COMPOSITIONS AND METHODS OF USE THEREOF
Disclosed herein are pharmaceutical compositions for delivery of a chimpanzee adenovirus (ChAdV)-based expression system.
1 . A pharmaceutical composition comprising a viral based expression system, further comprising at least two excipients selected from the group consisting of a buffer, a surfactant, a tonicity modifier, a cryoprotectant, and a stabilizing agent.
2 . The pharmaceutical composition of claim 1 , wherein the viral based expression system is a chimpanzee adenovirus (ChAdV)-based expression system.
3 . The pharmaceutical composition of claims 1 or 2 , wherein the buffer is an amino acid.
4 . The pharmaceutical composition of claim 3 , wherein the amino acid is selected from histidine, lysine, arginine, glutamine, and arginine or a pharmaceutically acceptable salt thereof.
5 . The pharmaceutical composition of claim 5 , wherein the amino acid is histidine.
6 . The pharmaceutical composition of any of claims 4 - 5 , wherein the amino acid has a concentration of 5-35 nM.
7 . The pharmaceutical composition of any of claims 4 - 5 , wherein the amino acid has a concentration of 10-30 nM.
8 . The pharmaceutical composition of any of claims 4 - 5 , wherein the amino acid has a concentration of 15-25 nM.
9 . The pharmaceutical composition of any of claims 4 - 5 , wherein the amino acid has a concentration of about 20 nM.
10 . The pharmaceutical composition of claims 1 - 9 , wherein the composition further comprises an antioxidant.
11 . The pharmaceutical composition of claims 1 - 10 , wherein the composition has a pH of 5.0-9.0.
12 . The pharmaceutical composition of claim 11 , wherein the pH is 6.3-6.6.
13 . The pharmaceutical composition of claim 11 , wherein the pH is about 6.5.
14 . The pharmaceutical composition of any of claims 1 - 13 , wherein the pharmaceutical composition comprises a surfactant.
15 . The pharmaceutical composition of claim 14 , wherein the surfactant is a non-ionic surfactant.
16 . The pharmaceutical composition of claim 15 , wherein the non-ionic surfactant is selected from the group consisting of SPAN, a polysorbate, glyceryl laurate, Brij, Triton-X, and a poloxamer.
17 . The pharmaceutical composition of claim 16 , wherein the non-ionic surfactant is a polysorbate.
18 . The pharmaceutical composition of claim 17 , wherein the polysorbate is PS-20 or PS-80.
19 . The pharmaceutical composition of any of claims 15 - 18 , wherein the non-ionic surfactant is 0.005-0.035 v/v % of the pharmaceutical composition.
20 . The pharmaceutical composition of any of claims 15 - 18 , wherein the non-ionic surfactant is 0.010-0.030 v/v % of the pharmaceutical composition.
21 . The pharmaceutical composition of any of claims 15 - 18 , wherein the non-ionic surfactant is about 0.02 v/v % of the pharmaceutical composition.
22 . The pharmaceutical composition of any of claims 1 - 21 , wherein the pharmaceutical composition comprises a tonicity modifier.
23 . The pharmaceutical composition of any of claims 1 - 24 , wherein the tonicity modifier is selected from the group consisting of NaCl, MgCl 2 , and other pharmaceutically acceptable ionic salts.
24 . The pharmaceutical composition of claim 23 , wherein the tonicity modifier is NaCl.
25 . The pharmaceutical composition of any of claims 23 - 24 , wherein the tonicity modifier has a concentration of 40-60 mM.
26 . The pharmaceutical composition of any of claims 23 - 24 , wherein the tonicity modifier has a concentration of about 50 mM.
27 . The pharmaceutical composition of any of claims 1 - 26 , wherein the pharmaceutical composition comprises a cryoprotectant.
28 . The pharmaceutical composition of claim 27 , wherein the cryoprotectant is selected from the group consisting of ethanol, sucrose, maltose, lactose, glucose, galactose, trehalose, raffinose, other polyols and polyhydric alcohols.
