Formulations of DR5 Binding Polypeptides
Provided herein are formulations of DR5-binding polypeptides. Uses of the DR5-binding polypeptides are also provided.
1 . A pharmaceutical formulation comprising a DR5-binding polypeptide, wherein the formulation comprises 20-70 mg/mL DR5-binding polypeptide, 5-20 mM histidine, 7-10% w/v sucrose, and 0.1-0.8% poloxamer P188 at a pH of 5.3-6.7; and wherein the DR5-binding polypeptide comprises at least one VHH domain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 1, a CDR2 comprising the amino acid sequence of SEQ ID NO: 2, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 3.
2 . (canceled)
3 . The pharmaceutical formulation of claim 1 , wherein the formulation comprises 50 mg/mL DR5-binding polypeptide.
4 . (canceled)
5 . The pharmaceutical formulation of claim 1 , wherein the formulation comprises 10 mM histidine.
6 . The pharmaceutical formulation of claim 1 , wherein the histidine is histidine HCl.
7 . (canceled)
8 . The pharmaceutical formulation of claim 1 , wherein the formulation comprises 8% sucrose or 9% sucrose.
9 . (canceled)
10 . The pharmaceutical formulation of claim 1 , wherein the formulation comprises 0.2% poloxamer P188.
11 . (canceled)
12 . The pharmaceutical formulation of claim 1 , wherein the formulation comprises 5 mM methionine.
13 . (canceled)
14 . The pharmaceutical formulation of claim 1 , wherein the pH of the formulation is about 6.
15 . The pharmaceutical formulation of claim 1 , wherein the formulation comprises 50 mg/mL DR5-binding polypeptide, 10 mM histidine HCl, 8% sucrose, and 0.2% poloxamer P188, and wherein the pH of the formulation is about 6.
16 . The pharmaceutical formulation of claim 15 , wherein the formulation consists essentially of 50 mg/mL DR5-binding polypeptide, 10 mM histidine HCl, 8% sucrose, 0.2% poloxamer P188, and water, and wherein the pH of the formulation is about 6.
17 . The pharmaceutical formulation of claim 1 , wherein the DR5-binding polypeptide comprises a VHH domain comprising the amino acid sequence of SEQ ID NO: 4.
18 . The pharmaceutical formulation of claim 1 , wherein the DR5-binding polypeptide comprises an Fc region.
19 . The pharmaceutical formulation of claim 18 , wherein the Fc region comprises the amino acid sequence of SEQ ID NO: 6.
20 . The pharmaceutical formulation of claim 1 , wherein the DR5-binding polypeptide has the structure VHH-linker-VHH-linker-Fc.
21 . The pharmaceutical formulation of claim 20 , wherein the VHH-linker-VHH comprises the amino acid sequence of SEQ ID NO: 5.
22 . The pharmaceutical formulation of claim 1 , wherein the DR5-binding polypeptide comprises the amino acid sequence of SEQ ID NO: 7.
23 . The pharmaceutical formulation of claim 1 , wherein the DR5-binding polypeptide consists of the amino acid sequence of SEQ ID NO: 7.
24 . A lyophilized formulation comprising a DR5-binding polypeptide, wherein the DR5-binding polypeptide comprises at least one VHH domain comprising a CDR1 comprising the amino acid sequence of SEQ ID NO: 1, a CDR2 comprising the amino acid sequence of SEQ ID NO: 2, and a CDR3 comprising the amino acid sequence of SEQ ID NO: 3; and wherein upon reconstitution of the lyophilized formulation in water to form an aqueous formulation, the aqueous formulation comprises 20-70 mg/mL DR5-binding polypeptide, 5-20 mM histidine, 7-10% sucrose, and 0.1-0.5% poloxamer P188, pH 5.3-6.7.
47 . A lyophilized formulation formed by lyophilizing the pharmaceutical formulation of claim 1 .
52 . A pharmaceutical formulation formed by reconstituting the lyophilized formulation of claim 24 in water.
53 . A method of treating cancer comprising administering to a subject with cancer the pharmaceutical formulation of claim 1 .
54 . The method of claim 53 , wherein the cancer is chondrosarcoma, mesothelioma, colorectal cancer, Ewing sarcoma, or pancreatic adenocarcinoma.
55 . The pharmaceutical formulation of claim 22 , wherein the formulation comprises 50 mg/mL DR5-binding polypeptide, 10 mM histidine HCl, 8% sucrose, and 0.2% poloxamer P188, and wherein the pH of the formulation is about 6.
56 . The pharmaceutical formulation of claim 22 , wherein the formulation consists essentially of 50 mg/mL DR5-binding polypeptide, 10 mM histidine HCl, 8% sucrose, 0.2% poloxamer P188, and water, and wherein the pH of the formulation is about 6.
57 . The pharmaceutical formulation of claim 23 , wherein the formulation comprises 50 mg/mL DR5-binding polypeptide, 10 mM histidine HCl, 8% sucrose, and 0.2% poloxamer P188, and wherein the pH of the formulation is about 6.
58 . The pharmaceutical formulation of claim 23 , wherein the formulation consists essentially of 50 mg/mL DR5-binding polypeptide, 10 mM histidine HCl, 8% sucrose, 0.2% poloxamer P188, and water, and wherein the pH of the formulation is about 6.