition comprises P188 present at a concentration of about 0.12% w / v. In some embodiments, the pharmaceutical composition comprises P188 present at a concentration of about 0.13% w / v. In some embodiments, the pharmaceutical composition comprises Pl88 present at a concentration of about 0.14% w / v. In some embodiments, the pharmaceutical composition comprises Pl 88 present at a concentration of about 0.15% w / v. In some embodiments, the pharmaceutical composition comprises Pl88 present at a concentration of about 0.16% w / v. In some embodiments, the pharmaceutical composition comprises Pl88 present at a concentration of about 0.17% w / v. In some embodiments, the pharmaceutical composition comprises Pl88 present at a concentration of about 0.18% w / v. In some embodiments, the pharmaceutical composition comprises P188 present at a concentration of about 0.19% w / v. In some embodiments, the pharmaceutical composition comprises Pl88 present at a concentration of about 0.20% w / v. In some embodiments, the pharmaceutical composition comprises Pl 88 present at a concentration of about 0.25% w / v. In some embodiments, the pharmaceutical composition comprises Pl88 present at a concentration of about 0.3% w / v. In some embodiments, the pharmaceutical composition comprises Pl88 present at a concentration of about 0.35% w / v. In some embodiments, the pharmaceutical composition comprises Pl 88 present at a concentration of about 0.4% w / v.

[0462] In some embodiments, the pharmaceutical composition comprises an antibody that is present at a concentration of about 25 mg / mL to about 300 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody that is present at a concentration of about 25 mg / mL to about 400 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody that is present at a concentration of about 25 mg / mL to about 500 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody that is present at a concentration of about 25 mg / mL to about 600 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody that is present at a concentration of about 25 mg / mL to about 200 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 25 mg / mL to about 275 mg / mL In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 25 mg / mL to about 250 mg / mL In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 25 mg / mL to about 225 mg / mL In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 25 mg / mL to about 200 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 25 mg / mL to about 175 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 25 mg / mL to about 150 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 25 mg / mL to about 125 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 25 mg / mL to about 100 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 25 mg / mL to about 75 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 50 mg / mL to about 300 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 50 mg / mL to about 275 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 50 mg / mL to about 250 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 50 mg / mL to about 225 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 50 mg / mL to about 200 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 50 mg / mL to about 175 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 50 mg / mL to about 150 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 50 mg / mL to about 125 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 50 mg / mL to about 100 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 50 mg / mL to about 75 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 75 mg / mL to about 300 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 75 mg / mL to about 275 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 75 mg / mL to about 250 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 75 mg / mL to about 225 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 75 mg / mL to about 200 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 75 mg / mL to about 175 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 75 mg / mL to about 150 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 75 mg / mL to about 125 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 75 mg / mL to about 100 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 100 mg / mL to about 300 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 100 mg / mL to about 275 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 100 mg / mL to about 250 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 100 mg / mL to about 225 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 100 mg / mL to about 200 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 100 mg / mL to about 175 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 100 mg / mL to about 150 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 100 mg / mL to about 125 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 125 mg / mL to about 300 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 125 mg / mL to about 275 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 125 mg / mL to about 250 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 125 mg / mL to about 225 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 125 mg / mL to about 200 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 125 mg / mL to about 175 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 125 mg / mL to about 150 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 150 mg / mL to about 300 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 150 mg / mL to about 275 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 150 mg / mL to about 250 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 150 mg / mL to about 225 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 150 mg / mL to about 200 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 150 mg / mL to about 175 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of or about 175 mg / mL to about 300 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of or about 175 mg / mL to about 275 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of or about 175 mg / mL to about 250 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of or about 175 mg / mL to about 225 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of or about 175 mg / mL to about 200 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of or about 200 mg / mL to about 300 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of or about 200 mg / mL to about 275 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of or about 200 mg / mL to about 250 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of or about 200 mg / mL to about 225 mg / mL. . In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of or about 225 mg / mL to about 300 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of or about 225 mg / mL to about 275 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of or about 225 mg / mL to about 250 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of or about 250 mg / mL to about 300 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of or about 250 mg / mL to about 275 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of or about 275 mg / mL to about 300 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of or about 100 mg / mL to about 200 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of or about 200 mg / mL to about 300 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of or about 300 mg / mL to about 400 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of or about 400 mg / mL to about 500 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of or about 500 mg / mL to about 600 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of or about 100 mg / mL to about 300 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of or about 200 mg / mL to about 400 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of or about 300 mg / mL to about 500 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of or about 400 mg / mL to about 600 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of or about 100 mg / mL to about 400 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of or about 200 mg / mL to about 500 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of or about 300 mg / mL to about 600 mg / mL.

[0463] In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 25 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 30 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 40 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 50 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 60 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 70 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 80 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 90 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 100 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 110 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 120 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 130 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 140 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 150 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 160 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 170 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 175 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 200 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 225 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 275 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 300 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 325 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 350 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 375 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 400 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 425 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 450 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 475 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 500 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 525 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 550 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 575 mg / mL. In some embodiments, the pharmaceutical composition comprises an antibody present at a concentration of about 600 mg / mL.

[0464] In some embodiments, the pharmaceutical composition comprises an antibody that is a monoclonal antibody. In some embodiments, the pharmaceutical composition comprises an antibody that is a polyclonal antibody. In some embodiments, the pharmaceutical composition comprises an antibody that is an immunoglobulin G4 (IgG4) type monoclonal antibody. In some embodiments, the pharmaceutical composition comprises an antibody selected from those provided herein. In some embodiments, the pharmaceutical composition comprises an antibody that comprises a heavy chain variable region selected from any heavy chain variable regions provided herein; and a light chain variable region selected from any light chain variable regions provided herein.

[0465] In some embodiments, the pharmaceutical composition comprises an antibody that comprises a heavy chain variable region with an amino acid sequence of SEQ ID NO: 17 and a light chain variable region with an amino acid sequence of SEQ ID NO: 18. In some embodiments, the pharmaceutical composition comprises an antibody that comprises a heavy chain variable region with an amino acid sequence of SEQ ID NO: 342 and a light chain variable region with an amino acid sequence of SEQ ID NO: 18. In some embodiments, the pharmaceutical composition comprises an antibody that comprises a heavy chain variable region with an amino acid sequence of SEQ ID NO: 17. In some embodiments, the pharmaceutical composition comprises an antibody that comprises a heavy chain variable region with an amino acid sequence of SEQ ID NO: 342. In some embodiments, the pharmaceutical composition comprises an antibody that comprises a light chain variable region with an amino acid sequence of SEQ ID NO: 18.

[0466] In some embodiments, the antibody or antigen binding fragment thereof, comprises a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the HCDR1 sequence has the amino acid sequence of SEQ ID NO: 61, the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO: 62, and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO: 78, or variants or convention equivalents of any of the foregoing; and a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence SEQ ID NO: 64, the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO: 65, and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO: 79, or variants or convention equivalents of any of the foregoing.

[0467] In some embodiments, the pharmaceutical composition is stable as defined herein. In some embodiments, the composition as described herein is stable under the conditions of manufacture and storage. In some embodiments, the composition remains stable and active even when subjected to stress and when stored in containers made of various materials, including glass. In some embodiments, the storage container is a vial with a stopper and a cover. In some embodiments, the container is a pre-filled glass syringe.

[0468] In some embodiments, the pharmaceutical composition is stable for 3 or more freeze / thaw cycles between about -70 °C and room temperature. In some embodiments, the pharmaceutical composition is stable for 4 or more freeze / thaw cycles between about -70 °C and room temperature. In some embodiments, the pharmaceutical composition is stable for 5 or more freeze / thaw cycles between about -70 °C and room temperature.

[0469] In some embodiments, the pharmaceutical composition is stable under agitation conditions from 80-120 rpm for 3 days. In some embodiments, the pharmaceutical composition is stable under agitation conditions from 80-120 rpm for 2 days. In some embodiments, the pharmaceutical composition is stable under agitation conditions from 80-120 rpm for 1 day. In some embodiments, the pharmaceutical composition is stable under agitation conditions from 80-120 rpm for up to 3 days. In some embodiments, the pharmaceutical composition is stable under agitation conditions at 100 rpm for up to 3 days. In some embodiments, the pharmaceutical composition is stable against agitation conditions. Tn some embodiments, the pharmaceutical composition is stable in agitation conditions at room temperature.

[0470] In some embodiments, the pharmaceutical composition is stable for up to 3 months when stored at about -80 °C. In some embodiments, the pharmaceutical composition is stable for up to 3 months when stored at about -70 °C. In some embodiments, the pharmaceutical composition is stable for up to 3 months when stored at about -60 °C. In some embodiments, the pharmaceutical composition is stable for up to 3 months when stored at about -50 °C. In some embodiments, the pharmaceutical composition is stable for up to 3 months when stored at about -40 °C. In some embodiments, the pharmaceutical composition is stable for up to 3 months when stored at about -30 °C. In some embodiments, the pharmaceutical composition is stable for up to 3 months when stored at about -20 °C. In some embodiments, the pharmaceutical composition is stable for up to 3 months when stored at about -10 °C. In some embodiments, the pharmaceutical composition is stable for up to 3 months when stored at about 0 °C. In some embodiments, the pharmaceutical composition is stable for up to 3 months when stored at about 10 °C. In some embodiments, the pharmaceutical composition is stable for up to 3 months when stored at about 20 °C. In some embodiments, the pharmaceutical composition is stable for up to 3 months when stored at about 30 °C. In some embodiments, the pharmaceutical composition is stable for up to 3 months when stored at about 40 °C. In some embodiments, the pharmaceutical composition is stable for up to 3 months when stored at about 50 °C.

[0471] In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is colorless in appearance. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is slightly opalescent in appearance. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of visible particles. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of sub-visible particles. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is essentially free of sub-visible particles. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is almost free of sub-visible particles. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of visible particles comprising high molecular weight molecules. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of sub-visible particles comprising high molecular weight molecules. Tn some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is essentially free of sub-visible particles comprising high molecular weight molecules. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is almost free of sub-visible particles comprising high molecular weight molecules. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of low molecular weight molecule degradants of the antibody, or fragment thereof.

[0472] In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of degradation products. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is consistently free of degradation products (e.g., HMWS, LMWS, or minor species) over time. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of degradation products at about 2°C to about 8°C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of product related impurities at about 2°C to about 8°C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of degradation products at about 0°C or below. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of product related impurities at about 0°C or below. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is consistently free of oxidation products. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is consistently free of oxidation degradation products. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is consistently free of tryptophan oxidation products. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is consistently free of advanced glycation end-product (AGE) products. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is consistently free of adduct degradation. In some embodiments, the color of the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is consistent over time. In some embodiments, the appearance (e.g., color and / or clarity) of the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is consistent over time. In some embodiments, the color and clarity of the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is consistent over time. In some embodiments, the color of the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition does not significantly change over time. In some embodiments, the color of the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition changes slightly over time.

[0473] A change in color of a formulation can indicate the presence of degradation products over time. It is important that degradation products are minimized in antibody formulations; therefore, it is important that the color does not substantially change. In some embodiments, degradation products, such as tryptophan oxidants, AGE products, and adduct degradation, may change the color of a formulation; therefore, it is critical that the color of a formulation remains consistent over time. In some embodiments, the color of a formulation is not critical to its safety and / or stability. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of degradation products and is clear in appearance after between about 1 day and about 12 weeks at about -20 °C, at about 2 °C to 8 °C, or at about 40 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of degradation products and is clear in appearance after about 1 day, about 1 week, about 2 weeks, about 4 weeks, about 6 weeks, or about 12 weeks at about -20 °C, about 2 °C to 8 °C, or about 40 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of degradation products and is clear in appearance after about 1, 2, 3, 4, 5, or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of degradation products and is clear in appearance after about 3 or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of degradation products and is clear in appearance after about 5 or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of degradation products and is clear in appearance after agitation conditions at room temperature. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of degradation products and is free of degradation products and is clear in appearance after agitation conditions at room temperature after about 1, 2, 3, or more days. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of degradation products and is clear in appearance after agitation conditions at room temperature after about 1 or more days. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of degradation products and is clear in appearance after agitation conditions at room temperature after about 3 or more days.

[0474] In some embodiments, a substantial color change can be slight yellow, yellow, slight yellow brown, yellow brown, slight red, red, slight pink, pink, slight brown, or brown. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is mostly free of degradation products and is slightly yellow in appearance after between about 1 day and 12 weeks at about -20 °C, about 2 °C to 8 °C, or about 40 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is mostly free of degradation products and is slightly yellow in appearance after about 1 day, about 1 week, about 2 weeks, about 4 weeks, about 6 weeks, or about 12 weeks at about -20 °C, about 2 °C to 8 °C, or about 40 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is mostly free of degradation products and is slightly yellow in appearance after about 1, 2, 3, 4, 5, or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is mostly free of degradation products and is slightly yellow in appearance after about 3 or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is mostly free of degradation products and is slightly yellow in appearance after about 5 or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is mostly free of degradation products and is slightly yellow in appearance after about 1, 2, 3, or more days under agitation conditions at room temperature. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is mostly free of degradation products and is slightly brown in appearance after about 1, 2, 3, or more days under agitation conditions at room temperature. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is mostly free of degradation products and is colorless in appearance after about 1, 2, 3, or more days under agitation conditions at room temperature. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is mostly free of degradation products and is slightly yellow brown in appearance after about 1, 2, 3, or more days under agitation conditions at room temperature.

[0475] Opalescence indicates physical instability of a formulation because of the presence of aggregates or liquid-liquid phase separation in solution and has been reported for monoclonal antibody (mAb) formulations. Increased solution opalescence can be attributed to attractive protein-protein interactions (PPIs). It is critical that aggregates or liquid-liquid phase separation in formulations is minimal and that the opalescence of the formulation does not exceed slight opalescence. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is slightly opalescent in appearance after between about 1 day and 12 weeks at about -20 °C, about 2 °C to 8 °C, or about 40 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is slightly opalescent in appearance after about 1 day, about 1 week, about 2 weeks, about 4 weeks, about 6 weeks, or about 12 weeks at about -20 °C, about 2 °C to 8 °C, or about 40 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is slightly opalescent in appearance after about 1, 2, 3, 4, 5, or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is slightly opalescent in appearance after about 3 or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is slightly opalescent in appearance after about 5 or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is slightly opalescent in appearance after about 1, 2, 3, or more days under agitation conditions at room temperature.

[0476] In some embodiments, visible and sub-visible particulates in antibody products may pose safety and immunogenicity risks to patients and therefore it is important that formulations are free of visible and / or sub-visible particles. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of visible particles comprising high molecular weight molecules after between about 1 day and 12 weeks at about -20 °C, about 2 °C to 8 °C, or about 40 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of visible particles comprising high molecular weight molecules after about 1 day, about 1 week, about 2 weeks, about 4 weeks, about 6 weeks, or about 12 weeks at about -20 °C, about 2 °C to 8 °C, or about 40 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of visible particles comprising high molecular weight molecules after about 1, 2, 3, 4, 5, or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of visible particles comprising high molecular weight molecules after about 3 or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of visible particles comprising high molecular weight molecules after about 5 or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of visible particles comprising high molecular weight molecules after about 1, 2, 3, or more days under agitation conditions at room temperature. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of sub-visible particles comprising high molecular weight molecules after between about 1 day and 12 weeks at about -20 °C, about 2 °C to 8 °C, or about 40 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of sub-visible particles comprising high molecular weight molecules after about 1 day, about 1 week, about 2 weeks, about 4 weeks, about 6 weeks, or about 12 weeks at about -20 °C, about 2 °C to 8 °C, or about 40 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of sub-visible particles comprising high molecular weight molecules after about 1, 2, 3, 4, 5, or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of sub-visible particles comprising high molecular weight molecules after about 3 or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of sub-visible particles comprising high molecular weight molecules after about 5 or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of sub-visible particles comprising high molecular weight molecules after about 1, 2, 3, or more days under agitation conditions at room temperature. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is essentially free of visible particles comprising high molecular weight molecules after between about 1 day and 12 weeks at about -20 °C, about 2 °C to 8 °C, or about 40 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is essentially free of visible particles comprising high molecular weight molecules after about 1 day, about 1 week, about 2 weeks, about 4 weeks, about 6 weeks, or about 12 weeks at about -20 °C, about 2 °C to 8 °C, or about 40 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is essentially free of visible particles comprising high molecular weight molecules after about 1,2, 3, 4, 5, or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is essentially free of visible particles comprising high molecular weight molecules after about 3 or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is essentially free of visible particles comprising high molecular weight molecules after about 5 or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is essentially free of visible particles comprising high molecular weight molecules after about 1, 2, 3, or more days under agitation conditions at room temperature. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is essentially free of sub-visible particles comprising high molecular weight molecules after between about 1 day and 12 weeks at about -20 °C, about 2 °C to 8 °C, or about 40 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is essentially free of sub-visible particles comprising high molecular weight molecules after about 1 day, about 1 week, about 2 weeks, about 4 weeks, about 6 weeks, or about 12 weeks at about -20 °C, about 2 °C to 8 °C, or about 40 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is essentially free of sub-visible particles comprising high molecular weight molecules after about 1, 2, 3, 4, 5, or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is essentially free of sub-visible particles comprising high molecular weight molecules after about 3 or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is essentially free of sub-visible particles comprising high molecular weight molecules after about 5 or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is essentially free of sub-visible particles comprising high molecular weight molecules after about 1, 2, 3, or more days under agitation conditions at room temperature. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is controlled for visible particles comprising high molecular weight molecules after between about 1 day and 12 weeks at about -20 °C, about 2 °C to 8 °C, or about 40 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is controlled for visible particles comprising high molecular weight molecules after about 1 day, about 1 week, about 2 weeks, about 4 weeks, about 6 weeks, or about 12 weeks at about -20 °C, about 2 °C to 8 °C, or about 40 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is controlled for visible particles comprising high molecular weight molecules after about 1, 2, 3, 4, 5, or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is controlled for visible particles comprising high molecular weight molecules after about 3 or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is controlled for visible particles comprising high molecular weight molecules after about 5 or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is controlled for visible particles comprising high molecular weight molecules after about 1, 2, 3, or more days under agitation conditions at room temperature. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is controlled for sub-visible particles comprising high molecular weight molecules after between about 1 day and 12 weeks at about -20 °C, about 2 °C to 8 °C, or about 40 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is controlled for sub-visible particles comprising high molecular weight molecules after about 1 day, about 1 week, about 2 weeks, about 4 weeks, about 6 weeks, or about 12 weeks at about -20 °C, about 2 °C to 8 °C, or about 40 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is controlled for sub-visible particles comprising high molecular weight molecules after about 1, 2, 3, 4, 5, or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is controlled for sub-visible particles comprising high molecular weight molecules after about 3 or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is controlled for sub-visible particles comprising high molecular weight molecules after about 5 or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is controlled for sub-visible particles comprising high molecular weight molecules after about 1, 2, 3, or more days under agitation conditions at room temperature.

[0477] In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of low molecular weight molecule degradants after between about 1 day and 12 weeks at about -20 °C, about 2 °C to 8 °C, or about 40 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of low molecular weight molecule degradants after about 1 day, about 1 week, about 2 weeks, about 4 weeks, about 6 weeks, or about 12 weeks at about -20 °C, about 2 °C to 8 °C, or about 40 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of low molecular weight molecule degradants after about 1, 2, 3, 4, 5, or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of low molecular weight molecule degradants after about 3 or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of low molecular weight molecule degradants after about 5 or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the liquid or dissolved lyophilized powder formulation of the pharmaceutical composition is free of low molecular weight molecule degradants after about 1, 2, 3, or more days under agitation conditions at room temperature.

[0478] In some embodiments, the purity is not significantly reduced after between about 1 day and 12 weeks at about -20 °C, about 2 °C to 8 °C, or about 40 °C. In some embodiments, the purity is not significantly reduced after about 1 day, about 1 week, about 2 weeks, about 4 weeks, about 6 weeks, or about 12 weeks at about -20 °C, about 2 °C to 8 °C, or about 40 °C. In some embodiments, the purity is not significantly reduced after about 1, 2, 3, 4, 5, or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the purity is not significantly reduced after about 3 or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the purity is not significantly reduced after about 5 or more freeze / thaw cycles between about -70 °C and about 25 °C. In some embodiments, the purity is not significantly reduced after about 1, 2, 3, or more days under agitation conditions at room temperature.

[0479] In some embodiments, the pharmaceutical composition is stable at about -80 °C to about 40 °C. In some embodiments, the pharmaceutical composition is stable at about -25 °C to about -15 °C. In some embodiments, the pharmaceutical composition is stable at about 2-8 °C.

[0480] In some embodiments, the pharmaceutical composition is stable at about -80 °C. In some embodiments, the pharmaceutical composition is stable at about -70 °C. In some embodiments, the pharmaceutical composition is stable at about -60 °C. In some embodiments, the pharmaceutical composition is stable at about -50 °C. In some embodiments, the pharmaceutical composition is stable at about -40 °C. In some embodiments, the pharmaceutical composition is stable at about -30 °C. In some embodiments, the pharmaceutical composition is stable at about -25 °C. In some embodiments, the pharmaceutical composition is stable at about -20 °C. In some embodiments, the pharmaceutical composition is stable at about -15 °C. In some embodiments, the pharmaceutical composition is stable at about -10 °C. In some embodiments, the pharmaceutical composition is stable at about -5 °C. In some embodiments, the pharmaceutical composition is stable at about 0 °C. In some embodiments, the pharmaceutical composition is stable at about 1 °C. In some embodiments, the pharmaceutical composition is stable at about 2 °C. In some embodiments, the pharmaceutical composition is stable at about 3 °C. In some embodiments, the pharmaceutical composition is stable at 4 about °C. In some embodiments, the pharmaceutical composition is stable at about 5 °C. In some embodiments, the pharmaceutical composition in stable at about 6 °C. In some embodiments, the pharmaceutical composition is stable at about 7 °C. In some embodiments, the pharmaceutical composition is stable at about 8 °C. In some embodiments, the pharmaceutical composition is stable at about 9 °C. In some embodiments, the pharmaceutical composition is stable at about 10 °C. In some embodiments, the pharmaceutical composition is stable at about 15 °C. In some embodiments, the pharmaceutical composition is stable at about 20 °C. In some embodiments, the pharmaceutical composition is stable at about 25 °C. In some embodiments, the pharmaceutical composition is stable at about 30 °C. In some embodiments, the pharmaceutical composition is stable at about 35 °C. In some embodiments, the pharmaceutical composition is stable at about 40 °C.

[0481] In some embodiments, the pharmaceutical composition is stable for about 1 week to about 36 months.

[0482] In some embodiments, the pharmaceutical composition is stable for about 1 week. In some embodiments, the pharmaceutical composition is stable for about 2 weeks. In some embodiments, the pharmaceutical composition is stable for about 3 weeks. In some embodiments, the pharmaceutical composition is stable for about 1 month. In some embodiments, the pharmaceutical composition is stable for about 2 months. In some embodiments, the pharmaceutical composition is stable for about 3 months. In some embodiments, the pharmaceutical composition is stable for about 4 months. In some embodiments, the pharmaceutical composition is stable for about 5 months. In some embodiments, the pharmaceutical composition is stable for about 6 months. In some embodiments, the pharmaceutical composition is stable for about 7 months. In some embodiments, the pharmaceutical composition is stable for about 8 months. In some embodiments, the pharmaceutical composition is stable for about 9 months. In some embodiments, the pharmaceutical composition is stable for about 10 months. In some embodiments, the pharmaceutical composition is stable for about 11 months. In some embodiments, the pharmaceutical composition is stable for about 12 months. In some embodiments, the pharmaceutical composition is stable for about 13 months. In some embodiments, the pharmaceutical composition is stable for about 14 months. In some embodiments, the pharmaceutical composition is stable for about 15 months. In some embodiments, the pharmaceutical composition is stable for about 16 months. In some embodiments, the pharmaceutical composition is stable for about 17 months. In some embodiments, the pharmaceutical composition is stable for about 18 months. In some embodiments, the pharmaceutical composition is stable for about 19 months. In some embodiments, the pharmaceutical composition is stable for about 20 months. In some embodiments, the pharmaceutical composition is stable for about 21 months. In some embodiments, the pharmaceutical composition is stable for about 22 months. In some embodiments, the pharmaceutical composition is stable for about 23 months. In some embodiments, the pharmaceutical composition is stable for about 24 months. In some embodiments, the pharmaceutical composition is stable for about 25 months. In some embodiments, the pharmaceutical composition is stable for about 26 months. In some embodiments, the pharmaceutical composition is stable for about 27 months. In some embodiments, the pharmaceutical composition is stable for about 28 months. In some embodiments, the pharmaceutical composition is stable for about 29 months. In some embodiments, the pharmaceutical composition is stable for about 30 months. In some embodiments, the pharmaceutical composition is stable for about 31 months. In some embodiments, the pharmaceutical composition is stable for about 32 months. In some embodiments, the pharmaceutical composition is stable for about 33 months. In some embodiments, the pharmaceutical composition is stable for about 34 months. In some embodiments, the pharmaceutical composition is stable for about 35 months. In some embodiments, the pharmaceutical composition is stable for about 36 months.

[0483] In some embodiments, the pharmaceutical composition is stable at about -20 °C for about 1 week. In some embodiments, the pharmaceutical composition is stable at about -20 °C for about 2 weeks. In some embodiments, the pharmaceutical composition is stable at about -20 °C for about 3 weeks. In some embodiments, the pharmaceutical composition is embodiments, the pharmaceutical composition is embodiments, the pharmaceutical composition is embodiments, the pharmaceutical composition is embodiments, the pharmaceutical composition is embodiments, the pharmaceutical composition is embodiments, the pharmaceutical composition is embodiments, the pharmaceutical composition is embodiments, the pharmaceutical composition is embodiments, the pharmaceutical composition is embodiments, the pharmaceutical composition is embodiments, the pharmaceutical composition is embodiments, the pharmaceutical composition is embodiments, the pharmaceutical composition is embodiments, the pharmaceutical composition is embodiments, the pharmaceutical composition is embodiments, the pharmaceutical composition is embodiments, the pharmaceutical composition is embodiments, the pharmaceutical composition is embodiments, the pharmaceutical composition is embodiments, the pharmaceutical composition is embodiments, the pharmaceutical composition is embodiments, the pharmaceutical composition is embodiments, the pharmaceutical composition is embodiments, the pharmaceutical composition is embodiments, the pharmaceutical composition is stable at about -20 °C for about 1 month. In some stable at about -20 °C for about 2 months. In some stable at about -20 °C for about 3 months. In some stable at about -20 °C for about 4 months. In some stable at about -20 °C for about 5 months. In some stable at about -20 °C for about 6 months. In some stable at about -20 °C for about 7 months. In some stable at about -20 °C for about 8 months. In some stable at about -20 °C for about 9 months. In some stable at about -20 °C for about 10 months. In some stable at about -20 °C for about 11 months. In some stable at about -20 °C for about 12 months. In some stable at about -20 °C for about 13 months. In some stable at about -20 °C for about 14 months. In some stable at about -20 °C for about 15 months. In some stable at about -20 °C for about 16 months. In some stable at about -20 °C for about 17 months. In some stable at about -20 °C for about 18 months. In some stable at about -20 °C for about 19 months. In some stable at about -20 °C for about 20 months. In some stable at about -20 °C for about 21 months. In some stable at about -20 °C for about 22 months. In some stable at about -20 °C for about 23 months. In some stable at about -20 °C for about 24 months. In some stable at about -20 °C for about 25 months. In some stable at about -20 °C for about 26 months. In some embodiments, the pharmaceutical composition is stable at about -20 °C for about 27 months. In some embodiments, the pharmaceutical composition is stable at about -20 °C for about 28 months. In some embodiments, the pharmaceutical composition is stable at about -20 °C for about 29 months. In some embodiments, the pharmaceutical composition is stable at about -20 °C for about 30 months. In some embodiments, the pharmaceutical composition is stable at about -20 °C for about 31 months. In some embodiments, the pharmaceutical composition is stable at about -20 °C for about 32 months. In some embodiments, the pharmaceutical composition is stable at about -20 °C for about 33 months. In some embodiments, the pharmaceutical composition is stable at about -20 °C for about 34 months. In some embodiments, the pharmaceutical composition is stable at about -20 °C for about 35 months. In some embodiments, the pharmaceutical composition is stable at about -20 °C for about 36 months.

[0484] In some embodiments, the pharmaceutical composition is stable at -20 °C for at least 3 months. In some embodiments, the pharmaceutical composition is stable at -20 °C for at least 6 months. In some embodiments, the pharmaceutical composition is stable at 2-8 °C for at least 3 months. In some embodiments, the pharmaceutical composition is stable at 2-8 °C for at least 6 months. In some embodiments, the pharmaceutical composition is stable at 2-8 °C for at least 9 months.

[0485] In some embodiments, the pharmaceutical composition comprises any of the preceding embodiments.

[0486] In some embodiments, the pharmaceutical composition is stored in aliquots of about 1 mL to about 6 mL.

[0487] In some embodiments, the pharmaceutical composition is stored in aliquots of about 1 mL. In some embodiments, the pharmaceutical composition is stored in aliquots of about 2 mL. In some embodiments, the pharmaceutical composition is stored in aliquots of about 3 mL. In some embodiments, the pharmaceutical composition is stored in aliquots of about 4 mL. In some embodiments, the pharmaceutical composition is stored in aliquots of about 5 mL. In some embodiments, the pharmaceutical composition is stored in aliquots of about 6 mL.

[0488] In some embodiments, the pharmaceutical composition is stored in 1 mL to about 10 mL vials. In some embodiments, the pharmaceutical composition is stored in 1 mL to about 10 mL syringes.

[0489] In some embodiments, the pharmaceutical composition is stored in 1 mL vials. In some embodiments, the pharmaceutical composition is stored in 2 mL vials. In some embodiments, the pharmaceutical composition is stored in 3 mL vials. In some embodiments, the pharmaceutical composition is stored in 4 mL vials. In some embodiments, the pharmaceutical composition is stored in 5 mL vials. In some embodiments, the pharmaceutical composition is stored in 6 mL vials. In some embodiments, the pharmaceutical composition is stored in 7 mL vials. In some embodiments, the pharmaceutical composition is stored in 8 mL vials. In some embodiments, the pharmaceutical composition is stored in 9 mL vials. In some embodiments, the pharmaceutical composition is stored in 10 mL vials. In some embodiments, the pharmaceutical composition is stored in 1 mL syringes. In some embodiments, the pharmaceutical composition is stored in 2 mL syringes. In some embodiments, the pharmaceutical composition is stored in 3 mL syringes. In some embodiments, the pharmaceutical composition is stored in 4 mL syringes. In some embodiments, the pharmaceutical composition is stored in 5 mL syringes. In some embodiments, the pharmaceutical composition is stored in 6 mL syringes. In some embodiments, the pharmaceutical composition is stored in 7 mL syringes. In some embodiments, the pharmaceutical composition is stored in 8 mL syringes. In some embodiments, the pharmaceutical composition is stored in 9 mL syringes. In some embodiments, the pharmaceutical composition is stored in 10 mL syringes.

[0490] In some embodiments, the pharmaceutical composition is stored in vials with a stopper and a cover. In some embodiments, the pharmaceutical composition is stored in vials with about a 10 mm to about a 30 mm stopper, and about a 10 mm to about a 30 mm cover.

[0491] In some embodiments, the pharmaceutical composition is stored in vials with about a 10 mm stopper. In some embodiments, the pharmaceutical composition is stored in vials with about a 15 mm stopper. In some embodiments, the pharmaceutical composition is stored in vials with about a 20 mm stopper. In some embodiments, the pharmaceutical composition is stored in vials with about a 25 mm stopper. In some embodiments, the pharmaceutical composition is stored in vials with about a 10 mm cover. In some embodiments, the pharmaceutical composition is stored in vials with about a 15 mm cover. In some embodiments, the pharmaceutical composition is stored in vials with about a 20 mm cover. In some embodiments, the pharmaceutical composition is stored in vials with about a 25 mm cover.

[0492] In some embodiments, the pharmaceutical composition is stored in vials with an aluminum plastic cover. In some embodiments, the pharmaceutical composition is stored in vials with a plastic cover.

[0493] In some embodiments, the pharmaceutical composition is stored in 2 mb aliquots at -20 °C in 6 mL vials with a 20 mm stopper and a 20 mm aluminum plastic cover.

[0494] In some embodiments, the pharmaceutical composition is filtered prior to storage. In some embodiments, the pharmaceutical composition is filtered with a 0.22 pM PVDF filter prior to storage.

[0495] In some embodiments, the pharmaceutical composition is for intravenous or subcutaneous injection. In some embodiments, the pharmaceutical composition is for intravenous injection. In some embodiments, the pharmaceutical composition is for subcutaneous injection. In some embodiments, the pharmaceutical composition is for intramuscular injection. In some embodiments, the pharmaceutical composition is for intracistemal injection.

[0496] In some embodiments, the pharmaceutical composition is a liquid pharmaceutical composition. In some embodiments, the pharmaceutical composition is a lyophilized pharmaceutical composition.

[0497] In some embodiments, a dosage form in a container is provided. In some embodiments, the dosage form comprises a pharmaceutical composition such as those provided herein. In some embodiments, the container is a plastic vial or a glass vial.

[0498] Compositions and formulations can be administered with medical devices known in the art. For example, a pharmaceutical composition of the invention can be administered by injection with a hypodermic needle, including, e.g., a prefilled syringe or autoinjector.

[0499] In some embodiments, a kit, comprising a pharmaceutical composition, such as those provided herein, is provided.

[0500] Alternately, one may administer the pharmaceutical composition in a local rather than systemic manner, for example, via injection of the antibody directly into an arthritic joint or pathogen-induced lesion characterized by immunopathology, often in a depot or sustained release pharmaceutical composition. Furthermore, one may administer the antibody in a targeted drug delivery system, for example, in a liposome coated with a tissue-specific antibody, targeting, for example, arthritic joint or pathogen-induced lesion characterized by immunopathology. The liposomes will be targeted to and taken up selectively by the afflicted tissue.

