US2016319011A1PendingUtilityA1
Self-buffering protein formulations
Est. expiryJun 14, 2025(expired)· nominal 20-yr term from priority
A61P 43/00A61P 35/00C07K 16/2875C07K 16/2827C07K 2317/21A61K 47/26A61K 9/08A61K 47/02C07K 16/241A61K 47/10C07K 2317/565A61K 39/3955C07K 16/00C07K 16/2803A61K 39/39591C07K 16/2851C07K 16/2866C07K 2317/94A61K 39/395A61K 9/28
59
PatentIndex Score
0
Cited by
0
References
0
Claims
Abstract
The invention herein described, provides, among other things, self-buffering protein formulations. Particularly, the invention provides self-buffering pharmaceutical protein formulations that are suitable for veterinary and human medical use. The self-buffering protein formulations are substantially free of other buffering agents, stably maintain pH for the extended time periods involved in the distribution and storage of pharmaceutical proteins for veterinary and human medical use. The invention further provides methods for designing, making, and using the formulation. In addition to other advantages, the formulations avoid the disadvantages associated with the buffering agents conventionally used in current formulations of proteins for pharmaceutical use. The invention in these and other respects can be productively applied to a wide variety of proteins and is particularly useful for making and using self-buffering formulations of pharmaceutical proteins for veterinary and medical use, especially, in particular, for the treatment of diseases in human subjects.
Claims
exact text as granted — not AI-modified1 . (canceled)
2 . An aqueous pharmaceutical formulation consisting essentially of:
(a) an anti-tumor necrosis factor alpha antibody comprising a light chain variable region (LCVR) having a CDR3 domain comprising the amino acid sequence of SEQ ID NO:3, a CDR2 domain comprising the amino acid sequence of SEQ ID NO:5, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 7, and a heavy chain variable region (HCVR) having a CDR3 domain comprising the amino acid sequence of SEQ ID NO:4, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 6, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO:8, wherein the concentration of the antibody is 50 to 200 mg/ml; and (b) water.
3 . The formulation of claim 2 , wherein the antibody comprises a LCVR comprising the amino acid sequence set forth in SEQ ID NO: 1, and a HCVR comprising the amino acid sequence set forth in SEQ ID NO: 2.
4 . The formulation of claim 3 , wherein the antibody is adalimumab.
5 . The formulation of claim 2 , wherein the pH of the formulation is from 4 to 8.
6 . The formulation of claim 4 , wherein the pH of the formulation is from 4 to 8.
7 . An aqueous pharmaceutical formulation comprising:
(a) an anti-tumor necrosis factor alpha antibody comprising a light chain variable region (LCVR) having a CDR3 domain comprising the amino acid sequence of SEQ ID NO:3, a CDR2 domain comprising the amino acid sequence of SEQ ID NO:5, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 7, and a heavy chain variable region (HCVR) having a CDR3 domain comprising the amino acid sequence of SEQ ID NO:4, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 6, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO:8, wherein the concentration of the antibody is 50 to 200 mg/ml; and (b) water; wherein the formulation does not comprise a tonicity modifier.
8 . The formulation of claim 7 , wherein the antibody comprises a LCVR comprising the amino acid sequence set forth in SEQ ID NO: 1, and a HCVR comprising the amino acid sequence set forth in SEQ ID NO: 2.
9 . The formulation of claim 8 , wherein the antibody is adalimumab.
10 . The formulation of claim 7 , wherein the pH of the formulation is from 4 to 8.
11 . The formulation of claim 7 , wherein the pH of the formulation is from 4 to 6.
12 . The formulation of claim 7 , wherein the pH of the formulation is from 5 to 6.
13 . The formulation of claim 9 , wherein the pH of the formulation is from 4 to 8.
14 . The formulation of claim 9 , wherein the pH of the formulation is from 4 to 6.
15 . The formulation of claim 9 , wherein the pH of the formulation is from 5 to 6.
16 . The formulation of claim 9 , wherein the pH of the formulation is 5.
17 . An aqueous pharmaceutical formulation comprising:
(a) an anti-tumor necrosis factor alpha antibody comprising a light chain variable region (LCVR) having a CDR3 domain comprising the amino acid sequence of SEQ ID NO:3, a CDR2 domain comprising the amino acid sequence of SEQ ID NO:5, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO: 7, and a heavy chain variable region (HCVR) having a CDR3 domain comprising the amino acid sequence of SEQ ID NO:4, a CDR2 domain comprising the amino acid sequence of SEQ ID NO: 6, and a CDR1 domain comprising the amino acid sequence of SEQ ID NO:8, wherein the concentration of the antibody is 50 to 200 mg/ml; and (b) water; wherein the formulation does not comprise a buffering system.
