Antibody formulations containing amino acids

Abstract

Provided are stable protein formulations that contain at least one amino acid. In certain embodiments, amino acid combinations either at least two, or three, or four, or more amino acids are included. By virtue of inclusion of the amino acids, the formulation has low viscosity and a protein in the formulations is physically, chemically, and biological stable even at high concentrations. In further embodiments, by virtue of inclusion of the amino acids, a protein in the formulations is physically, chemically, and biological stable even at high concentrations.

1 - 327 . (canceled) 
     
     
         328 . A stable liquid pharmaceutical formulation comprising:
 an isolated antibody or binding fragment thereof,   one or more amino acids to stabilize the antibody in the formulation, the one or more amino acids to stabilize the antibody including serine, threonine, alanine, glycine and valine and one or more further amino acids selected from the group consisting of isoleucine, asparagine, glutamine and aspartic acid; and   one or more amino acids to reduce the viscosity of the formulation, the one or more amino acids—to reduce viscosity of the formulation including proline,   wherein the viscosity of the formulation is less than 100 cP.   
     
     
         329 . The formulation of  claim 328 , wherein the one or more amino acids to stabilize the antibody are serine, threonine, alanine, glycine, valine and isoleucine. 
     
     
         330 . The formulation of  claim 328 , wherein the one or more amino acids to stabilize the antibody are serine, threonine, alanine, glycine, valine and asparagine. 
     
     
         331 . The formulation of  claim 328 , wherein the one or more amino acids to stabilize the antibody are serine, threonine, alanine, glycine, valine and glutamine. 
     
     
         332 . The formulation of  claim 328 , wherein the one or more amino acids to stabilize the antibody are serine, threonine, alanine, glycine, valine and aspartic acid. 
     
     
         333 . The formulation of  claim 328 , wherein the one or more amino acids to stabilize the antibody are serine, threonine, alanine, glycine, valine, glutamine and asparagine. 
     
     
         334 . The formulation of  claim 328 , wherein the one or more amino acids to stabilize the antibody are serine, threonine, alanine, glycine, valine, glutamine and isoleucine. 
     
     
         335 . The formulation of  claim 328 , wherein the one or more amino acids to stabilize the antibody are serine, threonine, alanine, glycine, valine, glutamine and isoleucine. 
     
     
         337 . The formulation of  claim 328 , wherein the one or more amino acids to stabilize the antibody are serine, threonine, alanine, glycine, valine, glutamine and aspartic acid. 
     
     
         338 . The formulation of  claim 328 , wherein the one or more amino acids to stabilize the antibody are serine, threonine, alanine, glycine, valine, asparagine and isoleucine. 
     
     
         339 . The formulation of  claim 328 , wherein the one or more amino acids to stabilize the antibody are serine, threonine, alanine, glycine, valine, asparagine and aspartic acid. 
     
     
         340 . The formulation of  claim 328 , wherein the one or more amino acids to stabilize the antibody are serine, threonine, alanine, glycine, valine, isoleucine and aspartic acid. 
     
     
         341 . The formulation of  claim 328 , wherein the one or more amino acids to stabilize the antibody are glycine, serine, threonine, arginine, methionine, lysine, proline and asparagine. 
     
     
         342 . The formulation of  claim 328 , wherein the one or more amino acids to stabilize the antibody and the one or more amino acids to reduce viscosity of the formulation are each present at a concentration of at least 0.1 mg/mL. 
     
     
         343 . The formulation of  claim 328 , wherein when present in the formulation, the concentration of each of glutamine and/or aspartic acid is from about 1.5 mg/mL to about 10 mg/mL 
     
