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- Nachgewiesen in: USPTO Patent Applications
- Sprachen: English
- Document Number: 20120245089
- Publication Date: September 27, 2012
- Appl. No: 13/496385
- Application Filed: September 20, 2010
- Assignees: ABRAXIS BIOSCIENCE, LLC (Los Angeles, CA, US)
- Claim: 1. A method of treating a tumor in a mammal with a chemotherapeutic regimen comprising: a. Preparing a plurality of histologic sections of the tumor for immunohistology; b. immunostaining one or more of the histologic sections of the tumor with a first anti-SPARC antibody, wherein the first anti-SPARC antibody preferentially stains SPARC in tumor cells; c. immunostaining one or more of the histologic sections of the tumor with a second anti-SPARC antibody, wherein the second anti-SPARC antibody preferentially stains SPARC in fibroblasts; d. determining the staining of tumor cells, fibroblasts, inflammatory cells, acellular stroma/matrix, blood vessels, nerve tissue, and normal anatomy within the tumor, or any combinations thereof, with the first anti-SPARC antibody and the staining of tumor cells, fibroblasts, inflammatory cells, acellular stroma/matrix, blood vessels, nerve tissue, and normal anatomy within the tumor, or any combinations thereof, with the second antibody, thereby determining a SPARC microenvironment signature (SMS); e. administering a therapeutically effective amount of the chemotherapeutic regimen if the tumor SMS satisfies the criteria of a predefined SMS.
- Claim: 2. The method of claim 1, wherein the predefined SMS comprises immunostaining with a composite profile with at least 49% of the stroma staining positive with first antibody and at least a Fibroblast Score of 66, Fibroblast Intensity of 41, Tumor Intensity of 26, Inflammatory Cells Intensity of 51, Inflammatory Cells Score of 55, Blood Vessel % of 33, Tumor Score of 54, Blood Vessel Intensity of 64, Fibroblast % of 54, Blood Vessel Intensity of 64, Inflammatory Cells % of 43, and Stroma Score of 62 staining with the second antibody, wherein the therapy is a regimen comprising nab-paclitaxel and the tumor is pancreatic cancer.
- Claim: 3. The method of claim 1, wherein the tumor is selected from the group consisting of oral cavity tumors, pharyngeal tumors, digestive system tumors, respiratory system tumors, bone tumors, cartilaginous tumors, bone metastases, sarcomas, skin tumors, melanoma, breast tumors, genital system tumors, urinary tract tumors, orbital tumors, brain and central nervous system tumors, gliomas, endocrine system tumors, thyroid tumors, esophageal tumors, gastric tumors, small intestinal tumors, colonic tumors, rectal tumors, anal tumors, liver tumors, gall bladder tumors, pancreatic tumors, laryngeal tumors, tumors of the lung, bronchial tumors, non-small cell lung carcinoma, small cell lung carcinoma, uterine cervical tumors, uterine corpus tumors, ovarian tumors, vulvar tumors, vaginal tumors, prostate tumors, prostatic carcinoma, testicular tumors, tumors of the penis, urinary bladder tumors, tumors of the kidney, tumors of the renal pelvis, tumors of the ureter, head and neck tumors, parathyroid cancer, Hodgkin's disease, Non-Hodgkin's lymphoma, multiple myeloma, leukemia, acute lymphocytic leukemia, chronic lymphocytic leukemia, acute myeloid leukemia, and chronic myeloid leukemia.
- Claim: 4. The method of claim 3, wherein the tumor is a pancreatic cancer.
- Claim: 5. The method of claim 1, wherein the mammal is a human.
- Claim: 6. The method of claim 1, wherein the chemotherapeutic regimen comprises paclitaxel.
- Claim: 7. The method of claim 6, wherein the chemotherapeutic regimen comprises nab-paclitaxel.
- Claim: 8. A method for predicting the response of a tumor in a mammal to a chemotherapeutic regimen comprising: a. preparing a plurality of histologic sections of the tumor to obtain a SPARC microenvironment signature (SMS); b. immunostaining one or more of the histologic sections of the tumor with a first anti-SPARC antibody, wherein the first anti-SPARC antibody preferentially stains SPARC in tumor cells; c. immunostaining one or more of the histologic sections of the tumor with a second anti-SPARC antibody, wherein the second anti-SPARC antibody preferentially stains SPARC in fibroblasts; d. determining the staining of tumor cells, fibroblasts, inflammatory cells, acellular stroma/matrix, blood vessels, nerve tissue, and normal anatomy within the tumor, or any combinations thereof, with the first anti-SPARC antibody and the staining of tumor blood vessels and tumor stroma with the second antibody; and e. predicting a positive response to the chemotherapeutic regimen if a predefined SMS is demonstrated by the immunostaining.