18 . The formulation of claim 17 , wherein the antibody comprises a LCVR comprising the amino acid sequence set forth in SEQ ID NO: 1, and a HCVR comprising the amino acid sequence set forth in SEQ ID NO: 2.
19 . The formulation of claim 18 , wherein the antibody is adalimumab.
20 . The formulation of claim 17 , wherein the formulation further comprises a non-ionizable excipient.
21 . The formulation of claim 17 , wherein the formulation further comprises a polyol.
22 . The formulation of claim 21 , wherein the polyol is selected from the group consisting of mannitol, sorbitol, and sucrose.
23 . The formulation of claim 17 , wherein the formulation further comprises a surfactant.
24 . The formulation of claim 23 , wherein the surfactant is selected from the group consisting of polysorbate 80 and polysorbate 20.
25 . The formulation of claim 17 , wherein the pH of the formulation is from 4 to 8.
26 . The formulation of claim 17 , wherein the pH of the formulation is from 4 to 6.
27 . The formulation of claim 17 , wherein the pH of the formulation is from 5 to 6.
28 . The formulation of claim 19 , wherein the pH of the formulation is from 4 to 8.
29 . The formulation of claim 19 , wherein the pH of the formulation is from 4 to 6.
30 . The formulation of claim 19 , wherein the pH of the formulation is from 5 to 6.
31 . The formulation of claim 19 , wherein the pH of the formulation is 5.
32 . A self-buffering protein formulation consisting of:
water; and adalimumab or epratuzumab at a concentration between 20 and 200 mg/ml, wherein the formulation is self-buffering by the concentration of adalimumab in the water.
33 . The self-buffering protein formulation of claim 32 , wherein the self-buffering formulation consists of adalimumab and water.
34 . The self-buffering protein formulation of claim 33 , wherein the self-buffering formulation is a pharmaceutical formulation.
35 . The self-buffering protein formulation of claim 33 , wherein the pH of the self-buffering formulation is from 4 to 8.
36 . The self-buffering protein formulation of claim 33 , wherein the pH of the formulation is from 5 to 6.
37 . The self-buffering protein formulation of claim 33 , wherein the pH of the formulation is from 4 to 6.
38 . A formulation consisting of:
water; and adalimumab or epratuzumab at a concentration between 20 and 200 mg/ml, wherein the formulation has a pH of 4 to 6.
39 . The formulation of claim 38 , wherein the formulation consists of water and adalimumab.
40 . The formulation of claim 39 , wherein the formulation is a pharmaceutical formulation.
41 . The formulation of claim 39 , wherein the pH of the self-buffering formulation is from 4 to 8.
42 . The formulation of claim 39 , wherein the pH of the formulation is from 5 to 6.
43 . The formulation of claim 39 , wherein the pH of the formulation is from 4 to 6.
44 . A formulation comprising:
adalimumab or epratuzumab at concentration between 20 and 200 mg/ml; and water, wherein, the formulation has less than 25 mM total salt.
45 . The formulation of claim 44 , wherein the formulation comprises adalimumab.
46 . The formulation of claim 45 , wherein the pH of the formulation is from 4 to 8.
47 . The formulation of claim 45 , wherein the pH of the formulation is from 4 to 6.
48 . The formulation of claim 45 , wherein the pH of the formulation is from 5 to 6.
49 . The formulation of claim 45 , wherein the pH of the formulation is 5.
50 . The formulation of claim 45 , wherein the formulation, exclusive of the buffer capacity of the antibody, has a buffer capacity per unit volume of the solution at the pH of the solution, 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere of no more than that of 2.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 at 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere.
51 . The formulation of claim 45 , wherein, the formulation, exclusive of the buffer capacity of the antibody, has a buffer capacity per unit volume of the solution at the pH of the solution, 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere of no more than that of 2.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 at 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere, and wherein at the pH of the composition, 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere, the antibody has a buffer capacity per unit volume of at least that of 4.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 at 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere.
52 . The formulation of claim 45 , wherein the formulation is substantially free of any buffering agent other than the pharmaceutical protein.
