Claims for Patent: 8,583,380

Summary for Patent: 8,583,380

Title:	Methods for stratifying and annotating cancer drug treatment options
Abstract:	Personalized medicine involves the use of a patient\'s molecular markers to guide treatment regimens for the patient. The scientific literature provides multiple examples of correlations between drug treatment efficacy and the presence or absence of molecular markers in a patient sample. Methods are provided herein that permit efficient dissemination of scientific findings regarding treatment efficacy and molecular markers found in patient tumors to health care providers.
Inventor(s):	Stephan; Dietrich (San Francisco, CA), Norviel; Vern (San Jose, CA), Warrington; Janet (Los Altos, CA), Dolginow; Doug (Potomac, MD)
Assignee:	Aueon, Inc. (Menlo Park, CA)
Application Number:	13/060,425
Patent Claims:	1. A method for generating a personalized cancer drug treatment option report comprising: a. obtaining a sample from a subject, wherein the obtaining comprises fine needle aspiration; b. determining a status of more than one molecular marker in the sample, wherein the determining comprises de novo DNA sequencing; c. stratifying one or more cancer drug treatment options in a report based on the status of the more than one molecular marker, wherein the stratifying comprises indicating on the report one or more drug treatment options predicted to be efficacious in the subject based on scientific information and the status of the more than one molecular marker, and indicating on the report one or more drug treatment options predicted not to be efficacious in the subject based on scientific information and the status of the more than one molecular marker; d. annotating the report based on the status of the more than one molecular marker; and e. administering one or more drugs to the subject based on the stratifying. 2. The method of claim 1, wherein the subject is a cancer patient. 3. The method of claim 2, wherein the cancer patient is a colon cancer patient. 4. The method of claim 1, wherein the sample is a tumor biopsy. 5. The method of claim 1, wherein the sample is preserved by formalin-fixing and paraffin-embedding (FFPE). 6. The method of claim 1, wherein the de novo DNA sequencing comprises bridge amplification of DNA. 7. The method of claim 1, wherein the sample comprises genomic DNA from an FFPE sample and the determining comprises bridge amplification. 8. The method of claim 1, further comprising purifying cancer cells from the sample. 9. The method of claim 8, wherein the purifying comprises flow sorting or laser capture microdissection. 10. The method of claim 9, wherein the sample is a tumor biopsy, the sample is frozen, and the purifying comprises flow sorting. 11. The method of claim 1, wherein the stratifying comprises stratifying the drug treatment options for a condition in a clinical practice guideline. 12. The method of claim 11, wherein the condition is colon cancer. 13. The method of claim 1, wherein the stratifying is based on information in scientific literature. 14. The method of claim 1, wherein the stratifying is further based on a status of one or more molecular markers in drug absorption, distribution, metabolism, or excretion genes in a sample from the subject. 15. The method of claim 14, wherein the determining comprises analyzing a sequence of UGT1A1 for one or more SNPs. 16. The method of claim 1, wherein the stratifying is further based on whether the subject is hypermetabolic. 17. The method of claim 1, wherein the stratifying is further based on a CYP450 status of the subject. 18. The method of claim 1, wherein the stratifying and/or the annotating is further based on clinical information for the subject. 19. The method of claim 1, wherein the stratifying further comprises ranking one or more drug treatment options with a higher likelihood of efficacy higher than one or more drug treatment options with a lower likelihood of efficacy or for which no information exists with regard to treating subjects with the determined status of the more than one molecular marker. 20. The method of any one of claims 1 or 19, wherein the stratifying is indicated by color coding the listed drug treatment options on the report based on a rank of a predicted efficacy of the drug treatment options. 21. The method of claim 1, wherein the annotating comprises annotating the report for a condition in a clinical practice guideline. 22. The method of claim 1, wherein the annotating comprises listing one or more FDA-approved drugs for off-label use, one or more drugs listed in an anti-cancer treatment compendia, and/or one or more experimental drugs found in scientific literature, in the report. 23. The method of claim 1, wherein the annotating comprises connecting a listed drug treatment option to a reference containing scientific information regarding the drug treatment option. 24. The method of claim 23, wherein the scientific information is from a peer-reviewed article from a medical journal. 25. The method of claim 23, wherein the annotating comprises using information from a commercial database. 26. The method of claim 1, wherein the annotating comprises providing a link to information on a clinical trial for a drug treatment option in the report. 27. The method of claim 1, wherein the annotating comprises presenting information in a pop-up box or fly-over box near provided drug treatment options in an electronic based report. 