IDENTIFICATION OF MHC CLASS I PHOSPHO-PEPTIDE ANTIGENS FROM BREAST CANCER UTILIZING SHLA TECHNOLOGY AND COMPLEMENTARY ENRICHMENT STRATEGIES

• US 20150225456A1
• Filed: 05/28/2013
• Published: 08/13/2015
• Est. Priority Date: 05/25/2012
• Status: Active Grant

• Current Assignee: Agenus Inc.
• Original Assignee: PhosImmune Inc. (Agenus Inc.), The Board of Regents of the University of Colorado (University of Colorado System)
• Inventors: Hunt, Donald F., Norris, Andrew, Shabanowitz, Jeffrey, English, Ann Michelle, Hilderbrand, William H., Hawkins, Oriana E.
• Granted Patent: US 10,640,535 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 39/0011 Cancer antigens
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 37/04 Immunostimulants
• CPC Class Codes: C07K 14/4748 Tumour specific antigens; Tumour rejection antigen precursors [TRAP], e.g. MAGE
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 2317/24 containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
• CPC Class Codes: C07K 2317/55 Fab or Fab'
• CPC Class Codes: C07K 7/06 having 5 to 11 amino acids
• CPC Class Codes: C07K 7/08 having 12 to 20 amino acids gastrins C07K14/595; somatostatins C07K14/655; melanotropins C07K14/68

Abstract

The present invention describes novel tumor-specific phosphorylated peptides, nucleic acids encoding those peptides, and antibodies generated against said peptides. The genes, peptides, and antibodies described herein may be used as diagnostic indicators of the presence of breast cancer and/or used in therapeutics to treat breast cancer.

Claims

1. An isolated phosphopeptide comprising a sequence selected from the group consisting of SEQ ID NOs:

70-171.

2. The isolated phosphopeptide of claim 1, wherein said sequence is selected from group consisting of SEQ ID NOs:

84, 87, 96, 102, 118, 121, 125, 126, 128, 132, 138, 145, 155, 164, and 165.

3. The isolated phosphopeptide of claim 1, wherein said sequence is selected from the group consisting of SEQ ID NOs:

118, 121, 132, 145, 164, and 165.

4. A composition comprising one or more phosphopeptides of claim 1 and a pharmaceutically acceptable carrier wherein the number is selected from the group consisting of 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29 and 30.

5. The composition of claim 4, wherein said composition has the ability to stimulate a T cell mediated immune response to at least one of said phosphopeptides.

6. The composition of claim 4, comprising a peptide capable of binding to the HLA-B*0702 allele on the MHC class I molecule.

7. The composition of claim 4, wherein the composition is capable of increasing the 5-year survival rate of breast cancer patients treated with the composition relative to average 5-year survival rates that could have been expected without treatment with the composition.

8. The composition of claim 4, wherein said composition comprises one or more phosphopeptides comprising a sequence selected from the group consisting of SEQ ID NOs:

84, 87, 96, 102, 118, 121, 125, 126, 128, 132, 138, 145, 155, 164, and 165 and a pharmaceutical carrier.

9. An in vitro population of dendritic cells comprising the composition of claim 4.

15. A method of inducing an immunogenic response comprising administering to a patient in need thereof a dose of the composition of claim 4.

16. A method of treating or preventing cancer comprising administering to a patient in need thereof a dose of the composition of claim 4.

19. A method of treating or preventing breast cancer comprising administering to a patient in need thereof the population of the dendritic cells of claim 9 in combination with a pharmaceutically acceptable carrier.

10. An antibody that specifically binds to a phosphopeptide comprising the sequence selected from the group consisting of SEQ ID NOs:

70-171.

11. The antibody of claim 10, wherein the phosphopeptide comprises a sequence selected from the group consisting of SEQ ID NOs:

84, 87, 96, 102, 118, 121, 125, 126, 128, 132, 138, 145, 155, 164, and 165.

12. The antibody of claim 10, wherein the antibody is polyclonal, monoclonal, chimeric, Fab fragments, or fragments produced by a Fab expression library.

13. A composition comprising the antibody of claim 10, further comprising a pharmaceutically acceptable carrier.

14. The composition of claim 13, further comprising an adjuvant.

17. A method of treating or preventing breast cancer comprising administering to a patient in need thereof a dose of a composition comprising an isolated phosphopeptide comprising a sequence selected from the group consisting of SEQ ID NOs:

70-171 in combination with a pharmaceutically acceptable carrier.

18. The method of claim 17, wherein the isolated phosphopeptide comprises a sequence selected from the group consisting of SEQ ID NO:

84, 87, 96, 102, 118, 121, 125, 126, 128, 132, 138, 145, 155, 164, and 165.

20. (canceled)