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1. (WO2017193101) CONSTRUCTIONS D'ANTICORPS ANTI-ADN POUR UTILISATION CONTRE PSEUDOMONAS AERUGINOSA
Note: Texte fondé sur des processus automatiques de reconnaissance optique de caractères. Seule la version PDF a une valeur juridique

CLAIMS

What is claimed is:

1. A nucleic acid molecule encoding one or more DNA monoclonal antibody (DMAb), wherein the nucleic acid molecule comprises at least one selected from the group consisting of:

a) a nucleotide sequence encoding one or more of a variable heavy chain region and a variable light chain region of an anti-PcrV DMAb (DMAb-aPcrV), or a fragment or homolog thereof;

b) a nucleotide sequence encoding one or more of a variable heavy chain region and a variable light chain region of an anti-Psl DMAb (DMAb-aPsl), or a fragment or homolog thereof; and

c) a nucleotide sequence encoding one or more of a variable heavy chain region and a variable light chain region of a bispecific anti-PcrV anti-Psl DMAb (DMAb-BiSPA), or a fragment or homolog thereof.

2. The nucleic acid molecule of claim 1, further comprising a nucleotide sequence encoding a cleavage domain.

3. The nucleic acid molecule of claim 1, further comprising a nucleotide sequence encoding a signal peptide.

4. The nucleic acid molecule of claim 1, wherein a) is selected from the group consisting of:

a) a nucleotide sequence encoding an amino acid sequence having at least about 95% identity over an entire length of the amino acid sequence to an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO: 4, SEQ ID NO:6, SEQ ID NO:8; SEQ ID NO: 10; SEQ ID NO: 12; SEQ ID NO: 14 and SEQ ID NO: 16;

b) a nucleotide sequence encoding an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO: 4, SEQ ID NO:6, SEQ ID NO:8; SEQ ID NO: 10; SEQ ID NO: 12; SEQ ID NO: 14 and SEQ ID NO: 16;

c) a nucleotide sequence encoding a fragment of an amino acid sequence having at least about 95% identity over an entire length of the amino acid sequence to an amino acid sequence selected from the group consisting of SEQ ID NO:2, SEQ ID NO: 4, SEQ ID NO:6, SEQ ID NO:8; SEQ ID NO: 10; SEQ ID NO: 12; SEQ ID NO: 14 and SEQ ID NO: 16;

d) a nucleotide sequence encoding a fragment of an amino acid sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 4, SEQ ID NO: 6, SEQ ID NO:8; SEQ ID NO: 10; SEQ ID NO: 12; SEQ ID NO: 14 and SEQ ID NO: 16;

e) a nucleotide sequence having at least about 95% identity over an entire length of the nucleotide sequence to a nucleotide sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO:5, SEQ ID NO:7; SEQ ID NO:9; SEQ ID NO: l l ; SEQ ID NO: 13 and SEQ ID NO: 15;

f) a fragment of a nucleotide sequence having at least about 95% identity over an entire length of the nucleotide sequence to a nucleotide sequence selected from the group consisting of SEQ ID NO: l, SEQ ID NO: 3, SEQ ID NO:5, SEQ ID NO:7; SEQ ID NO:9; SEQ ID NO: l l ; SEQ ID NO: 13 and SEQ ID NO: 15;

g) a nucleotide sequence selected from the group consisting of SEQ ID NO: l, SEQ ID NO: 3, SEQ ID NO:5, SEQ ID NO:7; SEQ ID NO:9; SEQ ID NO: 11; SEQ ID NO: 13 and SEQ ID NO: 15; and

h) a fragment of a nucleotide sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO:5, SEQ ID NO:7; SEQ ID NO:9; SEQ ID NO: l l ; SEQ ID NO: 13 and SEQ ID NO: 15.