[0501] The pharmaceutical compositions provided herein can be provided by continuous infusion, or by doses administered, e.g., daily, 1-7 times per week, weekly, bi-weekly, monthly, bimonthly, quarterly, semiannually, annually etc. Doses may be provided, e.g., intravenously, subcutaneously, topically, orally, nasally, rectally, intramuscular, intracerebrally, intraspinally, or by inhalation. In some embodiments, the pharmaceutical composition is administered every two weeks, every three weeks, every four weeks, every five weeks, every six weeks, every seven weeks, or every eight weeks. In some embodiments, the pharmaceutical composition is administered every two weeks. In some embodiments, the pharmaceutical composition is administered every three weeks. In some embodiments, the pharmaceutical composition is administered every four weeks. In some embodiments, the pharmaceutical composition is administered every five weeks. In some embodiments, the pharmaceutical composition is administered every six weeks. In some embodiments, the pharmaceutical composition is administered every seven weeks. In some embodiments, the pharmaceutical composition is administered every eight weeks. In some embodiments, the pharmaceutical composition is administered for at least 21-52 weeks or longer. In some embodiments, the pharmaceutical composition is administered on such a schedule for at least 21 weeks. In some embodiments, the pharmaceutical composition is administered on such a schedule for at least 24 weeks. In some embodiments, the pharmaceutical composition is administered on such a schedule for at least 32 weeks. In some embodiments, the pharmaceutical composition is administered on such a schedule for at least 36 weeks. In some embodiments, the pharmaceutical composition is administered on such a schedule for at least 40 weeks. In some embodiments, the pharmaceutical composition is administered on such a schedule for at least 42 weeks. In some embodiments, the pharmaceutical composition is administered (e.g. infusion or subcutaneous injection) once. In some embodiments, the pharmaceutical composition is administered (e.g. infusion or subcutaneous injection) twice. In some embodiments, the pharmaceutical composition is administered (e.g. infusion or subcutaneous injection) three times. In some embodiments, the pharmaceutical composition is administered (e.g. infusion or subcutaneous injection) four times. In some embodiments, the pharmaceutical composition is administered (e.g. infusion or subcutaneous injection) five times. In some embodiments, the pharmaceutical composition is administered (e.g. infusion or subcutaneous injection) six times. In some embodiments, the pharmaceutical composition is administered (e.g. infusion or subcutaneous injection) seven times. In some embodiments, the pharmaceutical composition is administered (e.g. infusion or subcutaneous injection) eight times. In some embodiments, the antibody is administered (e.g. infusion or subcutaneous injection) nine times. In some embodiments, the pharmaceutical composition is administered (e.g. infusion or subcutaneous injection) 10 times. In some embodiments, the pharmaceutical composition is administered (e.g. infusion or subcutaneous injection) 11 times. In some embodiments, the pharmaceutical composition is administered (e.g. infusion or subcutaneous injection) 12 times. In some embodiments, the pharmaceutical composition is administered (e.g. infusion or subcutaneous injection) 13 times. In some embodiments, the pharmaceutical composition is administered (e.g. infusion or subcutaneous injection) 14 times. In some embodiments, the pharmaceutical composition is administered (e.g. infusion or subcutaneous injection) 15 times. In some embodiments, the pharmaceutical composition is administered (e.g. infusion or subcutaneous injection) 16 times. In some embodiments, the pharmaceutical composition is administered (e.g. infusion or subcutaneous injection) 17 times. In some embodiments, the pharmaceutical composition is administered (e.g. infusion or subcutaneous injection) 18 times. In some embodiments, the pharmaceutical composition is administered (e.g. infusion or subcutaneous injection) 19 times. In some embodiments, the pharmaceutical composition is administered (e.g. infusion or subcutaneous injection) 20 times. When the pharmaceutical composition is administered more than once it can be administered according to a schedule, such as the schedules provided for herein.

[0502] As used herein, “inhibit” or “treat” or “treatment” includes a postponement of development of the symptoms associated with a disorder and / or a reduction in the severity of the symptoms of such disorder. The terms further include ameliorating existing uncontrolled or unwanted symptoms, preventing additional symptoms, and ameliorating or preventing the underlying causes of such symptoms. Thus, the terms denote that a beneficial result has been conferred on a vertebrate subject with a disorder, disease or symptom, or with the potential to develop such a disorder, disease or symptom.

[0503] As used herein, the terms “therapeutically effective amount”, “therapeutically effective dose”, and “effective amount” refer to an amount of the antibody, or antigen binding fragment thereof, that, when administered alone or in combination with an additional therapeutic agent to a cell, tissue, or subject, is effective to cause a measurable improvement in one or more symptoms of a disease or condition or the progression of such disease or condition. A therapeutically effective dose further refers to that amount of the binding compound sufficient to result in at least partial amelioration of symptoms, e.g., treatment, healing, prevention or amelioration of the relevant medical condition, or an increase in rate of treatment, healing, prevention or amelioration of such conditions. When applied to an individual active ingredient administered alone, a therapeutically effective dose refers to that ingredient alone. When applied to a combination, a therapeutically effective dose refers to combined amounts of the active ingredients that result in the therapeutic effect, whether administered in combination, serially or simultaneously. An effective amount of a therapeutic will result in an improvement of a diagnostic measure or parameter by at least 10%; usually by at least 20%; preferably at least about 30%; more preferably at least 40%; and most preferably by at least 50%. An effective amount can also result in an improvement in a subjective measure in cases where subjective measures are used to assess disease severity. In some embodiments, an amount is a therapeutically effective amount if it is an amount that can be used to treat or ameliorate a condition as provided for herein.

[0504] “Effective amount” or “therapeutically effective amount” are used interchangeably herein, and refer to an amount of a compound, formulation, material, or composition, as described herein effective to achieve a particular biological result or provides a therapeutic or prophylactic benefit. Such results may include, but are not limited to an amount that when administered to a mammal, causes a detectable level of immune cell activation compared to the immune cell activation detected in the absence of the composition. The immune response can be readily assessed by a plethora of art-recognized methods. The skilled artisan would understand that the amount of the composition administered herein varies and can be readily determined based on a number of factors such as the disease or condition being treated, the age and health and physical condition of the mammal being treated, the severity of the disease, the particular compound being administered, and the like.

[0505] As used herein, the term “individual” or “subject” or “patient” used interchangeably, means any organism, including mammals, such as mice, rats, other rodents, rabbits, dogs, cats, swine, cattle, sheep, horses, or primates, such as humans. In one embodiment, the subject is a human. A subject can also be referred to as a patient. In some embodiments, the subject is a subject in need thereof. A subject that is “in need thereof’ refers to a subject that has been identified as requiring treatment for the condition that is to be treated and is treated with the specific intent of treating such condition. The conditions can be, for example, any of the conditions described herein.

[0506] Accordingly, in some embodiments, methods of treating a subject with a Cis mediated disorder are provided. In some embodiments, the method comprises administering a pharmaceutical composition comprising an antibody, or antigen binding fragment thereof, as provided herein. In some embodiments, the disorder is a Cis mediated disorder. As provided for herein, the antibodies, or antigen binding fragments thereof, can be administered with other therapeutics. These can be administered simultaneously or sequentially.

[0507] In some embodiments, the subject is a subject who has previously been treated with a different antibody than those provided herein.

[0508] In some embodiments, the pharmaceutical composition comprises an antibody at about 100 mg / mL, phosphate buffer at about 20 mM, L-methionine at about 10 mM, sucrose at about 4% w / v, L-Arg-HCL at about 70 mM, and Pl88 at about 0.1 % w / v, wherein the pharmaceutical composition is at a pH of about 7.2.

[0509] In some embodiments, the pharmaceutical composition comprises about 100 mg / mL of an antibody having a heavy chain and a light chain, wherein the heavy chain comprises an HCDR1 of SEQ ID NO: 61, an HCDR2 of SEQ ID NO: 62, and an HCDR3 of SEQ ID NO: 78, and wherein the light chain comprises an LCDR1 of SEQ ID NO: 64, an LCDR2 of SEQ ID NO: 65, and an LCDR3 of SEQ ID NO: 79; phosphate buffer at about 20 mM, L-methionine at about 10 mM, sucrose at about 4% w / v, L-Arg-HCL at about 70 mM, and Pl88 at about 0.1 % w / v, wherein the pharmaceutical composition is at a pH of about 7.2.

[0510] In some embodiments, the pharmaceutical composition comprises an antibody at about 150 mg / mL, phosphate buffer at about 20 mM, L-methionine at about 10 mM, sucrose at about 3.5% w / v, L-Arg-HCL at about 70 mM, and P188 at about 0.1% w / v, wherein the pharmaceutical composition is at a pH of about 7.2.

[0511] In some embodiments, the pharmaceutical composition comprises about 150 mg / mL of an antibody having a heavy chain and a light chain, wherein the heavy chain comprises an HCDR1 of SEQ ID NO: 61, an HCDR2 of SEQ ID NO: 62, and an HCDR3 of SEQ ID NO: 78, and wherein the light chain comprises an LCDR1 of SEQ ID NO: 64, an LCDR2 of SEQ ID NO: 65, and an LCDR3 of SEQ ID NO: 79; phosphate buffer at about 20 mM, L-methionine at about 10 mM, sucrose at about 4% w / v, L-Arg-HCL at about 70 mM, and Pl88 at about 0.1 % w / v, wherein the pharmaceutical composition is at a pH of about 7.2.

[0512] In some embodiments, the method provided herein comprise administering to a subject an antibody, or an antigen binding fragment thereof, that specifically binds to and inhibits Cis. In some embodiments, the antibody is as provided herein.

[0513] Kits are also provided which are useful for carrying out embodiments described herein. The present kits comprise a first container containing or packaged in association with the above-described antibodies. The kit may also comprise another container containing or packaged in association solutions necessary or convenient for carrying out the embodiments. The containers can be made of glass, polymer (e.g., plastic), metal (e.g., aluminum), and can be a vial, bottle, pouch, tube, bag, etc. The kit may also contain written information, such as procedures for carrying out the embodiments or analytical information, such as the amount of reagent contained in the first container means. The container may be in another container apparatus, e.g. a box or a bag, along with the written information.

[0514] In some embodiments, antibodies that bind to a Cis protein are provided. In some embodiments, the antibody is isolated. In some embodiments, the antibody binds specifically. In some embodiments, the antibody binds to a Cis protein that is properly folded. In some embodiments, the antibody is specific for a specific Cis conformational state (open or closed). In some embodiments, the antibody binds to a Cis protein in a cell membrane. In some embodiments, the antibody binds to a Cis protein that is in a cell membrane in an intact cell. In some embodiments, the antibody inhibits or neutralizes the function of a Cis protein. As used herein, the term “neutralize” means that the activity or function of the protein is inhibited. The inhibition can be complete or partial. In some embodiments, the activity or function of the protein is inhibited at least 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or 99%. The percent inhibition can be based upon the function or activity of the protein in the absence of the antibody. In some embodiments, the antibody inhibits the glucose transport facilitated by Cis. In some embodiments, the antibody inhibits the internalization of the Cis protein.

[0515] In some embodiments, the antibody comprises a sequence as provided for herein or antigen binding fragment thereof. In some embodiments, the antibody comprises a heavy chain CDR or an antigen binding fragment thereof described herein. The heavy chain may be one or more of the heavy chains described herein. In some embodiments, the antibody comprises a light chain, or an antigen binding fragment thereof as described herein.

[0516] In some embodiments, methods of treating, inhibiting or ameliorating a Cl s-associated pathology are provided. In some embodiments, the methods comprise administering a pharmaceutical composition described herein to a subject to treat, inhibit or ameliorate a Cls-associated pathology. In some embodiments, the pathology is as described herein.

[0517] In some embodiments, the pharmaceutical composition main peak, measured by SEC, decreases in area percent by less than 0.1%, less than 0.2%, less than 0.3%, less than 0.4%, less than 0.5%, less than 0.6%, less than 0.7%, less than 0.8%, less than 0.9%, or less than 1% after 24 months at a temperature of about -70 °C, relative to the initial value. In some embodiments, the pharmaceutical composition main peak, measured by SEC, decreases in area percent by less than 0.2% after 24 months at a temperature of about -70 °C, relative to the initial value.

[0518] In some embodiments, the pharmaceutical composition main peak, measured by SEC, decreases in area percent by less than 0.1%, less than 0.2%, less than 0.3%, less than 0.4%, less than 0.5%, less than 0.6%, less than 0.7%, less than 0.8%, less than 0.9%, or less than 1% after 24 months at a temperature of about -20 °C, relative to the initial value. In some embodiments, the pharmaceutical composition main peak, measured by SEC, decreases in area percent by less than 0.4% after 24 months at a temperature of about -20 °C, relative to the initial value.

[0519] In some embodiments, the pharmaceutical composition main peak, measured by SEC, decreases in area percent by less than 0.1%, less than 0.2%, less than 0.3%, less than 0.4%, less than 0.5%, less than 0.6%, less than 0.7%, less than 0.8%, less than 0.9%, or less than 1% after 6 months at a temperature of about 5 °C, relative to the initial value. In some embodiments, the pharmaceutical composition main peak, measured by SEC, decreases in area percent by less than 0.5% after 6 months at a temperature of about 5 °C, relative to the initial value.

[0520] In some embodiments, the pharmaceutical composition main peak, measured by SEC, decreases in area percent by less than 0.1%, less than 0.2%, less than 0.3%, less than 0.4%, less than 0.5%, less than 0.6%, less than 0.7%, less than 0.8%, less than 0.9%, less than 1%, less than 1.1%, less than 1.2%, less than 1.3%, less than 1.4%, less than 1.5%, less than 1.6%, less than 1.7%, less than 1.8%, less than 1.9%, less than 2%, less than 2.1%, less than 2.2%, less than 2.3%, less than 2.4%, less than 2.5%, less than 2.6%, less than 2.7%, less than 2.8%, less than 2.9%, less than 3%, less than 3.1%, less than 3.2%, less than 3.3%, less than 3.4%, less than 3.5%, less than 3.6%, less than 3.7%, less than 3.8%, less than 3.9%, less than 4%, less than 4.1%, less than 4.2%, less than 4.3%, less than 4.4%, less than 4.5%, less than 4.6%, less than 4.7%, less than 4.8%, less than 4.9%, or less than 5% after 6 months at a temperature of about 25 °C, relative to the initial value. In some embodiments, the pharmaceutical composition main peak, measured by SEC, decreases in area percent by less than 3% after 6 months at a temperature of about 25 °C, relative to the initial value.

[0521] In some embodiments, the pharmaceutical composition main peak, measured by SEC, decreases in area percent by less than 0.1%, less than 0.2%, less than 0.3%, less than 0.4%, less than 0.5%, less than 0.6%, less than 0.7%, less than 0.8%, less than 0.9%, less than 1%, less than 1.1%, less than 1.2%, less than 1.3%, less than 1.4%, less than 1.5%, less than 1.6%, less than 1.7%, less than 1.8%, less than 1.9%, less than 2%, less than 2.1%, less than 2.2%, less than 2.3%, less than 2.4%, less than 2.5%, less than 2.6%, less than 2.7%, less than 2.8%, less than 2.9%, less than 3%, less than 3.1%, less than 3.2%, less than 3.3%, less than 3.4%, less than 3.5%, less than 3.6%, less than 3.7%, less than 3.8%, less than 3.9%, less than 4%, less than 4.1%, less than 4.2%, less than 4.3%, less than 4.4%, less than 4.5%, less than 4.6%, less than 4.7%, less than 4.8%, less than 4.9%, less than 5%, less than 5.1%, less than 5.2%, less than 5.3%, less than 5.4%, less than 5.5%, less than 5.6%, less than 5.7%, less than 5.8%, less than 5.9%, less than 6%, less than 6.1%, less than 6.2%, less than 6.3%, less than 6.4%, less than 6.5%, less than 6.6%, less than 6.7%, less than 6.8%, less than 6.9%, less than 7%, less than 7.1%, less than 7.2%, less than 7.3%, less than 7.4%, less than 7.5%, less than 7.6%, less than 7.7%, less than 7.8%, less than 7.9%, less than 8%, less than 8.1%, less than 8.2%, less than 8.3%, less than 8.4%, less than 8.5%, less than 8.6%, less than 8.7%, less than 8.8%, less than 8.9%, less than 9%, less than 9.1%, less than 9.2%, less than 9.3%, less than 9.4%, less than 9.5%, less than 9.6%, less than 9.7%, less than 9.8%, less than 9.9%, or less than 10% after 1 month at a temperature of about 40 °C, relative to the initial value. In some embodiments, the pharmaceutical composition main peak, measured by SEC, decreases in area percent by less than 7.8% after 1 month at a temperature of about 40 °C, relative to the initial value.

[0522] In some embodiments, the main peak as measured by CE-SDS under non-reducing conditions is greater than 98% when stored at -20 C for up to 1, 3, 6, 9, 18, or 24 months.

[0523] In some embodiments, the percentage of low molecular weight species (LMWS) in the pharmaceutical composition as measured by CE-SDS under non-reducing conditions is less than, or about, 1.5, 1.1, or 1.0 % when stored at -20 C for up to 1, 3, 6, 9, 18, or 24 months.

[0524] In some embodiments, the percentage of high molecular weight species (HMWS) in the pharmaceutical composition as measured by SEC is less than 2.0% when stored at -20 C for up to 1, 3, 6, 9, 18, or 24 months.

[0525] In some embodiments, the main peak as measured by CE-SDS under non-reducing conditions is greater than 97% when stored at 5 C for up to 1, 3, 6, 9, 18, or 24 months.

[0526] In some embodiments, the percentage of low molecular weight species (LMWS) in the pharmaceutical composition as measured by CE-SDS under non-reducing conditions is less than, or about, 2.5%, 2.0%, or 1.7% when stored at 5 C for up to 1, 3, 6, 9, 18, or 24 months.

[0527] In some embodiments, the percentage of high molecular weight species (HMWS) in the pharmaceutical composition as measured by SEC is less than 2.0% when stored at 5 C for up to 1, 3, 6, 9, 18, or 24 months.

[0528] In some embodiments, the main peak as measured by CE-SDS under non-reducing conditions is greater than 93% when stored at 25 C for up to 1, 3, 6, 9, 18, or 24 months.

[0529] In some embodiments, the percentage of low molecular weight species (LMWS) in the pharmaceutical composition as measured by CE-SDS under non-reducing conditions is less than, or about, 5%, 3.5%, or 1.5% when stored at 25 C for up to 1, 3, 6, 9, 18, or 24 months.

[0530] In some embodiments, the percentage of high molecular weight species (HMWS) as measured by SEC is less than 5%, 3.5%, or 1.5% when stored at 25 C for up to 1, 3, 6, 9, 18, or 24 months.

[0531] The pharmaceutical compositions provided herein provide for high concentration antibody formulations that are stable for periods of time, such as those provided for herein and can be used to treat the conditions, but not limited to, those provided for herein. METHODS OF USE

[0532] In some embodiments, the methods comprise administering a therapeutically or prophylactically effective amount of one or more antibodies or antigen binding fragments of the antibodies described herein to a susceptible subject or to one exhibiting a condition in which Cis is known to have caused the pathology observed. Any active form of the antibody can be administered, including, but not limited to scFv, Fab and F(ab')2 fragments and other forms of antibodies provided for herein.

[0533] The present disclosure provides a method to treat an individual having a complement-mediated disease or disorder, the method comprising administering to the individual an anti-Cis antibody of any of the embodiments disclosed herein or a pharmaceutical composition thereof. In some embodiments, the individual is a mammal. In some embodiments, the individual is a human. In some embodiments, the administering is intravenous. In some embodiments, the administering is subcutaneous. In some embodiments, the administering is intrathecal. In some embodiments, the administering results in an outcome selected from the group consisting of: (a) a reduction in complement activation; (b) an improvement in cognitive function; (c) a reduction in neuron loss; (d) a reduction in phospho-Tau levels in neurons; (e) a reduction in glial cell activation; (f) a reduction in lymphocyte infiltration; (g) a reduction in macrophage infiltration; (h) a reduction in antibody deposition, (i) a reduction in glial cell loss; (j) a reduction in oligodendrocyte loss; (k) a reduction in dendritic cell infiltration; (1) a reduction in neutrophil infiltration; (m) a reduction in red blood cell lysis; (n) a reduction in red blood cell phagocytosis; (o) a reduction in platelet phagocytosis; (p) a reduction in platelet lysis; (q) an improvement in transplant graft survival; (r) a reduction in macrophage mediated phagocytosis; (s) an improvement in vision; (t) an improvement in motor control; (u) an improvement in thrombus formation; (v) an improvement in clotting; (w) an improvement in kidney function; (x) a reduction in antibody mediated complement activation; (y) a reduction in autoantibody mediated complement activation; (z) an improvement in anemia; (aa) reduction of demyelination; (ab) reduction of eosinophilia; (ac) a reduction in autoantibody mediated blister formation; (ad) a reduction in autoantibody induced pruritis; (ae) a reduction in autoantibody induced erythematosus; (af) a reduction in autoantibody mediated skin erosion; (ag) a reduction in red blood cell destruction due to transfusion reactions; (ah) a reduction in red blood cell lysis due to alloantibodies; (ai) a reduction in hemolysis due to transfusion reactions; (aj) a reduction in alloantibody mediated platelet lysis; (ak) a reduction in platelet lysis due to transfusion reactions; (al) a reduction in mast cell activation; (am) a reduction in mast cell histamine release; (an) a reduction in vascular permeability; (ao) a reduction in edema; (ap) a reduction in complement deposition on transplant graft endothelium; (aq) a reduction of anaphylatoxin generation in transplant graft endothelium; (ar) a reduction in the separation of the dermal-epidermal junction; (as) a reduction in the generation of anaphylatoxins in the dermal-epidermal junction; (at) a reduction in alloantibody mediated complement activation in transplant graft endothelium; (au) a reduction in antibody mediated loss of the neuromuscular junction; (av) a reduction in complement activation at the neuromuscular junction; (aw) a reduction in anaphylatoxin generation at the neuromuscular junction; (ax) a reduction in complement deposition at the neuromuscular junction; (ay) a reduction in paralysis; (az) a reduction in numbness; (ba) increased bladder control; (bb) increased bowel control; (be) a reduction in mortality associated with autoantibodies; and (bd) a reduction in morbidity associated with autoantibodies. In some embodiments, the reduction in glial cell activation comprises reduction in astrocyte activation or reduction in microglia activation.

[0534] In some embodiments, a method of treating a subject with a Cis mediated disorder is provided. In some embodiments, the method comprises administering to the subject an antibody or antigen-binding fragment thereof as provided for herein or a pharmaceutical composition comprising an antibody or antigen-binding fragment thereof as provided for herein, thereby treating the Cis mediated disorder. The antibody or antigen-binding fragment thereof of any of the embodiments provided for herein or the pharmaceutical compositions of any of the embodiments provided for herein inhibit complement Cis activity in an individual having a complement-mediated disease or disorder. In some embodiments, the individual is a mammal. In some embodiments, the individual is a human. In some embodiments, the administering is intravenous. In some embodiments, the administering is subcutaneous. In some embodiments, the administering is intrathecal. In some embodiments, the administering results in an outcome selected from the group consisting of: (a) a reduction in complement activation; (b) an improvement in cognitive function; (c) a reduction in neuron loss; (d) a reduction in phospho-Tau levels in neurons; (e) a reduction in glial cell activation; (f) a reduction in lymphocyte infdtration; (g) a reduction in macrophage infdtration; (h) a reduction in antibody deposition, (i) a reduction in glial cell loss; (j) a reduction in oligodendrocyte loss; (k) a reduction in dendritic cell infdtration; (1) a reduction in neutrophil infdtration; (m) a reduction in red blood cell lysis; (n) a reduction in red blood cell phagocytosis; (o) a reduction in platelet phagocytosis; (p) a reduction in platelet lysis; (q) an improvement in transplant graft survival; (r) a reduction in macrophage mediated phagocytosis; (s) an improvement in vision; (t) an improvement in motor control; (u) an improvement in thrombus formation; (v) an improvement in clotting; (w) an improvement in kidney function; (x) a reduction in antibody mediated complement activation; (y) a reduction in autoantibody mediated complement activation; (z) an improvement in anemia; (aa) reduction of demyelination; (ab) reduction of eosinophilia; (ac) a reduction in autoantibody mediated blister formation; (ad) a reduction in autoantibody induced pruritis; (ae) a reduction in autoantibody induced erythematosus; (af) a reduction in autoantibody mediated skin erosion; (ag) a reduction in red blood cell destruction due to transfusion reactions; (ah) a reduction in red blood cell lysis due to alloantibodies; (ai) a reduction in hemolysis due to transfusion reactions; (aj) a reduction in alloantibody mediated platelet lysis; (ak) a reduction in platelet lysis due to transfusion reactions; (al) a reduction in mast cell activation; (am) a reduction in mast cell histamine release; (an) a reduction in vascular permeability; (ao) a reduction in edema; (ap) a reduction in complement deposition on transplant graft endothelium; (aq) a reduction of anaphylatoxin generation in transplant graft endothelium; (ar) a reduction in the separation of the dermal-epidermal junction; (as) a reduction in the generation of anaphylatoxins in the dermal-epidermal junction; (at) a reduction in alloantibody mediated complement activation in transplant graft endothelium; (au) a reduction in antibody mediated loss of the neuromuscular junction; (av) a reduction in complement activation at the neuromuscular junction; (aw) a reduction in anaphylatoxin generation at the neuromuscular junction; (ax) a reduction in complement deposition at the neuromuscular junction; (ay) a reduction in paralysis; (az) a reduction in numbness; (ba) increased bladder control; (bb) increased bowel control; (be) a reduction in mortality associated with autoantibodies; and (bd) a reduction in morbidity associated with autoantibodies. In some embodiments, the reduction in glial cell activation comprises reduction in astrocyte activation or reduction in microglia activation.

[0535] In some embodiments, a method is provided comprising treating a subject with a Cis mediated disorder, the method comprising administering to the subject the pharmaceutical composition described in any one of the embodiments described herein. In some embodiments, the Cis mediated disorder is selected from the group including, but not limited to, hemolysis, Cold Agglutinin Disease, Immune Thrombocytopenia (ITP), Myasthenia Gravis, Glomerulopathies, Atypical Hemolytic uremic syndrome, antiphospholipid antibody syndrome, transplant rejection, Chronic inflammatory demyelinating polyneuropathy (CIDP), Multifocal motor neuropathy (MMN), Dermatomyositis, or Anti MAG neuropathy. In some embodiments, these conditions can be caused by stroke or due to spinal cord injury. In some embodiments, the Cis mediated disorder is hemolysis. In some embodiments, the Cis mediated disorder is Cold Agglutinin Disease. In some embodiments, the Cis mediated disorder is Immune Thrombocytopenia (ITP). In some embodiments, the Cis mediated disorder is Myasthenia Gravis. In some embodiments, the Cis mediated disorder is Glomerulopathies. In some embodiments, the Cis mediated disorder is Atypical Hemolytic uremic syndrome. In some embodiments, the Cis mediated disorder is antiphospholipid antibody syndrome. In some embodiments, the Cis mediated disorder is transplant rejection. In some embodiments, the Cis mediated disorder is Chronic inflammatory demyelinating polyneuropathy (CIDP). In some embodiments, the Cis mediated disorder is Multifocal motor neuropathy (MMN). In some embodiments, the Cis mediated disorder is Dermatomysositis. In some embodiments, the Cis mediated disorder is Anti MAG neuropathy. In some embodiments, the Cis mediated disorder is due to stroke. In some embodiments, the Cis mediated disorder is due to spinal cord injury.

[0536] In some embodiments, the antibody or antigen-binding fragment thereof of any of the embodiments as provided for herein, or a pharmaceutical composition comprising the antibody or antigenbinding fragment thereof of any of the embodiments as provided for herein is for the use in the treatment of a complement-mediated disease or disorder. In some embodiments, the complement-mediated disorder is selected from the group including, but not limited to, hemolysis, Cold Agglutinin Disease, Immune Thrombocytopenia (ITP), Myasthenia Gravis, Glomerulopathies, Atypical Hemolytic uremic syndrome, antiphospholipid antibody syndrome, transplant rejection, Chronic inflammatory demyelinating polyneuropathy (CIDP), Multifocal motor neuropathy (MMN), Dermatomyositis, or Anti MAG neuropathy. In some embodiments, these conditions can be due to stroke or due to spinal cord injury. In some embodiments, the Cis mediated disorder is hemolysis. In some embodiments, the Cis mediated disorder is Cold Agglutinin Disease. In some embodiments, the Cis mediated disorder is Immune Thrombocytopenia (ITP). In some embodiments, the Cis mediated disorder is Myasthenia Gravis. In some embodiments, the Cis mediated disorder is Glomerulopathies. In some embodiments, the Cis mediated disorder is Atypical Hemolytic uremic syndrome. In some embodiments, the Cis mediated disorder is antiphospholipid antibody syndrome. In some embodiments, the Cis mediated disorder is transplant rejection. In some embodiments, the Cis mediated disorder is Chronic inflammatory demyelinating polyneuropathy (CIDP). In some embodiments, the Cis mediated disorder is Multifocal motor neuropathy (MMN). In some embodiments, the Cis mediated disorder is Dermatomyositis. In some embodiments, the Cis mediated disorder is Anti MAG neuropathy. In some embodiments, the Cis mediated disorder is due to stroke. In some embodiments, the Cis mediated disorder is due to spinal cord injury. In some embodiments, the Cis mediated disorder is selected from the group including, but not limited to, hemolysis, Cold Agglutinin Disease, Immune Thrombocytopenia (ITP), Myasthenia Gravis, Glomerulopathies, Atypical Hemolytic uremic syndrome, antiphospholipid antibody syndrome, transplant rejection, Chronic inflammatory demyelinating polyneuropathy (CIDP), Multifocal motor neuropathy (MMN), Dermatomyositis, or Anti MAG neuropathy. In some embodiments, the Cis mediated disorder is hemolysis. In some embodiments, the Cis mediated disorder is Cold Agglutinin Disease. In some embodiments, the Cis mediated disorder is Immune Thrombocytopenia (ITP). In some embodiments, the Cis mediated disorder is Myasthenia Gravis. In some embodiments, the Cis mediated disorder is Glomerulopathies. In some embodiments, the Cis mediated disorder is Atypical Hemolytic uremic syndrome. In some embodiments, the Cis mediated disorder is antiphospholipid antibody syndrome. In some embodiments, the Cis mediated disorder is transplant rejection. In some embodiments, the Cis mediated disorder is Chronic inflammatory demyelinating polyneuropathy (CIDP). In some embodiments, the Cis mediated disorder is Multifocal motor neuropathy (MMN). In some embodiments, the Cis mediated disorder is Dermatomyositis. In some embodiments, the Cis mediated disorder is Anti MAG neuropathy. In some embodiments, the Cis mediated disorder is due to stroke. In some embodiments, the Cis mediated disorder is due to Spinal Cord Injury.

[0537] The present disclosure provides use of an anti-Cis antibody of any of the embodiments in the manufacture of a medicament for the treatment of an individual having a complement-mediated disease or disorder. Accordingly, in some embodiments, an antibody, or antigen binding fragment thereof, or a pharmaceutical composition is provided for use as a medicament. In some embodiments, an antibody, or antigen binding fragment thereof, is provided for use as a medicament. In some embodiments, a pharmaceutical composition is provided for use as a medicament. In some embodiments, the antibody, or antigen binding fragment thereof, is an antibody or antigen binding fragment as provided for herein. In some embodiments, the pharmaceutical composition comprises an antibody or antigen binding fragment as provided for herein. In some embodiments, the pharmaceutical composition is as provided for herein. In some embodiments, the medicament is for use in treatment of a Cis mediated disease or disorder. In some embodiments, the complement-mediated disorder is, but not limited to, hemolysis, Cold Agglutinin Disease, Immune Thrombocytopenia (ITP), Myasthenia Gravis, Glomerulopathies, Atypical Hemolytic uremic syndrome, antiphospholipid antibody syndrome, transplant rejection, Chronic inflammatory demyelinating polyneuropathy (CIDP), Multifocal motor neuropathy (MMN), Dermatomyositis, or Anti MAG neuropathy. In some embodiments, the conditions can be due to stroke or due to spinal cord injury. In some embodiments, the Cis mediated disorder is hemolysis. In some embodiments, the Cis mediated disorder is Cold Agglutinin Disease. In some embodiments, the Cis mediated disorder is Immune Thrombocytopenia (ITP). In some embodiments, the Cis mediated disorder is Myasthenia Gravis. In some embodiments, the Cis mediated disorder is Glomerulopathies. In some embodiments, the Cis mediated disorder is Atypical Hemolytic uremic syndrome. In some embodiments, the Cis mediated disorder is antiphospholipid antibody syndrome. In some embodiments, the Cis mediated disorder is transplant rejection. In some embodiments, the Cis mediated disorder is Chronic inflammatory demyelinating polyneuropathy (CIDP). In some embodiments, the Cis mediated disorder is Multifocal motor neuropathy (MMN). In some embodiments, the Cis mediated disorder is Dermatomyositis. In some embodiments, the Cis mediated disorder is Anti MAG neuropathy. In some embodiments, the Cis mediated disorder is due to stroke. In some embodiments, the Cis mediated disorder is due to spinal cord injury.

[0538] In some embodiments, a use of an antibody or antigen binding fragment as provided for herein or a pharmaceutical composition as provided for herein is provided. In some embodiments, the use is for the treatment of a Cis mediated disorder. In some embodiments, a use of an antibody or antigen binding fragment as provided for herein is provided, the use for the treatment of a Cis mediated disorder. In some embodiments, a use of a pharmaceutical composition comprising an antibody or antigen binging fragment as provided for herein is provided, the use for the treatment of a Cis mediated disorder. In some embodiments, the pharmaceutical composition is as provided for herein. The antibody of any of the embodiments or pharmaceutical compositions thereof inhibit complement Cis activity in an individual having a complement-mediated disease or disorder.

[0539] The present disclosure provides use of an anti-Cis antibody of any of the embodiments or a pharmaceutical composition thereof in the manufacture of a medicament for inhibiting complement Cis activity. In some embodiments, the present disclosure provides use of an anti-Cis antibody of any of the embodiments or a pharmaceutical composition thereof in the manufacture of a medicament for inhibiting complement Cis activity in an individual having a complement-mediated disease or disorder.

[0540] The present disclosure provides an anti-Cis antibody of any of the embodiments or a pharmaceutical composition thereof for use in medical therapy.

[0541] The present disclosure provides an anti-Cis antibody of any of the embodiments or a pharmaceutical composition thereof for treating an individual having a complement-mediated disease or disorder.

[0542] The present disclosure provides an anti-Cis antibody of any of the embodiments or a pharmaceutical composition thereof for inhibiting complement Cis protein activity. The present disclosure provides an anti-Cis antibody of any of the embodiments or a pharmaceutical composition thereof for inhibiting complement Cis protein activity in an individual having a complement-mediated disease or disorder.

[0543] The present disclosure provides a method to diagnose a complement-mediated disease or disorder in an individual, the method comprising: (a) determining the amount of a complement Cis protein in a biological sample obtained from the individual, wherein the step of determining comprises: (i) contacting the biological sample with an anti-Cis antibody of any of the embodiments; and (ii) quantitating binding of the antibody to complement Cis protein present in the sample; and (b) comparing the amount of the complement Cis protein to a normal control value that indicates the amount of complement Cis protein in a normal control individual, wherein a significant difference between the amount of Cis protein in the biological sample and the normal control value indicates that the individual has a complement-mediated disease or disorder. In some embodiments, the biological sample is selected from the group consisting of blood, serum, plasma, urine, saliva, cerebrospinal fluid, interstitial fluid, ocular fluid, synovial fluid, solid tissue sample, tissue culture sample, and cellular sample.

