US2021395744A1PendingUtilityA1

Compositions and methods for treating covid-19

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Assignee: VAST SEA BIOTECHNOLOGY INCPriority: Jun 19, 2020Filed: Jun 17, 2021Published: Dec 23, 2021
Est. expiryJun 19, 2040(~13.9 yrs left)· nominal 20-yr term from priority
Inventors:Norman Zhennan LaiYuebin TanYing-Ying Wang
A61K 38/556A61K 31/593A61K 31/7088A61P 31/14C12N 2770/20022C12N 2310/341A61K 31/714C12N 2310/346A61K 31/375A61K 33/30C12N 2310/14A23L 33/13C12N 15/1131C12N 2310/315A61K 38/4813C12N 2310/323A23L 33/18C12Y 304/17023C12N 2750/14143C12N 2310/3517A61K 31/198A61K 31/4415A61K 36/534C12N 2310/322A61K 48/00A23V 2002/00C12N 15/86C12N 2320/32C12N 2310/321
51
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Claims

Abstract

This disclosure is directed to inhibitory oligonucleotides, inhibitory peptides, compositions and methods for preventing or treating Coronavirus disease 2019 (COVID-19). In one aspect, the disclosure is directed to compositions that comprise inhibitory oligonucleotides against one or more SARS-CoV-2 virus genes. In another aspect, the disclosure is directed to compositions that comprise inhibitory peptides that inhibit SARS-COV-2 entry into cells. Another aspect of the disclosure is directed to gene therapy methods for treating COVID-19, and vectors for carrying out the same. Finally, the disclosure provides nutritional supplements to support human immunity and prevent or inhibit viral infections.

Claims

exact text as granted — not AI-modified
What is claimed is: 
     
         1 . A composition comprising a plurality of inhibitory oligonucleotides,
 wherein the plurality of inhibitory oligonucleotides targets at least two SARS-CoV-2 genes selected from the group consisting of ORF1ab, RdRp, the S-protein gene, the N-protein gene, and the E protein gene.   
     
     
         2 . The composition of  claim 1 , wherein the plurality of inhibitory oligonucleotides targets all of the ORF1ab, RdRp, S-protein, N-protein and E protein genes. 
     
     
         3 . The composition of  claim 1 , wherein a selected SARS-CoV-2 gene is targeted by at least two inhibitory oligonucleotides. 
     
     
         4 . The composition of any of the preceding claims, wherein the inhibitory oligonucleotides are selected from an antisense oligonucleotide, a small interfering RNA (siRNA), a Dicer-substrate RNA (DsiRNA), and a microRNA. 
     
     
         5 . The composition of  claim 1 , wherein the plurality of inhibitory oligonucleotides comprises at least two oligonucleotides which comprise a nucleotide sequence selected from the group consisting of SEQ ID NOS: 9-16 and modified forms of SEQ ID NOS: 9-16. 
     
     
         6 . The composition of  claim 1 , wherein the plurality of inhibitory oligonucleotides comprises eight oligonucleotides as shown in SEQ ID NOS: 9-16 or modified forms of SEQ ID NOS: 9-16. 
     
     
         7 . The composition of  claim 1 , wherein the plurality of inhibitory oligonucleotides comprises at least two pairs of Dicer-substrate RNAs (DsiRNAs) selected from the group consisting of DsiRNA pair 1 (SEQ ID NOs: 17 & 18), DsiRNA pair 2 (SEQ ID NOs: 19 & 20), DsiRNA pair 3 (SEQ ID NOs: 21 & 22), DsiRNA pair 4 (SEQ ID NOs: 23 & 24), DsiRNA pair 5 (SEQ ID NOs: 25 & 26), DsiRNA pair 6 (SEQ ID NOs: 27 & 28), DsiRNA pair 7 (SEQ ID NOs: 29 & 30), and DsiRNA pair 8 (SEQ ID NOs: 31 & 32). 
     
     
         8 . The composition of  claim 1 , wherein the plurality of inhibitory oligonucleotides comprises Dicer-substrate RNA (DsiRNA) pair 1 (SEQ ID NOs: 17 & 18), DsiRNA pair 2 (SEQ ID NOs: 19 & 20), DsiRNA pair 3 (SEQ ID NOs: 21 & 22), DsiRNA pair 4 (SEQ ID NOs: 23 & 24), DsiRNA pair 5 (SEQ ID NOs: 25 & 26), DsiRNA pair 6 (SEQ ID NOs: 27 & 28), DsiRNA pair 7 (SEQ ID NOs: 29 & 30), and DsiRNA pair 8 (SEQ ID NOs: 31 & 32). 
     
