Encapsulated rna polynucleotides and methods of use
AssigneeElevateBio Technologies, Inc.
InventorsLorena LERNER, Edward M. KENNEDY, Christophe QUÉVA, Jessica DETERLING, Jeffrey David BRYANT, Qi-Ying HU, Tooba A. CHEEMA, Sean ESSEX
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Abstract
The present disclosure relates to recombinant RNA molecules encoding an oncolytic virus genome. The present disclosure further relates to the encapsulation of the recombinant RNA molecules and the use of the recombinant RNA molecules and/or particles for the treatment and prevention of cancer.
Claims225
A lipid nanoparticle (LNP) comprising a synthetic RNA viral genome encoding an oncolytic Coxsackievirus virus, wherein the Coxsackievirus is a CVA21 strain selected from the Kuykendall strain, the EF strain and the KY strain.
A lipid nanoparticle (LNP) comprising a synthetic RNA viral genome encoding an oncolytic Seneca Valley Virus (SVV), wherein the synthetic RNA viral genome comprises a polynucleotide sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to SEQ ID NO:
- 68.
A lipid nanoparticle (LNP), comprising:
- a. a synthetic RNA viral genome encoding a Seneca Valley virus (SVV);
- and
- b. a cationic lipid, a helper lipid, a structural lipid, and a PEG-lipid, wherein the PEG-lipid is a compound of Formula (A″):
- or a pharmaceutically acceptable salt thereof, wherein:
- n is an integer between 10 to 200, inclusive of all endpoints;
- LP1″ is a bond, —[(CH2)0-3—C(O)O]1-3—, —(CH2)0-3—C(O)O—(CH2)1-3—OC(O)—, or —C(O)N(H)—;
- RP1″ is C5-C25 alkyl or C5-C25 alkenyl;
- and
- RP2″ is hydrogen or —CH3, and
- wherein the LNP has a molar ratio of about 0.001% to about 5% PEG-lipid.
A lipid nanoparticle (LNP), comprising:
- a. a synthetic RNA viral genome encoding a Coxsackievirus;
- and
- b. a cationic lipid, a helper lipid, a structural lipid, and a PEG-lipid, wherein the PEG-lipid is a compound of Formula (A″):
- or a pharmaceutically acceptable salt thereof, wherein:
- n is an integer between 10 to 200, inclusive of all endpoints;
- LP1″ is a bond, —[(CH2)0-3—C(O)O]1-3—, —(CH2)0-3—C(O)O—(CH2)1-3—OC(O)—, or —C(O)N(H)—;
- RP1″ is C5-C25 alkyl or C5-C25 alkenyl;
- and
- RP2″ is hydrogen or —CH3, and
- wherein the LNP has a molar ratio of about 0.001% to about 5% PEG-lipid.
A lipid nanoparticle (LNP), comprising:
- a. a synthetic RNA viral genome encoding a Seneca Valley virus (SVV);
- and
- b. a cationic lipid, a helper lipid, a structural lipid, and a PEG-lipid, wherein the PEG-lipid is a compound of Formula (B):
- or a pharmaceutically acceptable salt thereof, wherein:
- n is an integer between 10 to 200, inclusive of all endpoints;
- and
- RB1 is C5-C25 alkyl or C5-C25 alkenyl, and
- wherein the LNP has a molar ratio of about 0.001% to about 5% PEG-lipid.
A lipid nanoparticle (LNP), comprising:
- a. a synthetic RNA viral genome encoding a Coxsackievirus;
- and
- b. a cationic lipid, a helper lipid, a structural lipid, and a PEG-lipid, wherein the PEG-lipid is a compound of Formula (B):
- or a pharmaceutically acceptable salt thereof, wherein:
- n is an integer between 10 to 200, inclusive of all endpoints;
- and
- RB1 is C5-C25 alkyl or C5-C25 alkenyl, and
- wherein the LNP has a molar ratio of about 0.001% to about 5% PEG-lipid.
A recombinant RNA molecule comprising a synthetic RNA viral genome encoding an oncolytic Coxsackievirus virus, wherein the Coxsackievirus is a CVA21 strain selected from the Kuykendall strain, the EF strain and the KY strain.
A recombinant RNA molecule comprising a synthetic RNA viral genome encoding a Seneca Valley virus (SVV), wherein the SVV comprises is a chimeric SVV, and wherein the synthetic RNA viral genome comprises a polynucleotide sequence having at least 80%, at least 85%, at least 90%, at least 95%, or 100% sequence identity to SEQ ID NO:
- 68.
A recombinant DNA template comprising from 5′ to 3′, a promoter sequence, a 5′ junctional cleavage sequence, a polynucleotide sequence encoding an RNA molecule comprising a synthetic RNA viral genome, a poly-A tail, and a 3′ junctional cleavage sequence.
A recombinant DNA molecule comprising from 5′ to 3′, a promoter sequence, a leader sequence, a 5′ junctional cleavage sequence, a polynucleotide sequence encoding a recombinant RNA molecule comprising a synthetic RNA viral genome, a poly-A tail, and a 3′ junctional cleavage sequence.
A method of treating a cancer in a subject in need thereof comprising administering an effective amount of a CVA21-EF virus to the subject.
A method of treating a cancer in a subject in need thereof comprising administering an effective amount of a CVA21-KY virus to the subject
A method of treating a cancer in a subject in need thereof comprising administering an effective amount of a CVA21-Kuykendall virus to the subject.
A method of treating a cancer in a subject in need thereof, comprising administering a therapeutically effective amount of an oncolytic Coxsackievirus, wherein the Coxsackievirus is a CVA21 strain, or a polynucleotide encoding the CVA21 to the subject, wherein the cancer is classified as sensitive to CVA21 infection based on the expression of ICAM-1 and/or the percentage of ICAM-1 positive cancer cells.
A method of treating a cancer in a subject in need thereof, comprising:
- (a) determining the expression level of ICAM1 and/or the percentage of ICAM-1 positive cancer cells in the cancer;
- (b) classifying the cancer as sensitive to Coxsackievirus 21 (CVA21) infection based on the expression of ICAM-1 and/or the percentage of ICAM-1 positive cancer cells determined in (a);
- and
- (c) administering a therapeutically effective amount of CVA21 or a polynucleotide encoding the CVA21 to the subject if the cancer is classified as sensitive to CVA21 infection in step (b).
A method of selecting a subject suffering from a cancer for treatment with a Coxsackievirus 21 (CVA21) or a polynucleotide encoding the CVA21, comprising:
- (a) determining the expression level of ICAM-1 and/or the percentage of ICAM-1 positive cancer cells in the cancer;
- (b) classifying the cancer as sensitive to CVA21 infection based on the expression level of ICAM-1 and/or the percentage of ICAM1 positive cancer cells as determined in (a);
- (c) selecting the subject for treatment with the CVA21 or the polynucleotide encoding the CVA21 if the cancer is classified as sensitive to CVA21 infection in (b);
- and
- (d) administering the CVA21 or the polynucleotide encoding the CVA21 to the selected subjects
Dependencies are inferred from the claim text.