29 . The pharmaceutical composition of any of claims 27 - 28 , wherein the cryoprotectant is 0.1-1 wt % of the pharmaceutical composition.
30 . The pharmaceutical composition of any of claims 27 - 28 , wherein the cryoprotectant is 0.2-0.6 wt % of the pharmaceutical composition.
31 . The pharmaceutical composition of any of claims 27 - 28 , wherein the cryoprotectant is about 0.4 wt % of the pharmaceutical composition.
32 . The pharmaceutical composition of claims 1 - 31 , wherein the cryoprotectant is ethanol.
33 . The pharmaceutical composition of any of claims 1 - 32 , wherein the stabilizing agent comprises water, dextrose, dextran-6, dextran-10, dextran-40, a cyclodextrin, glycerol or mixtures thereof.
34 . The pharmaceutical composition of claim 33 , wherein the cyclodextrin is selected from α-cyclodextrin, β-cyclodextrin, γ-cyclodextrin, HPBCD, captisol and kleptose.
35 . The pharmaceutical composition of claim 34 , wherein the cyclodextrin is HPBCD.
36 . The pharmaceutical composition of any of claims 34 - 35 , wherein the cyclodextrin is 3-8 w/v % of the pharmaceutical composition.
37 . The pharmaceutical composition of any of claims 34 - 35 , wherein the cyclodextrin is about 5 w/v % of the pharmaceutical composition.
38 . A pharmaceutical composition comprising a chimpanzee adenovirus (ChAdV)-based expression system, and further comprising
10-30 mM histidine;
3-7 w/v % HPBCD;
0.2-0.6 wt % EtOH;
40-60 mM NaCl; and
0.01-0.03 wt % PS-80; and
wherein the pharmaceutical composition has a pH of 6.3-6.7.
39 . A pharmaceutical composition comprising a chimpanzee adenovirus (ChAdV)-based expression system, and further comprising
about 20 mM histidine;
about 5 w/v % HPBCD;
about 0.4 wt % EtOH;
about 50 mM NaCl; and
about 0.02 wt % PS-80; and
wherein the pharmaceutical composition has a pH of about 6.5
40 . A method for inducing an immune response in a subject, the method comprising administering to the subject the composition of claims 1 - 39 .
41 . The method of claim 40 , wherein the composition is administered intramuscularly (IM), intradermally (ID), subcutaneously (SC), or intravenously (IV).
42 . The method of any of claim 41 , wherein the composition is administered intramuscularly.
43 . The method of any of any of 40 - 42 , the method further comprising administration of one or more immune modulators, optionally wherein the immune modulator is administered before, concurrently with, or after administration of the composition or pharmaceutical composition.
44 . The method of claim 43 , wherein the one or more immune modulators are selected from the group consisting of: an anti-CTLA4 antibody or an antigen-binding fragment thereof, an anti-PD-1 antibody or an antigen-binding fragment thereof, an anti-PD-L1 antibody or an antigen-binding fragment thereof, an anti-4-1BB antibody or an antigen-binding fragment thereof, or an anti-OX-40 antibody or an antigen-binding fragment thereof.
45 . The method of claim 43 or 44 , wherein the immune modulator is administered intravenously (IV), intramuscularly (IM), intradermally (ID), or subcutaneously (SC).
46 . The method of claim 45 , wherein the subcutaneous administration is near the site of the composition or pharmaceutical composition administration or in close proximity to one or more vector or composition draining lymph nodes.
47 . The method of any one of any of 40 - 46 , further comprising administering to the subject a second vaccine composition.
48 . The method of claim 47 , wherein the second vaccine composition is administered prior to the administration of the composition of any of claims 1 - 39 .
49 . The method of claim 47 , wherein the second vaccine composition is administered subsequent to the administration of the composition of any of claims 1 - 39 .
50 . The method of claims 47 - 49 , wherein the second vaccine composition is the same as the composition of any of claims 1 - 39 .
51 . The method of claim 47 - 49 , wherein the second vaccine composition is different from the composition any of claims 1 - 39 .