- Claim: 9. The method of claim 8, wherein the predefined SMS comprises immunostaining with a composite profile with at least 82% of the stroma staining positive with first antibody and at least a Fibroblast Score of 87, Fibroblast Intensity of 68, Tumor Intensity of 49, Inflammatory Cells Intensity of 42, Inflammatory Cells Score of 67, Blood Vessel % of 68, Tumor Score of 76, Blood Vessel Intensity of 46, Fibroblast % of 51, Blood Vessel Intensity of 75, Inflammatory Cells % of 59, and Stroma Score of 62 staining with the second antibody, wherein the therapy is a regimen comprising nab-paclitaxel and the tumor is pancreatic cancer.
- Claim: 10. The method of claim 8, wherein the tumor is selected from the group consisting of oral cavity tumors, pharyngeal tumors, digestive system tumors, respiratory system tumors, bone tumors, cartilaginous tumors, bone metastases, sarcomas, skin tumors, melanoma, breast tumors, genital system tumors, urinary tract tumors, orbital tumors, brain and central nervous system tumors, gliomas, endocrine system tumors, thyroid tumors, esophageal tumors, gastric tumors, small intestinal tumors, colonic tumors, rectal tumors, anal tumors, liver tumors, gall bladder tumors, pancreatic tumors, laryngeal tumors, tumors of the lung, bronchial tumors, non-small cell lung carcinoma, small cell lung carcinoma, uterine cervical tumors, uterine corpus tumors, ovarian tumors, vulvar tumors, vaginal tumors, prostate tumors, prostatic carcinoma, testicular tumors, tumors of the penis, urinary bladder tumors, tumors of the kidney, tumors of the renal pelvis, tumors of the ureter, head and neck tumors, parathyroid cancer, Hodgkin's disease, Non-Hodgkin's lymphoma, multiple myeloma, leukemia, acute lymphocytic leukemia, chronic lymphocytic leukemia, acute myeloid leukemia, and chronic myeloid leukemia.
- Claim: 11. The method of claim 10, wherein the tumor is a pancreatic tumor.
- Claim: 12. The method of claim 8, wherein the mammal is a human.
- Claim: 13. The method of claim 8, wherein the chemotherapeutic regimen comprises the administration of paclitaxel.
- Claim: 14. The method of claim 8, wherein the chemotherapeutic regimen comprises the administration of nab-paclitaxel.
- Claim: 15. A method of predicting if a mammal with a tumor has a low risk of the progression of that tumor comprising: a. preparing a plurality of histologic sections of the tumor to obtain a SPARC microenvironment signature (SMS); b. immunostaining one or more of the histologic sections of the tumor with a first anti-SPARC antibody, wherein the first anti-SPARC antibody preferentially stains SPARC in tumor cells; c. immunostaining one or more of the histologic sections of the tumor with a second anti-SPARC antibody, wherein the second anti-SPARC antibody preferentially stains SPARC in fibroblasts; d. determining the staining of tumor cells, fibroblasts, inflammatory cells, acellular stroma/matrix, blood vessels, nerve tissue, and normal anatomy within the tumor, or any combinations thereof, with the first anti-SPARC antibody and the staining of tumor cells, fibroblasts, inflammatory cells, acellular stroma/matrix, blood vessels, nerve tissue, and normal anatomy within the tumor, or any combinations thereof, with the second antibody; and e. determining that there is a low risk of progression if the tumor SMS satisfies the criteria of a predefined SMS.
- Claim: 16. The method of claim 15, wherein the tumor is breast cancer and the predefined SMS comprises immunostaining with a composite profile with at least 82% of the stroma staining positive with first antibody and at least a Fibroblast Score of 87, Fibroblast Intensity of 68, Tumor Intensity of 49, Inflammatory Cells Intensity of 42, Inflammatory Cells Score of 67, Blood Vessel % of 68, Tumor Score of 76, Blood Vessel Intensity of 46, Fibroblast % of 51, Blood Vessel Intensity of 75, Inflammatory Cells % of 59, and Stroma Score of 62 staining with the second antibody, wherein the therapy is a regimen comprising the administration of nab-paclitaxel, and wherein the tumor is pancreatic cancer.