53 . A formulation comprising:
adalimumab or epratuzumab at concentration between 20 and 200 mg/ml; and water, wherein, the formulation lacks a tonicity agent.
54 . The formulation of claim 53 , wherein the formulation comprises adalimumab.
55 . The formulation of claim 54 , wherein a pH of the formulation is from 4 to 6.
56 . The formulation of claim 54 , wherein a pH of the formulation is from 4 to 8.
57 . The formulation of claim 54 , wherein a pH of the formulation is 5.
58 . The formulation of claim 54 , wherein a pH of the formulation is from 5 to 6.
59 . The formulation of claim 54 , wherein the formulation, exclusive of the buffer capacity of the antibody, has a buffer capacity per unit volume of the solution at the pH of the solution, 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere of no more than that of 2.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 at 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere.
60 . The formulation of claim 54 , wherein, the formulation, exclusive of the buffer capacity of the antibody, has a buffer capacity per unit volume of the solution at the pH of the solution, 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere of no more than that of 2.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 at 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere, and wherein at the pH of the composition, 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere, the antibody has a buffer capacity per unit volume of at least that of 4.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 at 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere.
61 . The formulation of claim 54 , wherein the formulation is substantially free of any buffering agent other than the pharmaceutical protein.
62 . A self-buffering protein formulation comprising:
adalimumab or epratuzumab at a concentration between 20 and 200 mg/ml; and water, wherein, apart from adalimumab, there is no buffer in the self-buffering formulation.
63 . The self-buffering protein formulation of claim 62 , wherein the formulation comprises adalimumab.
64 . The self-buffering protein formulation of claim 63 , wherein the formulation, exclusive of the buffer capacity of the antibody, has a buffer capacity per unit volume of the solution at the pH of the solution, 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere of no more than that of 2.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 at 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere.
65 . The self-buffering protein formulation of claim 63 , wherein, the formulation, exclusive of the buffer capacity of the antibody, has a buffer capacity per unit volume of the solution at the pH of the solution, 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere of no more than that of 2.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 at 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere, and wherein at the pH of the composition, 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere, the antibody has a buffer capacity per unit volume of at least that of 4.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 at 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere.
66 . The self-buffering protein formulation of claim 63 , wherein the formulation further comprises a polyol.
67 . The self-buffering protein formulation of claim 66 , wherein the polyol is selected from the group consisting of mannitol, sorbitol, and sucrose.
68 . The self-buffering protein formulation of claim 63 , wherein the formulation further comprises a surfactant.
69 . The self-buffering protein formulation of claim 68 , wherein the surfactant is selected from the group consisting of polysorbate 80 and polysorbate 20.
70 . The self-buffering protein formulation of claim 63 , wherein a pH of the formulation is from 4 to 8.
71 . The self-buffering protein formulation of claim 63 , wherein a pH of the formulation is from 4 to 6.
72 . The self-buffering protein formulation of claim 63 , wherein a pH of the formulation is from 5 to 6.
73 . The self-buffering protein formulation of claim 63 , wherein a pH of the formulation is 5.
74 . The self-buffering protein formulation of claim 64 , wherein the formulation has a pH between approximately 4 and 6.
75 . A formulation comprising:
adalimumab or epratuzumab at a concentration between 20 and 200 mg/ml; and water, wherein the formulation is substantially free of buffering agents other than adalimumab or epratuzumab.
76 . The formulation of claim 75 , wherein the formulation comprises adalimumab.
77 . The formulation of claim 76 , wherein the formulation has a pH between approximately 4 and 6.
78 . The formulation of claim 76 , wherein the formulation, exclusive of the buffer capacity of the antibody, has a buffer capacity per unit volume of the solution at the pH of the solution, 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere of no more than that of 2.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 at 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere.
79 . The formulation of claim 76 , wherein, the formulation, exclusive of the buffer capacity of the antibody, has a buffer capacity per unit volume of the solution at the pH of the solution, 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere of no more than that of 2.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 at 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere, and wherein at the pH of the composition, 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere, the antibody has a buffer capacity per unit volume of at least that of 4.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 at 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere.
80 . The formulation of claim 76 , wherein the formulation further comprises a polyol.
81 . The formulation of claim 80 , wherein the polyol is selected from the group consisting of mannitol, sorbitol, and sucrose.
82 . The formulation of claim 76 , wherein the formulation further comprises a surfactant.