[0544] The present disclosure provides a method to monitor progression of a complement-mediated disease or disorder in an individual, the method comprising: (a) determining a first amount of complement a Cis protein in a biological sample obtained from the individual at a first time point; (b) determining a second amount of complement a Cis protein in a biological sample obtained from the individual at a second time point; and (c) comparing the second amount of complement Cis protein with the first amount of complement Cis protein. The steps of determining comprise: (i) contacting the biological sample with an anti-Cis antibody of any of the embodiments; and (ii) quantitating binding of the antibody to complement Cis protein present in the sample. In some embodiments, the first time point is a time point before initiation of a treatment regimen, and the second time point is a time point after initiation of a treatment regimen. In some embodiments, the biological sample is selected from the group consisting of blood, serum, plasma, urine, saliva, cerebrospinal fluid, interstitial fluid, ocular fluid, synovial fluid, solid tissue sample, tissue culture sample, and cellular sample.

[0545] The present disclosure provides an in vitro method to detect complement Cis protein in a biological sample obtained from an individual, the method comprising: (a) contacting the biological sample with an anti-Cis antibody of any of the embodiments; and (b) detecting binding of the antibody to complement Cis protein present in the sample. In some embodiments, the biological sample is selected from the group consisting of blood, serum, plasma, urine, saliva, cerebrospinal fluid, interstitial fluid, ocular fluid, synovial fluid, solid tissue sample, tissue culture sample, and cellular sample. In some embodiments, the method is quantitative.

[0546] The present disclosure provides a method to detect complement Cis protein in a living individual in vivo, the method comprising: (a) administering to the individual an anti-Cis antibody of any of the embodiments; and (b) detecting binding of the antibody to complement Cis protein in the individual using an imaging method. In some embodiments, the binding is detected in the individual at a site altered by a complement-mediated disease or disorder. In some embodiments, the binding is detected in the brain of the individual. In some of the embodiments, the antibody comprises a contrast agent suitable for use in the imaging method. In some embodiments, the imaging method is selected from the group consisting of magnetic resonance imaging, positron emission tomography, and IVIS instrumentation. In some embodiments, the method is quantitative.

[0547] In some embodiments, the biological sample is selected from the group consisting of blood, serum, plasma, urine, saliva, cerebrospinal fluid, interstitial fluid, ocular fluid, synovial fluid, solid tissue sample, tissue culture sample, and a cellular sample.

[0548] In some embodiments, the methods of the present disclosure provide that the individual is suspected of having a complement-mediated disease or disorder, has been diagnosed as having a complement-mediated disease or disorder, or has a genetic predisposition to developing a complement-mediated disease or disorder.

[0549] The present disclosure provides a composition comprising: (a) an anti-Cl s antibody of any of the embodiments; and (b) a solution comprising one or more agents that maintain an organ or a tissue intended for transplantation into a recipient individual. In some embodiments, the solution is an organ preservation solution or a tissue preservation solution. In some embodiments, the solution is an organ perfusion solution or a tissue perfusion solution. In some embodiments, the solution comprises: i) a salt; ii) an agent that reduces edema; iii) an oxygen free radical scavenger; and iii) an energy supply system component. In some embodiments, the composition comprises potassium lactobionate, KH2PO4, MgSO4, raffinose, adenosine, glutathione, allopurinol, and / or hydroxyethyl starch.

[0550] The present disclosure provides an organ or tissue preservation solution comprising an anti-Cis antibody of any of the embodiments or a pharmaceutical composition thereof.

[0551] The present disclosure provides an organ or tissue perfusion solution comprising an anti-Cis antibody of any of the embodiments or a pharmaceutical composition thereof.

[0552] The present disclosure provides a method for maintaining an organ or tissue for transplant, the method comprising contacting the organ or the tissue with a composition comprising: (a) an anti-Cis antibody of any of the embodiments; and (b) an organ or tissue preservation solution of any of the embodiments or an organ or tissue perfusion solution of any of the embodiments.

[0553] The present disclosure provides an isolated organ or tissue maintained in a composition comprising: (a) an anti-Cis antibody of any of the embodiments; and (b) an organ or tissue preservation solution of any of the embodiments or an organ or tissue perfusion solution of any of the embodiments. In some embodiments, the organ is selected from the group consisting of an eye, a heart, an intestine, a kidney, a liver, a lung, a pancreas, a stomach, and a thymus. In some embodiments, the tissue is selected from the group consisting of bone, bone marrow, cornea, heart valve, islet of Langerhans, tendon, skin, and vein.

[0554] The present disclosure provides an in vitro method for inhibiting complement Cis activity in an organ or a tissue, the method comprising contacting the organ or the tissue with an anti-Cis antibody of any of the embodiments or a pharmaceutical composition thereof.

[0555] Treatment of individuals may comprise the administration of a therapeutically effective amount of the antibodies described herein. The antibodies can be provided in a kit, such as those provided herein. The antibodies can be used or administered alone or in admixture with another therapeutic, analgesic, or diagnostic agent, such as provided for herein. In providing a patient with an antibody, or fragment thereof, capable of binding to Cis, or an antibody capable of protecting against Cis in a recipient patient, the dosage of administered agent will vary depending upon such factors as the patient's age, weight, height, sex, general medical condition, previous medical history, etc.

[0556] An antibody, capable treating a condition associated with Cis activity or use to treat a Cis related pathology, is intended to be provided to subjects in an amount sufficient to affect a reduction, resolution, or amelioration in the Cis related symptom or pathology. Examples of such pathologies are provided for herein.

[0557] Accordingly, in some embodiments, methods of treating a subject with a Cis mediated disorder are provided. In some embodiments, the method comprises administering a pharmaceutical composition comprising an antibody, or antigen binding fragment thereof, as provided herein. In some embodiments, the disorder is as provided for herein.

[0558] As provided for herein, the antibodies, or antigen binding fragments thereof, can be administered with other therapeutics. These can be administered simultaneously or sequentially.

[0559] Kits are also provided which are useful for carrying out embodiments described herein. The present kits can comprise a first container containing or packaged in association with the above-described antibodies. The kit may also comprise another container containing or packaged in association solutions necessary or convenient for carrying out the embodiments. The containers can be made of glass, plastic or foil and can be a vial, bottle, pouch, tube, bag, etc. The kit may also contain written information, such as procedures for carrying out the embodiments or analytical information, such as the amount of reagent contained in the first container means. The container may be in another container apparatus, e.g. a box or a bag, along with the written information.

[0560] In some embodiments, antibodies that bind to a Cis protein are provided. In some embodiments, the antibodies are antibodies or antigen binding fragments as provided for herein. In some embodiments, the antibodies or antigen binding fragments comprise an amino acid sequence as provided for herein, or a variant thereof as provided for herein. In some embodiments, the antibody is isolated. In some embodiments, the antibody binds specifically to the active form of Cis.

[0561] In some embodiments, the antibody inhibits or neutralizes the function of an active form of Cis protein. As used herein, the term “neutralize” means that the activity or function of the protein is inhibited. The inhibition can be complete or partial. In some embodiments, the activity or function of the protein is inhibited at least 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or 99%. The percent inhibition can be based upon the function or activity of the protein in the absence of the antibody. In some embodiments, the antibody inhibits the function facilitated by Cis.

[0562] Throughout the present disclosure, all expressions of percentage, ratio, and the like are "by weight" unless otherwise indicated. As used herein, "by weight" is synonymous with the term "by mass," and indicates that a ratio or percentage defined herein is done according to weight rather than volume, thickness, or some other measure. ENUMERATED EMBODIMENTS

[0563] In some embodiments, the following embodiments are provided. 1. A pharmaceutical composition comprising: about 25 mg / mL to about 300 mg / mL of an antibody having a heavy chain and a light chain, wherein the heavy chain comprises a HCDR1 of SEQ ID NO: 61, a HCDR2 of SEQ ID NO: 62, and a HCDR3 of SEQ ID NO: 78, and wherein the light chain comprises a LCDR1 of SEQ ID NO: 64, a LCDR2 of SEQ ID NO: 65, and a LCDR3 of SEQ ID NO: 79; one or more of a buffer, an antioxidant, a sugar, a viscosity modifying agent, or a surfactant; and wherein the pharmaceutical composition is at a pH of about 6.5 to about 8.0. 2. The pharmaceutical composition of embodiment 1, wherein the pharmaceutical composition comprises: a buffer at about 5 mM to about 50 mM, an antioxidant at about 5 mM to about 15 mM, a sugar at about 1% w / v to about 14% w / v, a viscosity modifying agent at about 20 mM to about 180 mM, and a surfactant at about 0.001 % w / v to about 0.4 % w / v. 3. The pharmaceutical composition of embodiment 1, wherein the pharmaceutical composition comprises: a buffer at about 15 mM to about 25 mM, an antioxidant at about 5 mM to about 15 mM, a sugar at about 1% w / v to about 10% w / v, a viscosity modifying agent at about 60 mM to about 150 mM, and a surfactant at about 0.001 % w / v to about 0.2 % w / v. 4. The pharmaceutical composition of embodiment 1, wherein the buffer is at a concentration of about 5 mM to about 15 mM, about 15 mM to about 20 mM, about 20 mM to about 25 mM, about 25 mM to about 30 mM, about 30 mM to about 35 mM, about 35 mM to about 40 mM, about 40 mM to about 45 mM, about 45 mM to about 50 mM, about 5 mM, about 10 mM, about 15 mM, about 20 mM, about 25 mM, about 30 mM, about 35 mM, about 40 mM, about 45 mM, or about 50 mM. 5. The pharmaceutical composition of embodiment 1, wherein the buffer is selected from tris buffer, histidine buffer, HEPES, phosphate buffer, acetate buffer, citrate buffer, succinate buffer, ascorbate buffer, glutamate buffer, lactate buffer, maleate buffer, trometamol buffer, gluconate buffer, or any combination thereof. 6. The pharmaceutical composition of any one of embodiments 1-5, wherein the buffer is a phosphate buffer. 7. The pharmaceutical composition of embodiment 6, wherein the phosphate buffer is present at about 5 mM to about 15 mM, about 25 mM to about 50 mM, or about 20 mM. 8. The pharmaceutical composition of embodiment 1, wherein the pharmaceutical composition has a pEI of about 6.5, about 6.6, about 6.7, about 6.8, about 6.9, about 7.0, about 7.1, about 7.2, about 7.3, about 7.4, about 7.5, about 7.6, about 7.7, about 7.8, about 7.9, or about 8.0. 9. The pharmaceutical composition of embodiment 1-8, wherein the pharmaceutical composition has a pH of about 6.5 to about 7.7. 10. The pharmaceutical composition of any one of embodiments 1-9, wherein the pharmaceutical composition has a pH of about 7.2. 11. The pharmaceutical composition of any one of embodiments 1-10, wherein the buffer is a phosphate buffer and the pharmaceutical composition has a pH of about 7.2. 12. The pharmaceutical composition of embodiment 1, wherein the antioxidant is present at about 10 mM to about 15 mM, or about 5 mM to about 10 mM. 13. The pharmaceutical composition of embodiment 1, wherein the antioxidant is present at a concentration of about 10 mM. 14. The pharmaceutical composition of embodiment 12 or 13, wherein the antioxidant is selected from L- methionine, ascorbic acid, EDTA, or any combination thereof. 15. The pharmaceutical composition of embodiment 14, wherein the antioxidant is L-methionine. 16. The pharmaceutical composition of embodiment 15, wherein the L-methionine is present at about 5 mM to about 15 mM, about 10 mM to about 15 mM, or about 5 mM to about 10 mM. 17. The pharmaceutical composition of embodiment 15 or 16, wherein the L-methionine is present at about 10 mM. 18. The pharmaceutical composition of embodiment 1, wherein the sugar is present at a concentration of about 1% w / v to about 14% w / v, about 2% w / v to about 14% w / v, about 2% w / v to about 12% w / v, 2% w / v to about 10% w / v, about 2% w / v to about 8% w / v, about 2% w / v to about 6% w / v, about 2% w / v to about 4% w / v, about 4% w / v to about 14% w / v, about 4% w / v to about 12% w / v, about 4% w / v to about 10% w / v, about 4% w / v to about 8% w / v, about 4% w / v to about 6% w / v, about 6% w / v to about 14% w / v, about 6% w / v to about 12% w / v, about 6% w / v to about 10% w / v, about 6% w / v to about 8% w / v, about 8% w / v to about 14% w / v, about 8% w / v to about 12% w / v, about 8% w / v to about 10% w / v, about 10% w / v to about 14% w / v, about 10% w / v to about 12% w / v, or about 12% w / v to about 14% w / v. 19. The pharmaceutical composition of embodiment 1, wherein the sugar is sucrose, trehalose, sorbitol, mannitol, or any combination thereof. 20. The pharmaceutical composition of embodiment 19, wherein the sugar is sucrose. 21. The pharmaceutical composition of embodiment 20, wherein the sucrose is present at a concentration of about 1% to about 14% w / v. 22. The pharmaceutical composition of embodiment 21, wherein the sucrose is present at a concentration of about 2% w / v to about 10% w / v. 23. The pharmaceutical composition of any one of embodiments 20-22, wherein the sucrose is present at a concentration of about 4% w / v. 24. The pharmaceutical composition of any one of embodiments 20-23, wherein the sucrose is present at a concentration of about 3.5% w / v. 25. The pharmaceutical composition of embodiment 1, wherein the viscosity modifying agent is present at a concentration of about 20 mM to about 180 mM, about 20 mM to about 170 mM, about 20 mM to about 160 mM, about 20 mM to about 150 mM, about 20 mM to about 140 mM, about 20 mM to about 130 mM, about 20 mM to about 120 mM, about 20 mM to about 110 mM, about 20 mM to about 100 mM, about 20 mM to about 90 mM, about 20 mM to about 80 mM, about 20 mM to about 70 mM, about 20 mM to about 60 mM, about 20 mM to about 50 mM, about 20 mM to about 40 mM, about 40 mM to about 180 mM, about 40 mM to about 170 mM, about 40 mM to about 160 mM, about 40 mM to about 150 mM, about 40 mM to about 140 mM, about 40 mM to about 130 mM, about 40 mM to about 120 mM, about 40 mM to about 110 mM, about 40 mM to about 100 mM, about 40 mM to about 90 mM, about 40 mM to about 80 mM, about 40 mM to about 70 mM, about 40 mM to about 60 mM, about 40 mM to about 50 mM, about 60 mM to about 180 mM, about 60 mM to about 170 mM, about 60 mM to about 160 mM, about 60 mM to about 150 mM, about 60 mM to about 140 mM, about 60 mM to about 130 mM, about 60 mM to about 120 mM, about 60 mM to about 110 mM, about 60 mM to about 100 mM, about 60 mM to about 90 mM, about 60 mM to about 80 mM, about 60 mM to about 70 mM, about 70 mM to about 180 mM, about 70 mM to about 170 mM, about 70 mM to about 160 mM, about 70 mM to about 150 mM, about 70 mM to about 140 mM, about 70 mM to about 130 mM, about 70 mM to about 120 mM, about 70 mM to about 110 mM, about 70 mM to about 100 mM, about 70 mM to about 90 mM, about 70 mM to about 80 mM, about 80 mM to about 180 mM, about 80 mM to about 170 mM, about 80 mM to about 160 mM, about 80 mM to about 150 mM, about 80 mM to about 140 mM, about 80 mM to about 130 mM, about 80 mM to about 120 mM, about 80 mM to about 110 mM, about 80 mM to about 100 mM, about 80 mM to about 90 mM, about 90 mM to about 180 mM, about 90 mM to about 170 mM, about 90 mM to about 160 mM, about 90 mM to about 150 mM, about 90 mM to about 140 mM, about 90 mM to about 130 mM, about 90 mM to about 120 mM, about 90 mM to about 110 mM, about 90 mM to about 100 mM, about 100 mM to about 180 mM, about 100 mM to about 170 mM, about 100 mM to about 160 mM, about 100 mM to about 150 mM, about 100 mM to about 140 mM, about 100 mM to about 130 mM, about 100 mM to about 120 mM, about 100 mM to about 110 mM, about 110 mM to about 180 mM, about 110 mM to about 150 mM, about 110 mM to about 120 mM, about 120 mM to about 160 mM, about 120 mM to about 130 mM, about 130 mM to about 160 mM, about 130 mM to about 180 mM, about 140 mM to about 150 mM, about 150 mM to about 170 mM, about 110 mM to about 140 mM, about 110 mM to about 180 mM, about 120 mM to about 150 mM, about 120 mM to about 180 mM, about 130 mM to about 150 mM, about 130 mM to about 170 mM, about 140 mM to about 180 mM, about 150 mM to about 160 mM, about 110 mM to about 130 mM, about 110 mM to about 170 mM, about 120 mM to about 140 mM, about 120 mM to about 170 mM, about 130 mM to about 140 mM, about 140 mM to about 160 mM, about 140 mM to about 170 mM, about 150 mM to about 160 mM, about 160 mM to about 180 mM, about 160 mM to about 170 mM, or about 170 mM to about 180 mM. 26. The pharmaceutical composition of embodiment 25, wherein the viscosity modifying agent is present at a concentration of about 70 mM. 27. The pharmaceutical composition of embodiment 25 or 26, wherein the viscosity modifying agent is L-arginine hydrochloride (L-Arg-HCL) or sodium chloride (NaCl). 28. The pharmaceutical composition of embodiment 25-27, wherein the viscosity modifying agent is L-Arg-HCL. 29. The pharmaceutical composition of embodiment 1, wherein the surfactant is present at a concentration of about 0.001% w / v to about 0.1% w / v, about 0.001% w / v to about 0.2% w / v, about 0.01% w / v to about 0.2% w / v, about 0.1% w / v to about 0.2% w / v, about 0.2% w / v to about 0.4% w / v, about 0.05% w / v to about 0.15% w / v, or about 0.001% w / v to about 0.01% w / v. 30. The pharmaceutical composition of embodiment 1, wherein the surfactant is Polysorbate 80, Polysorbate 20, polyethylene glycol 3350 (PEG3350), or Poloxamer (P)188. 31. The pharmaceutical composition of embodiment 30, wherein the surfactant is Pl 88. 32. The pharmaceutical composition of any one of embodiments 30 or 31, wherein the P188 is present at a concentration of about 0.1% w / v. 33. The pharmaceutical composition of embodiment 1, wherein the antibody is present at a concentration of about 25 mg / mL to about 300 mg / mL, about 25 mg / mL to about 275 mg / mL, about 25 mg / mL to about 250 mg / mL, about 25 mg / mL to about 225 mg / mL, about 25 mg / mL to about 200 mg / mL, about 25 mg / mL to about 175 mg / mL, about 25 mg / mL to about 150 mg / mL, about 25 mg / mL to about 125 mg / mL, about 25 mg / mL to about 100 mg / mL, about 25 mg / mL to about 75 mg / mL, about 50 mg / mL to about 300 mg / mL, about 50 mg / mL to about 275 mg / mL, about 50 mg / mL to about 250 mg / mL, about 50 mg / mL to about 225 mg / mL, about 50 mg / mL to about 200 mg / mL, about 50 mg / mL to about 175 mg / mL, about 50 mg / mL to about 150 mg / mL, about 50 mg / mL to about 125 mg / mL, about 50 mg / mL to about 100 mg / mL, about 50 mg / mL to about 75 mg / mL, about 75 mg / mL to about 300 mg / mL, about 75 mg / mL to about 275 mg / mL, about 75 mg / mL to about 250 mg / mL, about 75 mg / mL to about 225 mg / mL, about 75 mg / mL to about 200 mg / mL, about 75 mg / mL to about 175 mg / mL, about 75 mg / mL to about 150 mg / mL, about 75 mg / mL to about 125 mg / mL, about 75 mg / mL to about 100 mg / mL, about 100 mg / mL to about 300 mg / mL, about 100 mg / mL to about 275 mg / mL, about 100 mg / mL to about 250 mg / mL, about 100 mg / mL to about 225 mg / mL, about 100 mg / mL to about 200 mg / mL, about 100 mg / mL to about 175 mg / mL, about 100 mg / mL to about 150 mg / mL, about 100 mg / mL to about 125 mg / mL, about 125 mg / mL to about 300 mg / mL, about 125 mg / mL to about 275 mg / mL, about 125 mg / mL to about 250 mg / mL, about 125 mg / mL to about 225 mg / mL, about 125 mg / mL to about 200 mg / mL, about 125 mg / mL to about 175 mg / mL, about 125 mg / mL to about 150 mg / mL, about 150 mg / mL to about 300 mg / mL, about 150 mg / mL to about 275 mg / mL, about 150 mg / mL to about 250 mg / mL, about 150 mg / mL to about 225 mg / mL, about 150 mg / mL to about 200 mg / mL, about 150 mg / mL to about 175 mg / mL, about 175 mg / mL to about 300 mg / mL, about 175 mg / mL to about 275 mg / mL, about 175 mg / mL to about 250 mg / mL, about 175 mg / mL to about 225 mg / mL, about 175 mg / mL to about 200 mg / mL, about 200 mg / mL to about 300 mg / mL, about 200 mg / mL to about 275 mg / mL, about 200 mg / mL to about 250 mg / mL, about 200 mg / mL to about 225 mg / mL, about 225 mg / mL to about 300 mg / mL, about 225 mg / mL to about 275 mg / mL, about 225 mg / mL to about 250 mg / mL, about 250 mg / mL to about 300 mg / mL, about 250 mg / mL to about 275 mg / mL, about 275 mg / mL to about 300 mg / mL, about 100 mg / mL to about 200 mg / mL, or about 200 mg / mL to about 300 mg / mL, about 300 mg / mL to about 400 mg / mL, about 400 mg / mL to about 500 mg / mL, about 500 mg / mL to about 600 mg / mL, about 100 mg / mL to about 300 mg / mL, about 200 mg / mL to about 400 mg / mL, about 300 mg / mL to about 500 mg / mL, about 400 mg / mL to about 600 mg / mL, about 100 mg / mL to about 400 mg / mL, about 200 mg / mL to about 500 mg / mL, or about 300 mg / mL to about 600 mg / mL. 34. The pharmaceutical composition of embodiment 33, wherein the antibody is a monoclonal antibody. 35. The pharmaceutical composition of embodiment 34, wherein the monoclonal antibody is an immunoglobulin G4 (IgG4) type monoclonal antibody. 36. The pharmaceutical composition of embodiment 1, wherein the antibody comprises a heavy chain variable region with an amino acid sequence of SEQ ID NO: 17 and a light chain variable region with an amino acid sequence of SEQ ID NO: 18. 37. The pharmaceutical composition of embodiment 1, wherein the antibody comprises a heavy chain variable region with an amino acid sequence of SEQ ID NO: 342 and a light chain variable region with an amino acid sequence of SEQ ID NO: 18. 38. The antibody of embodiment 1-37, or an antigen binding fragment thereof, wherein the antibody or antibody fragment comprises a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO: 61; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO: 62; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO: 78, or variants or convention equivalents of any of the foregoing; and (ii) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence SEQ ID NO: 64; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO: 65; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO: 79; or variants or convention equivalents of any of the foregoing. 39. The pharmaceutical composition of any one of preceding embodiments , wherein the antibody is present at a concentration of about 100 mg / mL. 40. The pharmaceutical composition of any one of preceding embodiments, wherein the antibody is present at a concentration of about 150 mg / mL. 41. The pharmaceutical composition of embodiment 1-40, wherein the pharmaceutical composition is stable at about-25 °C, about -20 °C, about -15 °C, about -5 °C, about 0 °C, about 5 °C, or about 10 °C. 42. The pharmaceutical composition of embodiment 39, wherein the pharmaceutical composition is stable for 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 20 months, 21 months, 22 months, 23 months, 24 months, 25 months, 26 months, 27 months, 28 months, 29 months, 30 months, 31 months, 32 months, 33 months, 34 months, 35 months, or 36 months. 43. The pharmaceutical composition of embodiment 1-42, wherein the pharmaceutical composition is stable at -20 °C for at least 3 months. 44. The pharmaceutical composition of embodiment 1-43, wherein the pharmaceutical composition is stable at -20 °C for at least 6 months. 45. The pharmaceutical composition of embodiment 1-44, wherein the pharmaceutical composition is stable at 2-8 °C for at least 3 months. 46. The pharmaceutical composition of embodiment 1-45, wherein the pharmaceutical composition is stable at 2-8 °C for at least 6 months. 47. The pharmaceutical composition of embodiment 1-46, wherein the pharmaceutical composition is stable at 2-8 °C for at least 9 months. 48. The pharmaceutical composition of embodiment 1-47, wherein the pharmaceutical composition is stored in pre-filled syringes or 2 mL aliquots in 6 mL vials. 49. The pharmaceutical composition of embodiment 1-48, wherein the pharmaceutical composition is stored in 2 mL aliquots in 6 mL vials with a 20 mm stopper. 50. The pharmaceutical composition of embodiment 1-49, wherein the pharmaceutical composition is stored in 2 mL aliquots at-20 °C in 6 mL vials with a 20 mm stopper and a 20 mm aluminum plastic cover. 51. The pharmaceutical composition of embodiment 1-50, wherein the pharmaceutical composition is for intravenous or subcutaneous injection. 52. A method of treating a subject with Cis mediated disorder, the method comprising administering to the subject the pharmaceutical composition of any one of embodiments 1-51. 53. The method of embodiment 52, wherein the Cis mediated disorder is hemolysis, Cold Agglutinin Disease, Immune Thrombocytopenia (TTP), Myasthenia Gravis, Glomerulopathies, Atypical Hemolytic uremic syndrome, antiphospholipid antibody syndrome, transplant rejection, chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN), dermatomyositis, anti MAG neuropathy, due to stroke, or due to spinal cord injury. 54. The pharmaceutical composition of embodiment 1, wherein: the antibody is at about 100 mg / mL , the buffer is phosphate buffer at about 20 mM, the antioxidant is L-methionine at about 10 mM, the sugar is sucrose at about 4% w / v, the viscosity modifying agent is L-arginine hydrochloride at about 70 mM, and the surfactant is Pl88 at about 0.1 % w / v; wherein the pharmaceutical composition is at a pH of about 7.2. 55. The pharmaceutical composition of embodiment 1, wherein: the antibody is at about 150 mg / mL, the buffer is phosphate buffer at about 20 mM, the antioxidant is L-methionine at about 10 mM, the sugar is sucrose at about 3.5% w / v, the viscosity modifying agent is L-arginine hydrochloride at about 70 mM, and the surfactant is Pl88 at about 0.1 % w / v; wherein the pharmaceutical composition is at a pH of about 7.2. EXAMPLES

[0564] The subject matter is now described with reference to the following examples. These examples are provided for the purpose of illustration only and the claims should in no way be construed as being limited to these examples, but rather should be construed to encompass any and all variations which become evident as a result of the teaching provided herein. Those of skill in the art will readily recognize a variety of non-critical parameters that could be changed or modified to yield essentially similar results.

[0565] Example 1: High concentration formulation development. The formulation development utilizing 150 mg / mL protein was divided into two parts: 1) excipient and surfactant strength screening study to evaluate and select appropriate excipients and surfactants according to their stabilizing effect on the protein under stress conditions and 2) selected formulation evaluation and confirmation study, undertaken through a 6 month period under various conditions where a plethora of biophysical and analytical methods were employed to determine the potential chemical and physical changes that might occur to the formulated protein.

[0566] The analytical methods performed throughout both studies include examination of appearance, pH, protein concentration, osmolality, viscosity, SEC-HPLC, SEC-UPLC, Micro Flow Imaging, Sub-Visible Particles (HIAC), iCIEF, capillary-SDS-NR & R, CD-SDS-NR & R, ELISA, binding ELISA, DSC, peptide mapping, CDC potency assay, and mDSC and are described below.

[0567] The appearance of samples, including color, clarity and visible particles, was examined against black and white background using a YB-2 lightbox. The light intensity of lightbox was set as 2000-3750 lux.

[0568] The pH value was measured using a pH meter with a glass electrode. The pH meter was calibrated with three different standard solutions (pH 4.01, 7.00 and 9.21) prior to usage. The calibration pass criteria were the slope of calibration landed between 95.0%-105.0%. Each sample was measured twice, an average result was reported.

[0569] Protein concentration was determined by a Big Lunatic UV Spectrophotometer. According to the Lambert-Beer law, the concentration of a protein solution can be calculated based on its absorbance at a given wavelength, the cuvette cell path length, and extinction coefficient value. The absorbance in 280 nm relies on the absorption properties of the aromatic amino acid residues in protein. The EC used in all evaluation studies was 1.53 AU*mL*mg'1*cm'1. All samples were performed without any dilution. After loading a 2.0 pL sample volume, Lunatic measured the absorbance in two cuvettes in parallel and calculated the concentration value. All sample measurements were conducted after a blank control using water.

[0570] Osmolality was measured using an Advanced 2020 Multi-Sample Osmometer. Before and after the sample tests, the accuracy of osmometer was confirmed with a Clinitrol 290 mOsm / kg reference solution. The sample volume for each testing was 20 pL and only one test was performed for each sample.

[0571] Viscosity was measured by a DHR-2 Rotational Rheometer. The testing temperature was controlled at 21 °C. The accuracy of the Rheometer was confirmed with a certified viscosity reference N35. The testing shear rate was raised from 10 to 1500 s'1 and data acquisition frequency was set as 10 points per decade. Prior to recording a point, the sample was allowed to equilibrate for 30.0 s. 650 pL sample was loaded for each testing.

[0572] Size exclusion-high-performance liquid chromatography (SEC-HPLC) was used in pH buffer screening, excipients, and surfactant screening. SEC-HPLC is a purity analysis method that separates proteins based on their sizes. Measurements were performed on an Agilent HPLC system with an SEC column (300x7.8 mm, 5 pm). The sampler temperature was set to 5 ± 3 °C, and the column oven temperature was set to 25 ± 3 °C. The mobile phase was 50 mM PB, 300 mM sodium chloride (NaCl), pH 6.8 ± 0.1, and the flow rate was set as 1.0 mL / min. Samples were diluted to 10 mg / mL with mobile phase, and 100 pg samples were injected. UV detection wavelength was set at 280 nm and the run time was 20 minutes (min). Data were analyzed by Agilent CDS Software.

[0573] Size exclusion-ultra-performance liquid chromatography (SEC-UPLC) was used in the formulation confirmation study. In this study, 10 pg protein samples were injected into a Waters H-Class, separated on a Waters ACQUITY UPLC Protein BEH SEC Column (200 A, 1.7 pm, 4.6 mm x 150 mm). UV absorbance at 280 nm wavelength was monitored and logged to generate chromatograms. 50 mM PB, 300 mM NaCl, pH 6.8 + 0.1 was used as the mobile phase and an isocratic gradient was applied for 8 min at a flow rate of 0.4 mL / min. All the results were rounded to one decimal place.

[0574] Sub-visible particles were monitored by an MFI system (MFI 5200). 1.3 mL of each sample was transferred into an MFI 96-well plate in a bio-safety hood for analysis. The results were analyzed by the vendor’s MVAS 1.3 software. The sub-visible particle amount in the equivalent circular diameter between 2~5 pm, 5—10 pm, 10-25 pm and over 25 pm was reported.

[0575] A Liquid Particle Counting Systems (HIAC 9703+) was utilized to measure the size and counts of sub-visible particles under a laminar flow cabinet. To avoid introducing air bubbles and interference during examination, all samples were held in the cabinet before testing for approximately 15-20 minutes. Each sample was tested for four consecutive runs and 1 mL for each run. The first run was discarded and results were presented as average number of particles >2 pm, >5 pm, >10 pm, and >25 pm per mL from the last 3 runs.

[0576] Imaged capillary isoelectric focusing (iCIEF) is a purity method used to monitor the charge variant species by determining the isoelectric point (pl) and distribution of each variant. Charge variants of the protein are separated based on their unique pl. pl is an intrinsic property of each charge variant of the protein and is equal to the pH at which the protein molecule does not carry any net charge. Under an external electric field, the charge variants move along a continuous pH gradient formed by the ampholytes and stop at the position where the pH equals to its pl. In this study, protein samples were diluted to 1.0 mg / mL with ultrapure water. Then, a 20 pL diluted sample was mixed with 80 pL master mixture (composed of pl markers 7.65 / 10.10, carrier ampholytes (3-10 and 8-10.5), methyl cellulose, arginine, and urea), before being loaded into a capillary for electric focusing by ICE3. Data were processed with the Empower 3. The percentage of the main peak, acidic peaks and basic peaks was reported in the final results, along with the pl of the main peak. All the results were rounded to one decimal place.

[0577] Capillary-Sodium Dodecyl Sulfate (capillary-SDS) is a purity method utilized to determine the truncation or fragmentation level of the biomolecules during the production and storage processes. Capillary-SDS employs a microchip to separate proteins based on their electrophoretic mobility, with proteins of smaller size migrating further than proteins of larger size in a capillary. In this study, the samples were diluted to 1.0 mg / mL with ultrapure water, and then mixed with the denaturing solution (composed of sample buffer, SDS and N-ethylmaleimide (NEM, for the NR method) or dithiothreitol (DTT, for the R method)). The mixtures were incubated at 70 °C for 10 min, and then transferred into a 96-well plate. After the plate was loaded onto the plate holder of the instrument, samples were injected, stained, separated and detected in the microchip. Data were acquired with LabChip GX Reviewer and analyzed with the Empower 3. The percentage of the main peak was reported as the purity of the sample in the non-reduced capillary-SDS. While for the reduced method, the percentage of light chain (LC), heavy chain (HC), and the sum of LC + HC (purity) was reported. All results were rounded to one decimal place.

[0578] Capillary Electrophoresis Sodium Dodecyl Sulfate (CE-SDS) is a popular technology employed to determine the truncation or fragmentation level of the biomolecules during the production and storage processes. CE-SDS separates proteins based on their electrophoretic mobility, with proteins of smaller sizes move faster and of larger sizes move slower in a capillary. In this study, both NR and R methods were applied. In the non-reduced CE-SDS analysis, samples were diluted to 4.0 mg / mL with the diluent (PB-CA buffer). 25 pL of the diluted sample was transferred to a 1.5 mL centrifuge tube, followed by the addition of 5 pL alkylation reagent (100 mM NEM). 75 pL of 1.0% (w / v) SDS sample buffer was then added into the vial to make a final volume of 105 pL. The samples were incubated at 60 °C for 10 minutes, followed by the analysis with PA800 Plus. In contrast, reduced CE-SDS shares the same principle but differs in the sample preparation. Samples were diluted to 4.0 mg / mL with the diluent (PB-CA buffer). 25 pL of the diluted sample was transferred to a 1.5 mL centrifuge tube, followed by the addition of 75 pL 1.0% (w / v) SDS sample buffer. Then, 5 pL of P-mercaptoethanol (BME) was added to make a total volume of 105 pL. The samples were incubated at 70 °C for 10 minutes, followed by the analysis with PA800 Plus. The percentage of the total protein in the main peak was reported as the purity of the sample in the non-reduced CE-SDS. In addition, total proportion of pre-peaks and HMWS were also reported. The SOP method (PD-AS-LAB-173) is followed. While for the reduced method, the percentage of LC, HC, and the sum of LC + HC (purity) was reported. Meanwhile, the total percentage of minor species was reported as well. All the results were rounded to one decimal place.

