US10087240B2 · US · B2
| Field | Value |
|---|---|
| Publication number | US-10087240-B2 |
| Application number | US-201415103970-A |
| Country | US |
| Kind code | B2 |
| Filing date | Dec 13, 2014 |
| Priority date | Dec 13, 2013 |
| Publication date | Oct 2, 2018 |
| Grant date | Oct 2, 2018 |
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The present invention relates to a composition including a recombinant nucleic acid sequence that encodes an antibody and a method of generating a synthetic antibody in a subject by administering the composition to the subject. The invention also provides a method of preventing and/or treating disease in a subject using the composition and method of generation.
Opening claim text (preview).
What is claimed is: 1. A nucleic acid molecule encoding a synthetic antibody comprising a nucleic acid sequence having at least about 95% identity over an entire length of the nucleic acid sequence selected from the group consisting of: (a) a nucleic acid sequence as set forth in SEQ ID NO:67; (b) a nucleic acid sequence as set forth in SEQ ID NO:69; (c) a nucleic acid sequence as set forth in SEQ ID NO:71; (d) a nucleic acid sequence as set forth in SEQ ID NO:73; (e) a nucleic acid sequence as set forth in SEQ ID NO:75; (f) a nucleic acid sequence as set forth in SEQ ID NO:77; (g) a nucleic acid sequence as set forth in SEQ ID NO:65. 2. The nucleic acid molecule of claim 1 , wherein the nucleic acid sequence is selected from the group consisting of: (a) the nucleic acid sequence as set forth in SEQ ID NO:67; (b) the nucleic acid sequence as set forth in SEQ ID NO:69; (c) the nucleic acid sequence as set forth in SEQ ID NO:71; (d) the nucleic acid sequence as set forth in SEQ ID NO:73; (e) the nucleic acid sequence as set forth in SEQ ID NO:75; (f) the nucleic acid sequence as set forth in SEQ ID NO:77; and (g) the nucleic acid sequence as set forth in SEQ ID NO:65. 3. A nucleic acid molecule encoding a synthetic antibody comprising a nucleic acid sequence encoding a protein having at least about 95% identity over an entire length of the amino acid sequence selected from the group consisting of: (a) an amino acid sequence as set forth in SEQ ID NO:68; (b) an amino acid sequence as set forth in SEQ ID NO:70; (c) an amino acid sequence as set forth in SEQ ID NO:72; (d) an amino acid sequence as set forth in SEQ ID NO:74; (e) an amino acid sequence as set forth in SEQ ID NO:76; (f) an amino acid sequence as set forth in SEQ ID NO:78; and (g) an amino acid sequence as set forth in SEQ ID NO:66. 4. The nucleic acid molecule of claim 3 , wherein the nucleic acid encodes a protein having the amino acid sequence selected from the group consisting of: (a) an amino acid sequence as set forth in SEQ ID NO:68; (b) an amino acid sequence as set forth in SEQ ID NO:70; (c) an amino acid sequence as set forth in SEQ ID NO:72; (d) an amino acid sequence as set forth in SEQ ID NO:74; (e) an amino acid sequence as set forth in SEQ ID NO:76; an amino acid sequence as set forth in SEQ ID NO:78; and (g) an amino acid sequence as set forth in SEQ ID NO:66. 5. The nucleic acid molecule of claim 1 , wherein the nucleic acid sequence encodes a light chain polypeptide, a heavy chain polypeptide, both a light chain polypeptide and a heavy chain polypeptide, or fragments thereof. 6. The nucleic acid molecule of claim 5 , wherein when the nucleic acid sequence encodes a light chain polypeptide and a heavy chain polypeptide, the nucleic acid sequence also encodes a protease cleavage site. 7. The nucleic acid molecule of claim 6 , wherein the protease cleavage site is located between the light chain polypeptide and the heavy chain polypeptide and wherein the protease cleavage site includes a furin cleavage site and 2A peptide sequence. 8. The nucleic acid molecule of claim 1 , wherein the nucleic acid molecule further encodes an immunoglobulin (Ig) signal peptide. 9. The nucleic acid molecule of claim 8 , wherein the Ig signal peptide comprises an IgE signal peptide. 