     
         9 . The composition of any of the preceding claims, wherein the inhibitory oligonucleotides are modified oligonucleotides. 
     
     
         10 . The composition of  claim 9 , wherein the modified inhibitory oligonucleotides are 2′-Deoxy, 2′-Fluoroarabino Nucleic Acid (FANA)-modified antisense oligonucleotides. 
     
     
         11 . The composition of  claim 9 , wherein the modified inhibitory oligonucleotides are 2′ 0-Methyl RNA modified antisense oligonucleotides selected from the group consisting of SEQ ID NO: 33, SEQ ID NO: 34, SEQ ID NO: 35, SEQ ID NO: 36, SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, and SEQ ID NO: 40. 
     
     
         12 . The composition of any of the preceding claims, wherein at least one inhibitory oligonucleotide within the plurality of oligonucleotides comprises a detectable label. 
     
     
         13 . The composition of  claim 12 , wherein the label is a fluorescent label. 
     
     
         14 . The composition of any of  claims 1 - 8 , wherein the plurality of inhibitory oligonucleotides is provided in one or more nucleic acid vectors. 
     
     
         15 . The composition of  claim 14 , wherein the nucleic acid vectors are selected from a viral vector, a non-viral vector, an integrative vector, or a non-integrative vector. 
     
     
         16 . The composition of any of the preceding claims, further comprising a pharmaceutically-acceptable carrier. 
     
     
         17 . The composition of  claim 16 , wherein the pharmaceutically acceptable carrier comprises nanoparticles or other delivery vehicles to which the plurality of inhibitory oligonucleotides is conjugated. 
     
     
         18 . A composition comprising at least one peptide mimicking a portion of the ligand binding domain (LBD) of human ACE2 protein, wherein the at least one peptide prevents binding of the S-protein of SARS-CoV-2 to the human ACE2 protein. 
     
     
         19 . The composition of  claim 18 , wherein the LBD of human ACE2 comprises the amino acid sequence of SEQ ID NO: 56. 
     
     
         20 . The composition of  claim 18 , wherein the composition comprises a plurality of peptides, each mimicking a different portion of the ligand binding domain (LBD) of human ACE2 protein. 
     
     
         21 . The composition of  claim 18 , wherein the at least one peptide comprises an amino acid sequence selected from the group consisting of SEQ ID NOs: 41-44, 54, and 63-82. 
     
     
         22 . The composition of  claim 18 , wherein the composition comprises a plurality of peptides comprising an amino acid sequence selected from the group consisting of SEQ ID NOs: 41-44, 54, and 63-82. 
     
     
         23 . The composition of  claim 22 , wherein the composition comprises at least five peptides, wherein the at least five peptides are selected from peptides comprising an amino acid sequence as shown in SEQ ID NOS: 41-44, 54, and 63-82. 
     
     
         24 . A composition comprising a peptide mimicking a portion of the receptor binding domain (RBD) of the S-Protein of SARS-CoV-2, wherein the peptide prevents binding of the S-protein of SARS-CoV-2 to a human ACE2 protein. 
     
     
         25 . The composition of  claim 24 , wherein the RBD of the S protein of SARS-CoV-2 comprises SEQ ID NO: 62. 
     
     
         26 . The composition of  claim 24 , wherein the peptide comprises an amino acid sequence as shown in SEQ ID NO: 45. 
     
     
         27 . The composition of any of  claims 18 - 26 , wherein the at least one peptide comprises a label or is conjugated with a probe, a nucleic acid or a chemical molecule. 
     
     
         28 . The composition of  claim 27 , wherein the label is a fluorescent label. 
     
     
         29 . The composition of  claims 18 - 28 , further comprising a pharmaceutically-acceptable carrier. 
     
     
         30 . The composition of  claim 29 , wherein the pharmaceutically acceptable carrier comprises nanoparticles or other delivery vehicles to which the at least one peptide is conjugated. 
     
     
         31 . A dietary supplement comprising a composition according to any one of  claims 1 - 17 . 
     
     
         32 . A dietary supplement comprising a composition according to any one of  claims 18 - 30 . 
     
     
         33 . A dietary supplement comprising a composition according to any one of  claims 1 - 17 , and a composition according to any one of  claims 18 - 30 . 
     