83 . The formulation of claim 82 , wherein the surfactant is selected from the group consisting of polysorbate 80 and polysorbate 20.
84 . The formulation of claim 76 , wherein a pH of the formulation is from 4 to 8.
85 . The formulation of claim 76 , wherein a pH of the formulation is from 4 to 6.
86 . The formulation of claim 76 , wherein a pH of the formulation is from 5 to 6.
87 . The formulation of claim 76 , wherein a pH of the formulation is 5.
88 . A formulation comprising:
adalimumab or epratuzumab at a concentration between 20 and 200 mg/ml; and water, wherein at least 95% of a total amount of buffering agent of the formulation is adalimumab or epratuzumab.
89 . The formulation of claim 88 , wherein the formulation comprises adalimumab.
90 . The formulation of claim 89 , wherein the formulation further comprises a polyol.
91 . The formulation of claim 90 , wherein the polyol is selected from the group consisting of mannitol, sorbitol, and sucrose.
92 . The formulation of claim 89 , wherein the formulation further comprises a surfactant.
93 . The formulation of claim 92 , wherein the surfactant is selected from the group consisting of polysorbate 80 and polysorbate 20.
94 . The formulation of claim 89 , wherein a pH of the formulation is from 4 to 8.
95 . The formulation of claim 89 , wherein a pH of the formulation is from 4 to 6.
96 . The formulation of claim 89 , wherein a pH of the formulation is from 5 to 6.
97 . The formulation of claim 89 , wherein a pH of the formulation is 5.
98 . The formulation of claim 89 , wherein the formulation, exclusive of the buffer capacity of the antibody, has a buffer capacity per unit volume of the solution at the pH of the solution, 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere of no more than that of 2.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 at 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere.
99 . The formulation of claim 89 , wherein, the formulation, exclusive of the buffer capacity of the antibody, has a buffer capacity per unit volume of the solution at the pH of the solution, 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere of no more than that of 2.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 at 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere, and wherein at the pH of the composition, 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere, the antibody has a buffer capacity per unit volume of at least that of 4.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 at 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere.
100 . The formulation of claim 89 , wherein the formulation is substantially free of any buffering agent other than the pharmaceutical protein.
101 . A formulation comprising:
adalimumab or epratuzumab at a concentration between 20 and 200 mg/ml; and water, wherein adalimumab provides at least 99% of a buffer capacity of the formulation.
102 . The formulation of claim 101 , wherein the formulation comprises adalimumab.
103 . The formulation of claim 102 , wherein the formulation further comprises a polyol.
104 . The formulation of claim 103 , wherein the polyol is selected from the group consisting of mannitol, sorbitol, and sucrose.
105 . The formulation of claim 102 , wherein the formulation further comprises a surfactant.
106 . The formulation of claim 105 , wherein the surfactant is selected from the group consisting of polysorbate 80 and polysorbate 20.
107 . The formulation of claim 102 , wherein a pH of the formulation is from 4 to 8.
108 . The formulation of claim 102 , wherein a pH of the formulation is from 4 to 6.
109 . The formulation of claim 102 , wherein a pH of the formulation is from 5 to 6.
110 . The formulation of claim 102 , wherein a pH of the formulation is 5.
111 . The formulation of claim 102 , wherein the formulation, exclusive of the buffer capacity of the antibody, has a buffer capacity per unit volume of the solution at the pH of the solution, 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere of no more than that of 2.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 at 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere.
112 . The formulation of claim 102 , wherein, the formulation, exclusive of the buffer capacity of the antibody, has a buffer capacity per unit volume of the solution at the pH of the solution, 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere of no more than that of 2.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 at 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere, and wherein at the pH of the composition, 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere, the antibody has a buffer capacity per unit volume of at least that of 4.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 at 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere.
113 . The formulation of claim 102 , wherein the formulation is substantially free of any buffering agent other than the pharmaceutical protein.
114 . The formulation of claim 102 , wherein adalimumab provides at least 99.5% of the buffer capacity of the formulation.
115 . An aqueous pharmaceutical formulation consisting of:
an antibody selected from the group consisting of: (a) an anti-tumor necrosis factor alpha antibody comprising a light chain variable region (LCVR) having a CDR3 domain of the CDR3 domain of adalimumab, a CDR2 domain of the CDR2 domain of adalimumab, and a CDR1 domain of the CDR1 domain of adalimumab, and a heavy chain variable region (HCVR) having a CDR3 domain of the CDR3 domain of adalimumab, a CDR2 domain of the CDR2 domain of adalimumab, and a CDR1 domain of the CDR1 domain of adalimumab, wherein the concentration of the antibody is 20 to 200 mg/ml; or (b) epratzumab; and water.