[0579] Enzyme-linked immunosorbent assay (ELISA) is a binding activity assay where the antibody molecule binds to the antigen, Cis, which had been immobilized on the plate and blocked by 2% non-fat milk. Serially diluted antibody was bound to the plate through Cis upon addition and incubation. After washing the plate, Goat anti-Human IgG (Fc specific)-Peroxidase, was added to the wells allowing interaction with antibody captured during previous step. After a final wash step, the 3,3”,5,5”-Tetramethylbenzidine (TMB) substrate solution was added to wells. TMB reacted with the peroxide for 3~25 min followed by loading 1 M sulfuric acid. The coated plate was placed in the plate reader, and absorbance read at 450 nm. The dose response curves were fitted using a 4-parameter logistic model and the results reported as Relative Potency using the EC50 values of the Reference Standard (RS) vs. the Sample.

[0580] Differential scanning calorimetry (DSC) is a thermo-analytical technique used to characterize the thermal stability of protein samples and assess conformational differences between them. Measurements were performed on MicroCalTM VP-Capillary DSC (Malvern) for thermal transition midpoint (Tm) and onset of unfolding (TmOnset) testing. Samples were diluted to 1 mg / mL with the reference buffer. 400 pL of respective reference buffers were added into the odd-numbered wells of a 96-well plate and 400 pL of samples were added into the even-numbered wells of the same plate. Experimental parameters were set such that the scan temperature ramped from 10 to 95 °C at a scan rate of 200 °C / h. Data analysis was performed in MicroCalTM VP-Capillary DSC ( software: MicroCai VP-Capillary DSC Software 2.0) automated data analysis software.

[0581] Tg' is the glass transition temperature (glass transition temperature is the temperature below which the phase change happens for amorphous (not crystalline) solids) of the maximally frozen concentrated solute, and is a critical parameter in determining the state of frozen DS. Below the Tg’, the formulated protein would be in glass state where potential physical or chemical change would be substantially limited. The Tg1 of the formulations were measured by a TA Q2000 DSC. 20 pL of the samples were sealed in aluminum pans and transferred into the equipment. A sealed empty pan was used as the reference. The samples were cooled to -60 °C by a cooling rate of 10 °C / minute, and kept at this temperature for 5 minutes, then were heated to 20 °C with heating rate of 10°C / minute. The results were recorded and analyzed by Universal Analysis Software.

[0582] Part 1: Excipient and Surfactant Strength Screening Study. The objective of this study was to screen the optimal excipient and surfactant that help to stabilize the selected concentration of protein the most. Briefly, For 150 mg / mL antibody, various concentrations of sucrose (2%, 3.5%, 5%), L-Arg-HCl (40 mM, 70 mM, 100 mM and 140 mM) and P188 (0.05%, 0.1%, 0.2%, w / v) were evaluated under stress conditions (40 °C for up to 3 M, agitation at 300 rpm for 3 days (D), and freeze / thaw (FT) for up to 5 cycles (CYS). Appearance, pH, protein cone., osmolality, SEC-HPLC, capillary-SDS-NR & R, iCIEF, MFI, DSC and potency testing were performed to test the quality of DS in this study. Table 2 below summarizes the results described in further detail below.

[0583] Table 2. Formulation candidates list of excipients and surfactant strength screening study. All % in the table means % (w / v). Formulation Number Buffer System, pH, Protein Concentration Excipients / Surfactant Fl-1 20 mM Phosphate Buffer, 10 mM L-Met, pH 7.2, 150 mg / mL Protein 5% sucrose, 40 mM L-Arg-HCl, 0.1% Pl88 Fl-2 3.5% sucrose, 40 mM L-Arg-HCl, 0.1% Pl88 Fl-3 2% sucrose, 100 mM L-Arg-HCl, 0.1% P188 Fl-4 140 mM L-Arg-HCl, 0.1% Pl88 Fl-5 3.5% sucrose, 70 mM L-Arg-HCl, 0.05% Pl88 Fl-6 3.5% sucrose, 70 mM L-Arg-HCl, 0.2% Pl88

[0584] Excipients and surfactant strength screening study was conducted with 150 mg / mL protein. In this study, all samples remained unchanged in appearance, protein cone, and pH. And the viscosity was in the range of 3.9-5.3 cP. Fl-4 (140 mM L-Arginine-HCl, 0.1% (w / v) P188) which only formulated with L-Arginine-HCl had lower viscosity (3.9 cP) than other formulations. The excipient L-Methionine is added to this formula to counteract oxidation that may occur in the sample. The SEC-HPLC results demonstrated that the monomer of all tested formulations declined in the range of 5.4%-6.6% after storage at 40 °C for 4 weeks. Among 6 candidates, Fl-3 and Fl-4 displayed slightly lower monomer than other formulations. The iCIEF data displayed that all samples remained stable under FT and agitation stress, but the main peak decreased by up to 39.8% when stored at 40 °C for 4 weeks. There was no obvious difference among all candidate formulations. Caliper-SDS-NR & R results showed that the purity for all formulations slightly decreased in the NR & R testing when stored at 40 °C for 4 weeks. For DSC, Fl-5 showed a slightly higher TmOnset of 52.0 °C than other formulation candidates. Since Fl-2 and Fl-5 showed less sub-visible particles after 8-week incubation at 25 °C, and then were chosen for longer stability evaluation at 5°C and 25°C for 3 months. After 3 months storage at 5°C, both samples were stable in the quality attributes of pH, concentration, purities of SEC-HPLC, iCIEF, caliper-SDS-NR & R. For samples stored at 25°C for 3 months, the pH, concentration, purity of Caliper-SDS-R and ELISA binding affinity remained stable. And the purities of iCIEF, SEC-HPLC and Caliper-SDS-NR reduced by similar levels in both formulations. The difference between the two formulations is the appearance results. Fl-2 showed visible particles in 5°C and 25°C. In summary, Fl-2 and Fl-5 showed comparable stability during excipients and surfactant screening study. But the P188 content of Fl-5 (0.05%) is lower and might be further decreased due to degradation in long-term storage. Thus the protection effect of Pl88 for the protein was limited. Together, Fl-2 (20 mM Phosphate Buffer, 10 mM L-Methionine, 70 mM L-Arginine-HC1, 3.5% (w / v) sucrose, 0.1 % (w / v) P188, at pH 7.2) was chosen as the formulation system for 150 mg / mL protein and evaluated in the following study.

[0585] Part 2: Formulation Evaluation and Confirmation Study. The objective of this study was to confirm the final selected formulation in the selected container closure system using the drug substance materials. Briefly, the selected formulation was confirmed through a 6 month stability study (-20 °C, 2-8 °C, 25 °C, and 40 °C incubation), agitation at 100 rpm for up to 3 days (D), and freeze / thaw for up to 5 cycles (CYS). Appearance, pH, protein cone., osmolality, Tg', viscosity, SEC-UPLC, CE-SDS-NR & R, iCIEF, HIAC and potency (ELISA) testing were conducted in this study.

[0586] Table 3. Sampling and testing plan of formulation confirmation study (X= Appearance, pH, Protein concentration, SEC-UPLC, CE-SDS-NR & R, iCIEF; Y= Sub-visible particles (HIAC); Z= potency (ELISA); W= Tg’ (mDSC), osmolality, viscosity; ()= Samples reserved, testing optional). Condition TO Sampling Points and Assay 2W 4W 12W 6M -20°C X, Y, Z, W / X, Y, (Z) X, Y, (Z) X, Y, Z 5°C / X, Y, (Z) X, Y, (Z) X, Y, Z 25°C / X, Y, (Z) X, Y, Z / 40°C X,(Z) X, Y, Z / / Agitation-100 rpm, 25°C ID 3 D X X, Y, Z Freeze / Thaw - 20°C / RT 3 CYS 5 CYS X X, Y, Z

[0587] The selected formulation for the protein with the determined fdling volume (2 mL) and container closure system (6 R vials and 20 mm nested stopper) was utilized in this formulation confirmation study. All samples remained colorless, slightly opalescent, and free of visible particles in the selected formulation (150 mg / mL protein (target), 20 mM Phosphate Buffer, 10 mM L-Methionine, 3.5% (w / v) sucrose, 70 mM L-Arginine-HCl, 0.1% (w / v) Pl 88, at pH 7.2) for the protein under all testing conditions in this study with the exception of purity measured by CE-SDS-NR & R, and the measured main peak from the SEC-HPLC and iCIEF analysis that declined following incubation at 40 °C for 4 weeks. Furthermore, the testing results also indicated no obvious effect on the stability of the protein under agitation and FT conditions. Overall, the ongoing confirmation study supported the selection of 20 mM phosphate buffer, 10 mM L-Methionine, 3.5% (w / v) sucrose, 70 mM L-Arginine-HCl, 0.1% (w / v) P188, at pH 7.2 as the final formulation for 150 mg / mL antibody protein in the final container closure system.

[0588] In conclusion, the excipients and surfactant screening study for 150 mg / mL protein, 6 designed formulations were evaluated in terms of their ability to maintain the protein stability under treatments of thermal stress condition at 25 °C and 40 °C, freeze / thaw cycles, and agitation. Finally, 20 mM Phosphate Buffer, 10 mM L-Methionine, 3.5% (w / v) sucrose, 70 mM L-Arginine-HCl, 0.1% (w / v) P188, at pH 7.2, was recommended as the final formulation for 150 mg / mL protein. And the potency remained stable under thermal stress in this selected formulation. In the confirmation study, no obvious differences in appearance, protein cone., pH and sub-visible particles were observed under -20 °C, 2-8 °C, 25 °C, agitation and freeze / thaw stress conditions compared to TO. While the purity data from SEC-UPLC, iCIEF and CE-SDS-NR & R declined following incubation at 40 °C for 4 weeks.

[0589] Example 2: Low concentration formulation development. The design of the formulation development study consisted of four parts: 1) pH / buffer screening study under stress conditions to select the optimal pH / buffer system which provided the most stabilization for the protein, 2) excipient and surfactant strength screening study for 50 mg / mL protein was performed to evaluate and select appropriate excipients and surfactants according to their stabilizing effect on the protein under stress conditions, 3) excipient and surfactant strength screening study for 100 mg / mL protein was conducted to evaluate its stability under stress conditions and to select an optimal formulation according to the stability results, and 4) selected formulation of the protein was evaluated and confirmed through a 3-month stability study under various conditions. Biophysical and analytical methods including appearance, pH, protein concentration, SE-UPLC, iCIEF, CE-SDS-NR&R, mDSC, sub-visible particles, and potency testing were used to determine the potential chemical and physical changes that might occur to formulated protein under these conditions. These methods were conducted as described previously in example 1 with the exception of the below parameters:

[0590] Protein concentration was determined at the absorbance at 280 nm using a Thermo UV (280 nm) (model: Nanodrop 2000) spectrophotometer. The extinction coefficient (El%) used in all evaluation studies was 1.53 AU*mL*mg-l*cm-l. All samples were performed without any dilution and measurements were repeated twice with 2.5 pL of sample for each sample and an average result was reported.

[0591] For reduced peptide mapping experiment, the protein was denatured with guanidine hydrochloride (Gdn-HCl) in Tris-HCl buffer, reduced by dithiothreitol (DTT), and followed by cysteine-alkylation with lodoacetamide (IAM). After sample clean-up, the protein was digested with endoproteinase Lys-C / trypsin sequential digestion to obtain peptides suitable for subsequent analysis. The online LC-MS analysis was performed on an Agilent / UHPLC 1290 system coupled to an Orbitrap mass spectrometer. The proteolytic peptides were separated by reversed phase liquid chromatography with an Agilent / Poroshell SB-C18 column, UV chromatograms were acquired with detector set at wavelength of 214 nm. The peptides were further detected by the mass spectrometer operating with full MS scan followed by tandem mass spectrometry (MS / MS) scans. Extracted ion chromatograms (EIC) ratio was reported to semi-quantitatively indicate the ratio of PTMs.

[0592] Part 1: pH / buffer screening study. The objective of this screening study was to select the optimal pH / buffer system to stabilize the protein most under stress conditions. Thus, eight pH / buffer systems under stress conditions (40 °C for up to 4 weeks (W)) were investigated in the pH / buffer screening study, and appearance, pH, protein cone., SEC-HPLC, iCIEF, DSC and caliper-SDS-NR & R were tested. Candidates and conditions tested are shown in table 4 below.

[0593] Table 4. Formulation candidates list of pH / buffer screening study. Formulation No. Buffer System Target pH F2-1 20 mM acetate 5.0 F2-2 5.5 F2-3 20 mM histidine 5.5 F2-4 7.0 F2-5 20 mM phosphate 7.0 F2-6 7.5 F2-7 20 mM Tris 7.0 F2-8 7.5

[0594] In summary, the pH / buffer screening study investigated 8 pH / buffer systems under stress conditions (40 °C for up to 4 weeks), and the results showed that the stability of the antibody was closely related with both pH and buffer type. From the appearance results, F2-1 (acetate, pH 5.0), F2-5 (PB, pH 7.0) and F2-6 (PB, pH 7.5) performed better than the other formulations. No obvious pH or protein concentration changes were observed in all tested buffer systems. The SEC-HPLC results indicated F2-5 (PB, pH 7.0) and F2-6 (PB, pH 7.5) supported higher purity when the protein was stored at 40 °C for 4 weeks. The iCIEF results indicated that, the main peak of F2-3 (histidine buffer, pH 5.5), F2-2 (acetate buffer, pH 5.5), and F2-1 (acetate buffer, pH 5.0) was higher than other candidates. The caliper-SDS-NR & R results showed no significant difference in purity among all formulations. Taking all results into consideration, samples in F2-2, F2-5 and F2-6 were selected to test by ELISA. The results showed that EC50 was comparable to the value at TO after incubation at 40 °C for 4 weeks, indicating the stable potency of the antibody. In summary, the antibody protein showed better appearance and higher purity tested by SEC-HPLC, indicating higher physical stability in 20 mM PB buffer. Though the iCIEF data displayed slightly lower chemical stability in PB buffer, the potency remained stable under thermal stress. Subsequently, 20 mM PB buffer was recommended for the antibody. For the sake of having buffer capacity of pH range, the buffer systems of 20 mM PB at pH 7.2 was selected for the excipients and surfactants screening study.

[0595] Part 2: Excipients / Surfactant strength screening study I (50 mg / mL). The objective of this study was to identify the optimal excipient and surfactant that would help to maximize the stability of the 50 mg / mL protein, and was tested under stress conditions. Thus, for 50 mg / mL antibody, different types of excipients (sucrose, trehalose dihydrate, sorbitol, etc.), various cone, of L-Arg-HCl (70 mM and 140 mM) and various cone, of PS80 (0.02% (w / v) and 0.04% (w / v)), PS20 (0.02%, w / v) and Pl 88 (0.1%, w / v) were evaluated under stress conditions (40 °C for up to 4 weeks (W), agitation at 300 rpm for 3 days (D), and freeze / thaw for up to 5 cycles (CYS). Appearance, pH, protein cone., osmolality, SE-HPLC, caliper-SDS-NR & R, iCIEF, MFI, DSC and potency (ELISA) testing were performed in this study. Candidates and conditions tested are shown in table 5 below.

[0596] Table 5. Formulation Candidates list of excipients and surfactant strength screening study I (all % in table means % (w / v)). Formulation No. Buffer System, pH, Protein Cone. Excipients / Surfactant F3-1 20 mM PB, 10 mM L-Methionine, pH 7.2, 50 mg / mL Protein 8% sucrose, 0.02% PS80 F3-2 8.8% trehalose 2H2O, 0.02% PS80 F3-3 4.5% sorbitol, 0.02% PS80 F3-4 70 mM L-Arg-HCl, 4% sucrose, 0.02% PS80 F3-5 70 mM NaCl, 4% sucrose, 0.02% PS80 F3-6 140 mM L-Arg-HCl, 0.02% PS80 F3-7 8% sucrose, 0.04% PS80 F3-8 8% sucrose, 0.02% PS20 F3-9 8% sucrose, 0.1% Pl88 F3-10 8% sucrose, 0.02% PS80, 0.1% P188

[0597] In summary, Excipients and surfactants strength screening study I was conducted with 50 mg / mL protein. In this study, F3-9 (8% (w / v) sucrose and 0.1% (w / v) P188) showed a better appearance and less sub-visible particles than other formulations after 4-week storage at 40 °C. Pl88 might be a better surfactant than PS20 and PS80 to inhibit particle formation. The SEC-HPLC results demonstrated that the monomer of all tested formulations declined by less than 5%. The iCIEF data displayed that all samples remained stable under FT and agitation stress, but the main peak decreased by up to 38.2% when stored at 40 °C for 4 weeks. There was no obvious difference among all candidate formulations. Caliper-SDS-NR & R results showed that the purity for all formulations slightly decreased in the NR testing and remained stable in the R testing when stored at 40 °C for 4 weeks. For DSC, F3-3 showed a slightly higher TmOnset of 56.9 °C than other formulation candidates. In summary, F3-9 (20 mM PB, 10 mM Met, 8% (w / v) sucrose, 0.1 % (w / v) Pl88, at pH 7.2), as well as F3-4 and F3-6 the formulations with L-Arg-HCl, were chosen as the formulation systems for 100 mg / mL protein formulation development and the formulation containing P188 and L-Arg-HCl with sucrose was also chosen to be evaluated in the following study. Though F3-4 and F3-6 performed poor in appearance and sub-visible particle tests under thermal stress, L-Arg-HCl may reduce the viscosity at high concentration. And whether PS80 was suitable for the antibody was further evaluated.

[0598] Part 3: Excipients / Surfactant strength screening study II (100 mg / mL). The objective of this study was to identify the optimal excipients that stabilize the antibody at a higher concentration (100 mg / mL) under stress conditions. Thus, for 100 mg / mL antibody, different cone, of sucrose (7%(w / v) and 4% (w / v)), various cone, of L-Arg-HCl (70mMand 140 mM), 0.02% PS80 and 0.1% Pl88 were evaluated under stress conditions (40 °C for up to 4 weeks, agitation at 300 rpm for 3 days (D), and freeze / thaw for up to 5 cycles (CYS). Appearance, pH, protein cone., osmolality, SEC-HPLC, caliper-SDS-NR & R, iCIEF, MFI, DSC and potency (ELISA) testing were performed in this study. Candidates and conditions tested are shown in table 6 below.

[0599] Table 6. Formulation candidates list of excipients and surfactant strength screening study (all % in the table means % (w / v); *to maintain the osmolality close to 300 mOsm / kg, the sucrose cone was reduced to 7%, compared to F3-9 with 8% sucrose). Formulation No. Buffer System, pH, Protein Cone. Excipients / Surfactant F3-11 7% sucrose*, 0.1% Pl88 F3-12 20 mM PB, 10 mM L-Methiomne, pH 7.2, 100 mg / mL protein 70 mM L-Arg-HCl, 4% sucrose, 0.02% PS80 F3-13 140 mM L-Arg-HCl, 0.02% PS80 F3-14 70 mM L-Arg-HCl, 4% sucrose, 0.1%P188

[0600] In summary, In the Excipients and Surfactant Strength Screening Study II, the pH value and protein cone, of all formulations remained stable. Appearance and MFI analysis showed that Fil (7% (w / v) sucrose, 0.1% (w / v) P188) and F3-14 (4% (w / v) sucrose, 70 mM L-Arg-HCl, 0.1% (w / v) P188 exhibited less particles than other formulations after a 4-week storage at 40 °C. In this study, formulations containing Pl88 showed better appearance and fewer sub-visible particles than ones containing PS80 but it is uncertain that the protection of Pl 88 or the degradation of PS80 can be attributed to this result. Based on the current result, P188 was more suitable for the antibody molecule. Although F3-11 possessed a higher TmOnset (57.0 °C), in the 4 tested formulations, it also presented a higher viscosity of 8.7 cP, which might bring difficulties for the production of high concentration DS. The 7% (w / v) sucrose might contribute to the elevated viscosity. The SEC-HPLC results demonstrated the monomer of all tested formulations had a slightly higher decline than 5% and there were no significant differences of monomer among 4 formulations. The iCIEF showed all samples remained stable under FT and agitation stress but the main peak decreased when stored at 40 °C for 4 weeks. The decline ratio of main peak among all tested formulations was consistent. Caliper-SDS-NR & R results displayed that the purity for all formulations slightly decreased in the NR & R testing when stored at 40 °C for 4 weeks. In conclusion, Pl88 was better to reduce particle numbers, while lower sucrose concentration and L-Arg-HCl was necessary to reduce viscosity. Therefore, F3-14 (20 mM PB, 10 mM L-Methionine, 4% (w / v) sucrose, 70 mM L-Arg-HCl, 0.1 % (w / v) Pl 88, at pH 7.2), was chosen as the final buffer and excipient system for the antibody formulation. The protein showed an 8% reduction in potency following 4 weeks at 40 °C in this final formulation.

[0601] Part 4: Formulation confirmation study. The objective of this study was to confirm the final selected formulation in the selected container closure system using the processed locked materials. Thus, the selected formulation was confirmed through a 3-month stability study (-70 °C, 2-8 °C, 25 °C, and 40 °C incubation), agitation at 100 rpm for up to 3 days (D), and freeze / thaw for up to 5 cycles (CYS). Appearance, pH, protein cone., osmolality, viscosity, SEC-UPLC, CE-SDS-NR & R, iCIEF, HIAC and potency (ELISA) testing were conducted in this study. Table 7 below shows the sampling and testing plan for the formulation confirmation study.

[0602] Table 7. Sampling and testing plan of formulation confirmation study (X= Appearance, pH, protein concentration, SEC-UPLC, CE-SDS-NR & R, iCIEF; Y= Sub-visible particles (HIAC); Z= potency (ELISA); W= Tg’ (mDSC), osmolality, viscosity; ()= Samples reserved, testing optional). Condition TO Sampling Points and Assay 2W 4W 12W -70°C X, Y, Z, W / X, Y, (Z) X, Y, (Z) 5°C / X, Y, (Z) X, Y, (Z) 25°C / X, Y, (Z) x, Y, Z 40°C X,(Z) X, Y,Z / Agitation- 100 rpm, 25°C 1 D 3D X X, Y Freeze / Thaw- 70°C / RT 3CYS 5CYS X X, Y, Z

[0603] In Summary, the selected formulation for the antibody protein with the determined filling volume (2 mL) and container closure system (6 mL vials, 20 mm stopper and 20 mm aluminum-plastic cover) was utilized in this formulation confirmation study. All samples remained colorless, slightly opalescent, and free of visible particles in the selected formulation (100 mg / mL protein (target), 20 mM PB, 10 mM L-Methionine, 4% (w / v) sucrose, 70 mM L-Arginine-HCl, 0.1% (w / v) Pl88, at pH 7.2) for protein under all testing conditions in this study, except for samples stored at 25°C for 9 weeks. The purity measured by CE-SDS-NR & R, and the measured the proportion of main peak from the SEC-HPLC and iCIEF analysis declined following incubation at 40 °C for 4 weeks. Furthermore, the testing results indicated no obvious effects on the stability of the protein under agitation and FT conditions. Overall, the confirmation study supported the selection of 20 mM PB, 10 mM L-Methionine, 4% (w / v) sucrose, 70 mM L-Arg-HCl, 0.1 % (w / v) P188, at pH 7.2 as the final formulation for 100 mg / mL protein in the final container closure system. As for the long-term storage temperature, the temperature of -20 °C is implemented into the stability study of DP from engineering batch, since visible particles were observed at 25 °C .

[0604] In conclusion, In the pH / buffer screening study, 8 formulations designed from 4 buffer systems were evaluated under the accelerated thermal condition of 40 °C. Based on the results obtained from appearance, pH, protein cone. SEC-HPLC, caliper-SDS-NR & R, iCIEF, and DSC, 20 mM PB with 10 mM L-Methionine buffer systems at pH 7.2 were selected for the excipients and surfactant screening study. Excipients and surfactant screening study for 50 mg / mL protein was performed first. In this study, 10 designed formulations (F3-1 - F3-10) were evaluated in terms of their ability to maintain the protein stability under treatments of thermal stress condition at 25 °C and 40 °C, freeze / thaw cycles, and agitation. Based on the results obtained from appearance, pH and protein cone, measurements, SEC-HPLC, caliper-SDS-NR & R, iCIEF, MFI and DSC, 20 mM PB, 10 mM L-Methionine, 8% (w / v) sucrose, 0.1 % (w / v) Pl88, at pH 7.2, was chosen as the base formulation for high concentration antibody formulation development. In the excipients and surfactant screening study for 100 mg / mL protein, 4 designed formulations (F3-11 - F3-14) were evaluated in terms of their ability to maintain the protein stability under treatments of thermal stress condition at 25 °C and 40 °C, freeze / thaw cycles, and agitation. Based on the results obtained from appearance, pH and protein cone., SEC-HPLC, caliper-SDS-NdR & R, iCIEF, MFI and DSC, 20 mM PB, 10 mM L-Methionine, 4% (w / v) sucrose, 70 mM L-Arg-HCl, 0.1 % (w / v) Pl 88, at pH 7.2, was recommended as the final formulation for 100 mg / mL protein and the potency remained stable under thermal stress in this selected formulation. In the confirmation study, no obvious differences in appearance, protein cone., pH and sub-visible particles were observed under 2-8 °C, -70 °C, agitation and freeze / thaw stress conditions compared to TO. It was observed that purity data from SE-UPLC, iCIEF and CE-SDS-NR & R declined following incubation at 40 °C for 4 weeks and the visible particles were observed in samples stored at 25 °C for 9 weeks. The particulate trend will be further monitored in other DP stability studies. And -20 °C is recommended as the long-term storage temperature of DP in the early stage.

[0605] Overall, 20 mM PB, 10 mM L-Methionine, 4% (w / v) sucrose, 70 mM L-Arg-HCl, 0.1% (w / v) Pl88, at pH 7.2 was recommended as the final formulation for 100 mg / mL antibody development.

[0606] Example 3: Formulation stability determination. The antibody was stored as a liquid, filled in glass vials to allow 2.0 mL to be extracted. Formulation testing lot 1 (process 1) comprised 100 mg / mL of the antibody, 20 mM phosphate buffer, 10 mM L-methionine, 70 mM L- arginine monohydrochloride, 4% (w / v) sucrose, 0.1% (w / v) poloxamer 188, and a pH 7.2. Formulation testing lot 2 (process 2) comprised 150 mg / mL of the antibody, 20 mM phosphate buffer, 10 mM L-methionine, 70 mM L-arginine monohydrochloride, 3.5% (w / v) sucrose, 0.1% (w / v) poloxamer 188, at a pH 7.2. Process 1 was stored using a 6 mL Type I glass vials, 20 mm chlorobutyl rubber stopper, and 20 mm Aluminum-plastic cap. Process 2 was stored using 6 mL Type I glass vials, 20 mm chlorobutyl rubber stopper nested in 20 mm polypropylene cap; or 6 mL Type I glass injection vials, made of glass tubing 20 mm chlorobutyl rubber stopper, and 20 mm Aluminum-plastic flip cap.

[0607] The presence of visible particles, sub-visible particulate matter, color, clarity, pH, protein concentration, iCIEF, SEC, CE-SDS (Reduced), CE-SDS (Non-reduced), ELISA binding, sterility, and container closure system integrity testing (CCIT), were measured. Sterility was performed at TO and at the end point of the stability study. CCIT was performed annually and at the end point of the stability study at the long-term stability condition. Starting with the DP lot 20231002, poloxamer 188 concentration was also monitored for the antibody lots on stability every 6 months for up to 24 months, and then at the annual time points. Analytical methods were as according to methods described in Example 1 and Example 2 above.

[0608] Container and Closure System Integrity Testing in Lieu of Sterility Testing as a Component of the Stability Protocol for Sterile Products (CCIT) was used as a substitute for sterility testing in drug product stability research to verify the package integrity based on USP. A vacuum decay leak testing, which is a nondestructive method, was used for stability studies. The container closure system was enclosed in a chamber that had a defined vacuum setting applied within a given time interval. The vacuum extracted headspace gas or liquid vapor content from the interior of the sample. This caused an increase in pressure of the enclosed test chamber. Vacuum decay measured this pressure increase (or vacuum decay), which needed to be above a threshold value to represent a leak. The result was reported as “pass” or “fail”.

[0609] Stability conditions and testing frequency are listed in Tables 64-68 below. Table 64: Stability Conditions and Testing Time Points Lot No. Stability Type Stability Condition Time Points (Month)a DP Lots (100 mg / mL & 150 mg / mL) monitored under Legacy Stability Panel and the Stability Conditions 2022050 2b Long Term -20 ± 5 °C, Upright 0, 1, 3, 6, 9, 12, 18, 24 Accelerated 5 ± 3 °C, Inverted 0, 1, 3, 6, 9, 12, 18, 24 Stress 25 ± 2°C / 60 ± 5%RH, Inverted 0, 1,3,6 Stress 40 ± 2°C / 75 ± 5%RH, Inverted 0, 1W. 2W, 1 2022090 2b Long Term -20 ± 5°C, Upright 0, 1, 3, 6, 9, 12, 18, 24 Long Term 5 ± 3 °C, Inverted 0, 1,3,6, 9, 12, 18 Accelerated 25 ± 2°C / 60% ± 5%RH, Inverted 0, 1,3,6 2023020 lb Long Term -20 ± 5°C, Upright 0, 1, 3, 6, 9, 12, 18, 24 Long Term 5 ± 3 °C. Inverted 0, 1. 3, 6, 9, 12, 18, 24 Long Term 5 ± 3 °C, Upright 0, 1, 3, 6, 9, 12 Accelerated 25 ± 2°C / 60 ± 5%RH, Inverted 0, 1,3,6,9 Stress 40 ± 2°C / 75 ± 5%RH, Inverted 0, 1W. 2W, 1 DP Lots (150 mg / mL ONLY) monitored under Current Stability Testing Panel, and tire Stability Conditions 2023060 3C Long Term -20 ± 5 °C, Upnght 0, 1.3 Long Term 5 ± 3 °C, Inverted 0, 1.3, 6, 9, 12, 18, 24, 36 Long Term 5 ± 3 °C, Upright 0, 1, 3, 6, 9, 12, 18, 24 Accelerated 25 ± 2°C / 60 ± 5%RH, Inverted 0, 1,3,6 Stress 40 ± 2°C / 75 ± 5%RH, Inverted 0, 1W. 2W, 1 2024060 3 Accelerated 25 ± 2°C / 60 ± 5%RH, Inverted 0, 1 Stress 40 ± 2°C / 75 ± 5%RH, Inverted 0, 1W, 2W, 1 Long Term 5 ± 3 °C, Inverted 0, 1 Long Term 5 ± 3 °C, Upright 0, 1 2023100 2 Long-Term 5°C ± 3°C, Inverted 0, 1,3,6, 9, 12, 18, 24, 36, 39 d Long-Tenn 5°C ± 3°C, Upright 0, 1,3,6, 9, 12, 18, 24 Accelerated 25°C ± 2°C / 60 ± 5%RH, Inverted 0, 1,3,6 Stress 40°C ± 2°C / 75 ± 5%RH, Inverted 0, 1W, 2W, 1 2024030 2 Long-Term 5°C ± 3°C, Inverted 0, 1,3,6, 9, 12, 18, 24, 36, 39 d Long-Term 5°C ± 3°C, Upright 0, 1,3,6, 9, 12, 18,24 Accelerated 25°C ± 2°C / 60 ± 5%RH, Inverted 0, 1,3,6 Stress 40°C ± 2°C / 75 ± 5%RH, Inverted 0, 1W, 2W, 1 Abbreviations: RH = relative humidity; W = week;a The timepoints are in months unless otherwise noted; b Long-term storage condition remained at -20 ± 5°C condition for this batch, irrespective of the manufacturing process (Process 1 or Process 2); c Long-term storage condition for the DP lot 20230603 was revised to 5 ± 3°C from the legacy storage condition -20 ± 5°C. This change in long-term storage temperature was supported by real-time stability data on the DP lot at 5 ± 3°C; d A 39-month timepoint was added to demonstrate the stability of the product beyond 36 months. Table 65: Legacy Stability Testing Panel for MAB39 Drug Product for 24 Months Long-Term Stability Stability Condition: 5°C ± 3°C (Inverted)3 and -20°C ± 5°C (Upright) Testing Timepoint (Month) Test Item Test Method 0 1 3 6 9 12 18 24 Visible particles USP X X X X X X X X Appearance (Color) USP X X X X X X X X Appearance (Clarity) USP X X X X X X X X pH USP X X X X X X X X Subvisible Particulate Matter USP; Light obscuration X X X X X X X X Protein Concentration UV X X X X X X X X Purity iCIEF (Charge Variants) X X X X X X X X Purity CE-SDS (Reduced) X X X X X X X X Purity CE-SDS (Non-rcduccd) X X X X X X X X Purity SEC X X X X X X X X Potency ELISA Binding (Bioasssay) X X X X X X X X Sterility7 USP; Membrane filtration X NT NT NT NT NT NT X Container Closure Integrity (CCIT)                 ' USP; Vacuum Decay Leak Test NT NT NT NT NT X NT X Abbreviations: CE-SDS=capillary electrophoresis sodium dodecyl sulfate; iCIEF= imaged capillary isoelectric focusing; NT = not tested; SEC= size exclusion chromatography; X = tested; a Upright condition at 5°C ± 3°C is being evaluated for up to 12 months. Applicable for Lots 20220502 (lOOm / mL), and 150 mg / mL DP lots 20220902, 20220903, and 20230201. Table 66: Current Stability Testing Panel for MAB39 Drug Product for 36 Months Long-Term Stability Stability Condition: 5°C ± 3°C (Inverted or Upright3) Testing Timepoint (Month) Test Item Test Method 0 1 3 6 9 12 18 24 36 39b Visible particles USP X X X X X X X X X X Appearance (Color) USP X X X X X X X X X X Appearance (Clanty) USP X X X X X X X X X X pH USP X X X X X X X X X X Subvisible Particulate Matterc USP; Light obscuration X X X X X X X X X X Protein Concentration UV X X X X X X X X X X Pol oxamer 188 Contentd UPLC-ELSD X NT NT X NT X X X X X Purity iCIEF (Charge Variants) X X X X X X X X X X Purity CE-SDS (Reduced) X X X X X X X X X X Purity CE-SDS (Non-reduced) X X X X X X X X X X Purity SEC X X X X X X X X X X Potency ELISA Binding (Bioasssav) X X X X X X X X X X Sterility USP; Membrane filtration X NT NT NT NT NT NT NT X X Container Closure Integrity (CC1T) USP; Vacuum Decay Leak Test NT NT NT NT NT X NT X X X Abbreviations: CE-SDS=capillary electrophoresis sodium dodecyl sulfate; iCIEF= imaged capillary isoelectric focusing; NT = not tested; SEC= size exclusion chromatography; X = tested; a Upright condition was evaluated for up to 24 months; b Tested for DP lot 20231002 only at 5°C ± 3°C (inverted) condition to evaluate stability of the DP beyond target shelf-life of 36 months;c For the upright condition (5 ± 3°C), sub-visible particulate was performed at the yearly timepoints. For the inverted, testing was performed at every timepoint for all lots, except for DP Lot 20230201 where all timepoints at 5°C were tested for sub-visible particulates (both upright and inverted); d Added to all lots with long-term stability (5°C ± 3°C (inverted)) and accelerated (25°C ± 2°C) conditions. P188 was tested for all future DP lots on stability at 6 mo time points until 24 mo, then at annual timepoints only. Table 67: Stability Testing Panel for MAB39 Drug Product for Accelerated Condition Stability Condition: 25°C ± 2°C / 60 ± 5%RH (Inverted) Testing Timepoint (Month) Test Item Test Method 0 1 3 6 9 Visible particles USP X X X X X Appearance (Color) USP X X X X X Appearance (Clanty) USP X X X X X pH USP X X X X X Subvisible Particulate Matter USP; Light obscuration X X X X X Protein Concentration uv X X X X X Poloxamer 188 Content UPLC-ELSD X NT X X NT Purity iCIEF (Charge Variants) X X X X X Purity CE-SDS (Reduced) X X X X X Purity CE-SDS (Non-reduced) X X X X X Purity SEC X X X X X Potency ELISA Binding (Bioasssay) X X X X X Abbreviations: CE-SDS=capil ary electrophoresis sodium dodecyl sulfate; iCIEF= imaged capillary isoelectric focusing; NT = not tested; SEC= size exclusion chromatography; X = tested. Table 68: Stability Testing Pannel for MAB39 Drug Product for Stress Condition Stability Condition: 40°C ± 2°C / 75 ± 5%RH (Inverted) Testing Timepoint Test Item Test Method 0 1W 2W 1 M Visible particles USP X X X X Appearance (Color) USP X X X X Appearance (Clarity) USP X X X X pH USP X X X X Subvisible Particulate Matter USP; Light obscuration X X X X Protein Concentration UV X X X X Purity iCIEF (Charge Variants) X X X X Purity CE-SDS (Reduced) X X X X Purity CE-SDS (Non-reduced) X X X X Purity SEC X X X X Potency ELISA Binding (Bioasssay) X X X X Abbreviations: CE-SDS=capillary electrophoresis sodium dodecyl sulfate; iCIEF= imaged capillary isoelectric focusing; SEC= size exclusion chromatography; M = month; W = week, X = tested.

