PROTEIN FORMULATIONS AND METHODS OF MAKING SAME
The invention provides an aqueous formulation comprising water and a protein, and methods of making the same. The aqueous formulation of the invention may be a high protein formulation and/or may have low levels of conductity resulting from the low levels of ionic excipients. Also included in the invention are formulations comprising water and proteins having low osmolality.
1 .- 101 . (canceled)
102 . An aqueous formulation comprising an antibody, or antigen-binding fragment thereof, and water, wherein the formulation has a conductivity of less than about 2.5 mS/cm and the antibody, or antigen-binding fragment thereof, has a molecular weight (Mw) greater than about 47 kDa
103 . An aqueous formulation comprising an antibody, or antigen-binding fragment thereof, at a concentration of at least about 50 mg/mL and water, wherein the formulation has an osmolality of no more than about 30 mOsmol/kg.
104 . An aqueous formulation comprising water and a given concentration of an antibody, or antigen-binding fragment thereof, wherein the antibody, or antigen-binding fragment thereof, has a hydrodynamic diameter (D h ) which is at least about 50% less than the D h of the antibody, or antigen-binding fragment thereof, in a buffered solution at the given concentration.
105 . An aqueous formulation comprising an antibody, or an antigen-binding fragment, at a concentration of at least about 10 mg/mL and water, wherein the antibody, or antigen-binding fragment, has a hydrodynamic diameter (D h ) of less than about 5 μm.
106 . The formulation of claim 102 , wherein the antibody, or antigen-binding fragment thereof, is an anti-TNFα antibody.
107 . The formulation of claim 102 , wherein the concentration of antibody, or antigen-binding fragment thereof, is 50 to 200 mg/ml.
108 . The formulation of claim 102 , further comprising a non-ionizable excipient.
109 . The formulation of claim 108 , wherein the non-ionizable excipient is selected from the group consisting of sugar alcohols and polyols such as mannitol or sorbitol, a non-ionic surfactant, sucrose, trehalose, raffinose, and maltose.
110 . A method of treating a subject having a disorder, comprising administering to the subject the formulation of claim 102 .
111 . A device comprising the formulation of claim 102 .
112 . An article of manufacture comprising the formulation of claim 102 .
113 . A method of preparing an aqueous formulation comprising an antibody, or antigen-binding fragment thereof, and water, the method comprising:
a) providing the antibody, or antigen-binding fragment thereof, in a first solution; and
b) subjecting the first solution to diafiltration using water as a diafiltration medium until at least a five-fold volume exchange with the water has been achieved to thereby prepare the aqueous formulation.
114 . An aqueous formulation prepared according to the method of claim 113 .
115 . The formulation of claim 103 , wherein the antibody, or antigen-binding fragment thereof, is an anti-TNFα antibody.
116 . The formulation of claim 103 , wherein the concentration of antibody, or antigen-binding fragment thereof, is 50 to 200 mg/ml.
117 . A method of treating a subject having a disorder, comprising administering to the subject the formulation of claim 103 .
118 . A device comprising the formulation of claim 103 .
119 . An article of manufacture comprising the formulation of claim 103 .
120 . The formulation of claim 104 , wherein the antibody, or antigen-binding fragment thereof, is an anti-TNFα antibody.
121 . The formulation of claim 104 , wherein the concentration of antibody, or antigen-binding fragment thereof, is 50 to 200 mg/ml.
122 . A method of treating a subject having a disorder, comprising administering to the subject the formulation of claim 104 .
123 . A device comprising the formulation of claim 104 .
124 . An article of manufacture comprising the formulation of claim 104 .
125 . The formulation of claim 105 , wherein the antibody, or antigen-binding fragment thereof, is an anti-TNFα antibody.
126 . The formulation of claim 105 , wherein the concentration of antibody, or antigen-binding fragment thereof, is 50 to 200 mg/ml.
127 . A method of treating a subject having a disorder, comprising administering to the subject the formulation of claim 105 .
128 . A device comprising the formulation of claim 105 .
129 . An article of manufacture comprising the formulation of claim 105 .