116 . The aqueous pharmaceutical formulation of claim 115 , wherein the antibody has a LCVR consisting of a LCVR of adalimumab, and a HCVR consisting of a HCVR of adalimumab.
117 . The aqueous pharmaceutical formulation of claim 115 , wherein the antibody is adalimumab.
118 . The aqueous pharmaceutical formulation of claim 117 , wherein a pH of the formulation is from 5 to 6.
119 . The aqueous pharmaceutical formulation of claim 117 , wherein a pH of the formulation is from 4 to 8.
120 . The aqueous pharmaceutical formulation of claim 117 , wherein a pH of the formulation is from 4 to 6.
121 . The aqueous pharmaceutical formulation of claim 116 , wherein a pH of the formulation is from 4 to 6.
122 . The aqueous pharmaceutical formulation of claim 115 , wherein a pH of the formulation is from 4 to 6.
123 . The aqueous pharmaceutical formulation of claim 115 , wherein, the formulation, exclusive of the buffer capacity of the antibody, has a buffer capacity per unit volume of the solution at the pH of the solution, 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere of no more than that of 2.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 at 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere, and wherein at the pH of the composition, 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere, the antibody has a buffer capacity per unit volume of at least that of 4.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 at 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere.
124 . An aqueous pharmaceutical formulation consisting essentially of:
an antibody selected from the group consisting of: (a) an anti-tumor necrosis factor alpha antibody comprising a light chain variable region (LCVR) having a CDR3 domain of the CDR3 domain of adalimumab, a CDR2 domain of the CDR2 domain of adalimumab, and a CDR1 domain of the CDR1 domain of adalimumab, and a heavy chain variable region (HCVR) having a CDR3 domain of the CDR3 domain of adalimumab, a CDR2 domain of the CDR2 domain of adalimumab, and a CDR1 domain of the CDR1 domain of adalimumab, wherein the concentration of the antibody is 20 to 200 mg/ml; or (b) epratzumumab; and water.
125 . The aqueous pharmaceutical formulation of claim 124 , wherein the antibody is adalimumab.
126 . An aqueous pharmaceutical formulation comprising:
an antibody selected from the group consisting of:
(a) an anti-tumor necrosis factor alpha antibody comprising a light chain variable region (LCVR) having a CDR3 domain comprising the LCDR3 domain of adalimumab, a CDR2 domain comprising the LCDR2 domain of adalimumab, and a CDR1 domain comprising the LCDR1 domain of adalimumab, and a heavy chain variable region (HCVR) having a CDR3 domain comprising the HCDR3 domain of adalimumab, a CDR2 domain comprising the HCDR2 domain of adalimumab, and a CDR1 domain comprising the HCDR1 domain of adalimumab, wherein the concentration of the antibody is 20 to 200 mg/ml, or
(b) epratuzumab; and
water;
wherein the formulation does not comprise a buffering agent.
127 . The aqueous pharmaceutical formulation of claim 126 , wherein the antibody has a LCVR consisting of a LCVR of adalimumab, and a HCVR consisting of a HCVR of adalimumab.
128 . The aqueous pharmaceutical formulation of claim 126 , wherein the antibody is adalimumab
129 . The aqueous pharmaceutical formulation of claim 128 , wherein the formulation further comprises a non-ionizable excipient.
130 . The aqueous pharmaceutical formulation of claim 128 , wherein the formulation further comprises a polyol.
131 . The aqueous pharmaceutical formulation of claim 130 , wherein the polyol is selected from the group consisting of mannitol, sorbitol, and sucrose.
132 . The aqueous pharmaceutical formulation of claim 128 , wherein the formulation further comprises a surfactant.
133 . The aqueous pharmaceutical formulation of claim 132 , wherein the surfactant is selected from the group consisting of polysorbate 80 and polysorbate 20.
134 . The aqueous pharmaceutical formulation of claim 128 , wherein the pH of the formulation is from 4 to 8.
135 . The aqueous pharmaceutical formulation of claim 128 , wherein the pH of the formulation is from 4 to 6.