5. The nucleic acid molecule of claim 1, wherein b) is selected from the group consisting of:

a) a nucleotide sequence encoding an amino acid sequence having at least about 95% identity over an entire length of the amino acid sequence to an amino acid of SEQ ID NO:20;

b) a nucleotide sequence encoding an amino acid sequence of SEQ ID

NO:20;

c) a nucleotide sequence encoding a fragment of an amino acid sequence having at least about 95% identity over an entire length of the amino acid sequence to an amino acid sequence of SEQ ID NO:20;

d) a nucleotide sequence encoding a fragment of an amino acid sequence of SEQ ID NO:20;

e) a nucleotide sequence having at least about 95% identity over an entire length of the nucleotide sequence to SEQ ID NO: 19;

f) a fragment of a nucleotide sequence having at least about 95% identity over an entire length of the nucleotide sequence to SEQ ID NO: 19;

g) a nucleotide sequence of SEQ ID NO: 19; and

h) a fragment of a nucleotide sequence of SEQ ID NO: 19.

6. The nucleic acid molecule of claim 1, wherein c) is selected from the group consisting of:

a) a nucleotide sequence encoding an amino acid sequence having at least about 95% identity over an entire length of the amino acid sequence to an amino acid sequence selected from the group consisting of SEQ ID NO: 18 and SEQ ID NO:22;

b) a nucleotide sequence encoding an amino acid sequence selected from the group consisting of SEQ ID NO: 18 and SEQ ID NO:22;

c) a nucleotide sequence encoding a fragment of an amino acid sequence having at least about 95% identity over an entire length of the amino acid sequence to an amino acid sequence selected from the group consisting of SEQ ID NO: 18 and SEQ ID NO:22;

d) a nucleotide sequence encoding a fragment of an amino acid sequence selected from the group consisting of SEQ ID NO: 18 and SEQ ID NO:22;

e) a nucleotide sequence having at least about 95% identity over an entire length of the nucleotide sequence to a nucleotide sequence selected from the group consisting of SEQ ID NO: 17 and SEQ ID NO: 19;

f) a fragment of a nucleotide sequence having at least about 95% identity over an entire length of the nucleotide sequence to a nucleotide sequence selected from the group consisting of SEQ ID NO: 17 and SEQ ID NO: 19;

g) a nucleotide sequence selected from the group consisting of SEQ ID NO: 17 and SEQ ID NO: 19; and

h) a fragment of a nucleotide sequence selected from the group consisting of SEQ ID NO: 17 and SEQ ID NO: 19.

7. The nucleic acid molecule of claim 1, wherein the nucleic acid molecule further comprises a nucleotide sequence encoding an IRES element.

8. The nucleic acid molecule of claim 6, wherein the IRES element is selected from the group consisting of a viral IRES and an eukaryotic IRES.

9. The nucleic acid molecule of any one of claims 1-8, wherein the nucleic acid molecule further comprises a nucleotide sequence encoding a signal peptide selected from the group consisting of SEQ ID NO: 24 and SEQ ID NO: 25.

10. The nucleic acid molecule of any one of claims 1-9, wherein the nucleic acid molecule is a ribonucleic acid molecule.

11. The nucleic acid molecule of any one of claims 1-10, comprising an expression vector.

12. A composition comprising the nucleic acid molecule of any one of claims 1- 11.

13. The composition of claim 12, further comprising a pharmaceutically acceptable excipient.

14. A method of treating a disease in a subject, the method comprising administering to the subject the nucleic acid molecule of any of claims 1-11 or a composition of any of claims 12-13.

15. The method of claim 14, wherein the disease is a Pseudomonas aeruginosa infection.

16. The method of claim 14, further comprising administering an antibiotic agent to the subject.

17. The method of claim 16, wherein an antibiotic is administered less than 10 days after administration of the nucleic acid molecule or composition.

18. A method of preventing or treating a biofilm formation in a subject, the method comprising administering to the subject the nucleic acid molecule of any of claims 1-11 or a composition of any of claims 12-13.

19. The method of claim 18, wherein the biofilm is a Pseudomonas aeruginosa biofilm.

20. The method of claim 18, further comprising administering an antibiotic agent to the subject.

21. The method of claim 20, wherein an antibiotic is administered less than 10 days after administration of the nucleic acid molecule or composition.

22. A composition for generating a synthetic bispecific antibody in a subject comprising one or more nucleic acid molecules encoding one or more antibodies or fragments thereof, wherein the bispecific antibody binds to a first and second target.

23. The composition of claim 22, wherein the first target is a tumor associated antigen.

24. The composition of claim 22, wherein the second target is a a cell surface marker on an immune cell.