[0610] Stability study results support long-term storage conditions of 5°C ± 3°C and -20°C ± 5°C for the antibody formulation. Data for Process 1 (100 mg / mL), stored at -20°C as a long-term stability condition, demonstrates no significant change over time and no significant variability. Stability results met all acceptance criteria through the 18-month time point. The Process 2 drug product (150mg / mL) was initially evaluated at -20°C as a risk mitigation storage condition pending availability of additional stability data at 5 C. As the stability data became available, it was concluded that Process 2 drug product stored at either -20°C or 5°C and demonstrates no significant change over time and no significant variability. Stability results meet all acceptance criteria through the 18-month time point.

[0611] In a separate experiment, the containers used for the stability studies were made of polycarbonate (PC), which was the same material used for the drug substance container closure system. Formulation testing lot 1 (process 1) comprised 100 mg / mL of the antibody, 20 mM phosphate buffer, 10 mM L-methionine, 70 mM L- arginine monohydrochloride, 4% (w / v) sucrose, 0.1% (w / v) poloxamer 188, and a pH 7.2. Formulation testing lot 2 (process 2) comprised 150 mg / mL of the antibody, 20 mM phosphate buffer, 10 mM L-methionine, 70 mM L-arginine monohydrochloride, 3.5% (w / v) sucrose, 0.1% (w / v) poloxamer 188, at a pH 7.2. All formulations were stored in 5 mL PC bottles.

[0612] The quality attributes monitored include color, clarity, pH, protein concentration, iCIEF, CE- SDS (Reduced), CE-SDS (Non-reduced), SEC, and ELISA Binding. Analytical methods were as according to methods described in Example 1 and Example 2 above.

[0613] Stability conditions and testing frequency are listed in Tables 8-12 below. Table 8: Stability Conditions and Testing Time Points for MAB39 DS Batch No. Stability Type Stability Condition Time Points (Month) Available Stability Data (Months) 100 mg / mL DS 2441S211215Y Long Term -70°C ± 10°C 0, 1, 3, 6, 9, 12, 18, 24, 36 24 Accelerated 5°C ± 3°C 0. 1, 3, 6 6 (completed) Stress 25°C±2°C / 60 ± 5% RH 0, 1. 2, 3 3 (completed) 24412201 Long Term -70°C ± 10°C 0, 1,3, 6, 9, 12, 18, 24, 36 18 Accelerated 5°C ± 3°C 0, L 3, 6 6 (completed) Stress 25°C±2°C / 60 ± 5% RH 0, 1, 2, 3 3 (completed) 150 mg / mL DS 2441S220510Y Long Term -70°C ± 10°C 0, 1,3, 6, 9, 12, 18, 24 18 Accelerated 5°C ± 3°C 0, L 3, 6 6 (completed) Stress 25°C ± 2°C / 60 ± 5% RH 0, 1, 2, 3 3 (completed) 24412202 Long Term -70°C ± 10°C 0, 1,3, 6, 9. 12, 18, 24,36, 39a 18 Accelerated 5°C ± 3°C 0, 1, 3, 6 6 (completed) Stress 25°C±2°C / 60 ± 5% RH 0, 1, 2, 3 3 (completed) 0000097275 Long Tenn -70°C ± 10°C 0, 1, 3, 6, 9, 12, 18, 24, 36 9 Accelerated 5°C ± 3°C 0, 1, 3, 6, 9, 12 6 Stress 25°C±2°C / 60 ± 5% RH 0, L 2, 3, 6 6 (completed) 0000114279 Long Term -70°C ± 10°C 0, 1,3, 6, 9, 12, 18, 24,36, 39a 3 Accelerated 5°C ± 3°C 0, 1, 3, 6, 9, 12 3 Stress 25°C ± 2°C / 60 ± 5% RH 0, L 2, 3, 6 3 0000124360 Long Term -70°C ± 10°C 0, 1,3, 6, 9, 12, 18, 24,36, 39a 1 Accelerated 5°C ± 3°C 0, 1, 3, 6, 9, 12 1 Stress 25°C±2°C / 60 ± 5% RH 0. L 2, 3, 6 1 aA 39- month timepoint was added for 3 batches only, to demonstrate the stability of the DS beyond the maximum shelf-life (36 months). Table 9: Long-term Stability Testing Plan for MAB39 100 mg / mL Drug Substance Stability Condition: -70°C ± 10°C Testing Timepoint (Month) Attribute Test Method 0 1 3 6 9 12 18 24 36a Appearance (Color) USP X X X X X X X X X Appearance (Clarity) USP X X X X X X X X X pH USP X X X X X X X X X Protein Concentration uv X X X X X X X X X Main Peak Charge Variants by iCIEF X X X X X X X X X Acidic Peaks X X X X X X X X X Basic Peaks X X X X X X X X X LC+HC Purity by CE-SDS (Reduced) X X X X X X X X X Total Minor Species X X X X X X X X X Main Peak Purity by CE-SDS (Non- X X X X X X X X X Total LMWS reduced) X X X X X X X X X Monomer (Main Peak) Purity by SEC X X X X X X X X X HMWS X X X X X X X X X Binding Bioassay ELISA X X X X X X X X X Abbreviations: CE-SDS=capillary electrophoresis; HMWS = high molecular weight species; iCIEF= imaged capillary isoelectric focusing; LC+HC = Light Chain + Heavy Chain; LMWS= high molecular weight species; SEC= size exclusion chromatography. aThe long-term stability plan for batch 2441S220510Y ends at 24 months. Table 10: Long-term Stability Testing Plan for MAB39 150 mg / mL Drug Substance Stability Condition: -70°C ± 10°C Testing Timepoint (Month) Attribute Test Method 0 1 3 6 9 12 18 24 36 39a Appearance (Color) USP X X X X X X X X X X Appearance (Clarity) USP X X X X X X X X X X PH USP X X X X X X X X X X Protein Concentration uv X X X X X X X X X X Main Peak Charge Variants by iCIEF X X X X X X X X X X Acidic Peaks X X X X X X X X X X Basic Peaks X X X X X X X X X X LC+HC Purity by CE-SDS (Reduced) X X X X X X X X X X Total Minor Species X X X X X X X X X X Main Peak Purity by CE-SDS (Nonreduced) X X X X X X X X X X Total LMWS X X X X X X X X X X Monomer (Main Peak) Purity by SEC X X X X X X X X X X HMWS X X X X X X X X X X Binding Bioassay ELISA X X X X X X X X X X Abbreviations: CE-SDS=capillary electrophoresis; HMWS = high molecular weight species; iCIEF= imaged capillary isoelectric focusing; LC+HC = Light Chain + Heavy Chain; LMWS= high molecular weight species; SEC= size exclusion chromatography. a A 39- month timepoint was added for 3 batches only. Table 11: Accelerated Stability Testing Plan for MAB39 Drug Substance (100 and 150 mg / mL)________________________________________________________ Stability Condition: 5°C ± 3°C Testing (Month Timepoint Attribute Test Method 0 1 3 6 9a 12a Appearance (Color) USP X X X X X X Appearance (Clarity) USP X X X X X X PH USP X X X X X X Protein Concentration uv X X X X X X Main Peak Charge Variants Purity by iCIEF X X X X X X Acidic Peaks X X X X X X Basic Peaks X X X X X X LC+HC Purity by CE-SDS (Reduced) X X X X X X Total Minor Species X X X X X X Main Peak Purity by CE-SDS (Non-reduced) X X X X X X Total LMWS X X X X X X Monomer (Main Peak) Purity by SEC X X X X X X HMWS X X X X X X Binding Bioassay ELISA X X X X X X Abbreviations: CE-SDS=capillary electrophoresis; HMWS = high molecular weight species; iCIEF= imaged capillary isoelectric focusing; LC+HC = Light Chain + Heavy Chain; LMWS= high molecular weight species; SEC= size exclusion chromatography. a 9- and 12-month timepoints were included only for some GMP batches for information only. Table 12: Stress Stability Testing Plan for MAB39 Drug Substance (100 and 150 mg / mL) Stability Condition: 25°C ± 2°C, 60% ±5% RH Testing Timepoint (Month) Attribute Test Method 0 1 3 6a Appearance (Color) USP X X X X Appearance (Clarity) USP X X X X pH USP X X X X Protein Concentration uv X X X X Main Peak Charge Variants Purity by iCIEF X X X X Acidic Peaks X X X X Basic Peaks X X X X LC+HC Purity by CE-SDS (Reduced) X X X X Total Minor Species X X X X Main Peak Purity by CE-SDS (Non-reduced) X X X X Total LMWS X X X X Monomer (Main Peak) Purity by SEC X X X X HMWS X X X X Binding Bioassay ELISA X X X X Abbreviations: CE-SDS=capillary electrophoresis; HMWS = high molecular weight species; iCIEF= imaged capillary isoelectric focusing; LC+HC = Light Chain + Heavy Chain; LMWS= high molecular weight species; NT = not tested; SEC= size exclusion chromatography.a 6-month timepoint was included only for some GMP batches.

[0614] Long-term stability of pharmaceutical formulations according to Table 13 was determined according to methods described herein and in Example 1 and Example 2. Table 13: Stability Study Batch and Test Stability Condition Summary Process(Strength) Lot# Stability Condition Individual Data Table Number #1 (100 mg / mL) 20220502 -20°C ± 5°C (Upright) Table 14 5°C ± 3°C (Inverted) Table 18 25°C ± 2°C / 60% ± 5%RH (Inverted) Table 28 40°C ± 2°C / 75% ± 5%RH (Inverted) Table 24 #2 (150 mg / mL) #2 (150 mg / mL) 20220902 -20°C ± 5°C (Upright) Table 15 5°C ± 3°C (Inverted) Table 19 25°C ± 2°C / 60% ± 5%RH (Inverted) Table 29 20230201 -20°C ± 5°C (Upright) Table 16 5°C ± 3°C (Inverted) Table 20 5°C ± 3°C (Upright) Table 24 25°C ± 2°C / 60% ± 5%RH (Inverted) Table 30 40°C ± 2°C / 75% ± 5%RH (Inverted) Table 35 20230603 -20°C ± 5°C (Upright) Table 17 5 °C ± 3 °C (Inverted) Table 21 5 °C ± 3 °C (Upright) Table 25 25°C ± 2°C / 60% ± 5%RH (Inverted) Table 31 40°C ± 2°C / 75% ± 5%RH (Inverted) Table 36 20240603 25 ± 2°C / 60 ± 5%RH, Inverted Table 60 40 ± 2°C / 75 ± 5%RH, Inverted Table 61 5 ± 3 °C, Inverted Table 62 5 ± 3°C, Upright Table 63 20231002 5°C ± 3°C (Inverted) Table 22 5°C ± 3°C (Upright) Table 26 25°C ± 2°C / 60% ± 5%RH (Inverted) Table 22 40°C ± 2°C / 75% ± 5%RH (Inverted) Table 37 20240302 5°C ± 3°C (Inverted) Table 23 5°C ± 3°C (Upright) Table 27