136 . The aqueous pharmaceutical formulation of claim 128 , wherein the pH of the formulation is from 5 to 6.
137 . The aqueous pharmaceutical formulation of claim 127 , wherein the pH of the formulation is from 4 to 6.
138 . The aqueous pharmaceutical formulation of claim 126 , wherein the pH of the formulation is from 4 to 6.
139 . The aqueous pharmaceutical formulation of claim 128 , wherein the pH of the formulation is 5.
140 . The aqueous pharmaceutical formulation of claim 128 , wherein, the formulation, exclusive of the buffer capacity of the antibody, has a buffer capacity per unit volume of the solution at the pH of the solution, 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere of no more than that of 2.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 at 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere, and wherein at the pH of the composition, 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere, the antibody has a buffer capacity per unit volume of at least that of 4.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 at 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere.
141 . A composition comprising a pharmaceutical protein, wherein at the pH of the composition, at 21° C., at one atmosphere, and at equilibrium with ambient atmosphere, the protein has a buffer capacity per unit volume of at least that of approximately 4.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 under the same conditions, wherein further, exclusive of the buffer capacity of said protein, the buffer capacity per unit volume of the composition under the same conditions is no more than that of 2.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 under the same conditions, wherein the protein provides at least 80% of the buffer capacity of the composition, wherein the protein is adalimumab or a CD22 antibody, and wherein the concentration of the protein is between approximately 20 and 400 mg/ml.
142 . The composition of claim 141 , wherein the antibody is adalimumab.
143 . The composition of claim 142 , wherein the antibody provides all of the buffer capacity of the composition.
144 . The composition of claim 142 , wherein the antibody provides at least 99% of the buffer capacity of the composition.
145 . The composition of claim 142 , wherein a pH maintained by the buffering action of the protein is between approximately 4 and 6.
146 . The composition of claim 142 , further comprising one or more pharmaceutically acceptable salts, wherein the total salt concentration is less than 100 mM.
147 . The composition of claim 142 , further comprising one or more pharmaceutically acceptable polyols.
148 . The composition of claim 147 , wherein the polyol is one or more of sorbitol, mannitol, sucrose, trehalose, or glycerol.
149 . The composition of claim 142 , further comprising one or more pharmaceutically acceptable surfactants.
150 . A composition comprising a pharmaceutical protein, wherein the pharmaceutical protein provides all of the buffer capacity of the composition, and wherein the protein is selected from the group consisting of adalimumab and a CD22 antibody, and wherein a concentration of the protein is between approximately 20 and 400 mg/ml.
151 . The composition of claim 150 , wherein the antibody is adalimumab.
152 . The composition of claim 151 , wherein the antibody provides at least 99% of the buffer capacity of the composition.
153 . The composition of claim 151 , wherein a pH maintained by the buffering action of the protein is between approximately 4 and 6.
154 . The composition of claim 151 , further comprising one or more pharmaceutically acceptable salts, wherein the total salt concentration is less than 100 mM.
155 . The composition of claim 151 , further comprising one or more pharmaceutically acceptable polyols.
156 . The composition of claim 155 , wherein the polyol is one or more of sorbitol, mannitol, sucrose, trehalose, or glycerol.
157 . The composition of claim 151 , further comprising one or more pharmaceutically acceptable surfactants.
158 . The composition of claim 157 , wherein the surfactant is one or more of polysorbate 20, polysorbate 80, polyethoxylates, and poloxamer 188.
159 . A bufferless antibody formulation comprising:
an antibody at a concentration of greater than 30 mg/ml; and water, wherein the formulation is bufferless other than the antibody, and wherein the formulation has a buffer capacity equivalent to 10 mM acetate in the pH 4.5-5.5 range.
160 . The bufferless antibody formulation of claim 159 , wherein the formulation maintains pH within 1 pH unit between pH 4.0 to 7.5.
161 . The bufferless antibody formulation of claim 159 , wherein the antibody is epratuzumab.
162 . A pharmaceutical protein formulation comprising:
an antibody in an amount sufficient for maintaining pH control; and a pharmaceutically acceptable excipient, wherein said pharmaceutical protein formulation is buffered by said antibody, and wherein the formulation lacks a buffer, apart from the antibody.
163 . The pharmaceutical protein formulation of claim 162 , wherein the formulation has a buffer capacity equivalent to 10 mM acetate in the pH 4.5-5.5 range.