     
         34 . The dietary supplement of any of  claims 31 - 33 , further comprising at least one additional nutrient selected from Vitamin C, Vitamin B6, Vitamin B12, Vitamin D, Zinc, polypeptides, nucleotide, L-arginine or peppermint oil. 
     
     
         35 . The dietary supplement of any of  claims 31 - 34 , wherein the dietary supplement is formulated for oral, nasal, eye, ear, or topical application. 
     
     
         36 . A method comprising expressing a plurality of inhibitory oligonucleotides in a target cell,
 wherein the plurality of inhibitory oligonucleotides targets at least two SARS-CoV-2 genes selected from the group consisting of ORF1ab, RdRp, the S-protein gene, the N-protein gene and the E protein gene.   
     
     
         37 . The method of  claim 36 , wherein a selected SARS-CoV-2 gene is targeted by at least two inhibitory oligonucleotides. 
     
     
         38 . The method of  claim 36 , wherein the plurality of inhibitory oligonucleotides targets all of ORF1ab, RdRp, S-protein, N-proteins and E protein genes. 
     
     
         39 . The method of any of  claims 36 - 38 , wherein the inhibitory oligonucleotides are selected from an antisense oligonucleotide, a small interfering RNA (siRNA), a Dicer-substrate RNA (DsiRNA), or a microRNA. 
     
     
         40 . The method of  claim 36 , wherein the plurality of inhibitory oligonucleotides comprises at least two oligonucleotides which comprise a nucleotide sequence selected from the group consisting of SEQ ID NOS: 9-16. 
     
     
         41 . The method of  claim 36 , wherein the plurality of inhibitory oligonucleotides comprises eight oligonucleotides as shown in SEQ ID NOS: 9-16. 
     
     
         42 . The method of  claim 36 , wherein the target cell is a human cell. 
     
     
         43 . The method of  claim 42 , wherein the target cell is a lung epithelial cell. 
     
     
         44 . The method of  claim 42 , wherein the target cell is selected from the group consisting of a small airway epithelial cell, a bronchial/tracheal epithelial cell, and a nasal epithelial cell. 
     
     
         45 . The method of any of  claims 36 - 44 , wherein the plurality of inhibitory oligonucleotides are expressed from at least one vector. 
     
     
         46 . The method of  claim 45 , wherein the at least one vector is selected from a viral vector, or a non-viral vector, an integrative vector, or a non-integrative vector. 
     
     
         47 . The method of  claim 45 , wherein the at least one vector is delivered to a subject in need via oral, nasal, i.v. injection or topical administration routes. 
     
     
         48 . A nucleic acid vector encoding a plurality of inhibitory oligonucleotides that targets at least two SARS-CoV-2 genes selected from the group consisting of ORF1ab, RdRp, the S-protein gene, the N-protein gene, and the E protein gene. 
     
     
         49 . A combination of nucleic acid vectors, wherein each nucleic acid vector encodes an inhibitory oligonucleotide that targets at least one SARS-CoV-2 genes selected from the group consisting of ORF1ab, RdRp, the S-protein gene, the N-protein gene, and the E protein gene, and wherein the combination of nucleic acid vectors target at least two SARS-CoV-2 genes. 
     
     
         50 . The nucleic acid vector of  claim 48  or the combination of nucleic acid vectors of  claim 49 , wherein the nucleic acid vector is a viral vector. 
     
     
         51 . The nucleic acid vector of  claim 48  or the combination of nucleic acid vectors of  claim 49 , wherein the nucleic acid comprises an AAV-based vector selected from AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, AAV12, AAV13 and AAV14. 
     
     
         52 . The nucleic acid vector of  claim 48  or the combination of nucleic acid vectors of  claim 49 , wherein the nucleic acid vector is a non-viral vector. 
     
     
         53 . A method of treating a SARS-CoV-2 infection in a subject in need thereof, comprising administering a subject an effective amount of a nucleic acid vector or a combination of nucleic acid vectors according to any one of  claims 48 - 52 . 
     
     
         54 . A method for treating a SARS-CoV-2 infection comprising administering to a subject an effective amount of a composition according to any one of  claims 1 - 17 , or a composition according to any one of  claims 18 - 30 . 
     
     
         55 . A method for treating a SARS-CoV-2 infection comprising administering to a subject an effective amount of a composition according to any one of  claims 1 - 17  and an effective amount of a composition according to any one of  claims 18 - 30 .

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