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1. WO2007005627 - TUBERCULOSIS ANTIGEN DETECTION ASSAYS AND VACCINES

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CLAIMS

What is claimed is:

1. An isolated polypeptide molecule comprising an immunogenic portion of a Mycobacterium tuberculosis antigen, or a variant of said antigen that differs only in conservative
substitutions and/or modifications, wherein said antigen comprises an amino acid sequence selected from the group consisting of:
a) an amino acid sequence encoded by a nucleic acid molecule having a sequence of
SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39,
41, 43, 45, 47, or combination thereof;
b) an amino acid sequence encoded by a nucleic acid molecule having the coding region of SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, or combination thereof;
c) an amino acid sequence encoded by a complement of SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, or combination
thereof;
d) an amino acid sequence encoded by a nucleic acid molecule that hybridizes to SEQ
ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, or combination thereof; and
e) an amino acid sequence set forth in SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, or combination thereof.

2. The isolated polypeptide molecule of Claim 1 , wherein the isolated polypeptide molecule stimulates an immunogenic specific Tuberculosis Bacterium (TB) response in a host.

3. An isolated polypeptide molecule comprising an immunogenic portion of a M. tuberculosis antigen, wherein said antigen comprises an amino acid sequence selected from the group consisting of: a) an amino acid sequence encoded by a nucleic acid having greater than or equal to
about 70% identity with SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, or combination thereof;
b) an amino acid sequence encoded by a nucleic acid molecule having greater than or
equal to about 70% identity with coding region of SEQ ID NO: 1, 3, 5, 7, 9, 11, 13,

15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, or combination
thereof;
c) a an amino acid sequence encoded by a complement having greater than or equal to
about 70% identity with of SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25,
27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, or combination thereof;
d) an amino acid sequence encoded by a nucleic acid molecule having greater than or
equal to about 70% identity with a molecule that hybridizes to SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, or
combination thereof; and
e) an amino acid sequence having greater than or equal to about 70% similarity to a
sequence set forth in SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, or combination thereof.

4. The isolated polypeptide molecule of Claim 3, wherein the isolated polypeptide molecule stimulates an immunogenic specific TB response in a host.

5. The isolated polypeptide molecule of Claim 3, wherein the nucleic acid molecule has greater than or equal to about 80% identity or similarity, respectively, with said sequences.

6. The isolated polypeptide molecule of Claim 5, wherein the nucleic acid molecule has greater than or equal to about 90% identity or similarity, respectively, with said sequences.

7. An isolated nucleic acid molecule that encodes a polypeptide molecule that comprises an immunogenic portion of a M tuberculosis antigen, or a variant of said antigen that differs only in conservative substitutions and/or modifications, wherein said antigen is encoded by a nucleic acid molecule having a sequence selected from the group consisting of:
a) SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39,
41, 43, 45, 47, or combination thereof;
b) the coding region of SEQ ID NO:1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29,

31, 33, 35, 37, 39, 41, 43, 45, 47, or combination thereof;
c) a complement of SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, or combination thereof;
d) that hybridizes to SEQ ID NO:1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, or combination thereof; and.
e) that encodes SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48 or combination thereof.

8. The isolated nucleic acid molecule of Claim 7, wherein the isolated nucleic acid molecule encodes a polypeptide molecule that stimulates an immunogenic specific TB response in a host.

9. The isolated nucleic acid molecule of Claim 7, wherein the nucleic acid molecule is an RNA molecule.

10. An isolated nucleic acid molecule that encodes a polypeptide molecule that comprises an immunogenic portion of a M. tuberculosis antigen, wherein said antigen is encoded by a nucleic acid molecule having greater than or equal to about 70 % identity with a sequence selected from the group consisting of:
a) SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39,
41, 43, 45, 47, or combination thereof;
b) the coding region of SEQ ID NO: 1 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27,
29, 31, 33, 35, 37, 39, 41, 43, 45, 47, or combination thereof;
c) a complement of SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, or combination thereof;

d) that hybridizes to SEQ ID NO: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, or combination thereof; and
e) that encodes SEQ ID NO: 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36, 38, 40, 42, 44, 46, 48, or combination thereof.

11. The isolated nucleic acid molecule of Claim 15, wherein the nucleic acid molecule has greater than or equal to about 80% identity with said sequences.

12. The isolated nucleic acid molecule of Claim 16, wherein the nucleic acid molecule has greater than or equal to about 90% identity with said sequences.

13. A vector or plasmid that comprises the nucleic acid molecule of Claim 7.

14. A host cell transformed with the nucleic acid sequence of Claim 7.

15. An antibody that binds to a polypeptide of Claim 1.

16. A fusion protein comprising a polypeptide selected from the group consisting of:
a) at least one of the polypeptides of Claim 1 ;
b) at least two of the polypeptides of Claim 1 ;
c) at least one polypeptide of Claim 1 and a known M. tuberculosis antigen; and
d) at least one polypeptide of Claim 1 and an M. tuberculosis antigen presented on a
MHC Class-2 molecule.

17. A method for stimulating a specific immunogenic TB response in an individual, or
preventing or reducing the severity of TB disease, the method comprises administering an amount of one or more of the polypeptide molecules of Claim 1

18. The method of Claim 17, wherein the polypeptide molecule or the nucleic acid molecule is administered in a carrier.

19. A method for stimulating a specific immunogenic TB response in an individual, or
preventing or reducing the severity of TB disease, the method comprises administering an amount of one or more of the nucleic acid molecules of Claim 7.