164 . The pharmaceutical protein formulation of claim 162 , wherein the formulation maintains pH within 1 pH unit between pH 4.0 to 7.5.
165 . The pharmaceutical protein formulation of claim 162 , wherein the antibody is epratuzumab.
166 . A composition comprising a pharmaceutical protein, wherein
the pharmaceutical protein is an antibody, wherein the antibody has a buffer capacity per unit volume of at least that of approximately 4.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 under the same conditions, wherein, exclusive of the buffer capacity of said antibody, the buffer capacity per unit volume of the composition under the same conditions is no more than that of 2.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 under the same conditions, and wherein the concentration of the antibody is between approximately 20 and 400 mg/ml.
167 . The composition of claim 166 , wherein the antibody is adalimumab.
168 . A composition comprising a pharmaceutical protein, wherein
the pharmaceutical protein is an antibody, wherein, exclusive of the buffer capacity of the antibody, the composition has a buffer capacity per unit volume of the solution at the pH of the solution, 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere of no more than that of 2.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 at 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere, wherein at the pH of the composition, 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere, the antibody has a buffer capacity per unit volume of at least that of 4.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 at 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere, and wherein the concentration of the antibody is between approximately 20 and 400 mg/ml.
169 . The composition of claim 168 , wherein the antibody is adalimumab.
170 . The composition of claim 169 , wherein a pH maintained by the antibody is between approximately 4 and 6.
171 . The composition of claim 169 , wherein a pH maintained by the antibody is between approximately 3.5 and 8.
172 . A composition comprising a pharmaceutical protein, wherein at the pH of the composition, 21° C., one atmosphere, and equilibrium with ambient atmosphere, the protein has a buffer capacity per unit volume of at least 1.50 mEq/liter-pH unit, wherein further, exclusive of the buffer capacity of the protein, the buffer capacity per unit volume of the composition is less than 0.5 mEq/liter-pH unit, wherein the pharmaceutical protein is adalimumab, and wherein the concentration of adalimumab is between approximately 20 and 400 mg/ml.
173 . The composition of claim 172 , wherein a pH maintained by the antibody is between approximately 4 and 6.
174 . The composition of claim 172 , wherein a pH maintained by the antibody is between approximately 3.5 and 8.
175 . A composition comprising adalimumab, wherein at the pH of the composition, 21° C., one atmosphere, and equilibrium with ambient atmosphere, the adalimumab has a buffer capacity per unit volume of at least 1.50 mEq/liter-pH unit, wherein further, exclusive of the buffer capacity of the adalimumab, the buffer capacity per unit volume of the composition is less than 0.5 mEq/liter-pH unit, and wherein the concentration of the adalimumab is between approximately 20 and 400 mg/ml.
176 . The composition of claim 175 , wherein a pH maintained by the antibody is between approximately 4 and 6.
177 . The composition of claim 175 , wherein a pH maintained by the antibody is between approximately 3.5 and 8.
178 . A composition comprising a pharmaceutical protein, wherein
the pharmaceutical protein is adalimumab, wherein, exclusive of the buffer capacity of the adalimumab, the composition has a buffer capacity per unit volume of the solution at the pH of the solution, 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere of no more than that of 2.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 at 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere, wherein at the pH of the composition, 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere, the adalimumab has a buffer capacity per unit volume of at least that of 4.0 mM sodium acetate buffer in pure water in the range of pH 5.0 to 4.0 or pH 5.0 to 5.5 at 21° C., one atmosphere of pressure, and equilibrium with ambient atmosphere, and wherein the concentration of the adalimumab is between approximately 20 and 400 mg/ml.
179 . The composition of claim 178 , wherein a pH maintained by the antibody is between approximately 4 and 6.
180 . The composition of claim 178 , wherein a pH maintained by the antibody is between approximately 3.5 and 8.
181 . A composition consisting of: adalimumab at a concentration of 20 to 400 mg/ml and water.
182 . The composition of claim 181 , wherein the composition is a pharmaceutical composition.
183 . A composition consisting essentially of: adalimumab at a concentration of 20 to 400 mg/ml; and water.
184 . The composition of claim 183 , wherein the composition is a pharmaceutical composition.
185 . The composition of claim 183 , wherein a pH maintained by the antibody is between approximately 4 and 6.
186 . The composition of claim 183 , wherein a pH maintained by the antibody is between approximately 3.5 and 8.Cited by (0)
No later patents cite this yet.
References (0)
No backward citations on record.