FILIP1L compositions and methods for treating cancer

• US 20160176935A1
• Filed: 03/01/2016
• Published: 06/23/2016
• Est. Priority Date: 12/03/2007
• Status: Abandoned Application

• Current Assignee: United States Department Of Health And Human Services
• Original Assignee: The United States of America As Represented By The Secretary of Agriculture
• Inventors: Libutti, Steven K., Kwon, Mijung, Tandle, Anita
• Application Number:
  US15/058,116
• Publication Number:
  US 20160176935A1
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 35/13 Tumour cells, irrespective of tissue of origin tumour vaccines A61K39/00
• CPC Class Codes: A61K 38/1709 from mammals
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 14/47 from mammals
• CPC Class Codes: C07K 14/4703 Inhibitors; Suppressors
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 2317/34 Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
• CPC Class Codes: G01N 2333/4703 Regulators; Modulating activity
• CPC Class Codes: G01N 2800/52 Predicting or monitoring the response to treatment, e.g. for selection of therapy based on assay results in personalised medicine; Prognosis
• CPC Class Codes: G01N 33/574 for cancer
• CPC Class Codes: G01N 33/57484 involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites

Abstract

A purified DOC1 polypeptide comprising a fragment of SEQ ID NO: 1 is provided, wherein the DOC1 polypeptide is not the full-length DOC1 polypeptide sequence. A method of inhibiting angiogenesis in a subject is provided comprising administering to a subject a nucleic acid encoding a DOC1 polypeptide, whereby a cell in the subject produces the DOC1 polypeptide, thus inhibiting angiogenesis. A method of inhibiting tumor growth in a subject is provided comprising administering to a subject a nucleic acid encoding a DOC1 polypeptide, whereby a cell in the subject produces the DOC1 polypeptide, thus inhibiting tumor growth.

Claims

1. A nucleic acid encoding a DOC1 polypeptide comprising a fragment of SEQ ID NO:

1, wherein the DOC1 polypeptide is not the full-length DOC1 polypeptide sequence, or encoding a polypeptide comprising an amino acid sequence that is at least about 95% identical to the DOC1 polypeptide.

2. A vector comprising the nucleic acid of claim 1.

3. A host cell comprising the vector of claim 2.

4. A method of inhibiting angiogenesis in a subject comprising administering to a subject a nucleic acid encoding a DOC1 polypeptide, whereby a cell in the subject produces the DOC1 polypeptide, thus inhibiting angiogenesis.

5. The method of claim 4, wherein the nucleic acid is administered locally.

6. The method of claim 4, wherein the nucleic acid is administered systemically.

7. The method of claim 4, wherein the nucleic acid is administered in a vector.

8. The method of claim 4, wherein the nucleic acid encodes SEQ ID NO:

1.

9. The method of claim 4, wherein the nucleic acid encodes a fragment of SEQ ID NO:

1.

10. The method of claim 9, wherein the fragment of SEQ ID NO:

1 is selected from the group consisting of amino acids amino acids 1-790 of SEQ ID NO;

1, amino acids 1-650 of SEQ ID NO;

1, amino acids 1-512 of SEQ ID NO;

1, amino acids 65-893 of SEQ ID NO;

1, amino acids 127-893 of SEQ ID NO;

1, and amino acids 127-650 of SEQ ID NO;

1.

11. A method of inhibiting tumor growth in a subject comprising administering to a subject a nucleic acid encoding a DOC1 polypeptide, whereby a cell in the subject produces the DOC1 polypeptide, thus inhibiting tumor growth.

12. The method of claim 11, wherein the nucleic acid is administered locally.

13. The method of claim 11, wherein the nucleic acid is administered systemically.

15. The method of claim 11, wherein the nucleic acid encodes SEQ ID NO:

1.

16. The method of claim 11, wherein the nucleic acid encodes a fragment of SEQ ID NO:

1.

17. The method of claim 16, wherein the fragment of SEQ ID NO:

1 is selected from the group consisting of amino acids 1-790 of SEQ ID NO;

1, amino acids 1-650 of SEQ ID NO;

1, amino acids 1-512 of SEQ ID NO;

1, amino acids 65-893 of SEQ ID NO;

1, amino acids 127-893 of SEQ ID NO;

1, and amino acids 127-650 of SEQ ID NO;

1.

18. An antibody that specifically binds to a DOC1 polypeptide comprising a fragment of SEQ ID NO:

1, wherein the DOC1 polypeptide is not the full-length DOC1 polypeptide sequence, with the proviso that the antibody does not specifically bind a fragment consisting of amino acids 3-52 or amino acids 510-893 of SEQ ID NO;

1.