[0615] Data for lots stored in the upright position at -20°C is shown in Table 14 through Table 17. Data for the inverted composition at 5°C (accelerated condition for lot 20220502) is shown in Table 18 through Table 23. Data for lots stored in the upright position at 5°C (accelerated condition for lot 20220502) are in Table 24 through Table 27. Data at the current accelerated condition at 25°C, 60% RH (stress condition for lot 20220502) is shown in Table 28 through Table 33. Data at the current stress condition at 40°C, 75% RH is shown in Table 34 through Table 38. Abbreviations: CCIT = container closure integrity testing; CE-SDS=capillary electrophoresis; EFOVP = essentially free of visible particles; ELISA = enzyme-linked immunosorbent assay; HMWS = high molecular weight species; iCIEF= imaged capillary isoelectric focusing; L = liquid; LC+HC = light chain + heavy chain; LMWS= low molecular weight species; ND = not detected; NG = no growth; NT = not tested; NTU = nephelometric turbidity units; p / c = particles per container; RH = relative humidity; SEC= size exclusion chromatography; w / v = weight per volume; and - = data not yet available. Table 14: Long-term Stability Data for Clinical Lot 20220502 at -20°C ± 5°C, Upright Test / Attribute Acceptance Criteria Timepoints (months) 0 1 3 6 9 12 18 24 Visible particles Liquid L L L L L L L L EFOVP EFOVP EFOVP EFOVP EFOVP EFOVP EFOVP EFOVP NE FO VP Color, compared to Standard Solution Not more colored than B6 B6 B6 B6 B6 B6 B6 B6 No. 3 Clarity, NTU <60.0 20.4 20.3 20.9 19.6 20.3 24.5 21.4 20.7 pH 6.7-7.7 7.2 7.2 7.2 7.2 7.2 7.3 7.2 7.2 Subvisibl e Particulat e Matter, p / c > 25 pm <600 0 0 0 0 0 0 0 0 > 10 pm <6000 7 12 6 2 3 0 4 6 > 5 pm Report Result 31 86 90 34 40 20 46 46 > 2 pm Report Result 232 533 1010 350 529 388 327 394 Protein Concentration, mg / mL 90.0-110.0 mg / mL 97.7 96.5 96.0 97.1 95.9 98.6 96.0 96.2 Charge Variant s Purity by iCIEF, % Main Peak >30.0 73.3 74.1 74.4 73.6 73.5 74.9 75.1 74.7 Acidic Peaks <60.0 20.2 20.8 20.6 21.1 21.0 20.6 20.4 20.8 Basic Peaks <20.0 6.5 5.1 5.1 5.3 5.5 4.4 4.6 4.4 Purity by CE-SDS (Reduced), % LC+HC >90.0 98.9 99.0 98.6 98.6 98.9 98.3 98.3 98.3 Total Min or Spec ies < 10.0 1.1 1.0 1.4 1.4 1.1 1.7 1.7 1.7 Purity by CE-SDS (Nonreduced), % Main Peak >90.0 99.0 98.9 98.8 98.8 98.8 98.9 98.9 98.7 Total LMWS < 10.0 0.9 1.0 1.1 1.1 1.0 1.0 1.0 1.1 Purity by SEC, % Monom er (Main Peak) >95.0 98.7 98.8% 98.5 98.5 98.6 98.4 98.5 98.5 HMWS <5.0 1.3 1.2 1.5 1.5 1.4 1.6 1.5 1.5 (ELISA Binding) Bioassay, %Relative Potency 60 - 140 100 98 87 107 102 88 94 93 Sterility No Growth NG NT NT NT NT NT NT NG CCIT Pass NT NT NT NT NT Pass NT Pass Table 15: Long-term Stability Data for Clinical Lot 20220902 at -20°C ± 5°C, Upright Test / Attribute Acceptance Criteria Timepoints (months) 0 1 3 6 9 12 18 24 Visible particles (Refer to USP / Ph. Eur.) Liquid L L L L L L L L EFOVP EFOV P EFOV P EFOV P EFOV P EFOV P EFOV P EFOV P EF OV P Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 B6 B6 B6 B6 B6 B6 B6 <B5 Clarity, NTU <60.0 19.7 19.7 19.0 21.7 22.9 20.7 19.1 20.1 PH 6.7-7.7 7.2 7.2 7.3 7.2 7.2 7.2 7.2 7.2 Sub vi sib le Particula te Matter, p / c > 25 pm <600 1 0 0 0 0 0 0 0 > 10 pm <6000 16 21 4 2 0 6 0 24 > 5 pm Report Result 168 164 24 16 44 50 6 189 > 2 pm Report Result 1502 829 303 690 917 679 205 131 7 Protein Concentration, mg / mL 135.0- 165.0 153.8 151.0 146.4 151.0 155.4 154.1 155.9 158. 2 Charge Variants Purity Main Peak >30.0 73.1 72.2 72.7 72.5 70.9 72.9 73.0 72.7 Acidic Peaks <60.0 22.2 22.8 22.4 22.5 22.7 21.9 22.3 22.1 Basic Peaks <20.0 4.7 5.0 4.8 5.0 5.1 5.1 4.7 5.3 by iCIEF, % Purity by CE-SDS (Reduced), % LC+HC >90.0 98.6 98.4 98.5 98.5 98.5 98.4 98.6 98.6 Total Minor Species Report Result 1.4 1.6 1.5 1.5 1.5 1.6 1.4 1.4 Purity by CE-SDS (Nonreduced), % Main Peak 85.0 98.7 98.6 98.7 98.7 98.6 98.6 98.7 98.6 Total LMWS Report Result 1.1 1.1 1.1 1.1 1.2 1.1 1.0 1.1 Purity by SEC, % Monomer (Main Peak) >90.0 98.3 98.3 98.4 98.2 98.3 98.3 98.2 98.1 HMWS <5.0 1.7 1.7 1.6 1.7 1.7 1.7 1.8 1.9 LMWS Report Result ND ND ND 0.1% ND ND ND ND (ELISA Binding) Bioassay, %Relative Potency 60-140 107 110 107 102 104 103 94 100 Sterility No Growth NG NT NT NT NT NT NT NG CCIT Pass NT NT NT NT NT Pass NT Pass Table 16: Long-term Stability Data for Clinical Lot 20230201 at -20°C ± 5°C, Upright Test / Attribute Acceptance Criteria Timepoints (months) 0 1 3 6 9 12 18 Visible particles (Refer to Liquid L L L L L L L USP / Ph. Eur.) EFOVP EFOVP EFOVP EFOVP EFOVP EFOVP EFOVP EFOVP Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 B6 B6 B6 B6 B6 B6 B5 Clarity, NTU <60.0 19.1 21.7 23.3 20.0 20.8 19.6 20.0 pH 6.7-7.7 7.2 7.2 7.2 7.2 7.2 7.2 7.2 Sub vi sib le Particula te Matter, p / c > 25 pm <600 0 0 0 0 2 0 1 > 10 pm <6000 2 3 1 10 4 3 24 > 5 pm Report Result 26 12 3 29 46 29 180 > 2 pm Report Result 252 152 116 509 506 514 1338 Protein Concentration, mg / mL 135.0 165.0 152.0 159.2 152.2 153.4 152.8 154.5 150.6 Charge Variants Purity by iCIEF, % Main Peak >30.0 72.8 72.5 73.1 74.0 73.7 72.1 73.0 Acidic Peaks <60.0 22.0 22.4 22.5 21.3 21.7 23.3 22.1 Basic Peaks <20.0 5.2 5.0 4.3 4.7 4.5 4.7 5.0 Purity by CE-SDS (Reduced) % LC+HC > 90.0% 98.7 98.5 98.4 98.5 98.3 98.4 98.5 Total Minor Species Report Result 1.3 1.5 1.6 1.5 1.7 1.6 1.5 Purity by CE-SDS (Nonreduced), % Main Peak > 85.0% 98.7 98.8 98.8 98.6 98.9 98.7 98.7 Total LMWS Report Result 1.1 1.0 1.1 1.1 1.0 1.1 1.2 Purity by SEC, % Monomer (Main Peak) > 90.0% 98.3 98.3 98.3 98.3 98.4 98.3 98.2 HMWS < 5.0% 1.7 1.7 1.7 1.7 1.6 1.7 1.8 LMWS Report Result ND 0.1% ND ND ND ND ND (ELISA Binding) Bioassay, %Relative Potency 60 - 140 103 100 108 102 87 104 105 Sterility No Growth NG NT NT NT NT NT NT CCIT Pass NT NT NT NT NT Pass NT Table 17: Long Term Stability Data for Clinical Lot 20230603 at -20°C ± 5°C, Upright Test / Attribute Acceptance Criteria Timepoints (months) 0 1 3 Visible particles (Refer to USP / Ph. Eur.) Liquid L L L EFOVP EFOVP EFOVP EFOVP Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 B6 B6 B6 Clarity, NTU <60.0 24.1 23.8 20.7 PH 6.7-7.7 7.2 7.2 7.2 Subvisibl e Particulat e Matter, p / c > 25 pm <600 0 0 0 > 10 pm <6000 0 0 1 > 5 pm Report Result 2 0 19 > 2 pm Report Result 11 21 236 Protein Concentration, mg / mL 135.0- 165.0 152.2 149.7 151.3 Charge Variants Purity by iCIEF, % Main Peak >30.0 76.3% 75.6% 76.1% Acidic Peaks <60.0 19.7% 19.7% 19.9% Basic Peaks <20.0 4.0% 4.7% 4.1% Purity by CE-SDS (Reduced), % LC+HC >90.0 98.3% 98.6% 98.7% Total Minor Species Report Result 1.7% 1.4% 1.3% Purity by CE-SDS (Nonreduced), % Main Peak >85.0 98.7% 98.7% 98.6% Total LMWS Report Result 1.1% 1.1% 1.2% Purity by SEC, % Monomer (Main Peak) >90.0 98.5% 98.5% 98.4% HMWS <5.0 1.5% 1.5% 1.6% LMWS Report Result ND ND ND (ELISA Binding) Bioassay, %Relative Potency 60 - 140 98 101 98 Sterility No Growth NG NT NT CCIT Pass NT NT NT Table 18: Accelerated Stability Data for Clinical Lot 20220502 at 5°C ± 3°C, Inverted Test / Attribute Acceptance Criteria Timepoints (months) 0 1 3 6 9 12 18 24 Visible particles (Refer to USP / Ph. Eur.) Liquid L L L L L L L L EFOVP EFOV P EFOV P EFOVP EFOVP EFOVP EFOVP EFOVP EFOVP Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 3 B6 B6 B6 B6 B6 B6 B5 B5 Clarity, NTU <60.0 20.4 20.2 20.2 19.7 20.3 23.4 21.2 20.3 pH 6.7-7.7 7.2 7.2 7.2 7.2 7.2 7.3 7.2 7.2 Subvisibl >25 pm <600 0 0 0 0 0 0 1 2 e Particulat e Matter, p / c > 10 pm <6000 7 12 12 5 6 5 22 30 > 5 pm Report Result 31 110 128 44 34 27 146 165 CM g Al =L Report Result 232 638 778 297 288 239 738 940 Protein Concentration, mg / mL 90.0-110.0 97.7 95.4 95.2 98.2 95.7 99.1 96.0 96.8 Charge Variants Purity by iCIEF, % Main Peak >30.0 73.3% 73.4 72.0 70.7 69.3 68.9 66.6 63.2 Acidi c Peaks <60.0 20.2% 21.8 22.4 24.2 25.5 27.0 29.4 32.7 Basic Peaks <20.0 6.5% 4.9 5.6 5.1 5.2 4.1 4.0 4.1 Purity by CE-SDS (Reduced), % LC+ HC >90.0 98.9 98.8 98.6 98.4 98.6 98.0 97.6 97.4 T ot al M in or S pe ci es < 10.0 1.1 1.2 1.4 1.6 1.4 2.0 2.4 2.6 Purity by CE-SDS (Nonreduced), % Main Peak >90.0 99.0 98.9 98.7 98.6 98.4 98.5 98.2 97.6 Total LM WS < 10.0 0.% 1.0 1.2 1.2 1.3 1.3 1.4 1.8 Purity by SEC, % Mon omer (Mai >95.0 98.7 98.7 98.4 98.3 98.3 97.9 97.9 97.6 n Peak ) HM WS <5.0 1.3 1.3 1.6 1.7 1.7 2.0 2.0 2.3 (ELISA Binding) Bioassay, %Relative Potency 60 - 140 100 99 106 107 104 85 86 95 Sterility No growth NG NT NT NT NT NT NT NT CCIT Pass NT NT NT NT NT NT NT NT Table 19: Long-term Stability Data for Clinical Lot 20220902 at 5°C ± 3°C, Inverted Test / Attribute Acceptance Criteria Timepoints (months) 0 1 3 6 9 12 18 Visible particles (Refer to USP / Ph. Eur.) Liquid L L L L L L L EFOVP EFOV P EFOVP EFOVP EFOVP EFOVP EFOVP EFOVP Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 B6 B6 B5 B5 B5 B5 B5 Clarity, NTU <60.0 19.7 19.8 18.8 21.4 23.9 19.9 19.6 PH 6.7-7.7 7.2 7.2 7.3 7.2 7.3 7.2 7.3 Subvisibl e Particulat e Matter, p / c > 25 pm <600 1 0 0 1 0 3 0 > 10 pm <6000 16 24 3 6 20 18 2 > 5 pm Report Result 168 192 20 45 120 107 48 > 2 pm Report Result 1502 960 300 305 525 794 434 Protein Concentration, mg / mL 135.0-165.0 153.8 150.0 147.3 152.1 155.0 153.9 156.5 Charge Variants Main Peak >30.0 73.1 71.1 71.7 69.9 67.2 67.9 66.5 Acidic Peaks <60.0 22.2 24.2 23.6 25.3 26.5 27.5 28.8 Purity by iCIEF, % Basic Peaks <20.0 4.7 4.7 4.8 4.8 6.2 4.5 4.7 Purity by CE- SDS (Reduced), % LC+HC > 90.0% 98.6 98.5 98.3 98.3 98.2 98.1 97.9 Total Minor Species Report Result 1.4 1.5 1.7 1.7 1.8 1.9 2.1 Purity by CE-SDS (Nonreduced), % Main Peak >85.0 98.7 98.6 98.6 98.4 98.1 98.1 97.8 Total LMWS Report Result 1.1 1.2 1.2 1.2 1.4 1.4 1.5 Purity by SEC, % Monomer (Main Peak) >90.0 98.3 98.2 98.2 97.8 97.7 97.6 97.4 HMWS <5.0 1.7 1.8 1.8 2.1 2.3 2.3 2.5 LMWS Report Result ND ND ND 0.1 % ND 0.0 0.1 (ELISA Binding) Bioassay, %Relative Potency 60 - 140 107 113 111 105 103 102 88 Sterility No Growth NG NT NT NT NT NT NG CCIT Pass NT NT NT NT NT Pass Pass Table 20: Long-term Stability Data for Clinical Lot 20230201 at 5°C ± 3°C, Inverted Test / Attribute Acceptance Criteria Timepoints (months) 0 1 3 6 9 12 18 Visible particles (Refer to Liquid L L L L L L L USP / Ph. Eur.) EFOVP EFOV P EFOV P EFOV P EFOV P EFOV P EFOV P EFOVP Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No.2 B6 B6 B6 B5 B5 B5 B5 Clarity, NTU <60.0 19.1 22.0 23.8 20.0 20.2 19.4 20.3 PH 6.7-7.7 7.2 7.2 7.2 7.2 7.2 7.3 7.2 Subvisibl e Parti culat e Matter, p / c > 25 gm <600 0 1 0 0 0 1 3 > 10 gm <6000 2 2 3 6 9 7 70 > 5 gm Report Result 26 20 25 43 96 50 390 > 2 gm Report Result 252 154 151 232 690 359 1789 Protein Concentration, mg / mL 135.0- 165.0 152.0 157.1 153.1 153.1 153.0 153.8 150.3 Charge Variants Purity by iCIEF, % Main Peak >30.0 72.8 71.9 71.9 71.6 70.6 67.2 66.4 Acidic Peaks <60.0 22.0 23.1 23.8 23.8 25.1 28.1 29.4 Basic Peaks <20.0 5.2 5.0 4.4 4.7 4.3 4.7 4.2 Purity by CE-SDS (Reduced), % LC+HC >90.0 98.7 98.6 98.4 98.3 98.0 98.1 97.9 Total Minor Species Report Result 1.3 1.4 1.6 1.7 2.0 1.9 2.1 Purity by CE-SDS (Nonreduced), % Main Peak > 85.0 98.7 98.7 98.6 98.4 98.5 98.2 98.0 Total LMWS Report Result 1.1 1.1 1.2 1.2 1.2 1.4 1.6 Purity by SEC, % Monomer (Main Peak) >90.0 98.3 98.1 98.0 97.9 97.9 97.6 97.4 HMWS <5.0 1.7 1.8 2.0 2.1 2.1 2.3 2.4 LMWS Report Result ND 0.1% ND ND ND 0.1% 0.2 (ELISA Binding) Bioassay, %Relative Potency 60 - 140 103 99 105 103 102 103 103 Sterility No Growth NG NT NT NT NT NT NT CCIT Pass NT NT NT NT NT Pass NT Table 21: Long Term Stability Data for Clinical Lot 20230603 at 5°C ± 3°C, Inverted Test / Attribute Acceptance Criteria Timepoints (months) 0 1 3 6 9 12 Visible particles (Refer to USP / Ph. Eur.) Liquid L L L L L L EFOVP EFOV P EFOV P EFOV P EFOV P EFOV P EFOVP Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 B6 B6 B6 B6 B6 B5 Clarity, NTU <60.0 24.1 23.9 20.4 21.1 19.6 19.5 PH 6.7-7.7 7.2 7.2 7.2 7.2 7.2 7.2 Sub vi sib le Particula te Matter, p / c > 25 pm <600 0 0 0 0 0 0 > 10 pm <6000 0 0 0 1 4 14 > 5 pm Report Result 2 0 11 14 38 112 > 2 pm Report Result 11 32 92 108 275 543 Protein Concentration, mg / mL 135.0- 165.0 152.2 151.3 153.7 150.6 151.0 152.9 Charge Variant s Purity by iCIEF, % Main Peak >30.0 76.3 75.4 74.2 72.5 71.6 71.5 Acidic Peaks <60.0 19.7 20.1 21.5 22.1 23.5 24.5 Basic Peaks <20.0 4.0 4.5 4.3 5.4 4.9 4.0 LC+HC >90.0 98.3 98.5 98.5 98.5 98.3 98.1 Purity by CE-SDS (Reduced), % Total Minor Species Report Result 1.7 1.5 1.5 1.5 1.7 1.9 Purity by CE-SDS (Nonreduced), % Main Peak > 85.0 98.7 98.7 98.6 98.5 98.5 98.3 Total LMWS Report Result 1.1 1.2 1.2 1.2 1.3 1.3 Purity by SEC, % Monomer (Main Peak) >90.0 98.5 98.4 98.3 98.2 98.1 98.0 HMWS 5.0 1.5 1.6 1.7 1.8 1.9 2.0 LMWS Report Result ND ND ND ND ND ND Poloxamer 188 Content, %(w / v) Report Result 0.09 NT NT 0.11 NT 0.10 (ELISA Binding) Bioassay, %Relative Potency 60 - 140 98 107 100 116 101 99 Sterility No Growth NG NT NT NT NT NT CCIT Pass NT NT NT NT NT Pass Table 22: Long Term Stability Data for Clinical Lot 20231002 at 5°C ± 3°C, Inverted Test / Attribute Acceptance Criteria Timepoints (months) 0 1 3 6 Visible particles (Refer Liquid L L L L to USP / Ph. Eur.) EFOVP EFOVP EFOVP EFOVP EFOVP Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 B6 B6 B6 B6 Clarity, NTU <60.0 21.5 20.5 20.1 20.0 PH 6.7-7.7 7.2 7.2 7.2 7.2 Subvisi ble Parti cul ate Matter, p / c > 25 pm <600 4 0 0 1 > 10 pm <6000 6 9 4 3 > 5 pm Report Result 14 74 27 16 > 2 pm Report Result 178 568 220 190 Protein Concentration, mg / mL 135.0- 165.0 152.1 151.7 149.8 151.0 Charge Variants Purity by iCIEF, % Main Peak >30.0 74.6 75.1 74.8 73.1 Acidic Peaks <60.0 20.5 20.7 20.7 23.0 Basic Peaks <20.0 4.9 4.2 4.5 3.8 Purity by CE- SDS ^Reduced), LC+HC >90.0 98.6 98.3 98.5 98.4 Total Minor Species Report Result 1.4 1.7 1.5 1.6 Purity by CE-SDS (Nonreduced), % Main Peak > 85.0 98.6 98.8 98.6 98.4 Total LMWS Report Result 1.1 1.1 1.2 1.3 Purity by SEC, % Monomer (Main Peak) >90.0 98.5 98.4 98.4 98.2 HMWS <5.0 1.5 1.6 1.6 1.8 LMWS Report Result ND ND ND ND Poloxamer 188 Content, %(w / v) Report Result 0.09 NT NT 0.11 (ELISA Binding) Bioassay, %Relative Potency 60 - 140 97 99 105 102 Sterility No Growth NG NT NT NT CCIT Pass NT NT NT NT Table 23: Long-term Stability Data for Clinical Lot 20240302 at 5°C ± 3°C, Inverted Test / Attribute Acceptance Criteria Timepoints (months) 0 1 3 6 Visible particles (Refer to USP / Ph. Eur.) Liquid L L L L EFOVP EFOVP EFOVP EFOVP EFOVP Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 B6 BY5 B5 B5 Clarity, NTU <60.0 19.6 19.4 20.3 19.9 pH 6.7-7.7 7.2 7.2 7.2 Subvisi ble Parti cul ate Matter, p / c > 25 pm <600 0 0 0 0 > 10 pm <6000 0 0 4 25 > 5 pm Report Result 16 12 21 130 > 2 pm Report Result 469 166 304 676 Protein Concentration, mg / mL 135.0 - 165.0 151.9 153.3 151.8 159.9 Charge Variants Purity by Main Peak >30.0 75.3 73.7 73.1 71.8 Acidic Peaks <60.0 20.5 22.4 22.9 23.8 Basic Peaks <20.0 4.2 3.9 4.0 4.4 iCIEF, % Purity by CE- SDS ^Reduced), LC+HC >90.0 98.5 98.5 98.4 98.5 Total Minor Species Report Result 1.5 1.5 1.6 1.5 Purity by CE-SDS (Nonreduced), % Main Peak >85.0 98.7 98.5 98.6 98.4 Total LMWS Report Result 1.1 1.3 1.1 1.2 Purity by SEC, % Monomer (Main Peak) >90.0 98.4 98.3 98.2 98.0 HMWS <5.0 1.6 1.7 1.8 2.0 LMWS Report Result ND ND ND ND Poloxamer 188 Content, %(w / v) Report Result 0.08 NT NT 0.09 (ELISA Binding) Bioassay, %Relative Potency 60 - 140 101 88 96 99 Sterility No Growth NG NT NT NT CCIT Pass NT NT NT NT Table 24: Long-term Stability Data for Clinical Lot 20230201 at 5°C ± 3°C, Upright Test / Attribute Acceptanc e Criteria Timepoints (months) 0 1 3 6 9 12 Visible particles (Refer to Liquid L L L L L L USP / Ph. Eur.) EFOVP EFOVP EFOVP EFOVP EFOVP EFOVP EFOVP Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 B6 B6 B6 B5 B5 B5 Clarity, NTU <60.0 19.1 21.6 23.1 20.3 20.3 19.7 PH 6.7-7.7 7.2 7.2 7.2 7.2 7.2 7.3 Sub visible Particulate Matter, p / c > 25 pm <600 0 0 0 0 0 2 > 10 pm <6000 2 4 2 3 10 10 > 5 pm Report Result 26 22 22 40 56 44 > 2 pm Report Result 252 212 193 316 428 380 Protein Concentration, mg / mL 135.0 165.0 152.0 158.6 153.4 153.2 153.5 154.7 Charge Variants Purity by iCIEF, % Main Peak >30.0 72.8 72.5 72.4 71.9 71.2 66.0 Acidic Peaks <60.0 22.0 22.5 23.6 23.5 25.0 28.3 Basic Peaks <20.0 5.2 4.9 4.0 4.6 3.9 5.7 Purity by CE-SDS (Reduced), % LC+HC >90.0 98.7 98.3 98.2 98.1 98.1 98.1 Total Minor Species Report Result 1.3 1.7 1.8 1.9 1.9 1.9 Purity by CE-SDS (Nonreduced), % Main Peak > 85.0 98.7 98.6 98.7 98.3 98.6 98.2 Total LMWS Report Result 1.1 1.2 1.1 1.2 1.1 1.4 Purity by SEC, % Monomer (Main Peak) >90.0 98.3 98.1 98.0 98.0 97.9 97.6 HMWS <5.0 1.7 1.8 2.0 2.0 2.1 2.3 LMWS Report Result ND 0.1 0.0 ND ND 0.1 (ELISA Binding) Bioassay, %Relative Potency 60 - 140 103 99 104 104 87 106 Sterility No Growth NG NT NT NT NT NT CCIT Pass NT NT NT NT NT NT Table 25: Long Term Stability Data for Clinical Lot 20230603 at 5°C ± 3°C, Upright Test / Attribute Acceptance Criteria Timepoints (months) 0 1 3 6 9 12 Visible particles (Refer to USP / Ph. Eur.) Liquid L L L L L L EFOVP EFOV P EFOVP EFOVP EFOVP EFOVP EFOVP Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 B6 B6 B6 B6 B6 B5 Clarity, NTU <60.0 24.1 23.4 20.5 20.7 19.6 19.7 pH 6.7-7.7 7.2 7.2 7.2 7.2 7.2 7.2 Subvisibl e Particulat e Matter, p / c > 25 pm <600 0 NT NT NT NT 1 > 10 pm <6000 0 NT NT NT NT 13 > 5 pm Report Result 2 NT NT NT NT 120 > 2 pm Report Result 11 NT NT NT NT 717 Protein Concentration, mg / mL 135.0 165.0 152.2 153.0 151.4 150.6 152.7 152.0 Charge Variants Purity by iCIEF, % Main Peak >30.0 76.3 75.5 74.8 72.7 71.1 71.8 Acidic Peaks <60.0 19.7 19.8 21.3 22.6 23.9 24.2 Basic Peaks <20.0 4.0 4.7 3.9 4.6 4.9 4.0 Purity by CE-SDS (Reduced), % LC+HC >90.0 98.3 98.5 98.7 98.3 98.3 98.3 Total Minor Species Report Result 1.7 1.5 1.3 1.7 1.7 1.7 Purity by CE-SDS (Nonreduced), % Main Peak >85.0 98.7 98.7 98.6 98.4 98.4 98.2 Total LMWS Report Result 1.1 1.2 1.1 1.3 1.2 1.4 Purity by SEC, % Monomer (Main Peak) >90.0 98.5 98.4 98.3 98.2 98.1 98.0 HMWS <5.0 1.5 1.6 1.7 1.8 1.9 2.0 LMWS Report Result ND ND ND ND ND ND Poloxamer 188 Content, %(w / v) Report Result 0.09 NT NT 0.11 NT 0.09 (ELISA Binding) Bioassay, %Relative Potency 60 - 140 98 105 99 106 98 96 Sterility No Growth NG NT NT NT NT NT CCIT Pass NT NT NT NT NT Pass Table 26: Long Term Stability Data for Clinical Lot 20231002 at 5°C ± 3°C, Upright Test / Attribute Acceptanc e Criteria Timepoints (months) 0 1 3 6 Visible particles Refer to USP / Ph. Eur.) Liquid L L L EFOVP EFOVP EFOVP EFOVP EFOVP Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 B6 B6 B6 B6 Clarity, NTU <60.0 21.5 20.3 20.3 19.8 PH 6.7-7.7 7.2 7.2 7.2 7.2 Subvisibl e > 25 pm <600 4 NT NT -NT > 10 pm <6000 6 NT NT -NT Particulat e Matter, p / c > 5 pm Report Result 14 NT NT NT > 2 pm Report Result 178 NT NT NT Protein Concentration, mg / mL 135.0 - 165.0 152.1 151.7 150.1 149.8 Charge Variants Purity by iCIEF, % Main Peak >30.0 74.6 74.6 74.6 72.8- Acidic Peaks <60.0 20.5 21.1 20.9 22.9 Basic Peaks <20.0 4.9 4.3 4.4 4.3 Purity by CE-SDS (Reduced), % LC+HC >90.0 98.6 98.5 98.8 98.4 Total Minor Species Report Result 1.4 1.5 1.2 1.6 Purity by CE-SDS (Nonreduced), % Main Peak > 85.0 98.6 98.8 98.7 98.4 Total LMWS Report Result 1.1 1.1 1.1 1.2 Purity by SEC, % Monomer (Main Peak) >90.0 98.5 98.4 98.4 98.2 HMWS <5.0 1.5 1.6 1.6 1.8 LMWS Report Result ND ND ND ND Poloxamer 188 Content, %(w / v) Report Result 0.09 NT NT 0.11 (ELISA Binding) Bioassay, %Relative Potency 60 - 140 97 105 104 110 Sterility No Growth NG NT NT NT CCIT Pass NT NT NT NT Table 27: Long-term Stability Data for Clinical Lot 20240302 at 5°C ± 3°C, Upright Test / Attribute Acceptanc e Criteria Timepoints (months) 0 1 3 6 Visible particles (Refer to USP / Ph. Eur.) Liquid L L L L EFOVP EFOVP EFOVP EFOVP EFOVP Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 B6 BY5 B5 B5 Clarity, NTU <60.0 19.6 19.3 19.8 19.8 pH 6.7-7.7 7.2 7.2 7.2 7.2 Subvisibl e Particulat e Matter, p / c > 25 pm <600 0 NT NT NT > 10 pm <6000 0 NT NT NT > 5 pm Report Result 16 NT NT NT > 2 pm Report Result 469 NT NT NT Protein Concentration, mg / mL 135.0 - 165.0 151.9 153.3 151.2 160.6 Charge Variant s Purity by iCIEF, % Main Peak >30.0 75.3 73.5 73.7 71.6 Acidic Peaks <60.0 20.5 22.3 22.4 24.1 Basic Peaks <20.0 4.2 4.2 3.9 4.4 Purity by CE- SDS (Reduced), % LC+HC >90.0 98.5 98.4 98.3 98.4 Total Minor Species Rep ort Res ult 1.5 1.6 1.7 1.6 Purity Main Peak > 85.0 98.7 98.6 98.5 98.4 by CE- SDS (Nonreduced), % Total LMWS Rep ort Res ult 1.1 1.2 1.1 1.3 Purity by SEC, % Monomer (Main Peak) >90.0 98.4 98.3 98.2 98.0 HMWS <5.0 1.6 1.7 1.8 2.0 LMWS Rep ort Res ult ND ND ND ND Pol oxamer 188 Content, %(w / v) Rep ort Res ult 0.08 NT NT 0.10 (ELISA Binding) Bioassay, %Relative Potency 60 - 140 101 91 98 98 Sterility3 No Growth NG NT NT NT CCITb Pass NT NT NT NT Table 28: Stress Stability Data for Clinical Lot 20220502 at 25°C ± 2°C / 60% ± 5%RH, Inverted Test / Attribute Acceptance Criteria Timepoints (months) 0 1 3 6 Visible particles (Refer to USP / Ph. Eur.) Liquid L L L L EFOVP EFOVP EFOVP EFOVP EFOVP Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No.3 B6 B6 B5 B5 Clarity, NTU <60.0 20.4 20.4 20.0 19.3 PH 6.7-7.7 7.2 7.2 7.2 7.2 Subvisibl e Parti culat e Matter, p / c > 25 pm <600 0 2 2 1 > 10 pm <6000 7 52 38 19 > 5 pm Report Result 31 279 154 87 > 2 pm Report Result 232 1370 716 512 Protein Concentration, mg / mL 90.0-110.0 97.7 95.8 96.4 97.9 Charge Variants Purity by iCIEF, % Main Peak >30.0 73.3 65.2 50.6 34.0 Acidic Peaks <60.0 20.2 29.4 44.9 Basic Peaks <20.0 6.5 5.5 4.4 5.4 Purity by CE- SDS (Reduced), % LC+HC >90.0 98.9 98.3 96.6 93.5 Total Minor Species < 10.0 1.1 1.7 3.4 6.5 Purity by CE- SDS (Nonreduced), % Main Peak >90.0 99.0 98.2 96.1 93.8 Total LMWS < 10.0 0.9 1.5 3.2 4.7 Purity by SEC, % Monomer (Main Peak) >95.0 98.7 98.2 96.8 95.3 HMWS <5.0 1.3 1.8 3.1 4.6 (ELISA Binding) Bioassay, %Relative Potency 60 - 140 100 93 102 96 a Acceptance criterion was exceeded, indicating a significant change in the charge profile at the accelerated condition. Table 29: Accelerated Stability Data for Clinical Lot 20220902 at 25°C ± 2°C / 60% ± 5%RH, Inverted Test / Attribute Acceptance Criteria Timepoints (months) 0 1 3 6 Visible particles (Refer to USP / Ph. Eur.) Liquid L L L L EFOVP EFOVP EFOVP EFOVP EFOVP Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 B6 B5 B5 B5 Clarity, NTU <60.0 19.7 19.5 18.6 20.5 PH 6.7-7.7 7.2 7.2 7.3 7.2 Subvisibl e Particulat e Matter, p / c > 25 pm <600 1 2 1 7 > 10 pm <6000 16 50 28 135 > 5 pm Report Result 168 262 183 578 > 2 pm Report Result 1502 1453 984 2378 Protein Concentration, mg / mL 135.0- 165.0 153.8 154.3 148.3 152.9 Charge Variants Purity by iCIEF, % Main Peak >30.0 73.1 64.1 49.5 34.2 Acidic Peaks <60.0 22.2 31.9 45.2 60.6 Basic Peaks <20.0 4.7 4.0 5.3 60.6 a Purity by CE-SDS (Reduced), % LC+HC >90.0 98.6 97.9 96.5 5.2 Total Minor Species Report Result 1.4 2.1 3.5 94.3 Purity by CE-SDS (Nonreduced), % Main Peak > 85.0 98.7 97.7 96.1 5.7 Total LMWS Report Result 1.1 1.7 2.9 93.9 Purity by SEC, % Monomer (Main Peak) >90.0 98.3 97.5 96.7 4.4 HMWS <5.0 1.7 2.5 3.3 94.8 LMWS Report Result ND 0.1 ND 5.0 (ELISA Binding) Bioassay, %Relative Potency 60 - 140 107 106 103 100 Table 30: Accelerated Stability Data for Clinical Lot 20230201 at 25°C ± 2°C / 60% ± 5%RH, Inverted Test / Attribute Acceptance Criteria Timepoints (months) 0 1 3 6 9 Visible particles (Refer to USP / Ph. Eur.) Liquid L L L L L EFOVP EFOVP EFOVP EFOVP EFOVP EFOVP Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 B6 B5 B5 B5 B4 Clarity, NTU <60.0 19.1 21.3 23.0 19.3 19.9 PH 6.7-7.7 7.2 7.2 7.2 7.3 7.3 Subvisibl e Particulat e Matter, p / c > 25 pm <600 0 4 2 2 2 > 10 pm <6000 2 36 21 36 42 > 5 pm Report Result 26 166 108 175 222 > 2 pm Report Result 252 822 411 791 1293 Protein Concentration, mg / mL 135.0- 165.0 152.0 156.0 153.1 154.7 153.4 Charge Variants Purity by iCIEF, % Main Peak >30.0 72.8 64.7 51.1 35.2 25.2 a Acidic Peaks <60.0 22.0 30.2 45.2 59.7 70.0 a Basic Peaks <20.0 5.2 5.0 3.7 5.1 4.8 Purity LC+HC >90.0 98.7 98.0 96.5 94.6 92.6 by CE- SDS (Reduced), % Total Minor Species Report Result 1.3 2.0 3.5 5.4 5.9 Purity by CE-SDS (Nonreduced), % Main Peak > 85.0 98.7 98.0 96.5 94.2 92.1 Total LMWS Report Result 1.1 1.6 2.5 4.2 7.4 Purity by SEC, % Monomer (Main Peak) >90.0 98.3 97.6 96.7 95.4 93.9 HMWS 5.0 1.7 2.3 3.3 4.5 5.9 LMWS Report Result ND 0.1 0.1 0.1 0.2 (ELISA Binding) Bioassay, %Relative Potency 60 - 140 103 104 105 96 94 a Acceptance criterion was exceeded, indicating a significant change in the charge profile at the accelerated condition. Table 31: Accelerated Stability Data for Clinical Lot 20230603 at 25°C ± 2°C / 60%RH ± 5%RH, Inverted Test / Attribute Acceptance Criteria Timepoints (months) TO 1 Month 3 Month s 6 Months Visible particles (Refer to USP / Ph. Eur.) Liquid L L L L EFOVP EFOVP EFOVP EFOVP EFOVP Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 B6 B5 B5 B5 Clarity, NTU <60.0 24.1 23.7 19.7 20.1 pH 6.7-7.7 7.2 7.2 7.2 7.2 Subvisibl e Particulat e Matter, p / c > 25 pm <600 0 0 1 0 > 10 pm <6000 0 6 32 40 > 5 pm Report Result 2 27 194 255 > 2 pm Report Result 11 159 998 1406 Protein Concentration, mg / mL 135.0- 165.0 152.2 153.0 153.7 150.7 Charge Variants Purity by iCIEF, % Main Peak >30.0 76.3 68.4 50.9 36.4 Acidic Peaks <60.0 19.7 27.0 43.8 57.8 Basic Peaks <20.0 4.0 4.5 5.3 5.8 Purity by CE-SDS (Reduced), % LC+HC >90.0 98.3 97.9 96.6 94.5 Total Minor Species Report Result 1.7 2.1 3.4 5.5 Purity by CE-SDS (Nonreduced), % Main Peak >90.0 98.7 98.2 96.5 94.4 Total LMWS Report Result 1.1 1.4 2.6 4.0 Purity by SEC, % Monomer (Main Peak) >95.0 98.5 97.9 96.8 95.5 HMWS <5.0 1.5 2.1 3.1 4.4 LMWS Report Result ND 0.1 0.1 0.1 Poloxamer 188 Content %(w / v) Report Result 0.09 NT NT 0.11 (ELISA Binding) Bioassay, %Relative Potency 60 - 140 98 99 94 102 Table 32: Accelerated Stability Data for Clinical Lot 20231002 at 25°C ± 2°C / 60%RH ± 5%RH, Inverted Test / Attribute Acceptance Criteria Timepoints (months) 0 1 3 6 Visible particles (Refer to USP / Ph. Eur.) Liquid L L L L EFOVP EFOVP EFOVP EFOVP EFOVP Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 B6 B5 B5 B5 Clarity, NTU <60.0 21.5 20.7 19.5 19.2 PH 6.7-7.7 7.2 7.2 7.2 7.3 Subvisibl e > 25 pm <600 4 0 0 0 > 10 pm <6000 6 12 16 10 Particulat e Matter, p / c > 5 pm Report Result 14 77 98 63 > 2 pm Report Result 178 399 608 410 Protein Concentration, mg / mL 135.0- 165.0 152.1 151.6 150.1 150.9 Charge Variants Purity by iCIEF, % Main Peak >30.0 74.6 67.7 53.9 38.2 Acidic Peaks <60.0 20.5 28.2 41.8 59.1 Basic Peaks <20.0 4.9 4.1 4.2 2.8 Purity by CE-SDS (Reduced), % LC+HC >90.0 98.6 98.0 96.6 94.3 Total Minor Species Report Result 1.4 2.0 3.4 5.7 Purity by CE-SDS (Nonreduced), % Main Peak >90.0 98.6 98.1 96.6 94.2 Total LMWS Report Result 1.1 1.5 2.5 4.2 Purity by SEC, % Monomer (Main Peak) >95.0 98.5 97.9 97.1 95.4 HMWS <5.0 1.5 2.1 2.7 4.4 LMWS Report Result ND ND 0.2 0.2 Poloxamer 188 Content % (w / v)a Report Result 0.09 NT 0.10 0.11 (ELISA Binding) Bioassay, %Relative Potency 60 - 140 97 100 99 102 Table 33: Accelerated Stability Data for Clinical Lot 20240302 at 25°C ± 2°C, 60% ± 5%RH, Inverted Test / Attribute Acceptance Criteria Timepoints (months) 0 1 3 6 Visible particles (Refer to USP / Ph. Eur.) Liquid L L L L EFOVP EFOVP EFOVP EFOVP EFOVP Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 B6 B5 B5 B5 Clarity, NTU <60.0 19.6 19.1 19.4 20.1 PH 6.7-7.7 7.2 7.2 7.2 7.2 Subvisibl e Parti culat e Matter, p / c > 25 pm <600 0 0 0 9 > 10 pm <6000 0 12 26 106 > 5 pm Report Result 16 56 126 537 > 2 pm Report Result 469 442 691 2628 Protein Concentration, mg / mL 135.0- 165.0 151.9 154.2 152.5 160.8 Charge Variants Purity by iCIEF, % Main Peak >30.0 75.3 66.6 52.0 35.9 Acidic Peaks <60.0 20.5 29.4 44.3 59.6 Basic Peaks <20.0 4.2 4.0 3.8 4.5 Purity by CE-SDS (Reduced), % LC+HC >90.0 98.5 97.7 96.2 94.5 Total Minor Species Report Result 1.5 2.3 3.8 5.5 Purity by CE-SDS (Nonreduced), % Main Peak >85.0 98.7 97.9 96.7 94.2 Total LMWS Report Result 1.1 1.6 2.5 4.3 Purity by SEC, % Monomer (Main Peak) >90.0 98.4 97.7 96.8 95.1 HMWS <5.0 1.6 2.2 3.0 4.7 LMWS Report Result ND 0.1 0.2 0.3 Poloxamer 188 Content % (w / v) Report Result 0.08 NT 0.09 0.10 (ELISA Binding) Bioassay, %Relative Potency 60 - 140 101 97 96 96 Table 34: Stress Stability Data for Clinical Lot 20220502 at 40°C ± 2°C / 75% ± 5%RH, Inverted Test / Attribute Acceptance Criteria Timepoints TO 1 Week 2 Weeks 1 Month Visible particles (Refer to USP / Ph. Eur.) Liquid L L L L EFOVP EFOVP EFOVP EFOVP EFOVP Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 3 B6 B5 B5 B5 Clarity, NTU <60.0 20.4 20.3 20.8 21.4 PH 6.7-7.7 7.2 7.2 7.1 7.2 Subvisible Particulate Matter, p / c > 25 pm <600 0 0 0 1 > 10 pm <6000 7 5 15 19 > 5 pm Report Result 31 30 77 118 > 2 pm Report Result 232 316 607 810 Protein Concentration, mg / mL 90.0-110.0 97.7 97.5 96.7 96.3 Charge Variants Purity by iCIEF, % Main Peak >30.0 73.3 60.4 48.0 28.7 a Acidic Peaks <60.0 20.2 33.9 46.7 67.0 a Basic Peaks <20.0 6.5 5.7 5.3 4.3 Purity by CE-SDS (Reduced), % LC+HC >90.0 98.9 98.2 96.2 93.9 Total Minor Species < 10.0 1.1 1.8 3.8 6.1 Main Peak >90.0 99.0 98.0 96.2 92.6 Purity by CE-SDS (Nonreduced), % Total LMWS < 10.0 0.9 1.7 3.1 5.9 Purity by SEC, % Monomer (Main Peak) >95.0 98.7 97.0 95.6 92.3 HMWS <5.0 1.3 2.7 4.2 7.1 (ELISA Binding) Bioassay, %Relative Potency 60 - 140 100 98 97 89 a Acceptance criterion was exceeded, indicating a significant change in the charge profile at the stress condition. Table 35: Stress Stability Data for Clinical Lot 20230201 at 40°C ± 2°C / 75% ± 5%RH, Inverted Test / Attribute Acceptance Criteria Timepoints TO 1 Week 2 Weeks 1 Month Visible particles (Refer to USP / Ph. Eur.) Liquid L L L L EFOVP EFOVP EFOVP EFOVP EFOVP Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 B6 B5 B5 B5 Clarity, NTU <60.0 19.1 19.8 20.0 22.6 PH 6.7-7.7 7.2 7.2 7.2 7.2 Subvisible Particulate Matter, p / c > 25 pm <600 0 0 0 0 > 10 pm <6000 2 7 3 11 > 5 pm Report Result 26 62 31 68 > 2 pm Report Result 252 213 244 482 Protein Concentration, mg / mL 135.0- 165.0 152.0 154.2 155.8 156.0 Charge Variants Purity by iCIEF, % Main Peak >30.0 72.8 59.4 48.2 29.2 a Acidic Peaks <60.0 22.0 35.2 46.7 67.0 a Basic Peaks <20.0 5.2 5.4 5.1 3.9 Purity by CE-SDS (Reduced) LC+HC >90.0 98.7 97.8 96.4 93.7 Total Minor Species Report Result 1.3 2.2 3.6 6.3 Purity by CE-SDS (Nonreduced), % Main Peak > 85.0 98.7 97.3 96.6 92.9 Total LMWS Report Result 1.1 2.1 2.8 5.7 Purity by SEC, % Monomer (Main Peak) >90.0 98.3 96.9 95.2 91.4 HMWS <5.0 1.7 3.1 4.6 8.2 LMWS Report Result ND ND 0.3 0.4 (ELISA Binding) Bioassay, %Relative Potency 60 - 140 103 102 99 95 a Acceptance criterion was exceeded, indicating a significant change in the charge profile at the stress condition. Table 36: Stress Stability Data for Clinical Lot 20230603 at 40°C ± 2°C / 75%RH ± 5%RH, Inverted Test / Attribute Acceptance Criteria Timepoints TO 1 Week 2 Weeks 1 Month Visible particles (Refer to USP / Ph. Eur.) Liquid L L L L EFOVP EFOVP EFOVP EFOVP EFOVP Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 B6 B5 B5 B5 Clarity, NTU <60.0 24.1 23.3 23.4 23.6 PH 6.7-7.7 7.2 7.2 7.2 7.2 Subvisible Particulate Matter, p / c > 25 pm <600 0 0 0 0 > 10 pm <6000 0 0 8 0 > 5 pm Report Result 2 8 50 9 > 2 pm Report Result 11 65 455 146 Protein Concentration, mg / mL 135.0- 165.0 152.2 149.3 152.3 153.5 Charge Variants Purity by iCIEF, % Main Peak >30.0 76.3 63.3 50.1 32.2 Acidic Peaks <60.0 19.7 32.6 44.4 63.6 a Basic Peaks <20.0 4.0 4.1 5.6 4.1 Purity by CE-SDS (Reduced), % LC+HC >90.0 98.3 97.2 96.2 93.8 Total Minor Species Report Result 1.7 2.8 3.8 6.2 Purity by CE-SDS (Nonreduced), % Main Peak >90.0 98.7 97.6 96.2 93.5 Total LMWS Report Result 1.1 2.0 3.1 5.2 Purity by SEC, % Monomer (Main Peak) >95.0 98.5 97.0 95.5 92.3 HMWS <5.0 1.5 3.0 4.4 7.5 LMWS Report Result ND 0.0 0.1 0.2 (ELISA Binding) Bioassay, %Relative Potency 60 - 140 98 106 98 100 a Acceptance criterion was exceeded, indicating a significant change in the charge profile at the stress condition. Table 37: Stress Stability Data for Clinical Lot 20231002 at 40°C ± 2°C / 75%RH ± 5%RH, Inverted Test / Attribute Acceptance Criteria Timepoints TO 1 Week 2 Weeks 1 Month Visible particles (Refer to USP / Ph. Eur.) Liquid L L L L EFOVP EFOVP EFOVP EFOVP EFOVP Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 B6 B5 B5 B5 Clarity, NTU <60.0 21.5 21.8 22.2 20.6 PH 6.7-7.7 7.2 7.2 7.2 7.2 Subvisibl e Particulat e Matter, p / c > 25 pm <600 4 2 0 0 > 10 pm <6000 6 4 2 10 > 5 pm Report Result 14 18 16 48 > 2 pm Report Result 178 183 202 281 Protein Concentration, mg / mL 135.0- 165.0 152.1 152.7 157.1 147.4 Charge Variants Purity by iCIEF, % Main Peak >30.0 74.6 61.9 50.2 30.8 Acidic Peaks <60.0 20.5 33.3 45.1 64.8 a Basic Peaks <20.0 4.9 4.8 4.7 4.4 Purity by CE-SDS (Reduced), % LC+HC >90.0 98.6 97.2 96.6 93.4 Total Minor Species Report Result 1.4 2.8 3.4 6.6 Purity by CE-SDS (Nonreduced), % Main Peak >90.0 98.6 97.5 96.4 93.3 Total LMWS Report Result 1.1 2.0 2.8 5.5 Purity by SEC, % Monomer (Main Peak) >95.0 98.5 96.9 95.4 92.1 HMWS <5.0 1.5 3.0 4.4 7.7 LMWS Report Result ND 0.1 0.1 0.3 (ELISA Binding) Bioassay, %Relative Potency 60 - 140 97 105 102 98 a Acceptance criterion was exceeded, indicating a significant change in the charge profile at the stress condition. Table 38: Stress Stability Data for Clinical Lot 20240302 at 40°C ± 2°C / 75%RH ± 5%RH, Inverted Test / Attribute Acceptance Criteria Timepoints TO 1 Week 2 Weeks 1 Month Visible particles (Refer to USP / Ph. Eur.) Liquid L L L L EFOVP EFOVP EFOVP EFOVP EFOVP Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 B6 B5 B5 B5 Clarity, NTU <60.0 19.6 19.1 20.0 20.0 PH 6.7-7.7 7.2 7.2 7.2 7.3 Subvisibl e Particulat e Matter, p / c > 25 pm <600 0 5 0 0 > 10 pm <6000 0 13 2 1 > 5 pm Report Result 16 61 28 14 > 2 pm Report Result 469 342 301 226 Protein Concentration, mg / mL 135.0- 165.0 151.9 152.4 154.0 153.2 Charge Variants Purity by iCIEF, % Main Peak >30.0 75.3 61.5 19.6 31.3 Acidic Peaks <60.0 20.5 33.9 45.9 65.9 a Basic Peaks <20.0 4.2 4.6 4.5 2.8 Purity by CE-SDS (Reduced), % LC+HC >90.0 98.5 98.0 96.4 93.4 Total Minor Species Report Result 1.5 2.0 3.6 6.6 Purity by CE-SDS (Non- Main Peak >90.0 98.7 97.4 96.0 92.5 Total LMWS Report Result 1.1 2.1 3.1 6.0 reduced), % Purity by SEC, % Monomer (Main Peak) >95.0 98.4 96.8 95.4 91.6 HMWS <5.0 1.6 3.1 4.5 8.2 a LMWS Report Result ND 0.1 0.1 0.2 (ELISA Binding) Bioassay, %Relative Potency 60 - 140 101 96 97 89 a Acceptance criterion was exceeded, indicating a significant change in the charge profile at the stress condition.