10. The nucleic acid molecule of claim 1 , wherein the nucleic acid molecule comprises an expression vector. 11. A composition comprising the nucleic acid molecule of claim 1 . 12. The composition of claim 11 further comprising a pharmaceutically acceptable excipient. 13. A method of preventing a disease in a subject in need thereof, the method comprising administering the nucleic acid molecule of claim 1 . 14. The method of claim 13 , wherein the disease is infection by Chikungunya virus (CHIKV) or Dengue virus (DENV). 15. The method of claim 14 , wherein when the disease is infection by CHIKV, the nucleic acid sequence is the nucleic acid sequence as set forth in SEQ ID NO:65. 16. The method of claim 14 , wherein when the disease is infection by DENV, the nucleic acid sequence is selected from the group consisting of: (a) the nucleic acid sequence as set forth in SEQ ID NO:67; (b) the nucleic acid sequence as set forth in SEQ ID NO:69; (c) the nucleic acid sequence as set forth in SEQ ID NO:71; (d) the nucleic acid sequence as set forth in SEQ ID NO:73; (e) the nucleic acid sequence as set forth in SEQ ID NO:75; and (f) the nucleic acid sequence as set forth in SEQ ID NO:77. 17. The method of claim 14 , wherein when the disease is infection by CHIKV, the amino acid sequence is the amino acid sequence as set forth in SEQ ID NO:66. 18. The method of claim 14 , wherein when the disease is infection by DENV, the amino acid sequence is selected from the group consisting of: (a) the amino acid sequence as set forth in SEQ ID NO:68; (b) the amino acid sequence as set forth in SEQ ID NO:70; (c) the amino acid sequence as set forth in SEQ ID NO:72; (d) the amino acid sequence as set forth in SEQ ID NO:74; (e) the amino acid sequence as set forth in SEQ ID NO:76; and (f) the amino acid sequence as set forth in SEQ ID NO:78. 19. The method of claim 13 , wherein administering includes at least one of electroporation and injection. 20. A method of treating a disease in a subject in need thereof, the method comprising administering the nucleic acid molecule of claim 1 to the subject. 21. The method of claim 20 , wherein the disease is infection by Chikungunya virus (CHIKV) or Dengue virus (DENV). 22. The method of claim 21 , wherein when the disease is infection by CHIKV, the nucleic acid sequence is the nucleic acid sequence as set forth in SEQ ID NO:65. 23. The method of claim 21 , wherein when the disease is infection by DENV, the nucleic acid sequence is selected from the group consisting of: (a) the nucleic acid sequence as set forth in SEQ ID NO:67; (b) the nucleic acid sequence as set forth in SEQ ID NO:69; (c) the nucleic acid sequence as set forth in SEQ ID NO:71; (d) the nucleic acid sequence as set forth in SEQ ID NO:73; (e) the nucleic acid sequence as set forth in SEQ ID NO:75; and (f) the nucleic acid sequence as set forth in SEQ ID NO:77. 24. The method of claim 21 , wherein when the disease is infection by CHIKV, the amino acid sequence is the nucleic acid sequence as set forth in SEQ ID NO:66. 25. The method of claim 21 , wherein when the disease is infection by DENV, the amino acid sequence is selected from the group consisting of: (a) the amino acid sequence as set forth in SEQ ID NO:68; (b) the amino acid sequence as set forth in SEQ ID NO:70; (c) the amino acid sequence as set forth in SEQ ID NO:72; (d) the amino acid sequence as set forth in SEQ ID NO:74; (e) the amino acid sequence as set forth in SEQ ID NO:76; and (f) the amino acid sequence as set forth in SEQ ID NO:78. 26. The method of claim 20 , wherein administering includes at least one of electroporation and injection. 27. A method of generating an anti-CHIKV synthetic antibody or anti-DENV synthetic antibody in a cell, the method comprising administering to the cell a composition comprising a recombinant nucleic acid sequence encoding an anti-CHIKV or anti-DENV antibody or an antigen binding fragment thereof, wherein the recombinant nucleic acid sequence is expressed in the cell to genera
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