28. The method of claim 1, wherein the annotating comprises adding information to the report selected from the group consisting of one or more drug treatment options, scientific information regarding one or more drug treatment options, one or more links to scientific information regarding one or more drug treatment options, one or more links to citations for scientific information regarding one or more drug treatment options, and clinical trial information regarding one or more drug treatment options. 29. The method of claim 1, wherein the sample comprises colon cancer cells, the more than one molecular marker comprises c-kit, and the one or more drug treatment options comprise imatinib mesylate. 30. The method of claim 1, wherein the sample comprises colon cancer cells, the more than one molecular marker comprises Kras, and the one or more drug treatment options comprise cetuximab, panitumumab, or bevacizumab. 31. The method of claim 30, wherein exon 2 of Kras does not have a mutation, and the stratifying and/or annotating comprises recommending cetuximab or panitumumab monotherapy for the subject. 32. The method of claim 30, wherein exon 2 of Kras has a mutation, and the stratifying and/or annotating comprises recommending cetuximab or panitumumab monotherapy not be given to the subject. 33. The method of claim 1, wherein the sample comprises colon cancer cells, the more than one molecular marker comprises BRAF, and the one or more drug treatment options comprise cetuximab or panitumumab. 34. The method of claim 33, wherein the determining comprises determining a presence or absence of a BRAF V600E mutation. 35. The method of claim 33, wherein BRAF sequence encodes a V600E mutation, and the stratifying and/or annotating comprises providing a recommendation in the report to treat the subject with sorafenib and cetuximab and/or panitumumab. 36. The method of claim 1, wherein the determining comprises determining a status of microsatellite sequences. 37. The method of claim 36, wherein a. the microsatellite sequences display low-frequency microsatellite instability, and b. wherein the sample is a stage II or stage III colon cancer, and c. wherein the stratifying and/or annotating comprises recommending fluorouracil-based adjuvant chemotherapy for the subject. 38. The method of claim 36, wherein a. the microsatellite sequences display high-frequency microsatellite instability, and b. wherein the sample is a stage II or stage III colon cancer, and c. wherein the stratifying and/or annotating comprises making a recommendation to not administer fluorouracil-based adjuvant chemotherapy for the subject. 39. The method of claim 1, wherein the determining comprises determining EGFR copy number. 40. The method of claim 39, wherein the EGFR copy number is increased relative to normal, and the stratifying and/or annotating comprises recommending cetuximab or panitumumab monotherapy to the subject. 41. The method of claim 1, wherein the determining comprises determining if the sample has 18q chromosome loss. 42. The method of claim 41, wherein the subject is a stage II colorectal cancer patient with chromosome 18q allelic loss, and the stratifying and/or annotating comprises recommending adjuvant therapy for the subject. 43. The method of claim 1, wherein the determining comprises determining thymidylate synthase levels. 44. The method of claim 43, wherein the thymidylate synthase levels are high, and the stratifying and/or annotating comprises recommending adjuvant 5-FU-based chemotherapy not be given to the subject. 45. The method of claim 43, wherein the thymidylate synthase levels are low, and the stratifying and/or annotating comprises recommending to treat the subject with adjuvant 5-FU-based chemotherapy. 46. The method of claim 1, wherein the sample comprises colon cancer cells, the more than one molecular marker comprises Topo 1, and the one or more drug treatment options comprise 5-FU, irinotecan, or capecitabine. 47. The method of claim 46, wherein the Topol expression is low, and the stratifying and/or annotating comprises making a recommendation to not treat the subject with irinotecan. 48. The method of claim 46, wherein the Topo 1 expression is moderate to high, and the stratifying and/or annotating comprises making a recommendation to treat the subject with irinotecan. 49. The method of claim 1, further comprising sending a kit to a health care provider that provides health care to the subject. 50. The method of claim 49, wherein the kit comprises a reagent for preserving RNA in cells or tissues. 51. The method of claim 1, further comprising establishing an in vitro culture using the sample. 52. The method of claim 51, further comprising high-throughput screening of FDA approved off-label drugs or experimental drugs using the in vitro culture. 53. The method of claim 1, further comprising establishing a xenograft model using the sample. 54. The method of claim 53, further comprising high-throughput screening of FDA approved off-label drugs or experimental drugs using the xenograft model. 55. The method of claim 52 or 54, wherein the sample is a tumor biopsy, the subject is a cancer patient with end stage cancer, and results of the high- throughput screening are used to determine an adjuvant therapy for administration to the cancer patient. 56. The method of claim 1, further comprising monitoring tumor antigen for recurrence detection. 