14. The method of claim 19, wherein the nucleic acid is administered in a vector.

19. The antibody of claim 18, wherein the antibody specifically binds to a polypeptide selected from the group consisting of amino acids amino acids 1-790 of SEQ ID NO:

1, amino acids 1-650 of SEQ ID NO;

1, amino acids 1-512 of SEQ ID NO;

1, amino acids 65-893 of SEQ ID NO;

1, amino acids 127-893 of SEQ ID NO;

1, and amino acids 127-650 of SEQ ID NO;

1.

20. A method for classifying a cancer in a subject comprising:

a) contacting a test sample from a subject with an anti-DOC1 antibody;

b) detecting the binding of the anti-DOC1 antibody to a DOC1 polypeptide in the sample;

c) comparing the expression level of the DOC1 polypeptide in the test sample with the expression level of a DOC1 polypeptide in a reference sample for which a cancer classification is known; and

d) identifying a difference, if present, in the expression level of the DOC1 polypeptide in the test sample and reference sample, thereby classifying the cancer in the subject.

21. The method of claim 20, wherein a difference in the expression level of the DOC1 polypeptide in the test sample as compared to the reference sample indicates that the test sample has a different classification as the reference sample.

22. The method of claim 20, wherein a similar expression level of the DOC1 polypeptide in the sample as compared to the reference sample indicates that the test sample has the same classification as the reference sample.

23. The method of claim 20, wherein the reference sample is a sample from a subject with a known classification.

24. The method of claim 20, wherein the reference sample is from a database.

25. The method of claim 20, wherein the reference sample is a reference sample classified as a normal sample.

26. The method of claim 20, wherein the reference sample is a reference sample classified as cancerous.

27. A method for identifying a stage of cancer in a subject comprising:

a) contacting a test sample from a subject with an anti-DOC1 antibody;

b) detecting the binding of the anti-DOC1 antibody to a DOC1 polypeptide in the sample;

c) comparing the expression level of the DOC1 polypeptide in the test sample with the expression level of a DOC1 polypeptide in a reference sample for which a stage of cancer is known; and

d) identifying a difference, if present, in the expression level of the DOC1 polypeptide in the test sample and reference sample, thereby identifying the stage of cancer in the subject.

28. The method of claim 27, wherein a difference in the expression level of the DOC1 polypeptide in the test sample as compared to the reference sample indicates that the test sample has a different stage of cancer than the reference sample.

29. The method of claim 27, wherein a similar expression level of the DOC1 polypeptide in the test sample as compared to the reference sample indicates that the test sample has the same stage of cancer as the reference sample.

30. The method of claim 27, wherein the reference sample is a sample from a patient with a known stage of cancer.

31. The method of claim 27, wherein the reference sample is from a database.

32. A method of determining the efficacy of an anti-cancer treatment comprising:

a) determining the expression level of a DOC1 polypeptide in a sample obtained from the subject;

b) administering the anti-cancer treatment;

c) determining the expression level of a DOC1 polypeptide in a sample obtained from the subject after administration of the anti-cancer treatment; and

d) comparing the expression level of the DOC1 polypeptide in the sample obtained after the anti-cancer treatment with the sample obtained in step a) such that if there is a change in the expression level of the DOC1 polypeptide in the sample obtained after the anti-cancer treatment as compared to the sample obtained before administration of the anti-cancer treatment, wherein the change is associated with an improvement in the subject, the anti-cancer therapeutic is an effective anti-cancer therapeutic.

33. The method of claim 32, wherein the change is an increase in the expression levels of the DOC1 polypeptide.

34. The method of claim 32, wherein the change is a decrease in the expression levels of the DOC1 polypeptide.

35. A method of identifying a modulator of DOC1 expression comprising:

a) contacting a cell that is capable of expressing DOC1 with a putative modulator;

b) measuring DOC1 expression, wherein a change in DOC1 expression in the cell of step a) as compared to a cell that was not contacted with the putative modulator indicates the presence of a modulator of DOC1 expression.

36. The method of claim 35, wherein the change in DOC1 expression is an increase in DOC1 expression.

37. The method of claim 35, wherein the change in DOC1 expression is a decrease in DOC1 expression.

38. The method of claim 35, wherein DOC1 expression is measured by amplifying a DOC1 nucleic acid.

39. The method of claim 35, wherein DOC1 expression is measured by detecting a DOC1 polypeptide.

40. A purified DOC1 polypeptide comprising a fragment of SEQ ID NO:

2, wherein the DOC1 polypeptide is not the full-length DOC1 polypeptide sequence, and the fragment is at least 51 amino acids in length.

41. A purified DOC1 polypeptide comprising a fragment of SEQ ID NO:

3, wherein the DOC1 polypeptide is not the full-length DOC1 polypeptide sequence, and the fragment is at least 51 amino acids in length.

42. A purified DOC1 polypeptide comprising a fragment of SEQ ID NO:

1, wherein the DOC1 polypeptide is not the full-length DOC1 polypeptide sequence, and the fragment comprises amino acids 127-512 of SEQ ID NO;

1.