[0616] The stability data for development batches are summarized in Table 39 through Table 44 and data for clinical batches are summarized in Table 45 through Table 59. Table 39: Long-term Stability Data for Development and Non-clinical Batch 2441S211215Y at -70°C ± 10°C Test / Attribute Timepoints (months) 0 1 3 6 9 12 18 24 Color, compared to Standard Solution (Refer to Ph. Eur.) B6 B6 B6 B6 B6 B6 B6 B6 Clarity, NTU 21.5 21.5 22.4 21.6 22.6 21.8 21.4 22.2 PH 7.2 7.2 7.2 7.1 7.1 7.1 7.1 7.0 Protein Concentration, mg / mL 101.2 101.2 103. 1 101. 2 102. 5 102. 5 100. 5 102.1 Charge Variants Purity by iCIEF, % Main Peak 74.8 74.1 73.9 74.5 74.3 75.5 75.4 76.7 Acidic Peaks 20.3 20.4 20.6 20.9 20.8 20.0 19.9 19.0 Basic Peaks 4.8 5.5 5.5 4.5 4.9 4.5 4.7 4.3 Purity by CE-SDS (Reduced), % LC+HC 98.4 98.8 98.1 98.6 98.4 98.7 98.4 98.7 Total Minor Species 1.6 1.2 1.9 1.4 1.6 1.3 1.6 1.3 Purity by CE-SDS (Nonreduced), % Main Peak 99.0 98.8 99.1 99.0 98.8 99.0 98.9 98.9 Total LMWS 0.8 1.1 0.9 1.0 1.0 0.9 1.1 1.0 Purity by SEC, % Monomer (Main Peak) 98.8 98.8 98.8 98.9 98.8 98.8 98.7 98.7 HMWS 1.2 1.2 1.2 1.1 1.2 1.2 1.3 1.3 Binding Bioassay (ELISA), % Relative potency 102 105 98 94 104 104 102 100 Table 40: Long-term Stability Data for Development Batch 2441S220510Y at -70°C ± 10°C Test / Attribute Time joints (months) 0 1 3 6 9 12 18 24 Color, compared to Standard Solution (Refer to Ph. Eur.) B6 B6 B6 B6 B6 B6 B6 B6 Clarity, NTU 21.0 21.2 20.7 21.2 21.3 20.7 21.6 21.3 PH 7.2 7.2 7.1 7.1 7.1 7.2 7.1 7.2 Protein Concentration, mg / mL 154.5 152. 1 151. 2 151. 8 150. 7 148. 7 149. 9 152.9 Charge Variants Purity by iCIEF Main Peak 72.9 73.7 73.6 74.0 75.1 74.5 76.2 74.3 Acidic Peaks 21.3 21.1 21.3 20.6 20.0 19.9 19.6 20.1 Basic Peaks 5.8 5.2 5.0 5.4 4.9 5.5 4.3 5.5 Purity by CE-SDS (Reduced), % LC+HC 98.7 98.8 98.7 98.5 99.0 98.5 98.8 98.5 Total Minor Species 1.3 1.2 1.3 1.5 1.0 1.5 1.2 1.5 Purity by CE-SDS (Nonreduced), % Main Peak 98.9 98.9 98.9 98.8 98.9 98.9 98.8 99.0 Total LMWS 1.0 1.1 1.0 1.1 1.0 1.0 1.1 0.9 Purity by SEC, % Monomer (Main Peak) 98.8 98.8 98.7 98.7 98.8 98.7 98.6 98.8 HMWS 1.2 1.2 1.3 1.3 1.2 1.3 1.4 1.2 Binding Bioassay (ELISA), % Relative potency 88 95 99 99 98 100 102 102 Table 41: Accelerated Stability Data for Development and Non-clinical Batch 2441S211215Y at 5°C ± 3°C Test / Attribute Timepoints (months) 0 1 3 6 Color, compared to Standard Solution (Refer to Ph. Eur.) B6 B6 B6 B6 Clarity, NTU 21.5 20.9 22.5 21.2 pH 7.2 7.2 7.2 7.2 Protein Concentration, mg / mL 101.2 102.3 102.8 103.4 Charge Variants Purity by iCIEF, % Main Peak 74.8 73.3 73.2 72.6 Acidic Peaks 20.3 21.3 21.7 22.7 Basic Peaks 4.8 5.4 5.1 4.7 Purity by CE-SDS (Reduced), % LC+HC 98.4 99.0 97.7 98.5 Total Minor Species 1.6 1.0 2.3 1.5 Purity by CE-SDS (Nonreduced), % Main Peak 99.0 98.8 98.9 98.8 Total LMWS 0.8 1.1 0.9 1.0 Purity by SEC, % Monomer (Main Peak) 98.8 98.7 98.6 98.7 HMWS 1.2 1.3 1.4 1.3 Binding Bioassay (ELISA), % Relative Potency 102 101 94 89 Table 42: Accelerated Stability Data for Development Batch 2441S220510Y at 5°C ± 3°C Test / Attribute Timepoints (months) 0  13  6 Color, compared to Standard Solution (Refer to Ph. Eur.) B6 B6 B5 B5 Clarity, NTU 21.0 20.8 19.4 19.6 PH 7.2 7.2 7.2 7.2 Protein Concentration, mg / mL 154.5 151.4 153.2 158.3 Charge Variants Purity by iCIEF, % Main Peak 72.9 73.1 73.0 72.2 Acidic Peaks 21.3 22.1 22.3 22.6 Basic Peaks 5.8 4.8 4.7 5.2 Purity by CE-SDS (Reduced), % LC+HC 98.7 98.6 98.2 98.3 Total Minor Species 1.3 1.4 1.8 1.7 Purity by CE-SDS (Nonreduced), % Main Peak 98.9 98.8 98.6 98.9 Total LMWS 1.0 1.1 1.2 1.0 Purity by SEC, % Monomer (Main Peak) 98.8 98.7 98.4 98.3 HMWS 1.2 1.3 1.6 1.7 Binding Bioassay (ELISA), % Relative potency 88 106 94 92 Table 43: Stress Stability Data for Development and Non-clinical Batch 2441S211215Y at 25°C ± 2°C / 60 ± 5% RH Test / Attribute Timepoints (months) 0 1 2 3 Color, compared to Standard Solution (Refer to Ph. Eur.) B6 B6 B5 B5 Clarity, NTU 21.5 20.4 20.5 22.1 PH 7.2 7.3 7.2 7.2 Protein Concentration, mg / mL 101.2 105.5 103.4 108.9 Charge Variants Purity by iCIEF, % Main Peak 74.8 67.1 61.4 53.8 Acidic Peaks 20.3 27.5 34.0 41.6 Basic Peaks 4.8 5.4 4.5 4.7 Purity by CE-SDS (Reduced), % LC+HC 98.4 98.5 96.7 96.1 Total Minor Species 1.6 1.5 3.3 3.9 Purity by CE-SDS (Nonreduced), % Main Peak 99.0 98.4 98.0 97.1 Total LMWS 0.8 1.5 1.8 2.3 Purity by SEC, % Monomer (Main Peak) 98.8 98.3 97.9 97.6 HMWS 1.2 1.7 2.0 2.4 Binding Bioassay (ELISA), % Relative potency 102 101 103 100 Table 44: Stress Stability Data for Development Batch 2441S220510Y at 25°C ± 2°C / 60 ± 5% RH Test / Attribute Timepoints (months) 0 1 2 3 Color, compared to Standard Solution (Refer to Ph. Eur.) B6 B5 B5 B5 Clarity, NTU 21.0 20.2 19.5 18.8 PH 7.2 7.2 7.2 7.2 Protein Concentration, mg / mL 154.5 154.8 157.9 161.3 Charge Variants Purity by iCIEF Main Peak 72.9 66.1 60.1 53.7 Acidic Peaks 21.3 28.7 34.9 41.6 Basic Peaks 5.8 5.3 5.1 4.7 Purity by CE-SDS (Reduced) LC+HC 98.7 98.3 97.2 97.0 Total Minor Species 1.3 1.7 2.8 3.0 Purity by CE-SDS (Nonreduced) Main Peak 98.9 98.1 97.5 97.2 Total LMWS 1.0 1.6 1.8 2.3 Purity by SEC Monomer (Main Peak) 98.8 98.2 97.6 97.1 HMWS 1.2 1.8 2.3 2.8 Binding Bioassay (ELISA), % Relative potency 88 99 100 88 Table 45: Long-term Stability Data for lOOmg / mL Clinical Batch 24412201 at -70°C ± 10°C Test / Attribute Acceptanc e Criteria Timepoints (months) 0 1 3 6 9 12 18 24 Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 3 B6 B6 B6 B6 B6 B6 B6 B6 Clarity, NTU <60.0 21.0 20.2 20.4 21.6 20.8 21.4 22.4 21. 3 PH 6.7-7.7 7.1 7.2 7.2 7.1 7.1 7.1 6.9 7.0 Protein Concentration, mg / mL 90.0-110.0 96.8 96.0 95.8 96.4 96.1 96.2 98.1 96. 2 Charge Variants Purity by iCIEF, % Main Peak >30.0 74.6 73.4 73.7 74.0 74.3 73.9 73.8 74. 6 Acidic Peaks <60.0 21.3 20.3 21.7 21.0 20.2 20.6 20.5 20. 1 Basic Peaks <20.0 4.0 6.3 4.6 5.0 5.5 5.6 5.7 5.3 Purity by CE-SDS (Reduced), % LC+HC >90.0 98.3 98.9 99.0 98.6 98.6 98.7 98.8 98. 6 Total Minor Species < 10.0 1.7 1.1 1.0 1.4 1.4 1.3 1.2 1.4 Purity by CE-SDS (Nonreduced), % Main Peak >90.0 98.6 99.0 98.9 98.8 98.7 98.8 98.8 98. 6 Total LMWS < 10.0 1.2 0.9 1.0 1.0 1.1 1.1 1.0 1.2 Purity by SEC, % Monomer (Main Peak) >95.0 98.7 98.7 98.6 98.7 98.6 98.6 98.6 98. 6 HMWS <5.0 1.3 1.3 1.4 1.3 1.4 1.4 1.4 1.4 Binding Bioassay (ELISA), % Relative potency 60-140 100 102 104 108 93 103 94 10 2 Table 46: Long-term Stability Data for 150mg / mL Clinical Batch 24412202 at -70°C ± 10°C Test / Attribute Acceptanc e Criteria Timepoints (months) 0 1 3 6 9 12 18 24 Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 B6 B6 B6 B6 B6 B6 B6 BY5 Clarity, NTU <60.0 20.8 19.8 20.2 19.3 21.6 25.3 22.4 20.8 PH 6.7-7.7 7.1 7.2 7.1 7.0 7.0 7.1 7.0 7.0 Protein Concentration, mg / mL 135.0-165.0 154. 6 153. 8 153. 8 153. 4 155. 0 153. 1 160. 2 154.0 Charge Variants Purity by iCIEF, % Main Peak >30.0 71.1 73.4 73.2 73.4 72.4 73.4 73.0 72.9 Acidic Peaks <60.0 23.1 21.8 21.7 21.9 22.6 22.1 21.8 21.9 Basic Peaks <20.0 5.9 4.7 5.1 4.6 5.1 4.5 5.2 5.2 Purity by CE-SDS (Reduced), % LC+HC >90.0 98.9 98.2 98.5 98.5 98.5 98.5 98.5 98.5 Total Minor Species < 10.0 1.1 1.8 1.5 1.5 1.5 1.5 1.5 1.5 Purity by CE-SDS (Nonreduced), % Main Peak >90.0 99.0 98.9 98.7 98.8 98.8 98.7 98.6 98.9 Total LMWS < 10.0 0.9 1.0 1.1 1.1 1.0 1.1 1.1 1.0 Purity by SEC, % Monome r (Main Peak) >95.0 98.5 98.6 98.4 98.5 98.4 98.4 98.4 98.3 HMWS <5.0 1.5 1.4 1.6 1.5 1.6 1.6 1.6 1.7 Binding Bioassay (ELISA), % Relative potency 60-140 100 99 103 100 108 104 102 103 Table 47: Long-term Stability Data for 150mg / mL Clinical Batch 0000097275 at -70°C ± 10°C Test / Attribute Acceptanc e Criteria Timepoints (months) 0 1 3 6 9 12 Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 B6 B6 B6 B6 B6 B6 Clarity, NTU <60.0 20.2 24.5 20.5 22.8 20.3 20.4 PH 6.7-7.7 7.2 7.2 7.2 7.2 7.2 7.1 Protein Concentration, mg / mL 135.0-165.0 156. 3 157. 9 148. 0 154. 3 152. 1 151.3 Charge Variants Purity by iCIEF, % Main Peak >30.0 74.8 75.7 74.7 75.0 75.7 75.4 Acidic Peaks <60.0 19.8 19.9 20.1 20.1 19.2 19.8 Basic Peaks <20.0 5.4 4.3 5.3 4.9 5.2 4.8 Purity by CE-SDS (Reduced), % LC+HC >90.0 98.7 98.5 98.7 98.5 98.6 98.6 Total Minor Species < 10.0 1.3 1.5 1.3 1.5 1.4 1.4 Purity by CE-SDS (Nonreduced), % Main Peak >90.0 98.8 98.9 98.9 98.7 98.8 98.7 Total LMWS < 10.0 1.1 1.1 1.0 1.1 1.1 1.1 Purity by SEC, % Monomer (Main Peak) >95.0 98.5 98.5 98.5 98.5 98.5 98.6 HMWS <5.0 1.5 1.5 1.5 1.5 1.5 1.4 Binding Bioassay (ELISA), % Relative potency 60-140 100 94 109 106 103 97 Table 48: Long-term Stability Data for 150mg / mL Clinical Batch 0000114279 at -70°C ± 10°C Test / Attribute Timepoints (months) Acceptanc e Criteria 0 1 3 6 9 Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 B6 B6 B6 B6 B6 Clarity, NTU <60.0 20.9 20.8 19.5 20.3 21 PH 6.7-7.7 7.1 7.2 7.2 7.0 7.0 Protein Concentration, mg / mL 135.0-165.0 151. 8 152. 6 152. 5 152.7 150.8 Charge Variants Purity by iCIEF, % Main Peak >30.0 72.9 75.0 73.8 74.1 74.7 Acidic Peaks <60.0 21.9 20.9 21.5 21.2 20.8 Basic Peaks <20.0 5.1 4.2 4.8 4.7 4.5 Purity by CE-SDS (Reduced), % LC+HC >90.0 98.9 98.3 98.5 98.4 98.6 Total Minor Species < 10.0 1.1 1.7 1.5 1.6 1.4 Purity by CE-SDS (Nonreduced), % Main Peak >90.0 98.8 98.7 98.7 98.6 98.7 Total LMWS < 10.0 1.0 1.2 1.1 1.3 1.2 Purity by SEC, % Monom er (Main Peak) >95.0 98.6 98.5 98.5 98.5 98.5 HMWS <5.0 1.4 1.5 1.5 1.5 1.5 Binding Bioassay (ELISA), % Relative potency 60-140 104 86 100 101 102 Table 49: Long-term Stability Data for 150mg / mL Clinical Batch 0000124360 at -70°C ± 10°C Test / Attribute Acceptan ce Criteria Timepoints (months) 0 1 3 6 Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 BY5 BY5 BY5 B5 Clarity, NTU <60.0 20.3 19.8 19.9 20.8 PH 6.7-7.7 7.2 7.2 7.1 7.1 Protein Concentration, mg / mL 135.0 165.0 154. 7 156. 0 153.3 161.0 Charge Variants Purity by iCIEF Main Peak >30.0 74.0 72.1 72.5 72.0 Acidic Peaks <60.0 20.2 22.0 21.7 21.7 Basic Peaks <20.0 5.8 6.0 5.8 6.4 Purity by CE-SDS (Reduced), % LC+HC >90.0 98.5 98.6 98.5 98.5 Total Minor Species < 10.0 1.5 1.4 1.5 1.5 Purity by CE-SDS (Nonreduced), % Main Peak >90.0 98.6 98.7 98.7 98.5 Total LMWS < 10.0 1.2 1.1 1.1 1.3 Purity by SEC, % Monom er (Main Peak) >95.0 98.4 98.4 98.4 98.4 HMWS <5.0 1.6 1.6 1.6 1.6 Binding Bioassay (ELISA), % Relative potency 60-140 104 101 102 102 Table 50: Accelerated Stability Data for lOOmg / mL Clinical Batch 24412201 at 5°C ± 3°C Test / Attribute Acceptanc e Criteria Timepoints (months) 0 1 3 6 Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. B6 B6 B6 B6 3 Clarity, NTU <60.0 21.0 20.9 20.7 20.5 pH 6.7-7.7 7.1 7.2 7.2 7.2 Protein Concentration, mg / mL 90.0-110.0 96.8 97.2 99.4 100.2 Charge Variants Purity by iCIEF, % Main Peak >30.0 74.6 72.4 72.8 72.3 Acidic Peaks <60.0 21.3 20.7 22.4 23.0 Basic Peaks <20.0 4.0 6.9 4.7 4.7 Purity by CE-SDS (Reduced), % LC+HC >90.0 98.3 98.7 98.9 98.2 Total Minor Species < 10.0 1.7 1.3 1.1 1.8 Purity by CE-SDS (Nonreduced), % Main Peak >90.0 98.6 98.8 98.7 98.5 Total LMWS < 10.0 1.2 1.0 1.1 1.2 Purity by SEC, % Monome r (Main Peak) >95.0 98.7 98.7 98.4 98.4 HMWS <5.0 1.3 1.3 1.6 1.5 Binding Bioassay (ELISA), % Relative potency 60-140 100 107 100 110 Table 51: Accelerated Stability Data for 150mg / mL Clinical Batch 24412202 at 5°C ± 3°C Test / Attribute Acceptance Criteria Timepoints (months) 0 1 3 6 Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 B6 B6 B6 B5 Clarity, NTU <60.0 20.8 20.2 19.6 18.3 PH 6.7-7.7 7.1 7.1 7.2 7.2 Protein Concentration, mg / mL 135.0-165.0 154.6 153. 1 156.1 158. 4 Charge Variants Purity by iCIEF, % Main Peak > 30.0% 71.1 71.9 71.7 70.6 Acidic Peaks <60.0 23.1 22.3 23.1 24.4 Basic Peaks <20.0 5.9 5.8 5.1 5.0 Purity by CE-SDS (Reduced), % LC+HC >90.0 98.9 98.6 98.3 98.4 Total Minor Species < 10.0 1.1 1.4 1.7 1.6 Purity by CE-SDS (Nonreduced), % Main Peak >90.0 99.0 98.7 98.6 98.3 Total LMWS < 10.0 0.9 1.0 1.1 1.3 Purity by SEC, % Monomer (Main Peak) >95.0 98.5 98.5 98.1 98.0 HMWS <5.0 1.5 1.5 1.9 2.0 Binding Bioassay (ELISA), % Relative potency 60-140 100 101 111 99 Table 52: Accelerated Stability Data for 150mg / mL Clinical Batch 0000097275 at 5°C ± 3°C Test / Attribute Acceptance Criteria Timepoints (months) 0 1 3 6 Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 B6 B6 B6 B6 Clarity, NTU <60.0 20.2 24.0 20.0 21.4 PH 6.7-7.7 7.2 7.3 7.2 7.2 Protein Concentration, mg / mL 135.0-165.0 156. 3 159. 5 151. 0 160. 1 Charge Variants Purity by iCIEF, Main Peak >30.0 74.8 75.7 74.2 73.0 Acidic Peaks <60.0 19.8 20.8 21.1 22.4 % Basic Peaks <20.0 5.4 3.6 4.7 4.6 Purity by CE-SDS (Reduced), % LC+HC >90.0 98.7 98.4 98.4 98.6 Total Minor Species < 10.0 1.3 1.6 1.6 1.4 Purity by CE-SDS (Nonreduced), % Main Peak >90.0 98.8 98.7 98.6 98.5 Total LMWS < 10.0 1.1 1.2 1.1 1.2 Purity by SEC, % Monomer (Main Peak) >95.0 98.5 98.3 98.3 98.2 HMWS <5.0 1.5 1.7 1.7 1.8 Binding Bioassay (ELISA), % Relative potency 60-140 100 92 103 112 Table 53: Accelerated Stability Data for 150mg / mL Clinical Batch 0000114279 at 5°C ± 3°C Test / Attribute Acceptanc e Criteria Timepoints (months) 0 1 3 6 Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 B6 B6 BY5 B5 Clarity, NTU <60.0 20.9 20.5 18.9 18.9 PH 6.7-7.7 7.2 7.2 7.2 7.2 Protein Concentration, mg / mL 135.0-165.0 151.8 154. 1 152.9 158. 9 Charge Variants Purity by iCIEF, % Main Peak >30.0 72.9 73.9 73.3 72.2 Acidic Peaks <60.0 21.9 21.4 22.4 22.9 Basic Peaks <20.0 5.1 4.7 4.3 4.9 Purity by CE-SDS LC+HC >90.0 98.9 98.5 98.3 98.3 Total Minor Species < 10.0 1.1 1.5 1.7 1.7 (Reduced), % Purity by CE-SDS (Nonreduced), % Main Peak >90.0 98.8 98.7 98.6 98.4 Total LMWS < 10.0 1.0 1.2 1.2 1.2 Purity by SEC, % Monomer (Main Peak) >95.0 98.6 98.3 98.2 98.1 HMWS <5.0 1.4 1.7 1.8 1.9 Binding Bioassay (ELISA), % Relative Potency 60-140 104 101 110 89 Table 54: Accelerated Stability Data for 150mg / mL Clinical Batch 0000124360 at 5°C ± 3°C Test / Attribute Acceptance Criteria Timepoints (months) 0 1 3 6 Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 BY5 BY5 B5 B5 Clarity, NTU <60.0 20.3 20.0 19.6 18.9 PH 6.7-7.7 7.2 7.2 7.2 7.2 Protein Concentration, mg / mL 135.0-165.0 154.7 156.9 156.1 170.2 Charge Variants Purity by iCIEF, % Main Peak >30.0 74.0 71.8 70.9 70.1 Acidic Peaks <60.0 20.2 22.2 23.4 23.5 Basic Peaks <20.0 5.8 6.0 5.7 6.3 Purity by CE-SDS (Reduced), % LC+HC >90.0 98.5 98.4 98.4 98.3 Total Minor Species < 10.0 1.5 1.6 1.6 1.7 Purity by CE-SDS (Nonreduced), % Main Peak >90.0 98.6 98.6 98.6 98.4 Total LMWS < 10.0 1.2 1.1 1.1 1.3 Purity by SEC, % Monomer (Main Peak) >95.0 98.4 98.3 98.1 97.9 HMWS <5.0 1.6 1.7 1.9 2.1 Binding Bioassay (ELISA), % Relative Potency 60-140 104 103 105 95 Table 55: Stress Stability Data for lOOmg / mL Clinical Batch 24412201 at 25°C ± 2°C / 60 %± 5% RH Test / Attribute Acceptanc e Criteria Timepoints (months) 0 1 2 3 Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 3 B6 B6 B6 B5 Clarity, NTU <60.0 21.0 20.2 20.1 20.3 PH 6.7-7.7 7.1 7.2 7.2 7.2 Protein Concentration, mg / mL 90.0-110.0 96.8 99.4 101.7 103.3 Charge Variants Purity by iCIEF, % Main Peak >30.0 74.6 64.3 59.1 54.1 Acidic Peaks <60.0 21.3 28.7 35.1 42.4 Basic Peaks <20.0 4.0 7.0 5.8 3.6 Purity by CE-SDS (Reduced), % LC+HC >90.0 98.3 98.5 97.9 97.8 Total Minor Species < 10.0 1.7 1.5 2.1 2.2 Purity by CE-SDS (Nonreduced), % Main Peak >90.0 98.6 98.6 97.8 97.3 Total LMWS < 10.0 1.2 1.2 1.8 2.2 Purity by SEC, % Monomer (Main Peak) >95.0 98.7 98.3 98.0 97.3 HMWS <5.0 1.3 1.7 2.0 2.6 Binding Bioassay (ELISA), %Relative Potency 60-140 100 93 94 97 Table 56: Stress Stability Data for 150mg / mL Clinical Batch 24412202 at 25°C ± 2°C / 60 %± 5% RH Test / Attribute Acceptanc e Criteria Timepoints (months) 0 1 2 3 Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 B6 B5 B5 B5 Clarity, NTU <60.0 20.8 19.4 18.9 18.3 PH 6.7-7.7 7.1 7.2 7.2 7.2 Protein Concentration, mg / mL 135.0-165.0 154.6 154.8 159.1 161.2 Charge Variants Purity by iCIEF, % Main Peak >30.0 71.1 65.3 57.6 51.8 Acidic Peaks <60.0 23.1 30.2 37.4 43.7 Basic Peaks <20.0 5.9 4.5 5.1 4.5 Purity by CE-SDS (Reduced), % LC+HC >90.0 98.9 98.1 97.6 96.4 Total Minor Species < 10.0 1.1 1.9 2.4 3.6 Purity by CE-SDS (Nonreduced), % Main Peak >90.0 99.0 98.0 97.2 96.4 Total LMWS < 10.0 0.9 1.5 2.1 2.6 Purity by SEC, % Monomer (Main Peak) >95.0 98.5 97.9 96.9 96.5 HMWS <5.0 1.5 2.1 3.0 3.4 Binding Bioassay (ELISA), %Relative Potency 60-140 100 102 102 105 Table 57: Stress Stability Data for 150mg / mL Clinical Batch 0000097275 at 25°C ± 2°C / 60%± 5% RH Test / Attribute Acceptance Criteria Timepoints (months) 0 1 2 3 6 Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than B6 B6 B5 B5 B5 No. 2 Clarity, NTU <60.0 20.2 23.2 23.0 18.8 19.5 pH 6.7-7.7 7.2 7.3 7.2 7.2 7.2 Protein Concentration, mg / mL 135.0-165.0 156. 3 161. 3 157. 8 156. 7 167.2 Charge Variants Purity by iCIEF, % Main Peak >30.0 74.8 68.2 59.2 53.8 37.5 Acidic Peaks <60.0 19.8 27.9 35.2 41.0 56.5 Basic Peaks <20.0 5.4 3.9 3.8 5.2 6.0 Purity by CE-SDS (Reduced), % LC+HC >90.0 98.7 97.9 97.4 96.7 95.4 Total Minor Species < 10.0 1.3 2.1 2.6 3.3 4.6 Purity by CE-SDS (Nonreduced), % Main Peak >90.0 98.8 98.2 97.5 96.8 94.4 Total LMWS < 10.0 1.1 1.5 2.0 2.4 4.1 Purity by SEC, % Monomer (Main Peak) >95.0 98.5 97.8 97.4 97.0 95.7 HMWS <5.0 1.5 2.1 2.5 2.9 4.2 Binding Bioassay (ELISA), % Relative potency 60-140 100 93 100 99 106 Table 58: Stress Stability Data for 150mg / mL Clinical Batch 0000114279 at 25°C ± 2°C / 60 %± 5% RH Test / Attribute Acceptanc e Criteria Timepoints (months) 0 1 2 3 6 Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 B6 B5 B5 B5 B5 Clarity, NTU <60.0 20.9 19.5 19.0 18.4 16.7 PH 6.7-7.7 7.1 7.2 7.2 7.2 7.2 Protein Concentration, mg / mL 135.0-165.0 151.8 158.1 152.6 159.8 167.8 Charge Variants Purity by iCIEF, % Main Peak >30.0 72.9 67.1 60.5 54.3 38.8 Acidic Peaks <60.0 21.9 28.7 35.3 41.9 57.3 Basic Peaks <20.0 5.1 4.2 4.2 3.9 3.9 Purity by CE-SDS (Reduced), % LC+HC >90.0 98.9 98.0 97.4 96.7 95.0 Total Minor Species < 10.0 1.1 2.0 2.6 3.3 5.0 Purity by CE-SDS (Nonreduced), % Main Peak >90.0 98.8 97.9 97.2 96.6 94.4 Total LMWS < 10.0 1.0 1.7 2.0 2.5 4.2 Purity by SEC, % Monomer (Main Peak) >95.0 98.6 97.8 97.3 96.7 95.5 HMWS <5.0 1.4 2.1 2.6 3.1 4.4 Binding Bioassay (ELISA), % Relative potency 60-140 104 98 106 105 73 Table 59: Stress Stability Data for 150mg / mL Clinical Batch 0000124360 at 25°C ± 2°C / 60 %± 5% RH Test / Attribute Acceptance Criteria Timepoints (months) 0 1 2 3 6 Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 BY5 B5 B5 B5 B5 Clarity, NTU <60.0 20.3 19.0 19.0 18.4 17.2 pH 6.7-7.7 7.2 7.2 7.2 7.2 7.2 Protein Concentration, mg / mL 135.0-165.0 154.7 159.7 157.8 161.1 180.9 Charge Variants Purity by iCIEF, % Main Peak >30.0 74.0 64.7 58.3 52.5 36.2 Acidic Peaks <60.0 20.2 29.5 35.4 42.7 58.2 Basic Peaks <20.0 5.8 5.8 6.3 4.8 5.6 Purity by CE-SDS (Reduced), % LC+HC >90.0 98.5 97.8 96.9 96.4 94.6 Total Minor Species < 10.0 1.5 2.2 3.1 3.6 5.4 Purity by CE-SDS (Nonreduced), % Main Peak >90.0 98.6 97.8 97.2 96.6 94.4 Total LMWS < 10.0 1.2 1.6 2.0 2.5 4.0 Purity by SEC, % Monomer (Main Peak) >95.0 98.4 97.7 97.1 96.7 95.0 HMWS <5.0 1.6 2.3 2.7 3.2 4.8 Binding Bioassay (ELISA), % Relative potency 60-140 104 91 98 98 91 Table 60: Accelerated Stability Data for Clinical Lot 20240603 at 25°C ± 2°C / 60%RH ± 5%RH, Inverted Test / Attribute Acceptance Criteria Timepoints (months) TO 1 Month Visible particles (Refer to USP / Ph. Eur.) Liquid L L EFOVP EFOVP EFOVP Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 BY5 B5 Clarity, NTU <60.0 20.0 19.5 PH 6.7-7.7 7.2 7.2 Subvisibl e Parti cul at e Matter, p / c > 25 pm <600 1 0 > 10 pm <6000 2 16 > 5 pm Report Result 24 78 > 2 pm Report Result 189 454 Protein Concentration, mg / mL 135.0- 165.0 151.3 153.9 Charge Variants Purity by iCIEF, % Main Peak >30.0 71.8 63.2 Acidic Peaks <60.0 21.8 30.4 Basic Peaks <20.0 6.4 6.4 Purity by CE- LC+HC >90.0 98.4 97.9 Total Minor Species Report Result 1.6 2.1 SDS (Reduced), % Purity by CE-SDS (Nonreduced), % Main Peak >90.0 98.7 97.6 Total LMWS Report Result 1.1 1.8 Purity by SEC, % Monomer (Main Peak) >95.0 98.2 97.4 HMWS <5.0 1.8 2.4 LMWS Report Result ND 0.2 Poloxamer 188 Content %(w / v) Report Result 0.10 NT (ELISA Binding) Bioassay, %Relative Potency 60 - 140 104 107 Table 61: Stress Stability Data for Clinical Lot 20240603 at 40°C ± 2°C / 75%RH ± 5%RH, Inverted Test / Attribute Acceptance Criteria Timepoints TO 1 Week 2 Weeks 1 Month Visible particles (Refer to USP / Ph. Eur.) Liquid L L L L EFOVP EFOVP EFOVP EFOVP EFOVP Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 BY5 B5 B5 B5 Clarity, NTU <60.0 20.0 19.7 19.4 20.3 PH 6.7-7.7 7.2 7.2 7.2 7.2 Subvisible Particulate Matter, p / c > 25 pm <600 1 0 0 0 > 10 pm <6000 2 16 6 2 > 5 pm Report Result 24 111 30 22 > 2 pm Report Result 189 430 174 158 Protein Concentration, mg / mL 135.0- 165.0 151.3 152.7 154.3 154.8 Charge Variants Purity by iCIEF, Main Peak >30.0 71.8 59.8 49.3 25.8 Acidic Peaks <60.0 21.8 34.9 45.1 70.0 % Basic Peaks <20.0 6.4 5.3 5.6 4.3 Purity by CE-SDS (Reduced), % LC+HC >90.0 98.4 97.0 96.7 92.9 Total Minor Species Report Result 1.6 3.0 3.3 7.1 Purity by CE-SDS (Nonreduced), % Main Peak >90.0 98.7 96.9 96.2 91.9 Total LMWS Report Result 1.1 2.0 3.0 6.3 Purity by SEC, % Monomer (Main Peak) >95.0 98.2 96.5 95.1 90.4 HMWS <5.0 1.8 3.3 4.7 9.1 LMWS Report Result ND 0.2 0.3 0.5 (ELISA Binding) Bioassay, %Relative Potency 60 - 140 104 102 99 98 Polyxmaer 188 Content Report Result 0.10 NT NT NT Table 62: Long Term Stability Data for Clinical Lot 20240603 at 5°C ± 3°C, Inverted Test / Attribute Acceptance Criteria Timepoi (months nts 0 1 Visible particles (Refer to USP / Ph. Eur.) Liquid L L EFOVP EFOVP EFOVP Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 BY5 B5 Clarity, NTU <60.0 20.0 19.8 PH 6.7-7.7 7.2 7.2 Sub vi sib le Particula > 25 pm <600 1 0 > 10 pm <6000 2 2 > 5 pm Report Result 24 29 te Matter, p / c > 2 pm Report Result 189 269 Protein Concentration, mg / mL 135.0- 165.0 151.3 152.1 Charge Variant s Purity by iCIEF, % Main Peak >30.0 71.8 71.3 Acidic Peaks <60.0 21.8 22.8 Basic Peaks <20.0 6.4 5.9 Purity by CE-SDS (Reduced), % LC+HC >90.0 98.4 98.5 Total Minor Species Report Result 1.6 1.5 Purity by CE-SDS (Nonreduced), % Main Peak > 85.0 98.7 98.4 Total LMWS Report Result 1.1 1.3 Purity by SEC, % Monomer (Main Peak) >90.0 98.2 98.1 HMWS 5.0 1.8 1.9 LMWS Report Result ND ND Poloxamer 188 Content, %(w / v) Report Result 0.10 NT (ELISA Binding) Bioassay, %Relative Potency 60 - 140 104 104 Sterility No Growth NG NT CCIT Pass NT NT Table 63: Long Term Stability Data for Clinical Lot 20240603 at 5°C ± 3°C, Upright Test / Attribute Acceptance Criteria Timepoi (months' nts 0 1 Visible particles (Refer to USP / Ph. Eur.) Liquid L L EFOVP EFOVP EFOVP Color, compared to Standard Solution (Refer to Ph. Eur.) Not more colored than No. 2 BY5 B5 Clarity, NTU <60.0 20.0 20.0 PH 6.7-7.7 7.2 7.2 Subvisibl e Parti cul at e Matter, p / c > 25 pm <600 1 NT > 10 pm <6000 2 NT > 5 pm Report Result 24 NT > 2 pm Report Result 189 NT Protein Concentration, mg / mL 135.0 - 165.0 151.3 152.8 Charge Variants Purity by iCIEF, % Main Peak >30.0 71.8 71.4 Acidic Peaks <60.0 21.8 22.7 Basic Peaks <20.0 6.4 5.9 Purity by CE-SDS (Reduced), % LC+HC >90.0 98.4 98.5 Total Minor Species Report Result 1.6 1.5 Main Peak >85.0 98.7 98.4 Purity by CE-SDS (Nonreduced), % Total LMWS Report Result 1.1 1.3 Purity by SEC, % Monomer (Main Peak) >90.0 98.2 98.1 HMWS <5.0 1.8 1.9 LMWS Report Result ND ND Poloxamer 188 Content, %(w / v) Report Result 0.10 NT (ELISA Binding) Bioassay, %Relative Potency 60 - 140 104 104 Sterility No Growth NG NT CCIT Pass NT NT

[0617] The stability data demonstrate no significant change over time and no significant variability in stability measures. Stability results meet all acceptance criteria.

[0618] Thus the embodiments and examples provided for herein demonstrate the surprising and / or unexpected results that a high concentration formulation comprising the antibodies provided for herein can be sufficiently stable for sufficient periods of time to be used, for example, in the methods provided for herein. The formulations prevent sufficient aggregation as determined by the absence of a significant percentage of HMWS as well as prevents degradation, which would be measured by the presence of LMWS. The purity of the composition is also demonstrated the high percentage of the main peaks provided for in the examples.

[0619] All references cited herein are incorporated by reference to the same extent as if each individual publication, database entry (e.g. Genbank sequences or GenelD entries), patent application, or patent, was specifically and individually indicated to be incorporated by reference. This statement of incorporation by reference is intended by Applicants, pursuant to 37 C.F.R. § 1.57(b)(1), to relate to each and every individual publication, database entry (e.g. Genbank sequences or GenelD entries), patent application, or patent, each of which is clearly identified in compliance with 37 C.F.R. §1.57(b)(2), even if such citation is not immediately adjacent to a dedicated statement of incorporation by reference. The inclusion of dedicated statements of incorporation by reference, if any, within the specification does not in any way weaken this general statement of incorporation by reference. Citation of the references herein is not intended as an admission that the reference is pertinent prior art, nor does it constitute any admission as to the contents or date of these publications or documents.

[0620] The present embodiments are not to be limited in scope by the specific embodiments described herein. Indeed, various modifications in addition to those described herein will become apparent to those skilled in the art from the foregoing description. Such modifications are intended to fall within the scope of the embodiments and any appended claims.

[0621] The present specification is considered to be sufficient to enable one skilled in the art to practice the embodiments. Various modifications in addition to those shown and described herein will become apparent to those skilled in the art from the foregoing description and fall within the scope of the present disclosure and any appended claims.

Claims

WHAT IS CLAIMED:

1. A pharmaceutical composition comprising:about 25 mg / mL to about 300 mg / mL of an antibody having a heavy chain and a light chain, wherein the heavy chain comprises a HCDR1 of SEQ ID NO: 61, a HCDR2 of SEQ ID NO: 62, and a HCDR3 of SEQ ID NO: 78, and wherein the light chain comprises a LCDR1 of SEQ ID NO: 64, a LCDR2 of SEQ ID NO: 65, and a LCDR3 of SEQ ID NO: 79;one or more of a buffer;an antioxidant;a sugar;a viscosity modifying agent;a surfactant, andwherein the pharmaceutical composition is at a pH of about 6.5 to about 8.0.

2. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition comprises:a buffer at about 5 mM to about 50 mM;an antioxidant at about 5 mM to about 15 mM;a sugar at about 1% w / v to about 14% w / v;a viscosity modifying agent at about 20 mM to about 180 mM; anda surfactant at about 0.001 % w / v to about 0.4 % w / v.

3. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition comprises:a buffer at about 15 mM to about 25 mM;an antioxidant at about 5 mM to about 15 mM;a sugar at about 1% w / v to about 10% w / v;a viscosity modifying agent at about 60 mM to about 150 mM; anda surfactant at about 0.001 % w / v to about 0.2 % w / v.