57. The method of claim 1, wherein the stratifying is based on analysis of a Kaplan-Meier survival curve. 58. The method of claim 1, further comprising charging a fee for generating the report. 59. A method for generating a personalized cancer drug treatment option report comprising: a. obtaining a sample from a subject, wherein the obtaining comprises fine needle aspiration; b. determining a status of more than one molecular marker in the sample, wherein the determining comprises de novo DNA sequencing; c. stratifying drug treatment options listed in a clinical practice guideline for a condition based on the status of the more than one molecular marker in the sample, wherein the stratifying comprises indicating on the clinical practice guideline one or more drug treatment options predicted to be efficacious in the subject based on scientific information and the status of the more than one molecular marker, and indicating on the clinical practice guideline one or more drug treatment options predicted not to be efficacious in the subject based on scientific information and the status of the more than one molecular marker; d. optionally annotating the clinical practice guideline with information comprising information regarding one or more additional drug treatment options not listed in the clinical practice guideline for the condition, wherein the information is included based on the status of the more than one molecular marker in the sample; e. administering one or more drugs to the subject based on the stratifying. 60. The method of claim 59, wherein the one or more additional drug treatment options are described in an anti-cancer treatment compendium. 61. The method of claim 59, wherein the one or more additional drug treatment options comprise a drug used in a clinical trial. 62. The method of claim 59, wherein the one or more additional drug treatment options comprise a drug described in a scientific journal article. 63. The method of claim 59, wherein the annotating further comprises listing information in the clinical practice guideline referencing one or more scientific journal articles that describe use of one or more additional drug treatment options. 64. The method of claim 59, wherein the one or more additional drug treatment options target a molecular marker that is in a pathway for which a status of another molecular marker indicates that targeting the pathway would be efficacious for treating the subject. 65. The method of claim 59, wherein the stratifying is indicated by color coding drug treatment options listed on the clinical practice guideline. 66. The method of claim 65, wherein the color code comprises a shade of green, a shade of yellow, and a shade of red. 67. The method of claim 66, wherein a color coded drug treatment option comprising a green shade is a drug that is recommended to the subject based on the status of the more than one molecular marker. 68. The method of claim 66, wherein a color coded drug treatment option comprising a yellow shade is a drug that at least one piece of information supports recommending the drug as a treatment option to the subject based on the status of the more than one molecular marker and at least one piece of information does not support recommending the drug as a treatment option. 69. The method of claim 66, wherein a color coded drug treatment option comprising a red shade is a drug for which the status of the more than one molecular marker does not support recommending the drug treatment option to the subject. 70. The method of claim 1, wherein the more than one molecular marker comprises c-kit, Kras, BRAF, microsatellite sequence, EGFR, chromosome 18q, thymidylate synthase, and Topol. 71. The method of claim 70, wherein the one or more cancer drug treatment options comprise imatinib mesylate, cetuximab, panitumumab, bevacizumab, 5-FU, capecitabine, and/or irinotecan. 72. The method of claim 59, wherein the more than one molecular marker comprises c-kit, Kras, BRAF, microsatellite sequence, EGFR, chromosome 18q, thymidylate synthase, and Topol. 73. The method of claim 72, wherein the drug treatment options comprise imatinib mesylate, cetuximab, panitumumab, bevacizumab, 5-FU, capecitabine, and/or irinotecan. 74. The method of claim 1, wherein the status of the more than one molecular marker comprises a substitution, insertion, deletion, copy number alteration, and/or rearrangement. 75. The method of claim 1, wherein the determining the status of the more than one molecular marker is performed in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. 76. The method of claim 1, wherein the sample comprises greater than 15% tumor. 77. The method of claim 1, wherein the sample comprises greater than 20% tumor. 78. The method of claim 1, wherein the sample is reviewed by a pathologist. 79. The method of claim 1, wherein the sample comprises an unstained slide. 80. The method of claim 1, wherein the report comprises a hardcopy paper report. 81. The method of claim 1, wherein the report is accessed on a computer.

Details for Patent 8,583,380

Applicant	Tradename	Biologic Ingredient	Dosage Form	BLA	Approval Date	Patent No.	Expiredate
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	02/12/2004		2028-09-05
Eli Lilly And Company	ERBITUX	cetuximab	Injection	125084	03/28/2007		2028-09-05
Genentech, Inc.	AVASTIN	bevacizumab	Injection	125085	02/26/2004		2028-09-05
Amgen, Inc.	VECTIBIX	panitumumab	Injection	125147	09/27/2006		2028-09-05