     
         344 . The formulation of  claim 328 , wherein the antibody is selected from the group consisting of infliximab, bevacizumab, ranibizumab, cetuximab, ranibizumab, palivizumab, abagovomab, abciximab, actoxumab, adalimumab, afelimomab, afutuzumab, alacizumab, alacizumab pegol, ald518, alemtuzumab, alirocumab, alemtuzumab, altumomab, amatuximab, anatumomab mafenatox, anrukinzumab, apolizumab, arcitumomab, aselizumab, altinumab, atlizumab, atorolimiumab, tocilizumab, bapineuzumab, basiliximab, bavituximab, bectumomab, belimumab, benralizumab, bertilimumab, besilesomab, bevacizumab, bezlotoxumab, biciromab, bivatuzumab, bivatuzumab mertansine, blinatumomab, blosozumab, brentuximab vedotin, briakinumab, brodalumab, canakinumab, cantuzumab mertansine, caplacizumab, capromab pendetide, carlumab, catumaxomab, cc49, cedelizumab, certolizumab pegol, cetuximab, citatuzumab bogatox, cixutumumab, clazakizumab, clenoliximab, clivatuzumab tetraxetan, conatumumab, crenezumab, CR6261, dacetuzumab, daclizumab, dalotuzumab, daratumumab, demcizumab, denosumab, detumomab, dorlimomab aritox, drozitumab, duligotumab, dupilumab, ecromeximab, eculizumab, edobacomab, edrecolomab, efalizumab, efungumab, elotuzumab, elsilimomab, enavatuzumab, enlimomab pegol, enokizumab, enokizumab, enoticumab, enoticumab, ensituximab, epitumomab cituxetan, epratuzumab, erlizumab, ertumaxomab, etaracizumab, etrolizumab, exbivirumab, exbivirumab, fanolesomab, faralimomab, farletuzumab, fasinumab, FBTA05, felvizumab, fezakinumab, ficlatuzumab, figitumumab, flanvotumab, fontolizumab, foralumab, foravirumab, fresolimumab, fulranumab, futuximab, galiximab, ganitumab, gantenerumab, gavilimomab, gemtuzumab ozogamicin, gevokizumab, girentuximab, glembatumumab vedotin, golimumab, gomiliximab, GS6624, ibalizumab, ibritumomab tiuxetan, icrucumab, igovomab, imciromab, imgatuzumab, inclacumab, indatuximab ravtansine, infliximab, intetumumab, inolimomab, inotuzumab ozogamicin, ipilimumab, iratumumab, itolizumab, ixekizumab, keliximab, labetuzumab, lebrikizumab, lemalesomab, lerdelimumab, lexatumumab, libivirumab, ligelizumab, lintuzumab, lirilumab, lorvotuzumab mertansine, lucatumumab, lumiliximab, mapatumumab, maslimomab, mavrilimumab, matuzumab, mepolizumab, metelimumab, milatuzumab, minretumomab, mitumomab, mogamulizumab, morolimumab, motavizumab, moxetumomab pasudotox, muromonab-CD3, nacolomab tafenatox, namilumab, naptumomab estafenatox, narnatumab, natalizumab, nebacumab, necitumumab, nerelimomab, nesvacumab, nimotuzumab, nivolumab, nofetumomab merpentan, ocaratuzumab, ocrelizumab, odulimomab, ofatumumab, olaratumab, olokizumab, omalizumab, onartuzumab, oportuzumab monatox, oregovomab, orticumab, otelixizumab, oxelumab, ozanezumab, ozoralizumab, pagibaximab, palivizumab, panitumumab, panobacumab, parsatuzumab, pascolizumab, pateclizumab, patritumab, pemtumomab, perakizumab, pertuzumab, pexelizumab, pidilizumab, pintumomab, placulumab, ponezumab, priliximab, pritumumab, PRO 140, quilizumab, racotumomab, radretumab, rafivirumab, ramucirumab, ranibizumab, raxibacumab, regavirumab, reslizumab, rilotumumab, rituximab, robatumumab, roledumab, romosozumab, rontalizumab, rovelizumab, ruplizumab, samalizumab, sarilumab, satumomab pendetide, secukinumab, sevirumab, sibrotuzumab, sifalimumab, siltuximab, simtuzumab, siplizumab, sirukumab, solanezumab, solitomab, sonepcizumab, sontuzumab, stamulumab, sulesomab, suvizumab, tabalumab, tacatuzumab tetraxetan, tadocizumab, talizumab, tanezumab, taplitumomab paptox, tefibazumab, telimomab aritox, tenatumomab, tefibazumab, telimomab aritox, tenatumomab, teneliximab, teplizumab, teprotumumab, TGN1412, tremelimumab, ticilimumab, tildrakizumab, tigatuzumab, TNX-650, tocilizumab, toralizumab, tositumomab, tralokinumab, trastuzumab, TRBS07, tregalizumab, tremelimumab, tucotuzumab celmoleukin, tuvirumab, ublituximab, urelumab, urtoxazumab, ustekinumab, vapaliximab, vatelizumab, vedolizumab, veltuzumab, vepalimomab, vesencumab, visilizumab, volociximab, vorsetuzumab mafodotin, votumumab, zalutumumab, zanolimumab, zatuximab, ziralimumab and zolimomab aritox. 
     
     
         345 . The formulation of  claim 328 , wherein the antibody is selected from the group consisting of abciximab, adalimumab, alirocumab, arcitumomab, belimumab, besilesomab bezlotoxumab, brodalumab, brentuximab, canakinumab, capromab pendetide, catumaxomab, certolizumab pegol, cetuximab, denosumab, dupilumab, eculizumab, efalizumab, elotuzumab, fanolesomab, gemtuzumab ozogamicin, golimumab, ibritumomab tiuxetan, ipilimumab, mepolizumab, muromonab-CD3, natalizumab, necitumumab, nivolumab, nofetumomab merpentan, ocrelizumab, ofatumumab, omalizumab, olaratumab, palivizumab, pertuzumab, ramucirumab, raxibacumab, reslizumab, satumomab pendetide, secukinumab, siltuximab, sulesomab, tocilizumab, tositumomab, ustekinumab, vedolizumab, and votumumab. 
     
     
         346 . The formulation of  claim 328 , wherein the antibody is selected from the group consisting of abciximab, alirocumab, belimumab, brodalumab, canakinumab, catumaxomab, cetuximab, eculizumab, elotuzumab, and gemtuzumab ozogamicin. 
     
     
         347 . The formulation of  claim 328 , wherein the antibody is selected from the group consisting of nofetumomab merpentan, ofatumumab, olaratumab, pertuzumab, raxibacumab, satumomab pendetide, siltuximab, tocilizumab, ustekinumab and votumumab. 
     
     
         348 . The formulation of  claim 328 , wherein the antibody is selected from the group consisting of brentuximab, canakinumab, catumaxomab, cetuximab, denosumab, dupilumab, eculizumab, efalizumab, elotuzumab, and fanolesomab.