- Claim: 17. The method of claim 15, wherein the tumor is selected from the group consisting of oral cavity tumors, pharyngeal tumors, digestive system tumors, respiratory system tumors, bone tumors, cartilaginous tumors, bone metastases, sarcomas, skin tumors, melanoma, breast tumors, genital system tumors, urinary tract tumors, orbital tumors, brain and central nervous system tumors, gliomas, endocrine system tumors, thyroid tumors, esophageal tumors, gastric tumors, small intestinal tumors, colonic tumors, rectal tumors, anal tumors, liver tumors, gall bladder tumors, pancreatic tumors, laryngeal tumors, tumors of the lung, bronchial tumors, non-small cell lung carcinoma, small cell lung carcinoma, uterine cervical tumors, uterine corpus tumors, ovarian tumors, vulvar tumors, vaginal tumors, prostate tumors, prostatic carcinoma, testicular tumors, tumors of the penis, urinary bladder tumors, tumors of the kidney, tumors of the renal pelvis, tumors of the ureter, head and neck tumors, parathyroid cancer, Hodgkin's disease, Non-Hodgkin's lymphoma, multiple myeloma, leukemia, acute lymphocytic leukemia, chronic lymphocytic leukemia, acute myeloid leukemia, and chronic myeloid leukemia.
- Claim: 18. The method of claim 17, wherein the tumor is a pancreatic cancer.
- Claim: 19. The method of claim 17, wherein the tumor is a breast cancer.
- Claim: 20. The method of claim 15, wherein the mammal is a human.
- Claim: 21. The method of claim 15, wherein the mammal is treated with a chemotherapeutic regimen that comprises paclitaxel.
- Claim: 22. The method of claim 15, wherein the chemotherapeutic regimen comprises the administration of nab-paclitaxel.
- Claim: 23. A method of treating a tumor from a first mammal with a therapy comprising: a. determining two or more predictive SMS's for the therapy comprising: i. preparing a plurality of histologic sections of tumors from other mammals with known outcomes for the therapy; ii. immunostaining one or more of the histologic sections of each of the tumors from the other mammals with known outcomes for the therapy, with a first anti-SPARC antibody, wherein the first anti-SPARC antibody preferentially stains SPARC in tumor cells; iii. immunostaining one or more of the histologic sections of each of the tumors from the other mammals with known outcomes for the therapy, with a second anti-SPARC antibody, wherein the second anti-SPARC antibody preferentially stains SPARC in fibroblasts; iv. determining the immunostaining pattern of each of the tumors from other mammals with known outcomes for the therapy, for tumor cells, fibroblasts, inflammatory cells, acellular stroma/matrix, blood vessels, nerve tissue, and normal anatomy within the tumors from other mammals with known outcomes for the therapy, or any combinations thereof, with the first anti-SPARC antibody and the immunostaining of tumor cells, fibroblasts, inflammatory cells, acellular stroma/matrix, blood vessels, nerve tissue, and normal anatomy within the tumors from other mammals with known outcomes for the therapy, or any combinations thereof, with the second antibody, thereby determining the SMS of each tumor from the other mammals with known outcomes for the therapy; v. clustering the tumor SMS's of each tumor from the other mammals with known outcomes for the therapy into two or more outcome groups, wherein the SMS centroid of each outcome group defines a predictive SMS; b. determining the SMS of the tumor from the first mammal by a process comprising: i. preparing a plurality of histologic sections of the tumor from the first mammal; ii. immunostaining one or more of the histologic sections of the tumor from the first mammal with a first anti-SPARC antibody, wherein the first anti-SPARC antibody preferentially stains SPARC in tumor cells; iii. immunostaining one or more of the histologic sections of the tumor from the first mammal with a second anti-SPARC antibody, wherein the second anti-SPARC antibody preferentially stains SPARC in fibroblasts, iv. determining the immunostaining pattern of the tumor in the first mammal for tumor cells, fibroblasts, inflammatory cells, acellular stroma/matrix, blood vessels, nerve tissue, and normal anatomy within the tumor from the first mammal, or any combinations thereof, with the first anti-SPARC antibody and the immunostaining of the tumor from the first mammal of tumor cells, fibroblast, inflammatory cells, acellular stroma/matrix, blood vessels, nerve tissue, and normal anatomy within the tumor from the first mammal, or any combinations thereof, with the second antibody, thereby determining the first mammal's tumor SMS; c. determining the Euclidian distance of the tumor from the first mammal's SMS to the predictive SMS's determined in (a) and classify the tumor from the first mammal as a member of the outcome group with the closest predictive SMS; d. administering a therapeutically effective amount of the therapy to the first mammal if the tumor from the first mammal's SMS maps to an outcome group that responds to the therapy.
- Claim: 24. The method of claim 23, wherein the tumor from the first mammal is of the same type as at the tumors from other mammals with known outcomes for the therapy.
- Claim: 25. The method of claim 23, wherein the therapy comprises the administration of nab-paclitaxel.
- Claim: 26. The method of claim 23, wherein the tumor from the first mammal is a pancreatic cancer.
- Claim: 27. The method of claim 23, wherein the clustering of the tumor SMS's of each tumor from the other mammals with known outcomes for the therapy is performed by one or more of K-means, Self Organizing Maps and Hierarchical clustering.
- Current U.S. Class: 514/152
- Current International Class: 01; 40; 61; 61; 61; 61
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