20. A method for monitoring treatment of the TB disease in an individual, the method
comprises:
a) detecting the level of one or more of the polypeptide molecules of Claim 1 a sample from the individual; and
b) comparing the level of the one or more molecules with a standard;
wherein a level of molecules that is higher than the standard indicates that ineffective
treatment, and a level that is less than or equal to the level indicates effective treatment.

21. A method for monitoring treatment of the TB disease in an individual, the method
comprises:
a) detecting the level of one or more polypeptide molecules of Claim 1 in a sample
from the individual at more than one time points; and
b) comparing the level of the one or more polypeptide molecules at the one or more
time points;
wherein an increase in the level of the molecules indicates that ineffective treatment, and decrease or no change in the level indicates effective treatment.

22. A method of diagnosing TB disease in an individual, the method comprises detecting the presence or absence of one or more of the polypeptide molecules of Claim 1.

23. A method of distinguishing between TB disease and immunity to the TB disease in an individual, the method comprises:
a) detecting the presence or absence of one or more of the polypeptide molecules of

Claim 1 ; and
b) measuring the stimulation of a TB specific immune response in the individual.

24. The method of Claim 23, wherein measuring the stimulation of a TB specific immune
response includes measuring cell proliferation, interleukin-12 production, interferon-γ
levels, or a combination thereof, in a sample from the individual.

25. A method for detecting M. tuberculosis infection in a biological sample, the method
comprises assessing the presence of one or more of the polypeptide molecules of Claim 1 in the sample, wherein the presence of the molecule indicates the presence of M. tuberculosis infection; and the absence of the molecule indicates the absence of M. tuberculosis infection.

26. A method for detecting M. tuberculosis infection in a biological sample, the method
comprises:
a) contacting the sample with an antibody that binds with a polypeptide molecule of
Claim 1, sufficiently to allow formation of a complex between the sample and the
antibody, to thereby form an antigen-antibody complex; and
b) detecting the antigen-antibody complex;
wherein the presence of the complex indicates the presence of M. tuberculosis infection; and the absence of a complex indicates the absence of M. tuberculosis infection.

27. The method of Claim 26, wherein said antibody is detectably labeled.

28. The method of Claim 27, wherein the method further includes contacting the sample with a second antibody specific to said antigen or said antigen-antibody complex.

29. The method of Claim 28, wherein the polypeptide or the antibody is bound to a solid
support.

30. The method of Claim 26, wherein the biological sample is urine.

31. A method for detecting M. tuberculosis infection in a biological sample, the method
comprises:
a) contacting the sample with at least two oligonucleotide primers in a polymerase
chain reaction, wherein at least one of the oligonucleotide primers is specific for one or more of the isolated nucleic acid molecule of Claim 7, sufficiently to allow
amplification of the primers; and
b) detecting in the sample the amplified nucleic acid sequence;
wherein the presence the amplified nucleic acid sequence indicates M. tuberculosis
infection, and the absence of the amplified nucleic acid sequence indicates an absence of M. tuberculosis infection

32. The method of Claim 31, wherein at least one of the oligonucleotide primers comprises at least about 10 contiguous bases.

33. A method for detecting M. tuberculosis infection in a biological sample, the method
comprises:
a) contacting the sample with one or more oligonucleotide probes specific for the
nucleic acid molecule of Claim 7 under high stringency conditions, sufficiently to
allow hybridization between the sample and the probe; and
b) detecting the nucleic acid molecule that hybridizes to the oligonucleotide probe in
the sample;
wherein the presence of hybridization of the probe indicates M. tuberculosis infection, and the absence of hybridization indicates an absence of M tuberculosis infection.

34. The method of Claim 33, wherein the probe comprises at least about 15 contiguous bases.

35. A composition that comprises the polypeptide sequence of Claim 1 and a physiologically acceptable carrier.

36. The composition of Claim 35, further including an immune response enhancer.

37. The composition of Claim 36, wherein the immune response enhancer is an adjuvant or another TB antigen.

38. The composition of Claim 37, wherein the composition is a vaccine composition.

39. The composition of Claim 35, wherein the adjuvant includes at least one component selected from the group consisting of 3D-MPL and QS21.

40. The composition of Claim 35, wherein the composition is formulated in an oil in water emulsion.

41. The composition of Claim 36, wherein the immune response enhancer is an
immunostimulatory cytokine or chemokine.

42. A kit for diagnosing the presence or absence of M. tuberculosis infection in a person, the kit comprises one or more reagents for detecting the polypeptide molecule of Claim 1.

43. A kit that comprises:
a) one or more nucleic acid molecules having a sequence of SEQ ID NO: 1 , 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, or
combination thereof; the complements of said sequences, and nucleic acid sequences that hybridize to a sequence recited in SEQ ID NO:1, 3, 5, 7, 9, 11, 13, 15, 17, 19,
21, 23, 25, 27, 29, 31, 33, 35, 37, 39, 41, 43, 45, 47, or combination; and
b) a detection reagent.

44. A pharmaceutical composition comprising the polypeptide of Claim I5 and a carrier.