4. The pharmaceutical composition of claim 1, wherein the buffer is at a concentration of about 5 mM to about 15 mM, about 15 mM to about 20 mM, about 20 mM to about 25 mM, about 25 mM to about 30 mM, about 30 mM to about 35 mM, about 35 mM to about 40 mM, about 40 mM to about 45 mM, about45 mM to about 50 mM, about 5 mM, about 10 mM, about 15 mM, about 20 mM, about 25 mM, about 30 mM, about 35 mM, about 40 mM, about 45 mM, or about 50 mM.

5. The pharmaceutical composition of claim 4, wherein the buffer is present at a concentration of about 20 mM.

6. The pharmaceutical composition of any one of claims 1-5, wherein the buffer is selected from tris buffer, histidine buffer, HEPES, phosphate buffer, acetate buffer, citrate buffer, succinate buffer, ascorbate buffer, glutamate buffer, lactate buffer, maleate buffer, trometamol buffer, gluconate buffer, or any combination thereof.

7. The pharmaceutical composition of any one of claims 1-6, wherein the buffer is a phosphate buffer.

8. The pharmaceutical composition of claim 1, wherein the pharmaceutical composition has a pH of about 6.5, about 6.6, about 6.7, about 6.8, about 6.9, about 7.0, about 7.1, about 7.2, about 7.3, about 7.4, about 7.5, about 7.6, about 7.7, about 7.8, about 7.9, or about 8.0.

9. The pharmaceutical composition of claim 1-8, wherein the pharmaceutical composition has a pH of about 6.5 to about 7.7.

10. The pharmaceutical composition of any one of claims 1-9, wherein the pharmaceutical composition has a pH of about 7.2.

11. The pharmaceutical composition of claim 1, wherein the antioxidant is present at about 10 mM to about 15 mM, or about 5 mM to about 10 mM.

12. The pharmaceutical composition of any one of claims 1-11, wherein the antioxidant is present at a concentration of about 10 mM.

13. The pharmaceutical composition of any one of claims 1-12, wherein the antioxidant is selected from L-methionine, ascorbic acid, EDTA, or any combination thereof.

14. The pharmaceutical composition of claim 13, wherein the antioxidant is L-methionine.

15. The pharmaceutical composition of claim 1, wherein the sugar is present at a concentration of about 1% w / v to about 14% w / v, about 2% w / v to about 14% w / v, about 2% w / v to about 12% w / v, 2% w / v to about 10% w / v, about 2% w / v to about 8% w / v, about 2% w / v to about 6% w / v, about 2% w / v to about 4% w / v, about 4% w / v to about 14% w / v, about 4% w / v to about 12% w / v, about 4% w / v to about 10% w / v, about 4% w / v to about 8% w / v, about 4% w / v to about 6% w / v, about 6% w / v to about 14% w / v, about 6% w / v to about 12% w / v, about 6% w / v to about 10% w / v, about 6% w / v to about 8% w / v, about 8% w / v to about 14% w / v, about 8% w / v to about 12% w / v, about 8% w / v to about 10% w / v, about 10% w / v to about 14% w / v, about 10% w / v to about 12% w / v, or about 12% w / v to about 14% w / v.

16. The pharmaceutical composition of claim 15, wherein the sugar is present at a concentration of about 1% to about 14% w / v.

17. The pharmaceutical composition of claim 16, wherein the sugar is present at a concentration of about 2% w / v to about 10% w / v.

18. The pharmaceutical composition of any one of claims 15-17, wherein the sugar is present at a concentration of about 4% w / v.

19. The pharmaceutical composition of any one of claims 15-18, wherein the sugar is present at a concentration of about 3.5% w / v.

20. The pharmaceutical composition of any one of claims 1-19, wherein the sugar is sucrose, trehalose, sorbitol, mannitol, or any combination thereof.

21. The pharmaceutical composition of any one of claims 1-20, wherein the sugar is sucrose.

22. The pharmaceutical composition of claim 1, wherein the viscosity modifying agent is present at a concentration of about 20 mM to about 180 mM, about 20 mM to about 170 mM, about 20 mM to about160 mM, about 20 mM to about 150 mM, about 20 mM to about 140 mM, about 20 mM to about 130 mM, about 20 mM to about 120 mM, about 20 mM to about 110 mM, about 20 mM to about 100 mM, about 20 mM to about 90 mM, about 20 mM to about 80 mM, about 20 mM to about 70 mM, about 20 mM to about 60 mM, about 20 mM to about 50 mM, about 20 mM to about 40 mM, about 40 mM to about180 mM, about 40 mM to about 170 mM, about 40 mM to about 160 mM, about 40 mM to about 150 mM, about 40 mM to about 140 mM, about 40 mM to about 130 mM, about 40 mM to about 120 mM, about 40 mM to about 110 mM, about 40 mM to about 100 mM, about 40 mM to about 90 mM, about 40 mM to about 80 mM, about 40 mM to about 70 mM, about 40 mM to about 60 mM, about 40 mM to about 50 mM, about 60 mM to about 180 mM, about 60 mM to about 170 mM, about 60 mM to about 160 mM, about 60 mM to about 150 mM, about 60 mM to about 140 mM, about 60 mM to about 130 mM, about 60 mM to about 120 mM, about 60 mM to about 110 mM, about 60 mM to about 100 mM, about 60 mM to about 90 mM, about 60 mM to about 80 mM, about 60 mM to about 70 mM, about 70 mM to about180 mM, about 70 mM to about 170 mM, about 70 mM to about 160 mM, about 70 mM to about 150 mM, about 70 mM to about 140 mM, about 70 mM to about 130 mM, about 70 mM to about 120 mM,about 70 mM to about 110 mM, about 70 mM to about 100 mM, about 70 mM to about 90 mM, about 70 mM to about 80 mM, about 80 mM to about 180 mM, about 80 mM to about 170 mM, about 80 mM to about 160 mM, about 80 mM to about 150 mM, about 80 mM to about 140 mM, about 80 mM to about 130 mM, about 80 mM to about 120 mM, about 80 mM to about 110 mM, about 80 mM to about 100 mM, about 80 mM to about 90 mM, about 90 mM to about 180 mM, about 90 mM to about 170 mM, about 90 mM to about 160 mM, about 90 mM to about 150 mM, about 90 mM to about 140 mM, about 90 mM to about 130 mM, about 90 mM to about 120 mM, about 90 mM to about 110 mM, about 90 mM to about 100 mM, about 100 mM to about 180 mM, about 100 mM to about 170 mM, about 100 mM toabout 160 mM, about 100 mM to about 130 mM, about 100 mM to about 180 mM, about 110 mM to about 150 mM, about 110 mM to about 120 mM, about 120 mM to about 160 mM, about 120 mM to about 130 mM, about 130 mM to about 160 mM, about 130 mM to about 180 mM, about 140 mM toabout 150 mM, about 100 mM to about 120 mM, about 100 mM to about 170 mM, about 110 mM to about 140 mM, about 110 mM to about 180 mM, about 120 mM to about 150 mM, about 120 mM to about 180 mM, about 130 mM to about 150 mM, about 130 mM to about 170 mM, about 140 mM toabout 140 mM, about 100 mM to about 110 mM, about 110 mM to about 160 mM, about 110 mM to about 130 mM, about 110 mM to about 170 mM, about 120 mM to about 140 mM, about 120 mM to about 170 mM, about 130 mM to about 140 mM, about 140 mM to about 160 mM, about 140 mM toabout 150 mM, about 150 mM to about 180 mM, about 150 mM to about 170 mM, about 150 mM to about 160 mM, about 160 mM to about 180 mM, about 160 mM to about 170 mM, or about 170 mM to about 180 mM.

23. The pharmaceutical composition of any one of claims 1-22, wherein the viscosity modifying agent is present at a concentration of about 70 mM.

24. The pharmaceutical composition of any one of claims 1-23, wherein the viscosity modifying agent is L-arginine hydrochloride (L-Arg-HCL) or sodium chloride (NaCl).

25. The pharmaceutical composition of any one of claims 1-24, wherein the viscosity modifying agent is L-Arg-HCL26. The pharmaceutical composition of claim 1, wherein the surfactant is present at a concentration of about 0.001% w / v to about 0.1% w / v, about 0.001% w / v to about 0.2% w / v, about 0.01% w / v to about 0.2% w / v, about 0.1% w / v to about 0.2% w / v, about 0.2% w / v to about 0.4% w / v, about 0.05% w / v to about 0.15% w / v, or about 0.001% w / v to about 0.01% w / v.

27. The pharmaceutical composition of any one of claims 1-26, wherein the surfactant is present at a concentration of about 0.1% w / v.

28. The pharmaceutical composition of any one of claims 1-27, wherein the surfactant is Polysorbate 80, Polysorbate 20, polyethylene glycol 3350 (PEG3350), or Poloxamer (P)188.

29. The pharmaceutical composition of any one of claims 1-28, wherein the surfactant is P188.

30. The pharmaceutical composition of claim 1, wherein the antibody is present at a concentration of about 25 mg / mL to about 300 mg / mL, about 25 mg / mL to about 275 mg / mL, about 25 mg / mL to about 250 mg / mL, about 25 mg / mL to about 225 mg / mL, about 25 mg / mL to about 200 mg / mL, about 25 mg / mL to about 175 mg / mL, about 25 mg / mL to about 150 mg / mL, about 25 mg / mL to about 125 mg / mL, about 25 mg / mL to about 100 mg / mL, about 25 mg / mL to about 75 mg / mL, about 50 mg / mL to about 300mg / mL, about 50 mg / mL to about 275 mg / mL, about 50 mg / mL to about 250 mg / mL, about 50 mg / mL to about 225 mg / mL, about 50 mg / mL to about 200 mg / mL, about 50 mg / mL to about 175 mg / mL, about 50 mg / mL to about 150 mg / mL, about 50 mg / mL to about 125 mg / mL, about 50 mg / mL to about 100 mg / mL, about 50 mg / mL to about 75 mg / mL, about 75 mg / mL to about 300 mg / mL, about 75 mg / mL to about 275 mg / mL, about 75 mg / mL to about 250 mg / mL, about 75 mg / mL to about 225 mg / mL, about 75 mg / mL to about 200 mg / mL, about 75 mg / mL to about 175 mg / mL, about 75 mg / mL to about 150 mg / mL, about 75 mg / mL to about 125 mg / mL, about 75 mg / mL to about 100 mg / mL, about 100 mg / mL to about 300 mg / mL, about 100 mg / mL to about 275 mg / mL, about 100 mg / mL to about 250 mg / mL, about 100 mg / mL to about 225 mg / mL, about 100 mg / mL to about 200 mg / mL, about 100 mg / mL to about 175 mg / mL, about 100 mg / mL to about 150 mg / mL, about 100 mg / mL to about 125 mg / mL, about 125 mg / mL to about 300 mg / mL, about 125 mg / mL to about 275 mg / mL, about 125 mg / mL to about 250 mg / mL, about 125 mg / mL to about 225 mg / mL, about 125 mg / mL to about 200 mg / mL, about 125 mg / mL to about 175 mg / mL, about 125 mg / mL to about 150 mg / mL, about 150 mg / mL to about 300 mg / mL, about 150 mg / mL to about 275 mg / mL, about 150 mg / mL to about 250 mg / mL, about 150 mg / mL to about 225 mg / mL, about 150 mg / mL to about 200 mg / mL, about 150 mg / mL to about 175 mg / mL, about 175 mg / mL to about 300 mg / mL, about 175 mg / mL to about 275 mg / mL, about 175 mg / mL to about 250 mg / mL, about 175 mg / mL to about 225 mg / mL, about 175 mg / mL to about 200 mg / mL, about 200 mg / mL to about 300 mg / mL, about 200 mg / mL to about 275 mg / mL, about 200 mg / mL to about 250 mg / mL, about 200 mg / mL to about 225 mg / mL, about 225 mg / mL to about 300 mg / mL, about 225 mg / mL to about 275 mg / mL, about 225 mg / mL to about 250 mg / mL, about 250 mg / mL to about 300 mg / mL, about 250 mg / mL to about 275 mg / mL, about 275 mg / mL to about 300 mg / mL, about 100 mg / mL to about 200 mg / mL, or about 200 mg / mL to about 300 mg / mL.

31. The pharmaceutical composition of any one of claim 1-30, wherein the antibody is present at a concentration of about 150 mg / mL.

32. The pharmaceutical composition of any one of claim 1-31, wherein the antibody is present at a concentration of about 100 mg / mL.

33. The pharmaceutical composition of any one of claim 1-32, wherein the antibody is a monoclonal antibody.

34. The pharmaceutical composition of any one of claim 1-33, wherein the monoclonal antibody is an immunoglobulin G4 (IgG4) type monoclonal antibody.

35. The pharmaceutical composition of claim 1, wherein the antibody comprises a heavy chain variable region with an amino acid sequence of SEQ ID NO: 17; and a light chain variable region with an amino acid sequence of SEQ ID NO: 18.

36. The pharmaceutical composition of claim 1, wherein the antibody comprises a heavy chain variable region with an amino acid sequence of SEQ ID NO: 342; and a light chain variable region with an amino acid sequence of SEQ ID NO: 18.

37. The pharmaceutical composition of any one of claims 1-36, wherein the antibody, or antibody fragment thereof, comprises a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO: 61; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO: 62; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO: 78, or variants or convention equivalents of any of the foregoing; and (ii) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence SEQ ID NO: 64; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO: 65; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO: 79; or variants or convention equivalents of any of the foregoing.

38. The pharmaceutical composition of any one of claims 1-37, wherein the pharmaceutical composition is stable at about-25 °C, about -20 °C, about -15 °C, about -5 °C, about 0 °C, about 5 °C, or about 10 °C.

39. The pharmaceutical composition of any one of claims 1-38, wherein the pharmaceutical composition is stable for 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 20 months, 21 months, 22 months, 23 months, 24 months, 25 months, 26 months, 27 months, 28 months, 29 months, 30 months, 31 months, 32 months, 33 months, 34months, 35 months, or 36 months.

40. The pharmaceutical composition of any one of claims 1-39, wherein the pharmaceutical composition is stable at -20 °C for at least 3 months.

41. The pharmaceutical composition of any one of claims 1-40, wherein the pharmaceutical composition is stable at -20 °C for at least 6 months.

42. The pharmaceutical composition of any one of claims 1-41, wherein the pharmaceutical composition is stable at 2-8 °C for at least 3 months.

43. The pharmaceutical composition of any one of claims 1-42, wherein the pharmaceutical composition is stable at 2-8 °C for at least 6 months.

44. The pharmaceutical composition of any one of claims 1-43, wherein the pharmaceutical composition is stable at 2-8 °C for at least 9 months.

45. The pharmaceutical composition of any one of claims 1-44, wherein the pharmaceutical composition is stored in pre-filled syringes or 2 mL aliquots in 6 mL vials.

46. The pharmaceutical composition of any one of claims 1-45, wherein the pharmaceutical composition is stored in 2 mL aliquots in 6 mL vials with a 20 mm stopper.

47. The pharmaceutical composition of any one of claims 1-46, wherein the pharmaceutical composition is stored in 2 mL aliquots at-20 °C in 6 mL vials with a 20 mm stopper and a 20 mm aluminum plastic cover.

48. The pharmaceutical composition of any one of claims 1-47, wherein the pharmaceutical composition is for intravenous or subcutaneous injection.

49. The pharmaceutical composition of any one of claims 1-48, wherein:the antibody is at about 100 mg / mL;the buffer is phosphate buffer at about 20 mM;the antioxidant is L-methionine at about 10 mM;the sugar is sucrose at about 4% w / v;the viscosity modifying agent is L-arginine hydrochloride at about 70 mM; andthe surfactant is Pl88 at about 0.1 % w / v,wherein the pharmaceutical composition is at a pH of about 7.2.

50. The pharmaceutical composition of any one of claims 1-49, wherein:the antibody is at about 150 mg / mL;the buffer is phosphate buffer at about 20 mM;the antioxidant is L-methionine at about 10 mM;the sugar is sucrose at about 3.5% w / v;the viscosity modifying agent is L-arginine hydrochloride at about 70 mM; andthe surfactant is Pl88 at about 0.1 % w / v,wherein the pharmaceutical composition is at a pH of about 7.2.

51. The pharmaceutical composition of any one of claims 1-50, wherein the pharmaceutical composition main peak, measured by SEC, decreases in area percent by less than 0.2% after 24 months at a temperature of about -70 °C, relative to the initial value.

52. The pharmaceutical composition of any one of claims 1-50, wherein the pharmaceutical composition main peak, measured by SEC, decreases in area percent by less than 0.4% after 24 months at a temperature of about -20 °C, relative to the initial value.

53. The pharmaceutical composition of any one of claims 1-50, wherein the pharmaceutical composition main peak, measured by SEC, decreases in area percent by less than 0.5% after 6 months at a temperature of about 5 °C, relative to the initial value.

54. The pharmaceutical composition of any one of claims 1-50, wherein the pharmaceutical composition main peak, measured by SEC, decreases in area percent by less than 3% after 6 months at atemperature of about 25 °C, relative to the initial value.

55. The pharmaceutical composition of any one of claims 1-50, wherein the pharmaceutical composition main peak, measured by SEC, decreases in area percent by less than 7.8% after 1 month at a temperature of about 40 °C, relative to the initial value.

56. The pharmaceutical composition of any one of claims 1-50, wherein the main peak as measured by CE-SDS under non-reducing conditions is greater than 98% when stored at -20 C for up to 1, 3, 6, 9, 18, or 24 months.

57. The pharmaceutical composition of any one of claims 1-50, wherein the percentage of low molecular weight species (LMWS) as measured by CE-SDS under non-reducing conditions is less than, or about, 1.5, 1.1, or 1.0 % when stored at -20 C for up to 1, 3, 6, 9, 18, or 24 months.

58. The pharmaceutical composition of any one of claims 1-50, wherein the percentage of high molecular weight species (HMWS) as measured by SEC is less than 2.0% when stored at -20 C for up to 1, 3, 6, 9, 18, or 24 months.

59. The pharmaceutical composition of any one of claims 1-50, wherein the main peak as measured by CE-SDS under non-reducing conditions is greater than 97% when stored at 5 C for up to 1, 3, 6, 9, 18, or 24 months.

60. The pharmaceutical composition of any one of claims 1-50, wherein the percentage of low molecular weight species (LMWS) as measured by CE-SDS under non-reducing conditions is less than, or about, 2.5%, 2.0%, or 1.7% when stored at 5 C for up to 1, 3, 6, 9, 18, or 24 months.

61. The pharmaceutical composition of any one of claims 1-50, wherein the percentage of high molecular weight species (HMWS) as measured by SEC is less than 2.0% when stored at 5 C for up to 1, 3, 6, 9, 18, or 24 months.

62. The pharmaceutical composition of any one of claims 1-50, wherein the main peak as measuredby CE-SDS under non-reducing conditions is greater than 93% when stored at 25 C for up to 1, 3, 6, 9, 18, or 24 months.

63. The pharmaceutical composition of any one of claims 1-50, wherein the percentage of low molecular weight species (LMWS) as measured by CE-SDS under non-reducing conditions is less than, or about, 5%, 3.5%, or 1.5% when stored at 25 C for up to 1, 3, 6, 9, 18, or 24 months.

64. The pharmaceutical composition of any one of claims 1-50, wherein the percentage of high molecular weight species (HMWS) as measured by SEC is less than 5%, 3.5%, or 1.5% when stored at 25 C for up to 1, 3, 6, 9, 18, or 24 months.

65. A pharmaceutical composition comprising:about 25 mg / mL to about 300 mg / mL of an antibody having a heavy chain and a light chain, wherein the heavy chain comprises a HCDR1 of SEQ ID NO: 61, a HCDR2 of SEQ ID NO: 62, and a HCDR3 of SEQ ID NO: 78, and wherein the light chain comprises a LCDR1 of SEQ ID NO: 64, a LCDR2 of SEQ ID NO: 65, and a LCDR3 of SEQ ID NO: 79;a buffer at about 15 mM to about 25 mM;an antioxidant at about 5 mM to about 15 mM;a sugar at about 1% w / v to about 10% w / v;a viscosity modifying agent at about 60 mM to about 150 mM; anda surfactant at about 0.001 % w / v to about 0.2 % w / v,wherein the pharmaceutical composition is at a pH of about 6.5 to about 8.0.

66. The pharmaceutical composition of claim 65, wherein the buffer is at a concentration of about 15 mM, about 20 mM, or about 25 mM.

67. The pharmaceutical composition of claim 65, wherein the buffer is at a concentration of about 20 mM.

68. The pharmaceutical composition of claim 65, wherein the buffer is selected from tris buffer, histidine buffer, HEPES, phosphate buffer, acetate buffer, citrate buffer, succinate buffer, ascorbate buffer,glutamate buffer, lactate buffer, maleate buffer, trometamol buffer, gluconate buffer, or any combination thereof.

69. The pharmaceutical composition of any one of claims 65-68, wherein the buffer is a phosphate buffer.

70. The pharmaceutical composition of claim 65, wherein the pharmaceutical composition has a pH of about 6.5, about 6.6, about 6.7, about 6.8, about 6.9, about 7.0, about 7.1, about 7.2, about 7.3, about 7.4, about 7.5, about 7.6, about 7.7, about 7.8, about 7.9, or about 8.0.

71. The pharmaceutical composition of any one of claims 65-70, wherein the pharmaceutical composition has a pH of about 6.5 to about 7.7.

72. The pharmaceutical composition of claim 65, wherein the antioxidant is present at about 10 mM to about 15 mM, or about 5 mM to about 10 mM.

73. The pharmaceutical composition of any one of claims 65-72, wherein the antioxidant is present at a concentration of about 10 mM.

74. The pharmaceutical composition of any one of claims 65-73, wherein the antioxidant is selected from L-methionine, ascorbic acid, EDTA, or any combination thereof.

75. The pharmaceutical composition of any one of claims 65-74, wherein the antioxidant is L-methionine.

76. The pharmaceutical composition of claim 65, wherein the sugar is present at a concentration of about 2% w / v to about 10% w / v.

77. The pharmaceutical composition of any one of claims 65-76, wherein the sugar is present at a concentration of about 4% w / v.

78. The pharmaceutical composition of any one of claims 65-77, wherein the sugar is present at a concentration of about 3.5% w / v.

79. The pharmaceutical composition of any one of claims 65-78, wherein the sugar is sucrose, trehalose, sorbitol, mannitol, or any combination thereof.

80. The pharmaceutical composition of any one of claims 65-79, wherein the sugar is sucrose.

81. The pharmaceutical composition of claim 65, wherein the viscosity modifying agent is present at a concentration of about 60 mM to about 150 mM, about 60 mM to about 140 mM, about 60 mM to about 130 mM, about 60 mM to about 120 mM, about 60 mM to about 110 mM, about 60 mM to about 100 mM, about 60 mM to about 90 mM, about 60 mM to about 80 mM, or about 60 mM to about 70 mM.

82. The pharmaceutical composition of any one of claims 65-81, wherein the viscosity modifying agent is present at a concentration of about 70 mM.

83. The pharmaceutical composition of any one of claims 65-82, wherein the viscosity modifying agent is L-arginine hydrochloride (L-Arg-HCL) or sodium chloride (NaCl).

84. The pharmaceutical composition of any one of claims 65-83, wherein the viscosity modifying agent is L-Arg-HCL.

85. The pharmaceutical composition of claim 65, wherein the surfactant is present at a concentration of about 0.001% w / v to about 0.1% w / v, about 0.001% w / v to about 0.2% w / v, about 0.01% w / v to about 0.2% w / v, about 0.1% w / v to about 0.2% w / v, about 0.2% w / v to about 0.4% w / v, about 0.05% w / v to about 0.15% w / v, or about 0.001% w / v to about 0.01% w / v.

86. The pharmaceutical composition of any one of claims 65-85, wherein the surfactant is present at a concentration of about 0.1% w / v.

87. The pharmaceutical composition of any one of claims 65-86, wherein the surfactant is Polysorbate 80, Polysorbate 20, polyethylene glycol 3350 (PEG3350), or Poloxamer (P)188.

88. The pharmaceutical composition of any one of claims 65-87, wherein the surfactant is Pl 88.

89. The pharmaceutical composition of claim 65, wherein the antibody is present at a concentration of about 25 mg / mL to about 300 mg / mL, about 25 mg / mL to about 275 mg / mL, about 25 mg / mL to about 250 mg / mL, about 25 mg / mL to about 225 mg / mL, about 25 mg / mL to about 200 mg / mL, about 25 mg / mL to about 175 mg / mL, about 25 mg / mL to about 150 mg / mL, about 25 mg / mL to about 125 mg / mL, about 25 mg / mL to about 100 mg / mL, about 25 mg / mL to about 75 mg / mL, about 50 mg / mL to about 300 mg / mL, about 50 mg / mL to about 275 mg / mL, about 50 mg / mL to about 250 mg / mL, about 50 mg / mL to about 225 mg / mL, about 50 mg / mL to about 200 mg / mL, about 50 mg / mL to about 175 mg / mL, about 50 mg / mL to about 150 mg / mL, about 50 mg / mL to about 125 mg / mL, about 50 mg / mL to about 100 mg / mL, about 50 mg / mL to about 75 mg / mL, about 75 mg / mL to about 300 mg / mL, about 75 mg / mL to about 275 mg / mL, about 75 mg / mL to about 250 mg / mL, about 75 mg / mL to about 225 mg / mL, about 75 mg / mL to about 200 mg / mL, about 75 mg / mL to about 175 mg / mL, about 75 mg / mL to about 150 mg / mL, about 75 mg / mL to about 125 mg / mL, about 75 mg / mL to about 100 mg / mL, about 100 mg / mL to about 300 mg / mL, about 100 mg / mL to about 275 mg / mL, about 100 mg / mL to about 250 mg / mL, about 100 mg / mL to about 225 mg / mL, about 100 mg / mL to about 200 mg / mL, about 100 mg / mL to about 175 mg / mL, about 100 mg / mL to about 150 mg / mL, about 100 mg / mL to about 125 mg / mL, about 125 mg / mL to about 300 mg / mL, about 125 mg / mL to about 275 mg / mL, about 125 mg / mL to about 250 mg / mL, about 125 mg / mL to about 225 mg / mL, about 125 mg / mL to about 200 mg / mL, about 125 mg / mL to about 175 mg / mL, about 125 mg / mL to about 150 mg / mL, about 150 mg / mL to about 300 mg / mL, about 150 mg / mL to about 275 mg / mL, about 150 mg / mL to about 250 mg / mL, about 150 mg / mL to about 225 mg / mL, about 150 mg / mL to about 200 mg / mL, about 150 mg / mL to about 175 mg / mL, about 175 mg / mL to about 300 mg / mL, about 175 mg / mL to about 275 mg / mL, about 175 mg / mL to about 250 mg / mL, about 175 mg / mL to about 225 mg / mL, about 175 mg / mL to about 200 mg / mL, about 200 mg / mL to about 300 mg / mL, about 200 mg / mL to about 275 mg / mL, about 200 mg / mL to about 250 mg / mL, about 200 mg / mL to about 225 mg / mL, about 225 mg / mL to about 300 mg / mL, about 225 mg / mL to about 275 mg / mL, about 225 mg / mL to about 250 mg / mL, about 250 mg / mL to about 300 mg / mL, about 250 mg / mL to about 275 mg / mL, about 275 mg / mL to about 300 mg / mL, about 100 mg / mL to about 200 mg / mL, or about 200 mg / mL to about 300 mg / mL.

90. The pharmaceutical composition of any one of claims 65-89, wherein the antibody is present at aconcentration of about 150 mg / mL.

91. The pharmaceutical composition of any one of claims 65-90, wherein the antibody is present at a concentration of about 100 mg / mL.

92. The pharmaceutical composition of any one of claims 65-91, wherein the antibody is a monoclonal antibody.

93. The pharmaceutical composition of any one of claims 65-92, wherein the monoclonal antibody is an immunoglobulin G4 (IgG4) type monoclonal antibody.

94. The pharmaceutical composition of any one of claims 65-93, wherein the antibody comprises a heavy chain variable region with an amino acid sequence of SEQ ID NO: 17; and a light chain variable region with an amino acid sequence of SEQ ID NO: 18.

95. The pharmaceutical composition of any one of claims 65-94, wherein the antibody comprises a heavy chain variable region with an amino acid sequence of SEQ ID NO: 342; and a light chain variable region with an amino acid sequence of SEQ ID NO: 18.

96. The pharmaceutical composition of any one of claims 65-95, wherein the antibody, or antibody fragment thereof, comprises a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO: 61; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO: 62; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO: 78, or variants or convention equivalents of any of the foregoing; and (ii) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence SEQ ID NO: 64; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO: 65; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO: 79; or variants or convention equivalents of any of the foregoing.

97. The pharmaceutical composition of any one of claims 65-96, wherein the pharmaceutical compositionis stable at about-25 °C, about -20 °C, about -15 °C, about -5 °C, about 0 °C, about 5 °C, or about 10 °C.

98. The pharmaceutical composition of any one of claims 65-97, wherein the pharmaceutical composition is stable for 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months, 4 months, 5 months, 6 months, 7 months, 8 months, 9 months, 10 months, 11 months, 12 months, 13 months, 14 months, 15 months, 16 months, 17 months, 18 months, 19 months, 20 months, 21 months, 22 months, 23 months, or 24 months.

99. The pharmaceutical composition of any one of claims 65-98, wherein the pharmaceutical composition is stable at -20 °C for at least 3 months.

100. The pharmaceutical composition of any one of claims 65-99, wherein the pharmaceutical composition is stable at -20 °C for at least 6 months.

101. The pharmaceutical composition of any one of claims 65-100, wherein the pharmaceutical composition is stable at 2-8 °C for at least 3, 6 or 9 months.

102. The pharmaceutical composition of any one of claims 65-101, wherein:the antibody is at about 100 mg / mL;the buffer is phosphate buffer at about 20 mM;the antioxidant is L-methionine at about 10 mM;the sugar is sucrose at about 4% w / v;the viscosity modifying agent is L-arginine hydrochloride at about 70 mM; andthe surfactant is Pl88 at about 0.1 % w / v,wherein the pharmaceutical composition is at a pH of about 7.2.

103. The pharmaceutical composition of any one of claims 65-101, wherein:the antibody is at about 150 mg / mL;the buffer is phosphate buffer at about 20 mM;the antioxidant is L-methionine at about 10 mM;the sugar is sucrose at about 3.5% w / v;the viscosity modifying agent is L-arginine hydrochloride at about 70 mM; andthe surfactant is Pl 88 at about 0.1 % w / v,wherein the pharmaceutical composition is at a pH of about 7.2.

104. The pharmaceutical composition of any one of claims 65-103, wherein the pharmaceutical composition main peak, measured by SEC, decreases in area percent by less than 0.2% after 24 months at a temperature of about -70 °C, relative to the initial value.

105. The pharmaceutical composition of any one of claims 65-103, wherein the pharmaceutical composition main peak, measured by SEC, decreases in area percent by less than 0.4% after 24 months at a temperature of about -20 °C, relative to the initial value.

106. The pharmaceutical composition of any one of claims 65-103, wherein the pharmaceutical composition main peak, measured by SEC, decreases in area percent by less than 0.5% after 6 months at a temperature of about 5 °C, relative to the initial value.

107. The pharmaceutical composition of any one of claims 65-103, wherein the pharmaceutical composition main peak, measured by SEC, decreases in area percent by less than 3% after 6 months at a temperature of about 25 °C, relative to the initial value.

108. The pharmaceutical composition of any one of claims 65-103, wherein the pharmaceutical composition main peak, measured by SEC, decreases in area percent by less than 7.8% after 1 month at a temperature of about 40 °C, relative to the initial value.

109. A pharmaceutical composition comprising:about 150 mg / mL of an antibody having a heavy chain and a light chain, wherein the heavy chain comprises a HCDR1 of SEQ ID NO: 61, a HCDR2 of SEQ ID NO: 62, and a HCDR3 of SEQ ID NO: 78, and wherein the light chain comprises a LCDR1 of SEQ ID NO: 64, a LCDR2 of SEQ ID NO: 65, and a LCDR3 of SEQ ID NO: 79;the antibody is at about 150 mg / mL,the buffer is phosphate buffer at about 20 mM,the antioxidant is L-methionine at about 10 mM,the sugar is sucrose at about 3.5% w / v,the viscosity modifying agent is L-arginine hydrochloride at about 70 mM, andthe surfactant is Pl88 at about 0.1 % w / v;wherein the pharmaceutical composition is at a pH of about 7.2.

110. The pharmaceutical composition of claim 109, wherein the antibody comprises a heavy chain variable region with an amino acid sequence of SEQ ID NO: 17; and a light chain variable region with an amino acid sequence of SEQ ID NO: 18.

111. The pharmaceutical composition of claims 109 or 110, wherein the antibody comprises a heavy chain variable region with an amino acid sequence of SEQ ID NO: 342; and a light chain variable region with an amino acid sequence of SEQ ID NO: 18.

112. The pharmaceutical composition of any one of claims 109-111, wherein the antibody, or antibody fragment thereof, comprises a heavy chain variable region comprising heavy chain HCDR1, HCDR2, and HCDR3 sequences, wherein the heavy chain HCDR1 sequence has the amino acid sequence of SEQ ID NO: 61; the heavy chain HCDR2 has the amino acid sequence of SEQ ID NO: 62; and the heavy chain HCDR3 sequence has the amino acid sequence of SEQ ID NO: 78, or variants or convention equivalents of any of the foregoing; and (ii) a light chain variable region comprising light chain LCDR1, LCDR2, and LCDR3 sequences, wherein the light chain LCDR1 sequence has the amino acid sequence SEQ ID NO: 64; the light chain LCDR2 sequence has the amino acid sequence of SEQ ID NO: 65; and the light chain LCDR3 sequence has the amino acid sequence of SEQ ID NO: 79; or variants or convention equivalents of any of the foregoing.

113. A method of treating a subject with Cis mediated disorder, the method comprising administering to the subject the pharmaceutical composition of any one of claims 1-112.

114. The method of claim 113, wherein the Cis Myasthenia Gravis, mediated disorder is hemolysis, Cold Agglutinin Disease, Immune Thrombocytopenia (ITP), Glomerulopathies, Atypical Hemolytic uremic syndrome, antiphospholipid antibody syndrome, transplant rejection, chronic inflammatory demyelinating polyneuropathy (CIDP), multifocal motor neuropathy (MMN), dermatomyositis, anti MAG neuropathy, due to stroke, or due to spinal cord injury.

115. The method of claims 113 or 114, wherein the volume of the pharmaceutical composition administered is about 1 mL or about 2 mL.

116. A kit comprising container a container comprising the pharmaceutical composition of any one of claims 1-112.

117. An injector device comprising the pharmaceutical composition of any one of claims 1-112.