EXCIPIENT COMPOUNDS FOR PROTEIN FORMULATIONS
Disclosed herein are stability-enhanced formulations that comprise a therapeutic protein and a stability-improving amount of a stabilizing excipient, wherein the stabilized-enhanced formulation is characterized by an improved stability parameter in comparison to a control formulation otherwise identical to the stability-enhanced formulation but lacking the stabilizing excipient. Further disclosed herein are methods of improving stability of therapeutic formulations or improving parameters of protein-related processes.
1 . A stability-enhanced formulation comprising a therapeutic protein and a stability-improving amount of a stabilizing excipient, wherein the stability-enhanced formulation is characterized by an improved stability parameter in comparison to a control formulation comprising the therapeutic protein but lacking the stability-improving amount of the stabilizing excipient; and wherein the stabilizing excipient is risedronic acid, lactobionic acid, ascorbyl glucoside, gluconolactone, glucosamine, glucamine, sorbitol, inositol, maltose, melzitose, maltotriose, kestose, pinitol, or trimethylamine N-oxide.
2 . The stability-enhanced formulation of claim 1 , wherein the therapeutic protein is an antibody.
3 . The stability-enhanced formulation of claim 2 , wherein the antibody is an antibody-drug conjugate.
4 . The stability-enhanced formulation of claim 1 , wherein the stabilizing excipient is lactobionic acid.
5 . The stability-enhanced formulation of claim 1 , wherein the stabilizing excipient is ascorbyl glucoside.
6 . The stability-enhanced formulation of claim 1 , wherein the stabilizing excipient is kestose.
7 . The stability-enhanced formulation of claim 1 , wherein the stabilizing excipient is gluconolactone.
8 . The stability-enhanced formulation of claim 1 , wherein the stabilizing excipient is pinitol.
9 . (canceled)
10 . The stability-enhanced formulation of claim 1 , further comprising a second stabilizing excipient, wherein the second stabilizing excipient is sucrose, trehalose, arginine, proline, glycine, risedronic acid, lactobionic acid, ascorbyl glucoside, gluconolactone, glucosamine, glucamine, sorbitol, inositol, maltose, melzitose, maltotriose, kestose, pinitol, or trimethylamine N-oxide, wherein the stabilizing excipient is different from the second stabilizing excipient.
11 . The stability-enhanced formulation of claim 1 , wherein the stabilizing excipient is added in an amount of about 1 mM to about 500 mM.
12 . (canceled)
13 . (canceled)
14 . (canceled)
15 . The stability-enhanced formulation of claim 1 , wherein the improved stability parameter is thermal storage stability.
16 . The stability-enhanced formulation of claim 15 , wherein the thermal storage stability is improved at a temperature between about 10° C. and 30° C.
17 . The stability-enhanced formulation of claim 1 , wherein the improved stability parameter is improved freeze/thaw stability.
18 . The stability-enhanced formulation of claim 1 , wherein the improved stability parameter is improved shear stability.
19 . The stability-enhanced formulation of claim 1 , wherein the stability-enhanced formulation has a reduced number of particles in comparison to the control formulation.
20 . The stability-enhanced formulation of claim 1 , wherein the stability-enhanced formulation has an increased percent of the therapeutic protein in monomeric form in comparison to the control formulation.
21 . The stability-enhanced formulation of claim 1 , wherein the stability-enhanced formulation has an improved biological activity in comparison to the control formulation.
22 . A method of improving stability of a therapeutic formulation comprising a therapeutic protein, the method comprising: adding a stability-improving amount of a stabilizing excipient to the therapeutic formulation and thereby improving the stability of the therapeutic formulation, wherein the stability of the therapeutic formulation is measured in comparison to stability of a control formulation comprising the therapeutic protein but lacking the stability-improving amount of the stabilizing excipient, and wherein the stabilizing excipient is risedronic acid, lactobionic acid, ascorbyl glucoside, gluconolactone, glucosamine, glucamine, sorbitol, inositol, maltose, melzitose, maltotriose, kestose, pinitol, or trimethylamine N-oxide.
23 . The method of claim 22 , wherein the stabilizing excipient is lactobionic acid, ascorbyl glucoside, kestose, pinitol, or gluconolactone.
24 . The method of claim 22 , further comprising adding a second stabilizing excipient, wherein the second stabilizing excipient is sucrose, trehalose, arginine, proline, glycine, risedronic acid, lactobionic acid, ascorbyl glucoside, gluconolactone, glucosamine, glucamine, sorbitol, inositol, maltose, melzitose, maltotriose, kestose, pinitol, or trimethylamine N-oxide, wherein the stabilizing excipient is different from the second stabilizing excipient.
25 - 61 . (canceled)